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Hasso Plattner Institute 22

INTRODUCTION For patients with rheumatoid arthritis (RA) whose treatment with a tumour necrosis factor inhibitor (TNFi) is failing, several biological treatment options are available. Often, another TNFi or a biological with another mode of action is prescribed. The objective of this study was to compare the effectiveness and cost-effectiveness of three biologic treatments with different modes of action in patients with RA whose TNFi therapy is failing. METHODS We conducted a pragmatic, 1-year randomised trial in a multicentre setting. Patients with active RA despite previous TNFi treatment were randomised to receive abatacept, rituximab or a different TNFi. The primary outcome (Disease Activity Score in 28 joints) and the secondary outcomes (Health Assessment Questionnaire Disability Index and 36-item Short Form Health Survey scores) were analysed using linear mixed models. Cost-effectiveness was analysed on the basis of incremental net monetary benefit, which was based on quality-adjusted life-years (calculated using EQ-5D scores), and all medication expenditures consumed in 1 year. All analyses were also corrected for possible confounders. RESULTS Of 144 randomised patients, 5 were excluded and 139 started taking abatacept (43 patients), rituximab (46 patients) or a different TNFi (50 patients). There were no significant differences between the three groups with respect to multiple measures of RA outcomes. However, our analysis revealed that rituximab therapy is significantly more cost-effective than both abatacept and TNFi over a willingness-to-pay range of 0 to 80,000 euros. CONCLUSIONS All three treatment options were similarly effective; however, when costs were factored into the treatment decision, rituximab was the best option available to patients whose first TNFi treatment failed. However, generalization of these costs to other countries should be undertaken carefully. TRIAL REGISTRATION Netherlands Trial Register number NTR1605. Registered 24 December 2008.

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BACKGROUND Physical activity (PA) prevents chronic diseases. Self-determination theory (SDT) provides a useful framework to understand the nature of motivational interviewing (MI). OBJECTIVE This study aimed to determine the effect of MI-based intervention using SDT on the promotion of PA among women in reproductive age. METHODS Seventy women in reproductive age were selected by clustering sampling method for this randomized controlled trial. The questionnaire included the variables of physical fitness test, SDT, and global physical activity questionnaire (GPAQ). The validity of the questionnaires was approved using content validity ratio (CVR) and index (CVI). The reliability and internal consistency of the questionnaires and measures was approved using test-retest method and Cronbach's alpha test, respectively. The intervention group (n=35) received four MI sessions through theory and one standard education session about PA. The control group (n=35) received a standard education session about PA. RESULTS Four months after the intervention, an increase in the mean scores of total PA (p<0.001, ES=4.77), physical fitness tests including flexibility (p<0.001, ES=1.59), muscular endurance (p<0.001, ES=2.0), cardiorespiratory endurance (p<0.001, ES=0.51), and a decrease in mean scores of agility test (p<0.001, ES= - 0.51) and sedentary behavior (p<0.01, ES=- 0.74) was observed in the intervention group compared to the control group. The intervention group reported an increase in the scores of intrinsic motivation (p<0.001, ES=3.34), identified regulation (p<0.001, ES= 1.28), perceptions of competence (p<0.001, ES=0.81) and autonomy (p<0.001, ES=2.01), enjoyment (p<0.001, ES=0.98) and health motives (p<0.01, ES=0.19), health care climate (p<0.001, ES=4.6), and a decreased score of external regulation (p<0.01, ES=-0.55) and amotivation (p<0.01, ES= -0.56) over time, compared to the control group. CONCLUSION MI-based intervention using SDT was effective on the promotion of PA. TRIAL REGISTRATION The Trial was registered at the Iranian Registry of Clinical Trial (http://www.irct.ir) with the Irct ID: IRCT2015101924592N1.

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INTRODUCTION The purpose of this study was to compare shear bond strength (SBS) of orthodontic brackets bonded to enamel prepared by Er:YAG laser with two different powers and conventional acid-etching. MATERIALS AND METHODS Forty-five human premolars extracted for orthodontic purposes were randomly assigned to three groups based on conditioning method: Group 1- conventional etching with 37% phosphoric acid; Group 2- irradiation with Er:YAG laser at 1 W; and Group 3- irradiation with Er:YAG laser at 1.5 W. Metal brackets were bonded on prepared enamel using a light-cured composite. All groups were subjected to thermocycling process. Then, the specimens mounted in auto-cure acryle and shear bond strength were measured using a universal testing machine with a crosshead speed of 0.5 mm per second. After debonding, the amount of resin remaining on the teeth was determined using the adhesive remnant index (ARI) scored 1 to 5. One-way analysis of variance was used to compare shear bond strengths and the Kruskal-Wallis test was performed to evaluate differences in the ARI for different etching types. RESULTS The mean and standard deviation of conventional acid-etch group, 1W laser group and 1.5W laser group was 3.82 ± 1.16, 6.97 ± 3.64 and 6.93 ± 4.87, respectively. CONCLUSION The mean SBS obtained with an Er:YAG laser operated at 1W or 1.5W is approximately similar to that of conventional etching. However, the high variability of values in bond strength of irradiated enamel should be considered to find the appropriate parameters for applying Er:YAG laser as a favorable alternative for surface conditioning.

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OBJECTIVE Low glycemic index (GI) foods have been suggested to minimize large fluctuations in blood glucose levels and reduce food intake. However, the majority of studies have been conducted on Caucasian populations with limited data on Asians. The objective of this study was to investigate how the provision of a low GI breakfast and afternoon snack affected daily blood glucose profiles and food intake. MATERIALS AND METHODS In a randomized, controlled crossover non blind design, 11 healthy Chinese male adults (body mass index 22.4 ± 1.3 kg m -2 ) attended two sessions where they consumed either a high or low GI breakfast and afternoon snack, and a standardized buffet lunch. Daily changes in glycemic response (GR) were measured using the Medtronic MiniMed (Northridge, CA) iPro™2 continuous glucose monitoring system (CGMS). The GR was further calculated to obtain the incremental area under the curve (IAUC). Glycemic variability was calculated as mean amplitude of glycemic excursion (MAGE) and energy intake (kcal) was measured quantitatively at the buffet lunch. RESULTS Compared to the high GI intervention, the low GI intervention significantly reduced the GR following breakfast ( p  = 0.02), lunch ( p  = 0.02) and dinner ( p  = 0.05). The low GI treatment showed a reduction in daily AUC ( p  = 0.03). There was a significant reduction in IAUC after a low GI breakfast compared to the high GI breakfast ( p  = 0.03). The low GI breakfast resulted in a significantly lower food intake at lunch and a resulting decreased energy intake of 285 kcal ( p  = 0.02). The MAGE was significantly lower during the entire low GI treatment ( p  = 0.03). CONCLUSIONS Consumption of a low GI breakfast and afternoon snack was capable of attenuating 24-h blood glucose profiles, minimize glycemic excursions and reduce food intake in healthy Asian males. This simple dietary intervention may be an acceptable approach in improving overall glycemia and energy balance in Asians. CLINICAL TRIAL REGISTRATION NUMBER NCT02340507.

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BACKGROUND Sodium bicarbonate (SB) has been proposed as an ergogenic aid, as it improves high-intensity and resistance exercise performance. However, no studies have yet investigated SB application in CrossFit. This study examined the effects of chronic, progressive-dose SB ingestion on CrossFit-like performance and aerobic capacity. METHODS In a randomized, double-blind, cross-over trial, 21 CrossFit-trained participants were randomly allocated to 2 groups and underwent 2 trials separated by a 14-day washout period. Participants ingested either up to 150 mg∙kg-1 of SB in a progressive-dose regimen or placebo for 10 days. Before and after each trial, Fight Gone Bad (FGB) and incremental cycling (ICT) tests were performed. In order to examine biochemical responses, blood samples were obtained prior to and 3 min after completing each exercise test. RESULTS No gastrointestinal (GI) side effects were reported during the entire protocol. The overall FGB performance improved under SB by ~6.1% (p<0.001) and it was ~3.1% higher compared to post placebo (PLApost) (p = 0.040). The number of repetitions completed in each round also improved under SB (mean from baseline: +5.8% to +6.4%). Moreover, in ICT, the time to ventilatory threshold (VT) (~8:25 min SBpost vs. ~8:00 min PLApost, p = 0.020), workload at VT (~218 W SBpost vs. ~208 W PLApost, p = 0.037) and heart rate at VT (~165 bpm SBpost vs. ~161 bpm PLApost, p = 0.030) showed higher SBpost than PLApost. Furthermore, the maximum carbon dioxide production increased under SB by ~4.8% (from ~3604 mL∙min-1 to ~3776 mL∙min-1, p = 0.049). Pyruvate concentration and creatine kinase activity before ICT showed higher SBpost than PLApost (~0.32 mmol∙L-1 vs. ~0.26 mmol∙L-1, p = 0.001; ~275 U∙L-1 vs. ~250 U∙L-1, p = 0.010, respectively). However, the small sample size limits the wide-application of our results. CONCLUSIONS Progressive-dose SB ingestion regimen eliminated GI side effects and improved CrossFit-like performance, as well as delayed ventilatory threshold occurrence.

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BACKGROUND Lichen planus is recognized as an inflammatory disease of the skin with different morphologic patterns. Different treatment modalities, including topical and systemic corticosteroids, methotrexate, cyclosporine, azathioprine, topical calcineurin inhibitors, and psoralen plus UVA (PUVA), have been suggested for lichen planus. Although the efficacy of narrowband UVB (NBUVB) for treatment of lichen planus has been shown, no randomized clinical trial has compared NBUVB versus systemic corticosteroids for treatment of the disease. In the current study, we evaluated the efficacy of NBUVB versus systemic corticosteroids in the treatment of the lichen planus. METHODS Forty-six patients with confirmed diagnosis of lichen planus were randomly selected. The subjects were randomized into two groups of 23 to be treated with either systemic corticosteroids or NBUVB. All of the selected cases had generalized lichen planus that involved at least 20% of the body area and their pruritus was resistant to antihistamine drugs. Patients in the systemic corticosteroids group were treated with prednisolon 0.3 mg/kg for 6 weeks. NBUVB was performed three times a week for 6 weeks. The maximum dose of NBUVB was 9 J/cm(2). Data regarding demographic characteristics of the patients was also collected. All collected data was analyzed using SPSS(15) and statistical tests including analysis of variance (ANOVA), chi-square, and t-test. RESULTS 46 patients (23 patients in systemic steroid group and 23 patients in NBUVB group) were evaluated. There was a significant difference between the 2 groups regarding the efficacy of the treatment. According to chi-square test, NBUVB was significantly more effective than systemic steroid in treatment of generalized lichen planus (p = 0.008). According to the results, patient satisfaction was also significantly higher in the group treated with NBUVB as compared with the systemic corticosteroids (p = 0.012). CONCLUSIONS Overall, the results of our study and other previous studies showed that NBUVB may be regarded as an effective treatment for generalized cutaneous lichen planus. This treatment may be especially utilized when there is contraindication for systemic corticosteroids or other immunosuppressive drugs.

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OBJECTIVE Maternal asthma is the most common chronic disease complicating pregnancy and is a risk factor for bronchiolitis in infancy. Recurrent episodes of bronchiolitis are strongly associated with the development of childhood asthma. METHODS We conducted a follow-up study of infants born to women with asthma who completed a double-blind randomised controlled trial during pregnancy. In this trial, pregnant women with asthma were assigned to treatment adjustment by an algorithm using clinical symptoms (clinical group) or the fraction of exhaled nitric oxide (FeNO group) and we showed that the FeNO group had significantly lower asthma exacerbation rates in pregnancy. RESULTS 146 infants attended the 12-month follow-up visit. Infants born to mothers from the FeNO group were significantly less likely to have recurrent episodes of bronchiolitis in the first year of life (OR 0.08, 95% CI 0.01 to 0.62; p=0.016) as compared with the clinical group. CONCLUSIONS Optimised management of asthma during pregnancy may reduce recurrent episodes of bronchiolitis in infancy, which could potentially modulate the risk to develop or the severity of emerging childhood asthma.

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BACKGROUND Postpartum parental mental health problems pose a serious risk for child development and often remain undetected in postpartum primary care. Within the framework of the German Midwifes Prevention Study, the aim of this study was to investigate the presence of postpartum emotional distress in mothers and fathers, and the detection of distressed parents by midwives in a primary care setting. We also examined whether a temporal extension of the postpartum midwife care period is associated with greater use of midwife contacts and higher rates of referral to further professional support if needed. METHODS Mothers, fathers, and midwives filled out questionnaires at 2 weeks (t 1) and 6 months (t 2) postpartum. Compared to standard care in the control group (CG), midwives in an intervention group (IG) offered extended postpartum care of 6 months postpartum. Parental psychological distress was assessed using the Edinburgh postnatal depression scale (EPDS). Midwives reported on parental psychological distress as well as the number of postpartum contacts and referrals to additional social- and health-care providers. RESULTS Based on their ratings, midwives identified half of mothers and around one-quarter of fathers with elevated depressive symptoms according to the EPDS at t 1 and t 2. IG mothers used significantly more midwife contacts than CG mothers. IG mothers with high-postnatal psychological distress at t 2 used significantly more contacts than mothers with lower levels of distress. IG mothers with high-psychological distress at t 2 were referred to additional support services more often than mothers with lower levels of distress.

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OBJECTIVE To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3). METHODS All prerandomization and follow-up (24-48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518). RESULTS HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167). CONCLUSIONS IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.

