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t119 | t119_6 | yes | The review found promising evidence for the use of Chinese herbal medicine in reducing menstrual pain in the treatment of primary dysmenorrhoea, compared to conventional medicine such as NSAIDs and the oral contraceptive pill, acupuncture and heat compression. | Conventional treatment for primary dysmenorrhoea has a failure rate of 20% to 25% and may be contraindicated or not tolerated by some women. Chinese herbal medicine may be a suitable alternative. Objectives To determine the efficacy and safety of Chinese herbal medicine for primary dysmenorrhoea when compared with placebo, no treatment, and other treatment. Search methods The Cochrane Menstrual Disorders and Subfertility Group Trials Register (to 2006), MEDLINE (1950 to January 2007), EMBASE (1980 to January 2007), CINAHL (1982 to January 2007), AMED (1985 to January 2007), CENTRAL (The Cochrane Library issue 4, 2006), China National Knowledge Infrastructure (CNKI, 1990 to January 2007), Traditional Chinese Medicine Database System (TCMDS, 1990 to December 2006), and the Chinese BioMedicine Database (CBM, 1990 to December 2006) were searched. Citation lists of included trials were also reviewed. Selection criteria Any randomised controlled trials involving Chinese herbal medicine versus placebo, no treatment, conventional therapy, heat compression, another type of Chinese herbal medicine, acupuncture or massage. Exclusion criteria were identifiable pelvic pathology and dysmenorrhoea resulting from the use of an intra‐uterine contraceptive device. Data collection and analysis Quality assessment, data extraction and data translation were performed independently by two review authors. Attempts were made to contact study authors for additional information and data. Data were combined for meta‐analysis using either Peto odds ratios or relative risk (RR) for dichotomous data or weighted mean difference for continuous data. A fixed‐effect statistical model was used, where suitable. If data were not suitable for meta‐analysis, any available data from the trial were extracted and presented as descriptive data. Thirty‐nine randomised controlled trials involving a total of 3475 women were included in the review. A number of the trials were of small sample size and poor methodological quality. Results for Chinese herbal medicine compared to placebo were unclear as data could not be combined (3 RCTs). Chinese herbal medicine resulted in significant improvements in pain relief (14 RCTs; RR 1.99, 95% CI 1.52 to 2.60), overall symptoms (6 RCTs; RR 2.17, 95% CI 1.73 to 2.73) and use of additional medication (2 RCTs; RR 1.58, 95% CI 1.30 to 1.93) when compared to use of pharmaceutical drugs. Self‐designed Chinese herbal formulae resulted in significant improvements in pain relief (18 RCTs; RR 2.06, 95% CI 1.80 to 2.36), overall symptoms (14 RCTs; RR 1.99, 95% CI 1.65 to 2.40) and use of additional medication (5 RCTs; RR 1.58, 95% CI 1.34 to 1.87) after up to three months of follow‐up when compared to commonly used Chinese herbal health products. Chinese herbal medicine also resulted in better pain relief than acupuncture (2 RCTs; RR 1.75, 95% CI 1.09 to 2.82) and heat compression (1 RCT; RR 2.08, 95% CI 2.06 to 499.18). The review found promising evidence supporting the use of Chinese herbal medicine for primary dysmenorrhoea; however, results are limited by the poor methodological quality of the included trials. |
t120 | t120_1 | no | We investigated whether exhaled (breathing out) nitric oxide (a marker in the breath which can show a type of lung inflammation) can be useful to adjust asthma medications in children with asthma instead of following the usual ways that asthma medications are adjusted to get the best dose to control the asthma. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_2 | yes | Exhaled nitric oxide levels are easily obtained by getting the person to breathe into a commercially available analyser. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_3 | yes | We included all randomised controlled trials that compared adjustment of asthma medications by either usual clinical care (control group) versus using exhaled nitric oxide. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_4 | no | The participants included in the trials had asthma diagnosed as per relevant asthma guidelines. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_5 | no | The review included nine studies (involving 1426 children) that varied in a several ways including length of the study, exhaled nitric oxide cut‐off levels used for altering medicines and the way each study defined flare‐ups or attacks (called exacerbations). | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_6 | no | The exhaled nitric oxide cut‐off values used by the different studies as a basis for decreasing or increasing medicines also varied. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_7 | yes | The mean age of the participants ranged from 10 to 14 years old. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_8 | no | In this review, we found that guiding asthma medicines based on exhaled nitric oxide (compared to a control group) was beneficial in reducing the number of children who had at least one exacerbation during the study. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_9 | yes | In the control group where therapy was guided according to clinical symptoms, 40 children out of 100 had at least one exacerbation over 48.5 weeks, compared to 28 out of 100 children where treatment was guided by exhaled nitric oxide. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_10 | no | However, we found no difference between groups in other measures of asthma severity that impact on day‐to‐day clinical symptoms or inhaled corticosteroid dose (medications used to control asthma). | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_11 | no | Therefore, using exhaled nitric oxide levels to adjust asthma therapy may reduce the number of attacks that children with asthma have but does not impact on the day‐to‐day symptoms. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t120 | t120_12 | no | The level of evidence found ranged from moderate, when comparing the two groups for the number of children who had one or more exacerbations, to very low when comparing the number of exacerbations. