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t186 | t186_7 | no | All participants in these RCTs received a drug aimed at suppressing the immune response (cyclosporine or tacrolimus). | Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft‐versus‐host disease (GVHD) pose a serious challenge to wider applicability of allo‐HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo‐HCT. Conflicting results regarding various clinical outcomes following allo‐HCT have been observed when comparing mycophenolate mofetil‐based regimens against methotrexate‐based regimens for acute GVHD prophylaxis. Objectives Primary objective: to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo‐HCT. Secondary objectives: to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment‐related harms, nonrelapse mortality, and quality of life. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche‐trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. Selection criteria Two review authors independently reviewed all titles/abstracts and selected full‐text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo‐HCT in this review. Data collection and analysis Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time‐to‐event outcomes. We pooled the individual study effects using the random‐effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low‐quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low‐quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low‐quality evidence), non‐relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low‐quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low‐quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low‐quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low‐quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant‐associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high‐quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions. |
t186 | t186_8 | no | Our results show no clinically meaningful difference between mycophenolate mofetil and methotrexate on length of survival, incidence of GVHD, disease relapse, or treatment‐related death. | Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft‐versus‐host disease (GVHD) pose a serious challenge to wider applicability of allo‐HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo‐HCT. Conflicting results regarding various clinical outcomes following allo‐HCT have been observed when comparing mycophenolate mofetil‐based regimens against methotrexate‐based regimens for acute GVHD prophylaxis. Objectives Primary objective: to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo‐HCT. Secondary objectives: to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment‐related harms, nonrelapse mortality, and quality of life. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche‐trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. Selection criteria Two review authors independently reviewed all titles/abstracts and selected full‐text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo‐HCT in this review. Data collection and analysis Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time‐to‐event outcomes. We pooled the individual study effects using the random‐effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low‐quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low‐quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low‐quality evidence), non‐relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low‐quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low‐quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low‐quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low‐quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant‐associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high‐quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions. |
t186 | t186_9 | yes | People treated with mycophenolate mofetil had a shorter time to make new platelets (cells that help the blood to clot) from the donor cells compared with people treated with methotrexate. | Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft‐versus‐host disease (GVHD) pose a serious challenge to wider applicability of allo‐HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo‐HCT. Conflicting results regarding various clinical outcomes following allo‐HCT have been observed when comparing mycophenolate mofetil‐based regimens against methotrexate‐based regimens for acute GVHD prophylaxis. Objectives Primary objective: to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo‐HCT. Secondary objectives: to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment‐related harms, nonrelapse mortality, and quality of life. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche‐trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. Selection criteria Two review authors independently reviewed all titles/abstracts and selected full‐text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo‐HCT in this review. Data collection and analysis Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time‐to‐event outcomes. We pooled the individual study effects using the random‐effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low‐quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low‐quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low‐quality evidence), non‐relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low‐quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low‐quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low‐quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low‐quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant‐associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high‐quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions. |
t186 | t186_10 | yes | In addition, in terms of side effects, people treated with mycophenolate mofetil were less likely to have severe mucositis (inflammation of the mucus membranes), require parenteral nutrition (feeding through a vein), or pain medication. | Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft‐versus‐host disease (GVHD) pose a serious challenge to wider applicability of allo‐HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo‐HCT. Conflicting results regarding various clinical outcomes following allo‐HCT have been observed when comparing mycophenolate mofetil‐based regimens against methotrexate‐based regimens for acute GVHD prophylaxis. Objectives Primary objective: to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo‐HCT. Secondary objectives: to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment‐related harms, nonrelapse mortality, and quality of life. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche‐trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. Selection criteria Two review authors independently reviewed all titles/abstracts and selected full‐text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo‐HCT in this review. Data collection and analysis Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time‐to‐event outcomes. We pooled the individual study effects using the random‐effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low‐quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low‐quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low‐quality evidence), non‐relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low‐quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low‐quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low‐quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low‐quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant‐associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high‐quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions. |