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BACKGROUND Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD. METHODS HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms. RESULTS We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: -0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations. CONCLUSIONS In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs. TRIAL REGISTRATION ClinicalTrials.gov NCT00279110 NCT00279110&quest;term&hairsp;&equals;&hairsp;NCT00279110&rank&hairsp;&equals;&hairsp;1.

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BACKGROUND A plant-based strategy to improve long-chain (LC) omega (n)-3 PUFA supply in humans involves dietary supplementation with oils containing α-linolenic acid (ALA) alone or in combination with stearidonic acid (SDA). The study aimed to compare the effects of echium oil (EO) and linseed oil (LO) on LC n-3 PUFA accumulation in blood and on clinical markers. METHODS In two double-blind, parallel-arm, randomized controlled studies, all volunteers started with 17 g/d run-in oil (2 weeks). Thereafter, subjects received diets enriched in study 1 with EO (5 g ALA + 2 g SDA; n = 59) or in study 2 with LO (5 g ALA; n =  9) daily for 8 weeks. The smaller control groups received fish oil (FO; n = 19) or olive oil (OO; n = 18). Participants were instructed to restrict their dietary n-3 PUFA intake throughout the studies (e.g., no fish). To investigate the influence of age and BMI on the conversion of ALA and SDA as well as clinical markers, the subjects recruited for EO and LO treatment were divided into three subgroups (two age groups 20-35 y; 49-69 y with BMI 18-25 kg/m(2) and one group with older, overweight subjects (age 49-69 y; BMI >25 kg/m(2)). RESULTS In plasma, red blood cells (RBC), and peripheral blood mononuclear cells (PBMC), EPA and docosapentaenoic acid (DPA) were ~25 % higher following EO compared to LO. Comparing all treatments, the effectiveness of increasing EPA and DPA in plasma, RBC, and PBMC was on average 100:25:10:0 and 100:50:25:0 for FO:EO:LO:OO, respectively. EO led to a lower arachidonic acid/EPA-ratio compared to LO in plasma, RBC, and PBMC. Following EO, final DHA was not greater compared to LO. Higher BMI correlated negatively with increases in plasma EPA and DPA after EO supplementation, but not after LO supplementation. Decreasing effect on plasma LDL-C and serum insulin was greater with EO than with LO. CONCLUSIONS Daily intake of SDA-containing EO is a better supplement than LO for increasing EPA and DPA in blood. However, neither EO nor LO maintained blood DHA status in the absence of fish/seafood consumption. TRIAL REGISTRATION ClinicalTrials.gov Reg No. NCT01856179; ClinicalTrials.gov Reg No. NCT01317290.

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UNLABELLED Rabbit antithymocyte globulin (ATG) is commonly used as an induction therapy in renal transplant recipients, but the ideal dosage in tacrolimus-based early steroid withdrawal protocols has not been established. The purpose of this pilot study was to determine the immunophenotyping and efficacy of lower dose ATG in low immunological-risk kidney transplant recipients. In this prospective study, 45 patients were randomized (1∶1) to our standard dose ATG (total dose 3.75 mg/kg)(sATG) vs. lower dose 2.25 mg/kg (lowATG). All patients underwent early steroid withdrawal within 7 days. The primary end point was biopsy-proven acute rejection at 12 months. Prospective immunophenotyping of freshly isolated PBMCs was performed at baseline, 3, 6, 12 months post-transplant. The rate of acute rejection was 17% and 10% in the sATG and lowATG, respectively. Effector memory T cells, Tregs and recent thymic emigrants T cells had similar kinetics post-transplant in both groups. No statistically significant differences were found in graft survival, patient survival or infections between the two groups, though there was a non-significant increase in leukopenia (43%v s. 30%), CMV (8% vs. 0) and BK (4% vs. 0) infections in sATG group vs. lowATG. In sum, in low immunological risk kidney recipients undergoing steroid withdrawal, low dose ATG seems to be efficacious in preventing acute rejection and depleting T cells with potentially lower infectious complications. A larger study is warranted to confirm these findings. TRIAL REGISTRATION ClinicalTrials.gov NCT00548405.

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BACKGROUND Metabolic rate is known to rise above basal levels after eating, especially following protein consumption. Yet, this postprandial rise in metabolism appears to vary among individuals. This study examined changes in energy expenditure in response to ingestion of a high protein, high fat (HPHF) meal versus an isocaloric high protein, low fat (HPLF) meal in underweight, normal weight, or overweight females (n = 21) aged 19-28 years. METHODS Energy expenditure, measured using indirect calorimetry, was assessed before and every 30 minutes for 3.5 hours following consumption of the meals on two separate occasions. Height and weight were measured using standard techniques. Body composition was measured using bioelectrical impedance analysis. RESULTS Significant positive correlations were found between body mass index (BMI) and baseline metabolic rate (MR) (r = 0.539; p = 0.017), between body weight and baseline MR (r = 0.567; p = 0.011), between BMI and average total change in MR (r = 0.591; p = 0.008), and between body weight and average total change in MR (r = 0.464; p = 0.045). Metabolic rate (kcal/min) was significantly higher in the overweight group than the normal weight group, which was significantly higher than the underweight group across all times and treatments. However, when metabolic rate was expressed per kg fat free mass (ffm), no significant difference was found in postprandial energy expenditure between the overweight and normal groups. Changes in MR (kcal/min and kcal/min/kg ffm) from the baseline rate did not significantly differ in the underweight (n = 3) or in the overweight subjects (n = 5) following consumption of either meal at any time. Changes in MR (kcal/min and kcal/min/kg ffm) from baseline were significantly higher in normal weight subjects (n = 11) across all times following consumption of the HPHF meal versus the HPLF meal. CONCLUSION There is no diet-induced thermogenic advantage between the HPHF and HPLF meals in overweight and underweight subjects. In contrast, in normal weight subjects, ingestion of a HPHF meal significantly increases MR (69.3 kcal/3.5 hr) versus consumption of a HPLF meal and provides a short-term metabolic advantage.

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BACKGROUND Consumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption of cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources such as olive oil (OO) or omega-3 FA from fish oil (FO), known to exert potent hypotriglyceridemic effects. Our objective was to compare the actions of different FA esterified to PS on blood lipids, carotenoid bioavailability as well as inflammatory and coagulation markers. METHODS Twenty-one moderately overweight, hypercholesterolemic subjects consumed experimental isoenergetic diets enriched with OO (70% of fat), each lasting 28-day and separated by 4-week washout periods, using a randomized crossover design. Diets were supplemented with three PS esters preparations, PS-FO, PS-SO, or PS-OO. All PS treatments contained an equivalent of 1.7 PS g/d, and the PS-FO provided a total of 5.4 g/d FO FA (eicosapentaenoic and docosahexaenoic acids). RESULTS There were no differences between PS-containing diet effects on total cholesterol, LDL-cholesterol, or high-density lipoprotein (HDL)-cholesterol levels. However, PS-FO consumption resulted in markedly lower (P < 0.0001) fasting and postprandial triglyceride concentrations compared with PS-SO and PS-OO. These treatments affected plasma beta-carotene (P = 0.0169) and retinol (P = 0.0244), but not tocopherol (P = 0.2108) concentrations. Consumption of PS-FO resulted in higher beta-carotene (P = 0.0139) and retinol (P = 0.0425) levels than PS-SO and PS-OO, respectively. Plasma TNF-alpha, IL-6, C-reactive protein, prostate specific antigen, and fibrinogen concentrations were unaffected by the PS-interventions. In contrast, plasminogen activator inhibitor 1 (PAI-1) concentrations were lower (P = 0.0282) in the PS-FO-fed than the PS-SO, but not the PS-OO (P = 0.7487) groups. CONCLUSION Our findings suggest that, in hypercholesterolemic subjects consuming an OO-based diet, PS-FO results in lowered blood triglyceride and PAI-1 concentrations, and higher fat-soluble vitamin levels in comparison to the vegetable oil FA esters of PS (PS-SO and PS-OO). Thus, PS-FO may offer hyperlipidemic subjects a more comprehensive lipid lowering approach while reducing the potential risk of decreased plasma carotenoid concentrations.

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BACKGROUND Recombinant human endostatin (rh-endostatin) is a novel antiangiogenesis drug developed in China. Previous experiments have shown that rh-endostatin can inhibit the proliferation and migration of endothelial cells and some types of tumor cells. In this study, we evaluated the efficacy and safety profiles of combination therapy of rh-endostatin and neoadjuvant chemotherapy for breast cancer patients in a prospective, randomized, controlled, phase II trial. METHODS Sixty-eight patients with core-biopsy confirmed breast cancer were allocated randomly to two groups to receive 3 cycles of intravenous administration of either neoadjuvant DE (docetaxel: 75 mg/m2, d1, epirubicin: 75 mg/m2, d1, every 3 weeks), or neoadjuvant DE combined with rh-endostatin (7.5 mg/m2, d1-d14, every 3 weeks). The primary end point was clinical response based upon Response Evaluation Criteria in Solid Tumors, and the secondary end point was safety and quality of life. RESULTS All patients were assessable for toxicity and 64 (94.2%) were assessable for efficacy evaluation. The objective response rate was 67.7% for chemotherapy (n = 31) and 90.9% for rh-endostatin plus chemotherapy (n = 33) (P = 0.021). A retrospective subset analysis revealed that rh-endostatin was more effective in premenopausal patients and patients with ECOG score of zero (P = 0.002 and P = 0.049, respectively). Five patients in the rh-endostatin plus chemotherapy arm achieved pathologic complete response compared with 2 in the chemotherapy arm (P = 0.428). No significant difference was identified in quality of life score and side effects (P > 0.05). CONCLUSION The combination of rh-endostatin with chemotherapy produced a higher tumor response rate without increasing toxicity in breast cancer patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier, NCT00604435.

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BACKGROUND Despite the findings of several randomized clinical studies, the role of gentamicin collagen implant (GCI) in rectal cancer surgery is unclear. Local pelvic application of GCI following preoperative radiotherapy and total mesorectal excision (TME) was evaluated to determine the risk of surgical site infections (SSI). METHODS In this single-center trial, 176 patients with rectal cancer after preoperative, short-term radiotherapy (5 × 5 Gy) were randomized either to the study group in which GCI was used or in the control group without GCI. Prior to surgery and intraoperatively five patients were excluded from the study. The remaining 171 patients were analyzed; 86 were in the study group and 85 in the control group. RESULTS There were no statistically significant differences in the overall rate of early postoperative complications between the study and control group: 25.6 and 34.1 % respectively; p = 0.245, relative risk (RR) 0.750 [95 % confidence interval (CI) 0.471-1.195]. The reoperation rate was similar in both groups: 12.8 versus 9.4 %; p = 0.628; RR 1.359; (95 % CI 0.575-3.212). The total rate of SSI and organ space SSI were 22.2 and 15.8 % without differences between the study and control group. In patients without anastomotic leakage, the risk of organ space SSI was significantly reduced in patients who received GCI: 2.6 versus 13.0 %; p = 0.018. CONCLUSIONS Application of GCI in the pelvic cavity after short-term preoperative radiotherapy and TME may reduce the risk of organ space SSI but only in the absence of anastomotic leakage.

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UNLABELLED The aims were to compare the efficacy and tolerability of a new benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) versus placebo and to investigate the long-term tolerability of BP-C1 in the treatment of patients with metastatic breast cancer. MATERIAL AND METHODS A randomized, double-blind, placebo-controlled multicenter study was performed with a semi-crossover design. Patients allocated to placebo switched to BP-C1 after 32 days of treatment. Patients who completed 32 days of BP-C1 treatment were offered the opportunity to continue on BP-C1 for an additional 32 days in an open-label extension. Patients were then followed up for another 28 days. Thirty patients were given daily intramuscular injections of 0.035 mg/kg of body weight BP-C1 or placebo for 32 days. Biochemistry, hematology, National Cancer Institute Common Terminology Criteria for Adverse Events (CTC-NCI), European Organisation for Research and Treatment of Cancer quality of life questionnaire (QOL-C30 and the breast-cancer-specific BR23) data were recorded at screening and after every 16 days of treatment. Computed tomography was performed at screening and every 32 days. RESULTS The sum of target lesions increased 2.4% in the BP-C1 group and 14.3% in the placebo group. Only the increase in the placebo group was significant (P=0.013). The difference between the groups was significant in favor of BP-C1 (P=0.04). There was a significant difference (P=0.026) in favor of BP-C1 regarding Response Evaluation Criteria In Solid Tumors (RECIST) classification. The sum of lesions increased slightly in the patients receiving 64 days of continuous BP-C1 treatment, of whom 68.4% were classified as responders. The sum CTC-NCI toxicity score increased nonsignificantly in the BP-C1 group but significantly in the placebo group (P=0.05). The difference in increase between groups did not meet the level of significance (P=0.12). The sum toxicity score was reduced in the patients receiving 64 days of BP-C1 from 9.2 at screening to 8.9 at Day 48, but it increased again to 10.1 by Day 64 and 10.6 during the 28-day follow-up. "Breast cancer-related pain and discomfort" and "Breast cancer treatment problem last week" were significantly reduced (P=0.02) in the BP-C1 group but increased slightly in the placebo group; between-group differences were significant in favor of BP-C1 (P=0.05). "Breast cancer related pain and discomfort", "Breast cancer treatment problem last week," and "Physical activity problem" were significantly reduced during the 64 days of BP-C1 treatment (P≤0.05). CONCLUSION For patients suffering from stage IV metastatic breast cancer, treatment with BP-C1 reduces cancer growth, is well tolerated, improves quality of life, and produces few adverse events, which were mainly mild and manageable.