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t121 | t121_1 | no | Routine digital vaginal examination (examination of the cervix with a finger) during pregnancy, used to reduce the prevalence of preterm birth, is not supported by evidence from randomized controlled trials. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_2 | yes | Preterm labour is often preceded by changes in the cervix although the woman does not experience any symptoms. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_3 | yes | Effective detection and appropriate management of risk of preterm birth is key to improved care. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_4 | yes | Repeat digital cervical assessment is a simple inexpensive technique that uses a disposable glove and takes only one or two minutes to complete. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_5 | no | It has been promoted as a routine intervention during pregnancy as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation), which can then be managed. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_6 | yes | It is in standard use in many parts of Europe, Africa and to a lesser extent in the US. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_7 | no | The review included two randomized controlled trials that enrolled a total of 7163 pregnant women. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_8 | yes | The number of women experiencing preterm birth was similar with and without routine digital vaginal examination when it was not medically indicated. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_9 | yes | One was a multicentre performed in countries where the intervention was routine and in countries where it was not. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t121 | t121_10 | yes | Causes for concern included the potential risk of infection and preterm labour from the vaginal examination as well as discomfort and embarrassment for the woman. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t122 | t122_1 | yes | Abdominal tuberculosis (TB) is a type of TB that affects the gut, the peritoneum (the lining of the abdominal cavity), abdominal lymph nodes, and, more rarely, the solid organs in the abdomen (liver, pancreas, and spleen). | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_2 | yes | Abdominal TB leads to severe illness in adults and children, and can cause complications, such as bowel rupture, which can lead to death. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_3 | no | Most current guidelines recommend treating people that have abdominal TB with antituberculous treatment (ATT) for six months, but some clinicians treat for longer periods due to concerns that six months is not adequate to achieve cure and prevent relapse of the disease after the end of treatment. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_4 | yes | Longer ATT regimens have disadvantages: patients may find it more difficult to adhere to the tablets; patients are exposed to the risk of side effects of ATT for longer periods; and the cost to health systems and to patients is greater. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_5 | yes | We included three trials with 328 participants that compared six‐month ATT with nine‐month ATT; two were from India and one was from South Korea. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_6 | yes | The trials were mostly of high quality, although two had concerns of risk of bias for detecting relapse of the disease. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_7 | no | All the trials included HIV‐negative adults with TB of the gut (gastrointestinal TB), and one also included TB of the peritoneum (peritoneal TB). | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_8 | no | The results show that relapse was an uncommon event, but we are uncertain whether or not there is a difference between the six‐month and nine‐month groups as numbers of participants are small ( very low quality evidence ). | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_9 | no | Six‐month and nine‐month regimens are probably similarly effective in terms of the chances of achieving cure ( moderate quality evidence ). | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_10 | no | Death was uncommon in both groups, and all deaths occurred during the first four months of ATT, which suggests that duration of treatment did not have an effect on risk of death. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_11 | yes | Few people had poor treatment compliance, and few participants experienced side effects that led to their treatment being stopped or changed, and it was not possible to detect a difference between the groups. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_12 | no | Six‐month regimens are probably as good as nine‐month regimens in terms of numbers of people cured. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_13 | no | We found no evidence to suggest that six‐month regimens are less safe for gastrointestinal and peritoneal TB than nine‐month regimens, but we still do not know whether there is a difference in risk of relapse between the two regimens. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t122 | t122_14 | yes | Further studies are needed to increase our confidence as to whether six‐month regimens are as good as nine‐month regimens for preventing relapse; and to provide information about treating abdominal TB in children and in people with HIV. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t123 | t123_1 | yes | Many people in northern latitudes suffer from winter blues, which occurs as a reaction to reduced sunlight. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_2 | yes | Three‐quarters of those affected are women. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_3 | yes | Lethargy, overeating, craving for carbohydrates and depressed mood are common symptoms. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_4 | yes | In some people, winter blues becomes depression, which seriously affects their daily lives. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_5 | yes | Up to two‐thirds experience depressive symptoms every winter. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_6 | yes | In light of the seasonal pattern and the high rate of recurrence, beginning antidepressant therapy in early autumn (fall) when people are still free of depressive symptoms can prevent the onset of depressed mood. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_7 | no | The goal of this review is to examine whether benefits outweigh harms of antidepressants when they are used in healthy people with a history of winter depression to prevent onset of depression the next winter. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_8 | no | We searched databases up to June 2018 for studies on antidepressants given to prevent winter depression. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_9 | yes | Of 3745 records, we found three randomised controlled studies including 1100 people who received bupropion extended‐release (only one of many available antidepressants, but the only one licensed for prevention of winter depression) or placebo. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_10 | no | In populations with a high risk of developing a new depressive episode in the next winter, results show that antidepressants can prevent winter depression in about one in four people. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_11 | yes | In populations with a lower risk of recurrence, antidepressants can prevent a new depressive episode in one of eight people. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_12 | yes | The other seven people suffer from winter depression despite treatment or would not have suffered from winter depression anyway. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_13 | no | People using antidepressants are at slightly higher risk of experiencing headaches, nausea or insomnia when compared with people not taking antidepressants. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_14 | no | Doctors need to discuss with patients the advantages and disadvantages of antidepressants and other potentially preventive treatments for winter depression, such as light treatment, psychological therapies or lifestyle interventions. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t123 | t123_15 | no | As no available studies have compared these treatments, the decision for or against preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t124 | t124_1 | yes | The addition of anti‐leukotriene agents to inhaled corticosteroids versus placebo for chronic asthma Inhaled steroids remain the cornerstone of asthma treatment. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t124 | t124_2 | yes | Anti‐leukotrienes constitute a new class of drugs that can be taken by mouth and do not have the side effects associated with steroids. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t124 | t124_3 | no | We looked to see how effective these drugs were when they were added to the treatment of patients who needed steroid inhalers to control their asthma.In asthmatics that are not well controlled on inhaled steroids, the addition of anti‐leukotrienes brings modest improvement in asthma control but it remains unclear whether they are as effective as increasing the dose of inhaled steroids. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t124 | t124_4 | yes | Higher doses of anti‐leukotrienes are more effective, but associated with an increased risk of side effect that occurs with these particular drugs. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t124 | t124_5 | no | In asthmatics that are well controlled on inhaled steroids, the addition of anti‐leukotrienes did not allow a reduction in the amount of inhaled steroid used but they seemed to have a beneficial effect on the asthma control. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t124 | t124_6 | yes | There are only two studies that have looked at these issues in children; this is insufficient to firmly conclude whether anti‐leukotrienes are useful in children. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t125 | t125_1 | no | Subfertility due to the absence of ovulation is a common problem in women. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_2 | yes | Medical treatment may help these women ovulate. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_3 | yes | For example, oral antioestrogens such as clomiphene cause increased stimulation of the ovaries and aid ovulation. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_4 | no | Miscarriage, multiple pregnancy rates, and adverse events such as ovarian hyperstimulation syndrome were poorly reported. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_5 | no | We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_6 | no | There was no evidence of a difference between clomiphene and tamoxifen, a similar antioestrogen drug. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_7 | no | Women treated with clomiphene citrate were less likely to get pregnant or have a live baby compared with women who had received gonadotropins; there was no evidence for a difference in the chance of a multiple pregnancy. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_8 | no | The numbers of women getting pregnant in these trials were very small, therefore we cannot be certain of the results. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_9 | no | Both dexamethasone (a steroid) and combined oral contraceptives are used to supplement clomiphene and show promise, but more studies are needed to confirm this. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_10 | yes | Few studies reported beyond the establishment of early pregnancy; given the reported risks of miscarriage with clomiphene treatment, no definitive conclusions can be drawn about effective treatment. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_11 | yes | We found evidence suggesting that a 10‐day regimen of clomiphene citrate improved pregnancy outcomes when compared with a 5‐day regimen, although the volume of data is limited and further research is required. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t125 | t125_12 | no | There were insufficient data reported for early versus late regimens of clomiphene citrate to be able to make a judgement on differences for pregnancy outcomes. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t126 | t126_1 | no | Calcium channel blockers have not been shown to reduce preterm birth or improve the outcomes for babies when given to women after contractions of preterm labour have been stopped. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_2 | yes | Babies born premature (before 37 weeks of pregnancy) may not survive, or may have serious long‐term problems if they do survive. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_3 | yes | Women who have had their preterm labour stopped with tocolytic treatment (medication to reduce uterine contractions), remain at risk of giving birth preterm. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_4 | no | After this initial tocolytic treatment has been given to stop early labour, a maintenance tocolytic treatment may be given to try to prevent further early contractions and early birth. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_5 | no | Calcium channel blockers are one of the types of tocolytic therapy that have been used in an attempt to prevent the onset of further preterm contractions. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_6 | no | We identified six randomised controlled trials involving a total of 794 women and their babies for this review. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_7 | no | The trials did not demonstrate differences between calcium channel blocker maintenance therapy and placebo or no treatment in the prevention of preterm birth or perinatal death (fetal or neonatal deaths). | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_8 | no | None of the trials included any follow‐up of the infants to assess longer‐term development. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_9 | no | Calcium channel blocker maintenance therapy (with a drug called nifedipine) was more likely than placebo or no treatment to prolong pregnancy, however the infants of these mothers were more likely to have a longer hospital stay. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t126 | t126_10 | no | Based on the current studies, we found no convincing evidence that calcium channel blocker maintenance therapy prevents preterm birth for women after threatened preterm labour, or that it improves outcomes for babies. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t127 | t127_1 | yes | Children who need a general anaesthetic sometimes need a breathing tube placed in their throat, known as intubation. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_2 | yes | Intubations are also performed in emergency situations such as trauma, severe breathing difficulty, and heart dysfunction. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_3 | yes | Intubation is traditionally performed with a laryngoscope, a device that lifts the tongue to allow a direct view of the vocal cords. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_4 | yes | This is known as direct laryngoscopy. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_5 | yes | New devices have been developed that show the vocal cords through a fine video camera placed on the tip of the device; this is known as indirect laryngoscopy, or videolaryngoscopy. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_6 | no | Indirect laryngoscopes, or videolaryngoscopes, are thought to provide a better view of the vocal cords when compared with direct laryngoscopes, but whether this equipment allows easier placement of the breathing tube remains unclear. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_7 | no | We reviewed the evidence on how effective indirect laryngoscopy, or videolaryngoscopy, is when compared with direct laryngoscopy for intubation in children from 28 days to 18 years old. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_8 | no | We found 12 randomized controlled trials (803 children) that met our inclusion criteria. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_9 | no | For intubation, use of indirect laryngoscopy, or videolaryngoscopy, took longer and was more likely to be unsuccessful (very low‐quality evidence). | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_10 | no | No significant difference was found between direct and indirect laryngoscopy when success of the first attempt at intubation was assessed (low‐quality evidence). | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_11 | no | Only a few studies reported the effect of intubation on adverse haemodynamic response, including changes in oxygen saturation, heart rate, and trauma to the mouth and windpipe. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_12 | no | Therefore, it was difficult to conclude on the overall adverse effect (very low‐quality evidence). | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_13 | no | Indirect laryngoscopy might provide better views of the vocal cords. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_14 | yes | We found considerable variation in results from included studies in terms of assessment of intubation time, number of attempts at intubation, number of unsuccessful intubations, adverse effects, and assessments of how well the vocal cords were seen. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t127 | t127_15 | yes | None of the included studies was funded by a laryngoscope manufacturer, hence minimizing the risk of other bias. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t128 | t128_1 | no | Rupture of the anterior cruciate ligament (ACL) in the knee is a common injury in young, active individuals. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_2 | yes | It often results in an unstable knee that increases the risk of further knee damage, such as to the knee meniscii. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_3 | yes | Anterior cruciate ligament injuries in athletic individuals are often treated surgically. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_4 | yes | Surgery usually entails ACL reconstruction, that involves removing the torn ligament and replacing it with a tendon graft, often taken from another part of the patient's knee. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t128 | t128_5 | no | Conservative (non‐surgical) interventions are also used as treatment for this injury. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
Subsets and Splits