t186 | t186_11 | no | In summary, mycophenolate mofetil and methotrexate both remain acceptable medications for the prevention of GVHD; however, mycophenolate mofetil seems to be associated with a smaller incidence of harms such as severe mucositis and related supportive care. | Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft‐versus‐host disease (GVHD) pose a serious challenge to wider applicability of allo‐HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo‐HCT. Conflicting results regarding various clinical outcomes following allo‐HCT have been observed when comparing mycophenolate mofetil‐based regimens against methotrexate‐based regimens for acute GVHD prophylaxis. Objectives Primary objective: to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo‐HCT. Secondary objectives: to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment‐related harms, nonrelapse mortality, and quality of life. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche‐trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. Selection criteria Two review authors independently reviewed all titles/abstracts and selected full‐text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo‐HCT in this review. Data collection and analysis Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time‐to‐event outcomes. We pooled the individual study effects using the random‐effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low‐quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low‐quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low‐quality evidence), non‐relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low‐quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low‐quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low‐quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low‐quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant‐associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high‐quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions. |
t187 | t187_1 | no | Depression in physical illness is common. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_2 | no | Antidepressants have been shown to improve depression in people who are physically healthy, but there has been doubt about whether they are appropriate for people who are physically ill. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_3 | no | This review examined clinical trials of antidepressants in physically ill people to determine whether antidepressants help these patients, and in particular if they lessen depression. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_4 | no | We used standard methods recommended by Cochrane to identify and select studies and to collect and analyse the information. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_5 | no | Our results found that antidepressants are better than a placebo (inactive) drug in treating depression in physically ill people. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_6 | yes | Both the two main classes of antidepressant, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), were shown to be more effective than a placebo. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_7 | no | Antidepressants improved depressive symptoms within 4‐5 weeks of treatment, and this benefit persisted after 18 weeks. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_8 | no | However, patients taking an antidepressant were more likely to experience sexual dysfunction and dry mouth, and were more likely to stop taking their medication after 6‐8 weeks of treatment. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_9 | no | There are no grounds to recommend one antidepressant over another on the basis of this review. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_10 | no | We conclude that antidepressants appear to be useful in treating depression and should be considered for physically ill patients. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t187 | t187_11 | yes | The decision to prescribe antidepressants should take account of patients' preferences, symptoms, and possible interactions with other medicines they are taking. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t188 | t188_1 | no | We assessed the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for bacterial vaginosis (BV). | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_2 | no | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_3 | no | BV results in an imbalance of the normal vaginal flora. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_4 | no | Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of infection after antibiotic treatment. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_5 | no | Therefore, the treatment of sexual partners could offer the advantages of decreasing the recurrence of infection and possibly reducing the burden of the disease. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_6 | yes | The trials included sexually‐active non‐pregnant women between 17 and 56 years of age, either single or married, with symptomatic BV. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_7 | yes | Four studies only included women involved into a monogamous heterosexual relationship and there was no information about this for the remaining trials. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_8 | yes | Six trials used 5‐nitroimidazoles to treat the sexual partner, four trials used metronidazole and two trials used tinidazole; only one study used a lincosamide for treatment. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_9 | no | Five trials compared antibiotic versus placebo (854 participants) and two trials compared antibiotic treatment with no intervention (172 participants). | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_10 | no | Pharmaceutical companies funded four of the included trials. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_11 | no | Compared with placebo, antibiotic treatment for the sexual partners of women treated for BV had no effects on clinical or symptomatic improvement in women, regardless of the time period over which the trials assessed these outcomes (during the first, between the first and fourth, or after the fourth week). | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_12 | yes | Furthermore, antibiotic treatment of the sexual partner may have no effect on the recurrence of BV up to 12 weeks after treatment, but may increase the frequency of minor adverse events reported by sexual partners. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t188 | t188_13 | no | Compared with no intervention, treatment of sexual partners of women with BV may have no effect on decreasing the recurrence rate or over the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week, respectively. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t189 | t189_1 | no | This review update assessed evidence from 2641 participants in 20 randomised, double blind, placebo‐controlled clinical trials of oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t189 | t189_2 | no | Oral oxycodone 10 mg plus paracetamol 650 mg provided effective analgesia. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t189 | t189_3 | no | About half of those treated experienced at least half pain relief over 4 to 6 hours, and the effects lasting up to 10 hours. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t189 | t189_4 | no | Higher doses gave more effect. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t189 | t189_5 | yes | Associated adverse events (predominantly nausea, vomiting, dizziness and somnolence) were more frequent with oxycodone or oxycodone plus paracetamol than with placebo, but studies of this type are of limited use for studying adverse effects. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t189 | t189_6 | no | Limited information about oxycodone on its own suggests that it provided analgesia at doses greater than 5 mg, and that addition of paracetamol made it more effective. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t190 | t190_1 | no | We investigated if giving drugs before surgery for uterine fibroids improves outcomes. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_2 | yes | Uterine fibroids are smooth muscle tumours of the uterus (womb) that can cause fertility problems, heavy menstrual bleeding, repeated pregnancy loss and pelvic pain. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_3 | no | Fibroids are usually treated by surgery. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_4 | no | Some drugs, particularly gonadotropin‐releasing hormone analogues (GnRHa), have been used to temporarily control bleeding and reduce fibroid and uterine size before surgery. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_5 | yes | They are unsuitable for long‐term use because they may cause bone loss. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_6 | no | Other drugs, including progestins, dopamine agonists, selective progesterone receptor modulators (SPRMs), oestrogen receptor antagonists and selective oestrogen receptor modulators (SERMs), may also provide benefits used short‐term. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_7 | no | However, such therapies tend to be expensive. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_8 | no | We included 38 studies that involved 3623 women with fibroids that caused symptoms and who were scheduled for surgery to remove the fibroids. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_9 | no | Surgeries were either hysterectomy (uterus removal) or myomectomy or resection (removal of fibroids from the uterus wall). | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_10 | yes | Many women were anaemic (had low red blood cell or haemoglobin levels). | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_11 | no | The studies compared GnRHa with no treatment or sham treatment, GnRHa with other medical treatments, and SPRMs with sham treatment. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_12 | no | GnRHa increased haemoglobin levels before surgery and decreased uterine and fibroid size, compared with no treatment or placebo. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_13 | no | Blood loss, need for blood transfusion, operation time during hysterectomy and postoperative complications were reduced. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_14 | no | However, women were more likely to experience hot flushes during treatment. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t190 | t190_15 | no | An SPRM drug (ulipristal acetate) had similar benefits, particularly reduced bleeding. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t191 | t191_1 | no | Blockages in the arteries to the legs ‐ peripheral arterial disease ‐ affect 20% of people over 70 years of age and 4% to 12% of the population aged 55 to 70 years. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_2 | yes | Approximately 40% of those affected with peripheral arterial disease complain of pain in the legs on walking, this is known as intermittent claudication. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_3 | no | Intermittent claudication is characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_4 | yes | The symptoms of intermittent claudication are an indicator for the development of blocked arteries elsewhere in the body. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_5 | no | Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increased chance of dying as a result of cardiovascular events. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_6 | yes | The majority of patients with intermittent claudication are treated with best medical management. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_7 | no | Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, which includes smoking cessation and a structured exercise programme. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_8 | yes | Further cardiovascular risk modification includes treatment for hypertension, diabetes and cholesterol reduction. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_9 | yes | In practice, compliance with best medical treatment is poor and most people continue to have symptoms of intermittent claudication. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_10 | no | Some drug therapies are used specifically to help improve walking distance in intermittent claudication and cilostazol is one of these. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_11 | no | We have looked at the evidence supporting cilostazol in improving the symptoms of intermittent claudication. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_12 | no | This review included fifteen double‐blind, randomised controlled trials, with a total of 3718 participants. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t191 | t191_13 | no | The risk of bias was poor over all of the studies but the results from this review suggest that cilostazol improves walking distances and ankle‐brachial pressure (blood pressure in the legs) for people with intermittent claudication. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t192 | t192_1 | yes | Not taking enough physical activity leads to an increased risk of a number of chronic diseases including coronary heart disease. | Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library ( issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention‐to‐treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self‐reported physical activity and cardio‐respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. The effect of interventions on self‐reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio‐respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self‐directed with some professional guidance and when there was on‐going professional support. Our review suggests that physical activity interventions have a moderate effect on self‐reported physical activity, on achieving a predetermined level of physical activity and cardio‐respiratory fitness. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions. |
t192 | t192_2 | yes | Regular physical activity can reduce this risk and also provide other physical and possibly mental health benefits. | Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library ( issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention‐to‐treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self‐reported physical activity and cardio‐respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. The effect of interventions on self‐reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio‐respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self‐directed with some professional guidance and when there was on‐going professional support. Our review suggests that physical activity interventions have a moderate effect on self‐reported physical activity, on achieving a predetermined level of physical activity and cardio‐respiratory fitness. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions. |
t192 | t192_3 | yes | The majority of adults are not active at recommended levels. | Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library ( issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention‐to‐treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self‐reported physical activity and cardio‐respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. The effect of interventions on self‐reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio‐respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self‐directed with some professional guidance and when there was on‐going professional support. Our review suggests that physical activity interventions have a moderate effect on self‐reported physical activity, on achieving a predetermined level of physical activity and cardio‐respiratory fitness. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions. |