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INTRODUCTION Primary therapeutic aim in treatment of osteoarthritis of the knee is to relieve the pain of osteoarthritis. The aim of this study was to compare the efficacy of intra-articular triamcinolone with intra-articular morphine in pain relief due to osteoarthritis of the knee in the elderly population. MATERIALS AND METHODS Patients between 50 and 80 years of age were randomized into three groups. Group M received morphine plus bupivacaine intra-articularly, Group T received triamcinolone plus bupivacaine intra-articularly, and Group C received saline plus bupivacaine intra-articularly. Patients were evaluated before injection and in 2nd, 4th, 6th, and 12th weeks after injection. First-line supplementary analgesic was oral paracetamol 1500 mg/day. If analgesia was insufficient with paracetamol, oral dexketoprofen trometamol 50 mg/day was recommended to patients. RESULTS After the intra-articular injection, there was statistically significant decrease in visual analog scale (VAS) scores in Groups M and T, when compared to Group C. The decrease of VAS scores seen at the first 2 weeks continued steadily up to the end of 12th week. There was a significant decrease in Groups M and T in the WOMAC scores, when compared to Group C. There was no significant difference in the WOMAC scores between morphine and steroid groups. Significantly less supplementary analgesics was used in the morphine and steroid groups. CONCLUSION Intra-articular morphine was as effective as intra-articular triamcinolone for analgesia in patients with osteoarthritis knee. Intra-articular morphine is possibly a better option than intra-articular steroid as it has lesser side effects.

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OBJECTIVE The aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance, cardiovascular disease (CVD) risk factors, and inflammation in a high-risk population for type 2 diabetes (T2DM) and CVD. RESEARCH DESIGN AND METHODS We randomized 68 older individuals (mean age, 58±8 years) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks. All subjects were advised to decrease calorie intake by 500 kcal/day. Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Traditional CVD risk factors and inflammatory markers also were assessed. RESULTS Eleven out of 35 individuals (31%) assigned to liraglutide discontinued the study compared with 6 out of 33 (18%) assigned to placebo (P=0.26). Subjects who continued to use liraglutide (n=24) lost twice as much weight as those using placebo (n=27; 6.8 vs. 3.3 kg; P<0.001). Liraglutide-treated subjects also had a significant improvement in SSPG concentration (-3.2 vs. 0.2 mmol/L; P<0.001) and significantly (P≤0.04) greater lowering of systolic blood pressure (-8.1 vs. -2.6 mmHg), fasting glucose (-0.5 vs. 0 mmol/L), and triglyceride (-0.4 vs. -0.1 mmol/L) concentration. Inflammatory markers did not differ between the two groups, but pulse increased after liraglutide treatment (6.4 vs. -0.9 bpm; P=0.001). CONCLUSIONS The addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of T2DM and CVD.

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OBJECTIVE The purpose of the present study was to evaluate the efficacy of midazolam-ondansetron combination in prevention of postoperative nausea and vomiting (PONV) after middle ear surgery and its comparison with using midazolam or ondansetron alone. METHODS One hundred and forty patients were enrolled in four groups to receive midazolam 0.75 mg/kg in group M, ondansetron 4 mg in group O, midazolam 0.75 mg/kg and ondansetron 4 mg in group MO, and saline 0.90% in group S intravenously just before anesthesia. Assessment of nausea, vomiting, rescue antiemetic, and side effects of study drugs such as headache and dizziness was carried out postoperatively for 24 h. FINDINGS The incidence of PONV was significantly smaller in group MO than group M and group O, while there was no significant difference between group M and group O during the first 24 h postoperatively. Requirement to the additional antiemetic was significantly more in group S (71.4%) compared to other groups, while in group MO (11.4%) was lower than group M (31.4%) and group O (34.3%). CONCLUSION Our study showed that prophylactic administration of midazolam 0.75 mg/kg combined with ondansetron 4 mg was more effective than using midazolam or ondansetron alone in prevention of PONV after middle ear surgery.

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OBJECTIVE To determine whether droxidopa, an oral norepinephrine precursor, improves symptomatic neurogenic orthostatic hypotension (nOH). METHODS Patients with symptomatic nOH due to Parkinson disease, multiple system atrophy, pure autonomic failure, or nondiabetic autonomic neuropathy underwent open-label droxidopa dose optimization (100-600 mg 3 times daily), followed, in responders, by 7-day washout and then a 7-day double-blind trial of droxidopa vs placebo. Outcome measures included patient self-ratings on the Orthostatic Hypotension Questionnaire (OHQ), a validated, nOH-specific tool that assesses symptom severity and symptom impact on daily activities. RESULTS From randomization to endpoint (n = 162), improvement in mean OHQ composite score favored droxidopa over placebo by 0.90 units (p = 0.003). Improvement in OHQ symptom subscore favored droxidopa by 0.73 units (p = 0.010), with maximum change in "dizziness/lightheadedness." Improvement in symptom-impact subscore favored droxidopa by 1.06 units (p = 0.003), with maximum change for "standing a long time." Mean standing systolic blood pressure (BP) increased by 11.2 vs 3.9 mm Hg (p < 0.001), and mean supine systolic BP by 7.6 vs 0.8 mm Hg (p < 0.001). At endpoint, supine systolic BP >180 mm Hg was observed in 4.9% of droxidopa and 2.5% of placebo recipients. Adverse events reported in ≥ 3% of double-blind droxidopa recipients were headache (7.4%) and dizziness (3.7%). No patients discontinued double-blind treatment because of adverse events. CONCLUSIONS In patients with symptomatic nOH, droxidopa improved symptoms and symptom impact on daily activities, with an associated increase in standing systolic BP, and was generally well tolerated. CLASSIFICATION OF EVIDENCE This study provides Class I evidence that in patients with symptomatic nOH who respond to open-label droxidopa, droxidopa improves subjective and objective manifestation of nOH at 7 days.

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BACKGROUND Cigarette smoke contains free radicals and an have adverse effect to the immune system. Supplementation of palm oil vitamin E (palmvitee), is known has antioxidant properties is thought to be beneficial for system immune protection against free radicals activity. The objective of the study was to determine the effect of palmvitee supplementation on immune response in smokers. METHODS This study involved a group of smokers and nonsmokers who received 200 mg/day palmvitee and placebo for the control group. Blood samples were taken at 0, 12 and 24 weeks of supplementation. Plasma tocopherol and tocotrienol were determined by HPLC, lymphocyte proliferation by lymphocyte transformation test (LTT) and enumeration of lymphocytes T and B cells by flow cytometry. Statistical analysis was performed by Mann-Whitney U-test for non-parametric data distribution and correlation among the variables was examined by Spearman. RESULTS Plasma tocopherol and tocotrienol were increased in vitamin E supplemented group as compared to placebo group. Urine cotinine levels and serum α1-antitrypsin were significantly higher in smokers compared to nonsmokers. Lymphocyte proliferation induced by PHA showed an increasing trend with palmvitee supplementation in both smokers and nonsmokers. Natural killer cells were decreased; CD4+ cells and B cells were increased in smokers compared to nonsmokers but were unaffected with vitamin E supplementation except in the percentage of B cells which were increased in nonsmokers supplemented palmvitee compared to placebo. CD4+/CD8+ ratio was increased in smokers compared to nonsmokers. The high TWBC count observed in smokers correlated with the increased CD4+ and B cells. CONCLUSIONS Smoking caused alterations in certain immune parameters and palmvitee supplementation tended to cause an increase in lymphocytes transformation test but had no effect on CD3+, CD4+, CD8+, NK cells and B cells except B cells percentage in nonsmokers.

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BACKGROUND This pilot study aimed to test the acceptability and short-term effectiveness of a telephone-delivered multiple health behaviour change intervention for relatives of colorectal cancer survivors. METHODS A community-based sample of 22 first-degree relatives of colorectal cancer survivors were recruited via a media release. Data were collected at baseline and at six weeks (post-intervention). Outcome measures included health behaviours (physical activity, television viewing, diet, alcohol, body mass index, waist circumference and smoking), health-related quality of life (Short Form-36) and perceived colorectal cancer risk. Intervention satisfaction levels were also measured. The intervention included six telephone health coaching sessions, a participant handbook and a pedometer. It focused on behavioural risk factors for colorectal cancer [physical activity, diet (red and processed meat consumption, fruit and vegetable intake), alcohol, weight management and smoking], and colorectal cancer risk. RESULTS From baseline to six weeks, improvements were observed for minutes moderate-vigorous physical activity (150.7 minutes), processed meat intake (-1.2 serves/week), vegetable intake (1 serve/day), alcohol intake (-0.4 standard drinks/day), body mass index (-1.4 kg/m2), and waist circumference (-5.1 cm). Improvements were also observed for physical (3.3) and mental (4.4) health-related quality of life. Further, compared with baseline, participants were more likely to meet Australian recommendations post-intervention for: moderate-vigorous physical activity (27.3 vs 59.1%); fruit intake (68.2 vs 81.8%); vegetable intake (4.6 vs 18.2%); alcohol consumption (59.1 vs 72.7%); body mass index (31.8 vs 45.5%) and waist circumference (18.2 vs 27.3%). At six weeks participants were more likely to believe a diagnosis of CRC was related to family history, and there was a decrease in their perceived risk of developing CRC in their lifetime following participation in CanPrevent. The intervention retention rate was 100%, participants reported that it was highly acceptable and they would recommend it to others at risk of colorectal cancer. CONCLUSIONS Positive behaviour change achieved through this intervention approach has the potential to impact on the progression of CRC and other cancers or chronic diseases. A large scale randomised controlled trial is required to confirm the positive results of this acceptability and short-term effectiveness study. TRIAL REGISTRATION ACTRN12612000516886.

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BACKGROUND Dexmedetomidine, a selective alpha-2 agonist, has sedative, analgesic, and anxiolytic effects without respiratory depression. Dexmedetomidine can cause a biphasic cardiovascular response, and induce transient hypertension. Hypotension is a common complication of spinal anesthesia. Decreasing anxiety of patients before procedure is important for high quality of procedure. This study aimed to compare the incidence of hypotension and patients' anxiety and comfort levels when dexmedetomidine was intravenously administered before and after spinal anesthesia. METHODS Seventy-four patients with American Society of Anesthesiologists physical status classification I or II were randomly allocated into two groups. Spinal anesthesia was performed using 12 mg of 0.5% heavy bupivacaine. In Group A, 1 μg/kg of dexmedetomidine was intravenously administered for 10 min, followed by the maintenance infusion of dexmedetomidine 0.2 μg/kg/hr after 5 min of intrathecal bupivacaine injection. Patients in Group B received same dose of dexmedetomidine by intravenous administration before 5 min of intrathecal bupivacaine injection. Perioperative vital signs, anxiety (using the Spielberger's State-Trait Anxiety Inventory) and comfort (using the numerical rating scale) were evaluated. RESULTS The incidence of hypotension was significantly lower in Group A (16.1%) than in Group B (48.4%) during infusion of dexmedetomidine (p = 0.01). The need for treatment of hypotension is higher in Group B than Group A (p = 0.02). The incidence of bradycardia and desaturation did not significantly differ between the two groups. There were no statistically significant differences regarding the patients' anxiety and comfort. CONCLUSIONS Hypotension is more frequently occurred, and the treatment of hypotension is more needed in Group B. The intravenously administration of dexmedetomidine before spinal anesthesia has no advantages in hemodynamic status and patients' comfort compared to that after spinal anesthesia during lower limb surgery. TRIAL REGISTRATION ClinicalTrials.gov number, NCT02155010 . Retrospectively registered on May 22, 2014.

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BACKGROUND The rationale for injection of epidural medications through the needle is to promote sooner onset of pain relief relative to dosing through the epidural catheter given that needle injection can be performed immediately after successful location of the epidural space. Some evidence indicates that dosing medications through the epidural needle results in faster onset and improved quality of epidural anesthesia compared to dosing through the catheter, though these dosing techniques have not been compared in laboring women. This investigation was performed to determine whether dosing medication through the epidural needle improves the quality of analgesia, level of sensory blockade, or onset of pain relief measured from the time of epidural medication injection. METHODS In this double-blinded prospective investigation, healthy term laboring women (n=60) received labor epidural placement upon request. Epidural analgesia was initiated according to the assigned randomization group: 10 mL loading dose (0.125% bupivacaine with fentanyl 2 µg/mL) through either the epidural needle or the catheter, given in 5 mL increments spaced 2 minutes apart. Verbal rating scale (VRS) pain scores (0-10) and pinprick sensory levels were documented to determine the rates of analgesic and sensory blockade onset. RESULTS No significant differences were observed in onset of analgesia or sensory blockade from the time of injection between study groups. The estimated difference in the rate of pain relief (VRS/minute) was 0.04 (95% CI: -0.01 to 0.11; p =0.109), and the estimated difference in onset of sensory blockade (sensory level/minute) was 0.63 (95% CI: -0.02 to 0.15; p =0.166). The time to VRS ≤3 and level of sensory block 20 minutes after dosing were also similar between groups. No differences in patient satisfaction, or maternal or fetal complications were observed. CONCLUSION This investigation observed that epidural needle and catheter injection of medications result in similar onset of analgesia and sensory blockade, quality of labor analgesia, patient satisfaction, and complication rates.

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BACKGROUND The Phase 2b double-blinded, randomized Phambili/HVTN 503 trial evaluated safety and efficacy of the MRK Ad5 gag/pol/nef subtype B HIV-1 preventive vaccine vs placebo in sexually active HIV-1 seronegative participants in South Africa. Enrollment and vaccinations stopped and participants were unblinded but continued follow-up when the Step study evaluating the same vaccine in the Americas, Caribbean, and Australia was unblinded for non-efficacy. Final Phambili analyses found more HIV-1 infections amongst vaccine than placebo recipients, impelling the HVTN 503-S recall study. METHODS HVTN 503-S sought to enroll all 695 HIV-1 uninfected Phambili participants, provide HIV testing, risk reduction counseling, physical examination, risk behavior assessment and treatment assignment recall. After adding HVTN 503-S data, HIV-1 infection hazard ratios (HR vaccine vs. placebo) were estimated by Cox models. RESULTS Of the 695 eligible, 465 (67%) enrolled with 230 from the vaccine group and 235 from the placebo group. 38% of the 184 Phambili dropouts were enrolled. Enrollment did not differ by treatment group, gender, or baseline HSV-2. With the additional 1286 person years of 503-S follow-up, the estimated HR over Phambili and HVTN 503-S follow-up was 1.52 (95% CI 1.08-2.15, p = 0.02, 82 vaccine/54 placebo infections). The HR was significant for men (HR = 2.75, 95% CI 1.49, 5.06, p = 0.001) but not for women (HR = 1.12, 95% CI 0.73, 1.72, p = 0.62). CONCLUSION The additional follow-up from HVTN 503-S supported the Phambili finding of increased HIV-1 acquisition among vaccinated men and strengthened the evidence of lack of vaccine effect among women. TRIAL REGISTRATION clinicaltrials.gov NCT00413725 SA National Health Research Database DOH-27-0207-1539.

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PURPOSE We use different methods to train our undergraduates. The patient-oriented problem-solving (POPS) system is an innovative teaching-learning method that imparts knowledge, enhances intrinsic motivation, promotes self learning, encourages clinical reasoning, and develops long-lasting memory. The aim of this study was to develop POPS in teaching pathology, assess its effectiveness, and assess students' preference for POPS over didactic lectures. METHOD One hundred fifty second-year MBBS students were divided into two groups: A and B. Group A was taught by POPS while group B was taught by traditional lectures. Pre- and posttest numerical scores of both groups were evaluated and compared. Students then completed a self-structured feedback questionnaire for analysis. RESULTS The mean (SD) difference in pre- and post-test scores of groups A and B was 15.98 (3.18) and 7.79 (2.52), respectively. The significance of the difference between scores of group A and group B teaching methods was 16.62 (P < 0.0001), as determined by the z-test. Improvement in post-test performance of group A was significantly greater than of group B, demonstrating the effectiveness of POPS. Students responded that POPS facilitates self-learning, helps in understanding topics, creates interest, and is a scientific approach to teaching. Feedback response on POPS was strong in 57.52% of students, moderate in 35.67%, and negative in only 6.81%, showing that 93.19% students favored POPS over simple lectures. CONCLUSION It is not feasible to enforce the PBL method of teaching throughout the entire curriculum; However, POPS can be incorporated along with audiovisual aids to break the monotony of dialectic lectures and as alternative to PBL.

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BACKGROUND This study assessed the impact of closed suction drains and evaluated whether the intraoperative use of a fibrin sealant decreased time to drain removal and wound complications in melanoma patients undergoing inguino-femoral lymph node dissection. METHODS A pilot study (n = 18) assessed the impact of a closed suction drain following inguino-femoral lymph node dissection. A single-institution, prospective trial was then performed in which patients were randomized to a group that received intraoperative application of a fibrin sealant following inguino-femoral lymph node dissection or to a control group that did not receive sealant. RESULTS The majority of the patients enrolled felt the drains caused moderate or severe discomfort and difficulties with activities of daily living. Thirty patients were then randomized; the median time to drain removal in the control group (n = 14) was 30 days (range, 13-74) compared to 29 days (range, 11-45) in the fibrin sealant group (n = 16; P = 0.6). Major and minor complications were similar in the two groups. CONCLUSION Postoperative closed suction drains were associated with major patient inconvenience. Applying a fibrin sealant at the time of inguino-femoral lymph node dissection in melanoma patients did not reduce the time to drain removal or postoperative morbidity. Alternative strategies are needed.

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BACKGROUND To investigate whether Swedish physicians, contrary to Swedish health care policy, employ considerations of patient responsibility for illness when rationing expensive treatments. METHODS A random sample of oncologists and pulmonologists made up the main study-group (n = 296). A random sample of GPs (n = 289) and participants from the general population (n = 513) was used as contrast group. The participants randomly received one version of a questionnaire containing a case description of a terminally ill lung cancer patient. The two versions differed in only one aspect: in one version the patient was a smoker and in the other a non-smoker. The main questions were whether to offer a novel, expensive and marginally life-prolonging treatment and whether the patient could be held responsible for her illness. The quantitative data was analysed using Chi2-tests and comments were analysed using content analysis. RESULTS Among oncologists and pulmonologists, 78% (95% CI: 72-85) would offer the treatment to the non-smoker and 66% (95% CI: 58-74) to the smoker (Chi-2 = 5.4, df = 1, p = 0.019). Among the GPs, 69% (95% CI: 61-76) would treat the non-smoker and 56% (95% CI: 48-64) the smoker (Chi-1 = 4.9, df = 1 and p = 0.026). Among the general population the corresponding proportions were 84% (95% CI: 79-88) and 69% (95% CI: 63-74). CONCLUSION This study indicates that applying an experimental design allowed us to go beyond the official norms and to show that, compared to a smoking patient, both the general population and physicians are more inclined to treat a non-smoking patient. This clearly runs counter to the official Swedish health care norms. It also seems to run counter to the fact that among the physicians studied, there was no association between finding the patient responsible for her disease and the inclination to treat her. We think these paradoxical findings merit further studies.

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BACKGROUND Malnutrition is a major global public health issue and its impact on communities and individuals is more dramatic in Sub-Saharan Africa, where it is compounded by widespread poverty and generalized high prevalence of human immunodeficiency virus (HIV). Therefore, malnutrition should be addressed through a multisectorial approach, and malnourished individuals should have access to nutritional rehabilitation molecules that are affordable, accessible, rich in nutrient and efficient. We thus assessed the efficacy of two affordable and accessible nutritional supplements, spirulina platensis versus soya beans among malnourished HIV-infected adults. METHODS Undernourished patients, naïve of, but eligible to antiretroviral treatment (ART), aged 18 to 35 years were enrolled and randomly assigned to two groups. The first group received spirulina (Group A) as food supplement and the second received soya beans (Group B). Patients were initiated ART simultaneously with supplements. Food supplements were auto-administered daily, the quantity being calculated according to weight to provide 1.5 g/kg body weight of proteins with 25% from supplements (spirulina and soya beans). Patients were monitored at baseline and followed-up during twelve weeks for anthropometric parameters, body composition, haemoglobin and serum albumin, CD4 count and viral load. RESULTS Fifty-two patients were enrolled (Group A: 26 and Group B: 26). The mean age was 26.4 ± 4.9 years (Group A) and 28.7 ± 4.8 (Group B) with no significant difference between groups (P = 0.10). After 12 weeks, weight and BMI significantly improved in both groups (P < 0.001 within each group). The mean gain in weight and BMI in Group A and B were 4.8 vs. 6.5 kg, (P = 0.68) and 1.3 vs. 1.90 Kg/m(2), (P = 0.82) respectively. In terms of body composition, fat free mass (FFM) did not significantly increase within each group (40.5 vs. 42.2 Kg, P = 0.56 for Group A; 39.2 vs. 39.0 Kg, P = 0.22 for Group B). But when compared between the two groups at the end of the trial, FFM was significantly higher in the spirulina group (42.2 vs. 39.0 Kg, P = 0.01). The haemoglobin level rose significantly within groups (P < 0.001 for each group) with no difference between groups (P = 0.77). Serum albumin level did not increase significantly within groups (P < 0.90 vs. P < 0.82) with no difference between groups (P = 0.39). The increase in CD4 cell count within groups was significant (P < 0.01 in both groups), with a significantly higher CD4 count in the spirulina group compared to subjects on soya beans at the end of the study (P = 0.02). Within each group, HIV viral load significantly reduced at the end of the study (P < 0.001 and P = 0.04 for spirulina and soya beans groups respectively). Between the groups, the viral load was similar at baseline but significantly reduced in the spirulina group at the end of the study (P = 0.02). CONCLUSION We therefore conclude in this preliminary study, firstly, that both spirulina and soja improve on nutritional status of malnourished HIV-infected patients but in terms of quality of nutritional improvement, subjects on spirulina were better off than subjects on soya beans. Secondly, nutritional rehabilitation improves on immune status with a consequent drop in viral load but further investigations on the antiviral effects of this alga and its clinical implications are strongly needed.

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BACKGROUND Different therapeutic methods have been applied for the treatment of dysmenorrhea and the method with the lesser side effects is preferred. The aim of this study was to compare the effects of herbal products (fennelin and vitagnus) and mefenamic acid in the treatment of primary dysmenorrhea. MATERIALS AND METHODS This ouble-blind clinical trial was carried out in 105 students with mild and moderate dysmenorrhea. The students were randomly divided into four groups which received the extracts of fennelin and vitagnus, mefenamic acid, and placebo, respectively. Severity of pain was detected by the Visual Analog Scale (VAS) during one cycle before and two cycles after the intervention. Data were analyzed by SPSS version 16 and (P < 0.05 was considered significant. RESULTS Demographic characteristics of the students were similar in the four groups. There was no significant difference in the mean of severity of dysmenorrhea during one cycle before the intervention between the four groups, but the difference was significant during two cycles after the intervention. Fennelin had similar effects as vitagnus on dysmenorrhea. Mefenamic acid had less effect than both the drugs (P <0.05). CONCLUSION Fennelin and vitagnus had higher effect than mefenamic acid. Use of these products is suggested for dysmenorrhea.

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BACKGROUND Hyperphosphatemia is common in chronic kidney disease (CKD) and associated with mortality and morbidity. We aimed to evaluate the dose-dependent efficacy and safety of PA21 (sucroferric oxyhydroxide), an iron-based phosphate binder, in Japanese hemodialysis patients with hyperphosphatemia. METHODS In this double-blind, multicenter, Phase II study, 183 patients were randomized to placebo or PA21 at doses of 250, 500, 750, or 1000 mg (based on iron content) three times/day for 6 weeks. The primary efficacy endpoint was the mean change in serum phosphorus levels from baseline to end of treatment in each group. Adverse reactions were evaluated. RESULTS The change in serum phosphorus level was significantly greater in each PA21 group than in the placebo group (analysis of covariance: P < 0.001 for all groups). A dose-dependent change in serum phosphorus levels was observed in the PA21 groups. A notable decrease in mean serum phosphorus levels to the target level of ≤6 mg/dL was shown starting at Week 1 in all PA21 groups. The cumulative achievement rates for target serum phosphorus level at the end of treatment were generally >80 % in all PA21 groups. The major adverse reaction reported was diarrhea; however, most cases were mild. CONCLUSIONS PA21 was an effective and safe treatment that decreased serum phosphorus levels starting at 1 week of treatment when administered as one 250-mg tablet three times/day. PA21 demonstrated a dose-dependent phosphorus lowering effect up to 3000 mg/day. PA21 may be a new treatment alternative with relatively low pill burden for Japanese hemodialysis patients with hyperphosphatemia.

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BACKGROUND High post-operative pain scores after "minor" orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery. METHODS This randomized, observer-blinded, active-controlled prospective clinical trial had 2 co-primary endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale (NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score of the following events: Nausea, vomiting, constipation, sedation, vertigo, somnolence. The study was powered to detect superiority of tapentadol for at least one endpoint pending statistical proof of non-inferiority for both endpoints in a first step. RESULTS Two hundred sixty-six trauma patients were randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n = 133). Analgesic efficacy: Mean (±SD) daily pain levels in the first five post-operative days were 2.8 ± 1.3 in both groups. Mean maximum pain intensity during exercise in the first 24 h after surgery was 3.8 ± 1.9 (tapentadol) and 3.8 ± 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but not superior to oxycodone/naloxone. SAFETY Vomiting on day 1 occurred in 11%, constipation in 35% of the tapentadol patients and in 16% and 30% of the oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3, respectively). The sum score of side effect events was 51% in the tapentadol vs. 49% in the oxycodone/naloxone group; risk difference 3% [95% CI, -8 to 14%]; p = 0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non-inferiority margin was exceeded. CONCLUSIONS With both concepts, mean maximum pain intensity during exercise within the first 24 h after orthopedic/trauma surgery was reduced to a score of <4. This analgesic efficacy came at the cost of mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against nausea and vomiting and pre-emptive laxatives as part of these concepts. TRIAL REGISTRATION https://eudract.ema.europa.eu (EudraCT- Nr. 2011-003238-15 ); October 24th, 2012.

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BACKGROUND AND OBJECTIVES Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition that frequently presents with symptoms of pain and burning sensation. It is generally a very unrelenting disorder despite several kinds of treatment. Only symptomatic OLP requires treatment, and it remains a challenging predicament. Efforts are made in a sustained manner for searching for novel therapies for symptomatic OLP. Therefore, this study was aimed to compare the efficacy of treatment with topical pimecrolimus cream 1% with that of triamcinolone acetonide oral paste 0.1% in subjects with symptomatic OLP. MATERIALS AND METHODS A prospective, parallel-group, randomized, active control clinical study was conducted among 30 symptomatic OLP subjects (20 females and 10 males, with 15 patients in each treatment group) treated with topical pimecrolimus 1% cream and triamcinolone acetonide 0.1% oral paste four times daily for two consecutive months and treatment-free follow-up was performed for 2 months. Pain or burning sensation, mean clinical score and presence of erythematous areas were assessed. The data obtained were statistically analyzed using Wilcoxon's Rank test and the Mann Whitney test. RESULTS Subjects in both the groups showed significant improvement in symptom scores; however, the overall treatment response was higher in the pimecrolimus group compared with the triamcinolone acetonide group. On intergroup comparison, there was no statistically significant difference between the groups in the reduction in burning sensation (P = 0.18) and erythematous area (P = 0.07), but there was a statistically highly significant improvement in reduction of clinical scoring (P < 0.01%). Following the termination of the treatment, sustained remission of symptoms and long-lasting therapeutic effects was detected in 93.3% of the patients treated with pimecrolimus. INTERPRETATION AND CONCLUSION Topical pimecrolimus 1% cream showed better therapeutic response compared with triamcinolone acetonide 0.1% oral paste in subjects with symptomatic OLP.