t192 | t192_4 | no | The findings of this review indicate that professional advice and guidance with continued support can encourage people to be more physically active in the short to mid‐term. | Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library ( issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention‐to‐treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self‐reported physical activity and cardio‐respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. The effect of interventions on self‐reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio‐respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self‐directed with some professional guidance and when there was on‐going professional support. Our review suggests that physical activity interventions have a moderate effect on self‐reported physical activity, on achieving a predetermined level of physical activity and cardio‐respiratory fitness. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions. |
t192 | t192_5 | no | More research is needed to establish which methods of exercise promotion work best in the long‐term to encourage specific groups of people to be more physically active. | Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library ( issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention‐to‐treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self‐reported physical activity and cardio‐respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. The effect of interventions on self‐reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio‐respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self‐directed with some professional guidance and when there was on‐going professional support. Our review suggests that physical activity interventions have a moderate effect on self‐reported physical activity, on achieving a predetermined level of physical activity and cardio‐respiratory fitness. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions. |
t193 | t193_1 | no | Ingrowing toenails are a common problem and occur when the edge of the nail grows into flesh at the side of the nail, causing a painful injury. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_2 | yes | This punctured skin can become inflamed and infected. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_3 | no | This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_4 | yes | We have broadened the scope of this review to include all types of treatment for ingrowing toenails. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_5 | yes | As well as including non‐surgical treatments for ingrowing toenails, we have also looked at surgical interventions with pre‐ and postoperative interventions to reduce postoperative complications. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_6 | no | We included 24 randomised controlled trials, with a total of 2826 participants, and our aim was to determine which is the most effective treatment. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_7 | no | By comparison with non‐surgical interventions, surgical interventions are more effective in preventing the recurrence of an ingrowing toenail. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_8 | no | We found that none of postoperative treatments used, such as antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, reduced the risk of postoperative infection or postoperative pain, or gave a shorter healing time. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t193 | t193_9 | no | Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no agreement about a standard first‐choice treatment. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t194 | t194_1 | yes | Uterine fibroids are also known as uterine leiomyoma, myoma or fibromyoma and are non‐cancerous benign growths in the uterus. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_2 | no | Fibroids are the most common benign tumours in females and are typically found during the middle and later reproductive years. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_3 | yes | Common symptoms include heavy bleeding, menstrual pain, pressure in lower abdomen, infertility or miscarriage. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_4 | yes | Fibroids can be treated with surgery using either myomectomy (removal of fibroids leaving the uterus in place) or hysterectomy (removal of uterus). | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_5 | yes | Drugs such as mifepristone have been suggested as a therapeutic option. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_6 | no | This review includes three trials and 112 women with uterine fibroids under mifepristone treatment. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_7 | yes | These clinical trials included a small number of participants and show limited methodological quality. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_8 | no | The studies included in this review show that mifepristone had a moderate effect in relief of bleeding and showed an improvement in fibroid‐specific quality of life. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t194 | t194_9 | no | Determination of the effects of mifepristone on uterine fibroid volume requires much larger trials to draw a confident conclusion for mifepristone in clinical use. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t195 | t195_1 | yes | For low‐ and middle‐income families, in‐work tax credit for families (IWTC) interventions to reduce poverty and unemployment (both of which are thought to harm health) could be expected to improve health status in adults. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t195 | t195_2 | no | This review sought to assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t195 | t195_3 | no | The review included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after and interrupted time series studies of IWTCs in working‐age adults. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t195 | t195_4 | no | We looked for studies which reported adult self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t195 | t195_5 | no | Five studies comprising a total of 5,677,383 participants (all women) were included in the review. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t195 | t195_6 | no | Because all of these non‐experimental studies had considerable systematic errors in the way they conducted their analysis, we judged this body of evidence to have very low overall quality. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t195 | t195_7 | no | This review found weak evidence that in‐work tax credit for families interventions had no effect on health status, except for mixed evidence for tobacco use in adult women, where some studies suggested that rates of smoking reduced. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t196 | t196_1 | yes | Cancer patients develop neutropenia, a decrease in the neutrophil subset of the white blood cells, as a result of chemotherapy. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t196 | t196_2 | yes | Neutropenia exposes patients to infections, mainly bacterial. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t196 | t196_3 | yes | Without antibiotic treatment these infections may be fatal, therefore antibiotic treatment is administered when a patient with neutropenia develops fever. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t196 | t196_4 | yes | The objective of this review was to compare antibiotic treatments currently recommended in consensus guidelines for the initial treatment of cancer patients with fever and neutropenia. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t196 | t196_5 | no | We identified 44 studies comparing different antibiotics. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t196 | t196_6 | no | Cefepime resulted in significantly higher mortality compared to all other antibiotics combined, at the end of patients' hospital stay or 30 days after entry into the study. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t196 | t196_7 | no | The risk was 39% higher with cefepime, ranging from 4 to 86% increased risk. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
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