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BACKGROUND Vaginal atrophy is a common complication in menopause which does not improve with time and, if untreated, can affect the quality of life for women. The aim of this study was to compare the effectiveness of the vaginal cream of hyaluronic acid and conjugated estrogen (Premarin) in treatment of vaginal atrophy. METHODS This study was a randomized controlled clinical trial on 56 menopausal women with symptoms of vaginal atrophy; they were randomly allocated to two groups (recipient conjugated estrogen and hyaluronic acid). The severity of each sign of atrophy was evaluated by visual analog signals (VAS) and on the basis of a four point scale. Also to recognize the cellular maturation with pap smear and the maturation degree were calculated according to the formula and scores 0-100. As to the vaginal PH, we used PH marker band, the rate of which was divided into 4 degrees. Data were analyzed using SPSS, version 20, and P≤0.05 was considered as significant. RESULTS The results of this study showed that the symptoms of vaginal atrophy compared with the baseline level were relieved significantly in both groups. Dryness, itching, maturation index, PH and composite score of the vaginal symptoms were relieved significantly in both groups (P<0.001). Dyspareunia in Premarin (P<0.05) and hyaluronic acid (P<0.001) decreased compared with pre-treatment. Urinary incontinence only showed improvement in the hyaluronic acid group (P<0.05). Improvement in urinary incontinence, dryness, maturation index (P<0.05) and composite score of vaginal symptoms (P<0.001) in the hyaluronic acid group was better than those in the Premarin group. CONCLUSION According to the results of the present study, hyaluronic acid and conjugated estrogen improved the symptoms of vaginal atrophy. But hyaluronic acid was more effective and this drug is suggested for those who do not want to or cannot take local hormone treatment. TRIAL REGISTRATION NUMBER IRCT2013022712644N1.

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OBJECTIVE To investigate if modified pre-arrival instructions using patient's arm and nipple line as landmarks could avoid abdominal hand placements for chest compressions. METHOD Volunteers were randomized to one of two telephone instructions: "Kneel down beside the chest. Place one hand in the centre of the victim's chest and the other on top" (control) or "Lay the patient's arm which is closest to you, straight out from the body. Kneel down by the patient and place one knee on each side of the arm. Find the midpoint between the nipples and place your hands on top of each other" (intervention). Hand placement was conducted on an adult male and documented by laser measurements. Hand placement, quantified as the centre of the compressing hands in the mid-sagittal plane, was compared to the inter-nipple line (INL) for reference and classified as above or below. Fisher's exact test was used for comparison of proportions. RESULTS Thirty-six lay people, age range 16-60, were included. None in the intervention group placed their hands in the abdominal region, compared to 5/18 in the control group (p = 0.045). Using INL as a reference, the new instructions resulted in less caudal hand placement, and the difference in mean hand position was 47 mm [95% CI 21,73], p = 0.001. CONCLUSION New pre-arrival instructions where the patient's arm and nipple line were used as landmarks resulted in less caudal hand placements and none in the abdominal region.

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BACKGROUND/AIM Targeted radiotherapy of liver malignancies has found to be effective in selected patients. A key limiting factor of these therapies is the relatively low tolerance of the liver parenchyma to radiation. We sought to assess the preventive effects of a combined regimen of pentoxifylline (PTX), ursodeoxycholic acid (UDCA) and low-dose low molecular weight heparin (LMWH) on focal radiation-induced liver injury (fRILI). METHODS AND MATERIALS Patients with liver metastases from colorectal carcinoma who were scheduled for local ablation by radiotherapy (image-guided high-dose-rate interstitial brachytherapy) were prospectively randomized to receive PTX, UDCA and LMWH for 8 weeks (treatment) or no medication (control). Focal RILI at follow-up was assessed using functional hepatobiliary magnetic resonance imaging (MRI). A minimal threshold dose, i.e. the dose to which the outer rim of the fRILI was formerly exposed to, was quantified by merging MRI and dosimetry data. RESULTS Results from an intended interim-analysis made a premature termination necessary. Twenty-two patients were included in the per-protocol analysis. Minimal mean hepatic threshold dose 6 weeks after radiotherapy (primary endpoint) was significantly higher in the study treatment-group compared with the control (19.1 Gy versus 14.6 Gy, p = 0.011). Qualitative evidence of fRILI by MRI at 6 weeks was observed in 45.5% of patients in the treatment versus 90.9% of the control group. No significant differences between the groups were observed at the 12-week follow-up. CONCLUSIONS The post-therapeutic application of PTX, UDCA and low-dose LMWH significantly reduced the extent and incidence fRILI at 6 weeks after radiotherapy. The development of subsequent fRILI at 12 weeks (4 weeks after cessation of PTX, UDCA and LMWH during weeks 1-8) in the treatment group was comparable to the control group thus supporting the observation that the agents mitigated fRILI. TRIAL REGISTRATION EU clinical trials register 2008-002985-70 ClinicalTrials.gov NCT01149304.

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BACKGROUND The effect and safety of catgut implantation at acupoints o treat allergic rhinitis (ICD-10 code J30.4) remain controversial. Here, we used a sham catgut implantation group to determine whether catgut implantation at acupoints is an effective and safe treatment for allergic rhinitis. METHODS A randomized double-blind clinical trial, with parallel groups was conducted. Skin prick and puncture test (SPT) was performed to confirm the diagnosis before enrollment. The participants received two sessions of treatments of active or sham catgut implantation at acupoints (once every two weeks) with a follow-up phase of 8 weeks. The visual analogue scale (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were used to determine the severity of allergic rhinitis. The use of anti-allergic medication was used as a secondary indicator. The incidence of adverse events was also recorded and analyzed. RESULTS An improvement of the VAS and RQLQ scores was observed in both the active and sham-controlled group sat four and eight weeks after the treatment in the self-control analysis. Comparison revealed no significant difference between the treatment and sham-controlled groups until 8 weeks after the 2-week treatment regimen (t = -2.424, P = 0.017). However, the RQLQ scores significantly differed between the two groups after 4 weeks of treatment completion (t = -2.045, P = 0.05) and this difference lasted until the end of 8-week follow-up (t = -2.246, P = 0.033). Throughout the treatment regimen, none of the participants took any relief medication, and no severe adverse events occurred. CONCLUSION Our findings suggest that catgut implantation at acupoints is an effective and safe method for symptomatic treatment of allergic rhinitis. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR-TRC- 12002191 (Date of Registration: 2012-05-09).

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BACKGROUND AND AIMS Endotracheal intubation can produce severe maternal haemodynamic changes during caesarean sections under general anaesthesia. However, administration of narcotics before endotracheal intubation to prevent these changes may affect the Apgar score in neonates. This study was designed to evaluate the effect of intravenous alfentanil on haemodynamic changes due to endotracheal intubation in elective caesarean sections performed under general anaesthesia. METHODS Fifty parturients were randomly divided into two equal groups. Patients in the first group received alfentanil 10 μg/kg and in the second group received placebo intravenously 1 min before induction of anaesthesia for elective caesarean section. Haemodynamic parameters and bispectral index system (BIS) in mothers, peripheral capillary oxygen saturation (SpO2) and Apgar score in the newborn were assessed. RESULTS Changes in systolic blood pressure were significant at 1, 5 and 10 min after intubation between two groups. Changes in diastolic blood pressure were significantly less in alfentanil group, 1 min after induction of anaesthesia and 1 min after endotracheal intubation. Mean heart rate at 1 min after induction and at 1 and 5 min after intubation also reduced significantly in this group. CONCLUSION Alfentanil use was associated with decreases or minimal increases in maternal systolic and diastolic blood pressures and heart rate after endotracheal intubation.

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OBJECTIVE To assess, using structural image evaluation using normalization of atrophy (SIENA), the effect of teriflunomide, a once-daily oral immunomodulator, on brain volume loss (BVL) in patients with relapsing forms of MS enrolled in the phase 3 TEMSO study. METHODS TEMSO MR scans were analyzed (study personnel masked to treatment allocation) using SIENA to assess brain volume changes between baseline and years 1 and 2 in patients treated with placebo or teriflunomide. Treatment group comparisons were made via rank analysis of covariance. RESULTS Data from 969 patient MRI visits were included in this analysis: 808 patients had baseline and year 1 MRI; 709 patients had baseline and year 2 MRI. Median percentage BVL from baseline to year 1 and year 2 for placebo was 0.61% and 1.29%, respectively, and for teriflunomide 14 mg, 0.39% and 0.90%, respectively. BVL was lower for teriflunomide 14 mg vs placebo at year 1 (36.9% relative reduction, p = 0.0001) and year 2 (30.6% relative reduction, p = 0.0001). Teriflunomide 7 mg was also associated with significant reduction in BVL vs placebo over the 2-year study. The significant effects of teriflunomide 14 mg on BVL were observed in both patients with and without on-study disability worsening. CONCLUSIONS The significant reduction of BVL vs placebo over 2 years achieved with teriflunomide is consistent with its effects on delaying disability worsening and suggests a neuroprotective potential. CLASSIFICATION OF EVIDENCE Class II evidence shows that teriflunomide treatment significantly reduces BVL over 2 years vs placebo. CLINICALTRIALSGOV IDENTIFIER NCT00134563.

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BACKGROUND The objective of the present study was to assess the major immediate outcomes of eptifibatide therapy during intracoronary stent implantation. MATERIALS AND METHODS In an interventional study, patients undergoing percutaneous coronary intervention (PCI) were randomized into either the eptifibatide ( n = 100) or the control ( n = 107) group. In each group, demographic and clinical characteristics such as cardiac death, stent thrombosis (ST), myocardial infarction (MI), rates of target lesion and vessel revascularization, cerebral vascular accident (CVA), and emergency coronary artery bypass grafting (CABG) were recorded. RESULTS The overall rates of major adverse events such as mortality, Stent thrombosis (ST), Myocardial Infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), CVA, and emergency CABG within 24 h after stent implantation were low and comparable between the two groups; P > 0.05 considered significant for all comparisons. CONCLUSION There were no statistical differences between the clinical outcomes of groups administered with single-dose intracoronary eptifibatide and control groups among patients undergoing PCI during stent implantation.

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BACKGROUND Research has identified high failure rates of peripheral intravenous catheter (PIVC) and varied flushing practices. METHODS This is a single-centre, pilot, non-masked, factorial randomised controlled trial. Participants were adults, with a PIVC of expected use ≥24 hours (n = 160), admitted to general medical or surgical wards of a tertiary referral hospital in Queensland (Australia). Patients were randomly allocated to one of four flush groups using manually prepared syringes and 0.9 % sodium chloride: 10 mL or 3 mL flush, every 24 or 6 hours. The primary endpoint was PIVC failure, a composite measure of occlusion, infiltration, accidental dislodgement and phlebitis. RESULTS PIVC average dwell was 3.1 days. PIVC failure rates per 1000 hours were not significantly different for the volume intervention (4.84 [3 mL] versus 7.44 [10 mL], p = 0.06, log-rank). PIVC failure rates per 1000 hours were also not significantly different for the frequency intervention (5.06 [24 hour] versus 7.34 [6 hour], p = 0.05, log-rank). Cox proportional hazard regression found neither the flushing nor frequency intervention, or their interaction (p = 0.21) to be significantly associated with PIVC failure. However, female gender (hazard ratio [HR] 2.2 [1.3-3.6], p < 0.01), insertion in hand/posterior wrist (HR 1.7 [1.0-2.7], p < 0.05) and the rate per day of PIVC access (combined flushes and medication pushes) (HR 1.2 [1.1-1.4], p < 0.01) significantly predicted PIVC failure. CONCLUSION Neither increased flushing volume nor frequency significantly altered the risk of PIVC failure. Female gender, hand/posterior wrist placement and episodes of access (flushes and medication) may be more important. Larger, definitive trials are feasible and required. TRIAL REGISTRATION Australian and New Zealand Clinical Trials Registry: ACTRN12615000025538 . Registered on 19 January 2015.

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BACKGROUND Electroacupuncture (EA) is believed to modulate the pain pathway via the release of endogenous opioid substances and stimulation of descending pain inhibitory pathways. In this study, the use of intraoperative 2 Hertz EA stimulation is investigated to determine any opioid-sparing effect and reduction of postoperative nausea and vomiting (PONV) in patients undergoing gynaecological surgery. PATIENT AND METHODS This was a prospective, double blinded randomized study conducted in a tertiary hospital in Malaysia. Patients (n = 64) were randomly allocated to receive 2 Hertz EA and compared to a control group. EA was started intraoperatively till the end of the surgery (mean duration of surgery was 149.06 ± 42.64 minutes) under general anaesthesia. Postoperative numerical rating scale (NRS), the incidence of nausea, vomiting and usage of rescue antiemetics were recorded at 30 minutes, 2, 4, and 24 hours, respectively. The total morphine demand and usage from the patient-controlled analgesia Morphine (PCAM) were also recorded in the first 24 hours postoperatively. RESULTS The mean NRS was 2.75 (SD = 2.34) at 30 minutes and 2.25 (SD = 1.80) at 2 hours postoperatively in the EA group that was significantly lower than the mean NRS in the control group as 4.50 (SD = 2.37) at 30 minutes and 3.88 (SD = 2.21) at 2 hours. The mean PCA morphine demand was 27.28 (SD = 21.61) times pressed in the EA group and 55.25 (SD = 46.85) times pressed in the control group within 24 hours postoperatively, which showed a significant reduction in the EA group than the control group. Similarly, total morphine requirement was significantly lower in the EA group with the value of 21.38 (SD = 14.38) mg compared to the control group with the value of 33.94 (SD = 20.24) mg within 24 hours postoperatively. Incidence of postoperative nausea also significantly reduced in the EA group at 30 minutes (15.6%) compared to the control group (46.9%). CONCLUSIONS It can be concluded that subjects receiving EA intraoperatively experienced less pain and PONV. Hence, it is plausible that EA has an opioid-sparing effect and can reduce PONV.

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PURPOSE To evaluate, using subgroup analysis, the effect of treatment status on the intraocular pressure (IOP)-lowering efficacy of a preservative-free formulation of fixed-combination bimatoprost 0.03%/timolol 0.5% (FCBT PF). METHODS A primary, multicenter, randomized, double-masked, 12-week study compared the efficacy and safety of FCBT PF with preserved FCBT (Ganfort(®)) in 561 patients diagnosed with glaucoma or ocular hypertension. For this analysis, eligible patients were treatment-naïve or had inadequate IOP lowering and underwent a washout of previous treatment. IOP (8 am, 10 am, and 4 pm) was measured at baseline and weeks 2, 6, and 12. Subgroup analysis of the FCBT PF arm assessed changes in average eye IOP from baseline in treatment-naïve vs previously treated patients. To evaluate the effect of treatment status at baseline (treatment-naïve vs previously treated) on IOP reduction in the FCBT PF treatment group, an analysis of covariance model was used with treatment status and investigator as fixed effects, and baseline average eye IOP, age, glaucoma diagnosis, and baseline average eye corneal thickness as covariates. P-values and the 95% confidence intervals were determined using the model. RESULTS In the FCBT PF arm, IOP mean changes from baseline ranged from -8.7 mmHg to -9.8 mmHg in treatment-naïve patients (N=50), compared with -7.3 mmHg to -8.5 mmHg in previously treated patients (N=228). Baseline IOP, age, glaucoma diagnosis, and corneal thickness significantly affected IOP reduction in the FCBT PF group. Adjusting for these covariates, FCBT PF had a greater IOP-lowering effect (0.8-1.7 mmHg) in treatment-naïve patients than previously treated patients, which was statistically significant (P≤0.05) at seven of nine time points. CONCLUSION In this subgroup analysis, FCBT PF reduced IOP more effectively in treatment-naïve than in previously treated patients possibly due, in part, to altered responsiveness or tachyphylaxis that has been associated with prior ocular hypotensive agent treatment.

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PURPOSE The aim of this study is to evaluate the effect of dexmedetomidine on corrected QT (QTc) and Tp-e intervals in patients undergoing spinal anesthesia. MATERIALS AND METHODS We studied 50 patients who were scheduled to undergo spinal anesthesia before orthopedic surgeries. Patients were allocated to receive either an infusion of dexmedetomidine or normal saline after spinal anesthesia. RESULTS QTc intervals were significantly prolonged after spinal anesthesia, and the prolonged QTc interval returned to baseline values 10 minutes after either normal saline or dexmedetomidine administration in both groups. The QTc interval values after dexmedetomidine administration were significantly shorter compared to the QTc interval values just before dexmedetomidine administration. CONCLUSION Dexmedetomidine could promote the return of a prolonged QTc interval induced by spinal anesthesia and might be helpful in patients who have a prolonged QTc interval.

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OBJECTIVE The aim of this work was to evaluate the effectiveness of exercise with manual therapy and exercise alone in adhesive capsulitis of the shoulder. METHOD This randomized study was conducted at institute of physical medicine and rehabilitation Dow University of Health Sciences, Karachi between January, 2014 and July, 2014. Forty four participant age between 25-40 years were recruited. Twenty two participants were allocated to exercise and manual therapy group and 22 participants were allocated to exercise only group. Exercise and manual therapy group received general exercises and Maitland mobilization on shoulder joint whereas exercise group only received general exercises. Both interventions were carried out 3 times a week for 5 consecutive weeks. Pre and post intervention scores of Visual analogue scale (VAS), range of movement and Shoulder Pain and Disability Index (SPDI) were recorded. Paired sample t-test was used to analyze the results within groups. RESULTS After 5 weeks of intervention both groups made significant improvements in all outcome measures (p < 0.001). Intra group analysis showed no significant difference between two groups (p > 0.05). Mean VAS and SPADI difference was 2.23 and 22 in General exercise & manual therapy group and 2.33 and 23 in General exercise group respectively. CONCLUSION Both exercises with manual therapy and exercises alone are equally effective in the management of adhesive capsulits of the shoulder joint.

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BACKGROUND Weight loss benefits of multi-ingredient supplements in conjunction with a low-calorie, high-protein diet in young women are unknown. Therefore, the purpose of this study was to investigate the effects of a three-week low-calorie diet with and without supplementation on body composition. METHODS Thirty-seven recreationally-trained women (n = 37; age = 27.1 ± 4.2; height = 165.1 ± 6.4; weight = 68.5 ± 10.1; BMI = 25.1 ± 3.4) completed one of the following three-week interventions: no change in diet (CON); a high-protein, low-calorie diet supplemented with a thermogenic, conjugated linoleic acid (CLA), a protein gel, and a multi-vitamin (SUP); or the high-protein diet with isocaloric placebo supplements (PLA). Before and after the three-week intervention, body weight, %Fat via dual X-ray absorptiometry (DXA), segmental fat mass via DXA, %Fat via skinfolds, and skinfold thicknesses at seven sites were measured. RESULTS SUP and PLA significantly decreased body weight (SUP: PRE, 70.47 ± 8.01 kg to POST, 67.51 ± 8.10 kg; PLA: PRE, 67.88 ± 12.28 kg vs. POST, 66.38 ± 11.94 kg; p ≤ 0.05) with a greater (p ≤ 0.05) decrease in SUP than PLA or CON. SUP and PLA significantly decreased %Fat according to DXA (SUP: PRE, 34.98 ± 7.05% to POST, 32.99 ± 6.89%; PLA: PRE, 34.22 ± 6.36% vs. POST, 32.69 ± 5.84%; p ≤ 0.05), whereas only SUP significantly decreased %Fat according to skinfolds (SUP: PRE, 27.40 ± 4.09% to POST, 24.08 ± 4.31%; p ≤ 0.05). SUP significantly (p ≤ 0.05) decreased thicknesses at five skinfolds (chest, waist, hip, subscapular, and tricep) compared to PLA, but not at two skinfolds (axilla and thigh). CONCLUSIONS The addition of a thermogenic, CLA, protein, and a multi-vitamin to a three-week low-calorie diet improved weight loss, total fat loss and subcutaneous fat loss, compared to diet alone.

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BACKGROUND/AIMS Stem cell therapy has been applied to treat a variety of autoimmune diseases, including Crohn's disease (CD), but few studies have examined the use of umbilical cord mesenchymal stem cells (UC-MSCs). This trial sought to investigate the efficacy and safety of UC-MSCs for the treatment of CD. METHODS Eighty-two patients who had been diagnosed with CD and had received steroid maintenance therapy for more than 6 months were included in this study. Forty-one patients were randomly selected to receive a total of four peripheral intravenous infusions of 1×10 6 UC-MSCs/kg, with one infusion per week. Patients were followed up for 12 months. The Crohn's disease activity index (CDAI), Harvey-Bradshaw index (HBI), and corticosteroid dosage were assessed. RESULTS Twelve months after treatment, the CDAI, HBI, and corticosteroid dosage had decreased by 62.5±23.2, 3.4±1.2, and 4.2±0.84 mg/day, respectively, in the UC-MSC group and by 23.6±12.4, 1.2±0.58, and 1.2±0.35 mg/day, respectively, in the control group (p＜0.01, p＜0.05, and p＜0.05 for UC-MSC vs control, respectively). Four patients developed a fever after cell infusion. No serious adverse events were observed. CONCLUSIONS UC-MSCs were effective in the treatment of CD and produced mild side effects.

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BACKGROUND Colorectal cancer (CRC) screening rates are low in many areas and cost-effective interventions to promote CRC screening are needed. Recently in a randomized controlled trial, a mailed educational reminder increased CRC screening rates by 16.2% among U.S. Veterans. The aim of our study was to assess the costs and cost-effectiveness of a mailed educational reminder on fecal occult blood test (FOBT) adherence. METHODS In a blinded, randomized, controlled trial, 769 patients were randomly assigned to the usual care group (FOBT alone, n = 382) or the intervention group (FOBT plus a mailed reminder, n = 387). Ten days after picking up the FOBT cards, a 1-page reminder with information related to CRC screening was mailed to the intervention group. Primary outcome was number of returned FOBT cards after 6 months. The costs and incremental cost-effectiveness ratio (ICER) of the intervention were assessed and calculated respectively. Sensitivity analyses were based on varying costs of labor and supplies. RESULTS At 6 months after card distribution, 64.6% patients in the intervention group returned FOBT cards compared with 48.4% in the control group (P < 0.001). The total cost of the intervention was $962 or $2.49 per patient, and the ICER was $15 per additional person screened for CRC. Sensitivity analysis based on a 10% cost variation was $13.50 to $16.50 per additional patient screened for CRC. CONCLUSIONS A simple mailed educational reminder increases FOBT card return rate at a cost many health care systems can afford. Compared to other patient-directed interventions (telephone, letters from physicians, mailed reminders) for CRC screening, our intervention was more effective and cost-effective.

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BACKGROUND In research clinic settings, overweight adults undertaking HIIT (high intensity interval training) improve their fitness as effectively as those undertaking conventional walking programs but can do so within a shorter time spent exercising. We undertook a randomized controlled feasibility (pilot) study aimed at extending HIIT into a real world setting by recruiting overweight/obese, inactive adults into a group based activity program, held in a community park. METHODS Participants were allocated into one of three groups. The two interventions, aerobic interval training and maximal volitional interval training, were compared with an active control group undertaking walking based exercise. Supervised group sessions (36 per intervention) were held outdoors. Cardiorespiratory fitness was measured using VO2max (maximal oxygen uptake, results expressed in ml/min/kg), before and after the 12 week interventions. RESULTS On ITT (intention to treat) analyses, baseline (N = 49) and exit (N = 39) [Formula: see text]O2 was 25.3±4.5 and 25.3±3.9, respectively. Participant allocation and baseline/exit VO2max by group was as follows: Aerobic interval training N =  16, 24.2±4.8/25.6±4.8; maximal volitional interval training N = 16, 25.0±2.8/25.2±3.4; walking N = 17, 26.5±5.3/25.2±3.6. The post intervention change in VO2max was +1.01 in the aerobic interval training, -0.06 in the maximal volitional interval training and -1.03 in the walking subgroups. The aerobic interval training subgroup increased VO2max compared to walking (p = 0.03). The actual (observed, rather than prescribed) time spent exercising (minutes per week, ITT analysis) was 74 for aerobic interval training, 45 for maximal volitional interval training and 116 for walking (p =  0.001). On descriptive analysis, the walking subgroup had the fewest adverse events. CONCLUSIONS In contrast to earlier studies, the improvement in cardiorespiratory fitness in a cohort of overweight/obese participants undertaking aerobic interval training in a real world setting was modest. The most likely reason for this finding relates to reduced adherence to the exercise program, when moving beyond the research clinic setting. TRIAL REGISTRATION ACTR.org.au ACTRN12610000295044.

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BACKGROUND Polycystic ovary syndrome (PCOS) is the most common female endocrine disorder with unknown etiology and with different complications. The aim of this study was to evaluate the effect of omega-3 supplementation on PCOS symptoms and metabolic syndrome. MATERIALS AND METHODS This double-blind clinical trial was performed in 2015 in Alzahra and Shahid Beheshti Hospitals, Isfahan, Iran, on 88 patients with PCOS. Intervention group took omega-3 supplements with dose of 2 g/day for 6 months (two capsules), but control group received two olive oil capsules. Finally, ultrasound and laboratory findings and the recovery rate of menstrual disorders in both groups were compared. RESULTS After 6 months' intervention, waist circumference (WC) was significantly lower in omega-3 as compared to control (81.18 ± 2.87 vs. 84.22 ± 2.61 cm, respectively, P < 0.0001). High-density lipoprotein was increased (47.2 ± 1.37 vs. 41.56 ± 1.34 mg/dl, respectively, P < 0.0001) while low-density lipoprotein (107.79 ± 1.68 vs. 117.4 ± 1.57 mg/dl, respectively), triglyceride (116.02 ± 3.13 vs. 125.06 ± 2.91 mg/dl, respectively), and cholesterol (180.34 ± 6.34 vs. 189.56 ± 5.93 mg/dl, respectively) in omega-3 were significantly lower than control ( P < 0.0001). The interval between periods in omega-3 was significantly shorter than control (29.83 ± 4.68 vs. 47.11 ± 8.72 days, respectively, P < 0.001). CONCLUSION Omega-3 decrease lipid profiles, WC, and interval between periods while weight, hip circumference, fasting blood sugar, number of ovarian follicle, size of ovary, bleeding volume, menstrual bleeding, and hirsutism score did not change by administration of omega-3.

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INTRODUCTION Earlier studies show that a Cochlear Implant (CI), capable of providing intracochlear electrical stimulation independent of environmental sounds, appears to suppress tinnitus at least for minutes. The current main objective is to compare the long-term suppressive effects of looped (i.e. repeated) electrical stimulation (without environmental sound perception) with the standard stimulation pattern of a CI (with environmental sound perception). This could open new possibilities for the development of a "Tinnitus Implant" (TI), an intracochlear pulse generator for the suppression of tinnitus. MATERIALS AND METHODS Ten patients with single sided deafness suffering from unilateral tinnitus in the deaf ear are fitted with a CI (MED-EL Corporation, Innsbruck, Austria). Stimulation patterns are optimized for each individual patient, after which they are compared using a randomized crossover design, with a follow-up of six months, followed by a 3 month period using the modality of patient's choice. RESULTS Results show that tinnitus can be suppressed with intracochlear electrical stimulation independent of environmental sounds, even long term. No significant difference in tinnitus suppression was found between the standard clinical CI and the TI. CONCLUSION It can be concluded that coding of environmental sounds is no requirement for tinnitus suppression with intracochlear electrical stimulation. It is therefore plausible that tinnitus suppression by CI is not solely caused by an attention shift from the tinnitus to environmental sounds. Both the standard clinical CI and the experimental TI are potential treatment options for tinnitus. These findings offer perspectives for a successful clinical application of the TI, possibly even in patients with significant residual hearing. TRIAL REGISTRATION TrialRegister.nl NTR3374.

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INTRODUCTION Chronic kidney disease (CKD) patients' are at risk of low vitamin D and chronic inflammation. We studied the effect of 12 weeks calcitriol and calcium carbonate supplementation on inflammatory mediators serum; interleukin-6 (IL-6), interleukin-10 (IL-10) and highly sensitive C-reactive protein (hs-CRP). MATERIAL AND METHODS A prospective randomized study in CKD stages 2-4 with serum 25-hydroxyvitamin D (25-OHD) levels < 30 ng/ml. Patients were randomized into the Vitamin D + Calcium (Vitamin D + C) or Calcium group. Serums were analyzed at baseline, week 6 and 12. RESULTS Fifty patients, median age of 53 (13.5) years were recruited. Their median IL-10 was 13.35 (25.22) pg/ml. At week 12, serum IL-6 was reduced in both groups (p = 0.001), serum IL-10 was maintained in the Vitamin D + C group (p = 0.06) and was reduced in the Calcium group (p = 0.001). CKD-diabetic patients had reduced serum IL-6 in both study groups (p = 0.001) and a reduction was seen in the Vitamin D + C group of the non-diabetics counterparts (p = 0.005). Serum IL-10 was reduced in the Calcium group (p < 0.05) whereas serum 25-OHD rose in both groups, regardless of their diabetic status (p < 0.05). CONCLUSIONS Twelve weeks, calcitriol supplementation maintained IL-10, had no effects on hs- CRP and had no additional benefit compared to calcium carbonate in reducing serum IL-6 except in non-diabetics.

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BACKGROUND Since sugar-sweetened beverages (SSB) may contribute to the development of overweight in children, effective interventions to reduce their consumption are needed. Here we evaluated the effect of a combined school- and community-based intervention aimed at reducing children's SSB consumption by promoting the intake of water. Favourable intervention effects on children's SSB consumption were hypothesized. METHODS In 2011-2012, a controlled trial was conducted among four primary schools, comprising 1288 children aged 6-12 years who lived in multi-ethnic, socially deprived neighbourhoods in Rotterdam, the Netherlands. Intervention schools adopted the 'water campaign', an intervention developed using social marketing. Control schools continued with their regular health promotion programme. Primary outcome was children's SSB consumption, measured using parent and child questionnaires and through observations at school, both at baseline and after one year of intervention. RESULTS Significant positive intervention effects were found for average SSB consumption (B -0.19 litres, 95% CI -0.28;-0.10; parent report), average SSB servings (B -0.54 servings, 95% CI -0.82;-0.26; parent report) and bringing SSB to school (OR 0.51, 95% CI 0.36;0.72; observation report). CONCLUSIONS This study supports the effectiveness of the water campaign intervention in reducing children's SSB consumption. Further studies are needed to replicate our findings. TRIAL REGISTRATION Current Controlled Trials: NTR3400.

1significant effect

BACKGROUND Cognitive Behavioral Therapy (CBT) for depression is efficacious, but effectiveness is limited when implemented in low-income settings due to engagement difficulties including nonadherence with skill-building homework and early discontinuation of treatment. Automated messaging can be used in clinical settings to increase dosage of depression treatment and encourage sustained engagement with psychotherapy. OBJECTIVES The aim of this study was to test whether a text messaging adjunct (mood monitoring text messages, treatment-related text messages, and a clinician dashboard to display patient data) increases engagement and improves clinical outcomes in a group CBT treatment for depression. Specifically, we aim to assess whether the text messaging adjunct led to an increase in group therapy sessions attended, an increase in duration of therapy attended, and reductions in Patient Health Questionnaire-9 item (PHQ-9) symptoms compared with the control condition of standard group CBT in a sample of low-income Spanish speaking Latino patients. METHODS Patients in an outpatient behavioral health clinic were assigned to standard group CBT for depression (control condition; n=40) or the same treatment with the addition of a text messaging adjunct (n=45). The adjunct consisted of a daily mood monitoring message, a daily message reiterating the theme of that week's content, and medication and appointment reminders. Mood data and qualitative responses were sent to a Web-based platform (HealthySMS) for review by the therapist and displayed in session as a tool for teaching CBT skills. RESULTS Intent-to-treat analyses on therapy attendance during 16 sessions of weekly therapy found that patients assigned to the text messaging adjunct stayed in therapy significantly longer (median of 13.5 weeks before dropping out) than patients assigned to the control condition (median of 3 weeks before dropping out; Wilcoxon-Mann-Whitney z=-2.21, P=.03). Patients assigned to the text messaging adjunct also generally attended more sessions (median=6 sessions) during this period than patients assigned to the control condition (median =2.5 sessions), but the effect was not significant (Wilcoxon-Mann-Whitney z=-1.65, P=.10). Both patients assigned to the text messaging adjunct (B=-.29, 95% CI -0.38 to -0.19, z=-5.80, P<.001) and patients assigned to the control conditions (B=-.20, 95% CI -0.32 to -0.07, z=-3.12, P=.002) experienced significant decreases in depressive symptom severity over the course of treatment; however, the conditions did not significantly differ in their degree of symptom reduction. CONCLUSIONS This study provides support for automated text messaging as a tool to sustain engagement in CBT for depression over time. There were no differences in depression outcomes between conditions, but this may be influenced by low follow-up rates of patients who dropped out of treatment.

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RATIONALE Coffee is often consumed to counteract driver sleepiness. There is limited information on the effects of a single low dose of coffee on prolonged highway driving in non-sleep deprived individuals. OBJECTIVES The aim of this study was to examine the effects of a single cup of coffee (80 mg caffeine) on simulated highway driving performance. METHODS Non-sleep deprived healthy volunteers (n024) participated in a double-blind, placebo-controlled, crossover study. After 2 h of monotonous highway driving, subjects received caffeinated or decaffeinated coffee during a 15-min break before continuing driving for another 2 h. The primary outcome measure was the standard deviation of lateral position (SDLP), reflecting the weaving of the car. Secondary outcome measures were speed variability, subjective sleepiness, and subjective driving performance. RESULTS The results showed that caffeinated coffee significantly reduced SDLP as compared to decaffeinated coffee, both in the first (p00.024) and second hour (p00.019) after the break. Similarly, the standard deviation of speed (p0 0.024; p00.001), mental effort (p00.003; p00.023), and subjective sleepiness (p00.001; p00.002) were reduced in both the first and second hour after consuming caffeinated coffee. Subjective driving quality was significantly improved in the first hour after consuming caffeinated coffee (p00.004). CONCLUSIONS These findings demonstrate a positive effect of one cup of caffeinated coffee on driving performance and subjective sleepiness during monotonous simulated highway driving.

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STUDY DESIGN This is a double-blind, randomized, placebo-controlled cross-over study of melatonin in complete tetraplegia. OBJECTIVES Tetraplegic patients have an increased risk of venous thrombosis despite prophylaxis, blunted variations in melatonin and altered circadian variation of several hemostatic markers. To examine whether melatonin could modify the regulation of hemostasis, we measured plasma melatonin and several markers of hemostasis in tetraplegic subjects with or without melatonin supplement. SETTING The study was conducted in the Section for Spinal Cord Injury, Sunnaas Hospital, Nesoddtangen, Norway. METHODS Six subjects with long-standing complete tetraplegia were included in this cross-over study with 2 mg of melatonin or placebo given 4 days before sampling. We also included six able-bodied men without any intervention. Plasma samples were then collected frequently during a 24-h awake/sleep cycle. The plasma concentrations of melatonin and the various markers were analyzed using linear mixed models. RESULTS The 24-h profiles of prothrombin fragment 1+2 and von Willebrand factor, but not D-dimer, activated FVII, tissue factor pathway inhibitor and plasminogen activator inhibitor type 1, differed (P<0.05) between tetraplegic patients and able-bodied subjects. The absolute plasma concentration of activated FVII was higher (P<0.05) among the able-bodied compared with the tetraplegic groups. Supplementation of melatonin had no impact on these findings. CONCLUSIONS We found differences in circadian variation of several hemostatic markers between able-bodied and tetraplegics. These differences were apparently unrelated to fluctuations in the melatonin concentrations, suggesting little or no role of melatonin in the regulation of hemostasis in tetraplegia. SPONSORSHIP Financial support was provided from the Throne Holst Foundation.

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BACKGROUND Necrotizing enterocolitis (NEC) is one of the most destructive diseases associated with conditions of neonatal prematurity. Supplementation with enteral prebiotics may reduce the incidence of NEC, especially in infants who fed exclusively with breast-milk. Therefore, we compared the efficacy and safety of enteral supplementation of a prebiotic mixture (short chain galacto-oligosaccharides/long chain fructo-oligosaccharides [SCGOS/LCFOS]) versus no intervention on incidence of NEC in preterm infants. METHODS In a single-center randomized control trial 75 preterm infants (birth weight [BW] ≤1500 g, gestational age ≤34 weeks and were not fed with formula) on 30 ml/kg/day volume of breast-milk were randomly allocated to have enteral supplementation with a prebiotic mixture (SCGOS/LCFOS; 9:1) or not receive any prebiotic. The incidence of suspected NEC, feeding intolerance, time to full enteral feeds, duration of hospitalization were investigated. RESULTS Differences in demographic characteristics were not statistically important. SCGOS/LCFOS mixture significantly reduced the incidence of suspected NEC, (1 [4.0%] vs. 11 [22.0%]; hazard ratio: 0.49 [95% confidence interval: 0.29-0.84]; P = 0.002), and time to full enteral feeds (11 [7-21] vs. 14 [8-36] days; P - 0.02]. Also duration of hospitalization was meaningfully shorter in the prebiotic group (16 [9-45] vs. 25 [11-80]; P - 0.004]. Prebiotic oligosaccharides were well tolerated by very low BW (VLBW) infants. CONCLUSIONS Enteral supplementation with prebiotic significantly reduced the incidence of NEC in VLBW infants who were fed exclusively breast-milk. This finding suggests that it might have been the complete removal of formula which caused a synergistic effect between nonhuman neutral oligosaccharides (prebiotic) and human oligosaccharides.

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BACKGROUND Obtaining hemostasis during cardiovascular procedures can be a challenge, particularly around areas with a complex geometry or that are difficult to access. While several topical hemostats are currently on the market, most have caveats that limit their use in certain clinical scenarios such as pulsatile arterial bleeding. The aim of this study was to assess the effectiveness and safety of Veriset™ hemostatic patch in treating cardiovascular bleeding. METHODS Patients (N=90) scheduled for cardiac or vascular surgery at 12 European institutions were randomized 1:1 to treatment with either Veriset™ hemostatic patch (investigational device) or TachoSil ® (control). After application of the hemostat, according to manufacturer instructions for use, time to hemostasis was monitored. Follow-up occurred up to 90 days post-surgery. RESULTS Median time to hemostasis was 1.5 min with Veriset™ hemostatic patch, compared to 3.0 min with TachoSil ® ( p <0.0001). Serious adverse events within 30 days post-surgery were experienced by 12/44 (27.3%) patients treated with Veriset™ hemostatic patch and 10/45 (22.2%) in the TachoSil ® group ( p =0.6295). None of these adverse events were device-related, and no reoperations for bleeding were required within 5 days post-surgery in either treatment group. CONCLUSION This study reinforces the difference in minimum recommended application time between Veriset™ hemostatic patch and TachoSil ® (30 s versus 3 min respectively). When compared directly at 3 min, Veriset™ displayed no significant difference, showing similar hemostasis and safety profiles on the cardiovascular bleeding sites included in this study.

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BACKGROUND Extending contact with participants after initial, intensive intervention may support maintenance of weight loss and related behaviors. OBJECTIVE This community-wide trial evaluated a text message (short message service, SMS)-delivered, extended contact intervention ('Get Healthy, Stay Healthy' (GHSH)), which followed on from a population-level, behavioral telephone coaching program. METHODS This study employed a parallel, randomized controlled trial: GHSH compared with no continued contact (standard practice). Participants (n=228) were recruited after completing a 6-month lifestyle telephone coaching program: mean age = 53.4 (standard deviation (SD)=12.3) years; 66.7% (152/228) female; mean body mass index (BMI) upon entering GHSH=29.5 kg/m2 (SD = 6.0). Participants received tailored text messages over a 6-month period. The message frequency, timing, and content of the messages was based on participant preference, ascertained during two tailoring telephone calls. Primary outcomes of body weight, waist circumference, physical activity (walking, moderate, and vigorous sessions/week), and dietary behaviors (fruit and vegetable serves/day, cups of sweetened drinks per day, takeaway meals per week; fat, fiber and total indices from the Fat and Fiber Behavior Questionnaire) were assessed via self-report before (baseline) and after (6-months) extended contact (with moderate-vigorous physical activity (MVPA) also assessed via accelerometry). RESULTS Significant intervention effects, all favoring the intervention group, were observed at 6-months for change in weight (-1.35 kg, 95% confidence interval (CI): -2.24, -0.46, P=.003), weekly moderate physical activity sessions (0.56 sessions/week, 95% CI: 0.15, 0.96, P=.008) and accelerometer-assessed MVPA (24.16 minutes/week, 95% CI: 5.07, 43.25, P=.007). Waist circumference, other physical activity outcomes and dietary outcomes, did not differ significantly between groups. CONCLUSIONS The GHSH extended care intervention led to significantly better anthropometric and physical activity outcomes than standard practice (no contact). This evidence is useful for scaling up the delivery of GHSH as standard practice following the population-level telephone coaching program.

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BACKGROUND We examined the effect of four weeks of β-alanine supplementation on isometric endurance of the knee extensors at 45% maximal voluntary isometric contraction (MVIC). METHODS Thirteen males (age 23 ± 6 y; height 1.80 ± 0.05 m; body mass 81.0 ± 10.5 kg), matched for pre-supplementation isometric endurance, were allocated to either a placebo (n = 6) or β-alanine (n = 7; 6.4 g·d-1 over 4 weeks) supplementation group. Participants completed an isometric knee extension test (IKET) to fatigue, at an intensity of 45% MVIC, before and after supplementation. In addition, two habituation tests were completed in the week prior to the pre-supplementation test and a further practice test was completed in the week prior to the post-supplementation test. MVIC force, IKET hold-time, and impulse generated were recorded. RESULTS IKET hold-time increased by 9.7 ± 9.4 s (13.2%) and impulse by 3.7 ± 1.3 kN·s-1 (13.9%) following β-alanine supplementation. These changes were significantly greater than those in the placebo group (IKET: t(11) = 2.9, p ≤0.05; impulse: t(11) = 3.1, p ≤ 0.05). There were no significant changes in MVIC force in either group. CONCLUSION Four weeks of β-alanine supplementation at 6.4 g·d-1 improved endurance capacity of the knee extensors at 45% MVIC, which most likely results from improved pH regulation within the muscle cell as a result of elevated muscle carnosine levels.

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INTRODUCTION Intensive care unit (ICU) patients are predisposed to thromboembolism. Routine prophylactic anticoagulation is widely recommended. Low-molecular-weight heparins, such as enoxaparin, are increasingly used because of predictable pharmacokinetics. This study aims to determine the subcutaneous (SC) dose of enoxaparin that would give the best anti-factor Xa levels in ICU patients. METHODS The 72 patients admitted to a mixed ICU at Odense University Hospital (OUH) in Denmark were randomised into four groups to receive 40, 50, 60, or 70 mg SC enoxaparin for a period of 24 hours. Anti-factor Xa activity (aFXa) was measured before, and at 4, 12, and 24 hours after administration. An AFXa level between 0.1 to 0.3 IU/ml was considered evidence of effective antithrombotic activity. RESULTS Median peak (4 hours after administration), aFXa levels increased significantly with an increase in enoxaparin dose, from 0.13 IU/ml at 40 mg, to 0.14 IU/ml at 50 mg, 0.27 IU/ml at 60 mg, and 0.29 IU/ml at 70 mg (P = 0.002). At 12 hours after administration, median aFXa levels were still within therapeutic range for those patients who received 60 mg (P = 0.02). CONCLUSIONS Our study confirmed that a standard dose of 40 mg enoxaparin yielded subtherapeutic levels of aFXa in critically ill patients. Higher doses resulted in better peak aFXa levels, with a ceiling effect observed at 60 mg. The present study seems to suggest inadequate dosage as one of the possible mechanisms for the higher failure rate of enoxaparin in ICU patients. TRIAL REGISTRATION ISRCTN03037804.

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BACKGROUND This study aimed to assess the push-out bond strength of mineral trioxide aggregate (MTA) to root canal dentin after irrigation with Smear Clear in comparison with 2.5% sodium hypochlorite (NaOCl), 2% chlorhexidine (CHX) and saline as commonly used root canal irrigants. MATERIAL AND METHODS The coronal and mid-root areas of maxillary anterior teeth were horizontally sectioned into one-millimeter thick slices. The root canal lumen of dentinal slices was dilated using a diamond bur with 1.3 mm diameter. After the application of MTA, the samples were incubated in 100% humidity for 10 minutes and were then randomly divided into four groups (n=20) and immersed in Smear Clear, 2.5% NaOCl, 2% CHX and saline for 30 minutes. No irrigant was used for the control group (n=20). A wet cotton pellet was placed on the samples and after 48 hours of incubation, push-out bond strength was measured using a universal testing machine. The samples were evaluated under a stereomicroscope to determine the mode of failure. One-way ANOVA was used to assess statistical differences among the groups. RESULTS The control group showed the highest bond strength with significant differences with other groups ( P <0.05). Among the experimental groups, the saline group had no significant difference with CHX (P=0.09) but it had significant differences with Smear Clear and NaOCl groups ( P <0.05). No significant difference in bond strength to MTA was noted after irrigation with Smear Clear, CHX and NaOCl ( P >0.05). Other pairwise comparisons showed no significant difference ( P >0.05). CONCLUSIONS Irrigation with Smear Clear, CHX and NaOCl did not cause a significant change in bond strength of MTA to dentin. Key words: Root Canal Irrigants, push-out, Mineral Trioxide Aggregate, dentin.

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BACKGROUND Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects. Lately, a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough. Therefore, the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD. METHODS This was a randomized, controlled, parallel-group, exploratory study with 4-week baseline (T0), 12-week treatment phase (T1) and 12-week follow-up period (T2). Patients with mild to moderate AD meeting the included criteria were randomly allocated into either acupuncture or donepezil hydrochloride groups. The acupuncture group(AG) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG) group was administered donepezil hydrochloride once daily (5 mg/day for the first 4 weeks and 10 mg/day thereafter). Primary efficacy was measured using Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog) and Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). The second outcomes were measured with 23-Item Alzheimer's disease Cooperative Study Activities of Daily Living Scales (ADAS-ADL 23 ) and Neuropsychiatric Index (NPI). RESULTS Of 87 participants enrolled in the study, 79 patients finished their treatment and follow-up processes. The ADAS-cog scores for AG group showed obvious decreases at T2 and ∆(T2-T0)when compared with DG group, and significant between-group differences were detected (all p < 0.05). The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group, and there were significant differences between the two groups (푃<0.05). There were no significant between-group differences in the scores of ADAS-ADL 23 and NPI during the study period. Treatment discontinuations due to adverse events were 0 (0%) and 4 (9.09%) for the AG and DG groups, respectively. CONCLUSIONS Acupuncture is safe, well tolerated and effective in improving the cognitive function, global clinical status of AD. TRIAL REGISTRATION ChiCTR-IOR-17010465 (Retroactively registered on 18 JAN 2017).

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BACKGROUND Most public health guidelines recommend that adults participate in 30 minutes of moderate intensity physical activity on most days of the week. Establishing new ways to achieve these targets in sedentary populations need to be explored. This research evaluated whether the daily use of pedometers could increase physical activity and improve health outcomes in sedentary overweight and obese women. METHODS Twenty six overweight and obese middle-aged women were randomized into two groups: The control group was not able to record their steps daily, whilst the pedometer group, were asked to record the number of steps on a daily basis for 12 weeks. RESULTS Our data showed that the pedometer group significantly increased their steps/day, by 36%, at the end of the 12 weeks, whereas the control group's physical activity levels remained unchanged. There was no significant difference in weight or body fat composition in the pedometer group compared to the control group. However, there was a significant decrease in systolic blood pressure in the pedometer group (112.8 +/- 2.44 mm Hg) compared to the control group (117.3 +/- 2.03 mm Hg) (p = 0.003). CONCLUSION In conclusion, this pilot study shows that the combination of having step goals and immediate feedback from using a pedometer was effective in increasing physical activity levels in sedentary overweight and obese women. TRIAL REGISTRATION ACTRN12609000176268.

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BACKGROUND We investigated the effects of vildagliptin or alogliptin on blood glucose and hemoglobin A1c (HbA1c) in patients with type 2 diabetes inadequately controlled by sitagliptin. METHODS In a single-center open-label trial, 35 patients with inadequate glycemic control on sitagliptin therapy (50 mg once daily) were randomly switched to treatment with vildagliptin (50 mg twice daily) or alogliptin (25 mg once daily). After 12 weeks, patients who failed to achieve the target HbA1c level of < 7.0% with vildagliptin or alogliptin treatment were switched to high-dose sitagliptin (100 mg once daily) and the effect on glycemic control was assessed. RESULTS Vildagliptin did not significantly alter the mean plasma glucose level (175.5 ± 54.4 mg/dL vs. 179.1 ± 73.4 mg/dL) or HbA1c (8.01% vs. 8.02%) after 12 weeks. With alogliptin, mean plasma glucose increased from 175.4 ± 50.9 mg/dL to 195.3 ± 55.0 mg/dL after 12 weeks and HbA1c increased significantly from 8.0% to 8.3% (P < 0.05). At 12 weeks after switching from vildagliptin to high-dose sitagliptin (100 mg daily), HbA1c was increased to 8.3%, but it was significantly (P < 0.05) reduced to the baseline level of 8.0% after switching from alogliptin. The reduction of HbA1c was significantly greater in the vildagliptin group than the alogliptin group (P = 0.008), but the response rate (achieving the target HbA1c < 7.0%) did not differ significantly between the two groups. CONCLUSION The glucose-lowering effects of these three dipeptidyl peptidase-4 (DPP-4) inhibitors (vildagliptin, alogliptin, and sitagliptin) were different, and the effects of vildagliptin and sitagliptin were stronger than that of alogliptin.

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AIMS To compare two different clopidogrel regimens on the outcomes of patients undergoing elective coronary angiography (CAG)+/-ad hoc percutaneous coronary intervention (PCI). METHODS AND RESULTS Open-trial randomized 1028 patients with stable angina to group A ('non-selective'-clopidogrel 600 mg > 6 h before CAG; n = 513) or group B ('selective'-clopidogrel 600 mg in the cath-lab after CAG, only in case of PCI; n = 515). Combined primary endpoint was death/periprocedural myocardial infarction (MI)/stroke/re-intervention within 7 days. Secondary endpoints were troponin elevation and bleeding complications. Primary endpoint occurred in 0.8% group A patients vs. 1% group B (P = 0.749; 90% CI for the percentage difference -1.2-0.8). Periprocedural troponin elevation (> 3 x ULN) was detected in 2.6% group A vs. 3.3% group B (P = 0.475; 90% CI -2.5-1.0). Bleeding complications occurred in 3.5% group A patients vs. 1.4% group B (P = 0.025). After adjustment for covariates and factors that may influence the bleeding risk, patients in group A were shown to have more likely bleeding complications when compared with group B (OR = 3.03; 95% CI 1.14-8.10; P = 0.027). CONCLUSION High (600 mg) loading dose of clopidogrel before elective CAG increased the risk of minor bleeding complications, while the benefit on periprocedural infarction was not significant. Clopidogrel can be given safely in the catheterization laboratory between CAG and PCI in chronic stable angina patients.

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BACKGROUND In patients with suspected angina pectoris, CT coronary angiography (CTCA) clarifies the diagnosis, directs appropriate investigations and therapies, and reduces clinical events. The effect on patient symptoms is currently unknown. METHODS In a prospective open-label parallel group multicentre randomised controlled trial, 4146 patients with suspected angina due to coronary heart disease were randomised 1:1 to receive standard care or standard care plus CTCA. Symptoms and quality of life were assessed over 6 months using the Seattle Angina Questionnaire and Short Form 12. RESULTS Baseline scores indicated mild physical limitation (74±0.4), moderate angina stability (44±0.4), modest angina frequency (68±0.4), excellent treatment satisfaction (92±0.2) and moderate impairment of quality of life (55±0.3). Compared with standard care alone, CTCA was associated with less marked improvements in physical limitation (difference -1.74 (95% CIs, -3.34 to -0.14), p=0.0329), angina frequency (difference -1.55 (-2.85 to -0.25), p=0.0198) and quality of life (difference -3.48 (-4.95 to -2.01), p<0.0001) at 6 months. For patients undergoing CTCA, improvements in symptoms were greatest in those diagnosed with normal coronary arteries or who had their preventative therapy discontinued, and least in those with moderate non-obstructive disease or had a new prescription of preventative therapy (p<0.001 for all). CONCLUSIONS While improving diagnosis, treatment and outcome, CTCA is associated with a small attenuation of the improvements in symptoms and quality of life due to the detection of moderate non-obstructive coronary artery disease. TRIAL REGISTRATION NUMBER NCT01149590.

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BACKGROUND Multiple sclerosis (MS) is a central nervous system disorder with periods of recurrence and recovery. Mitoxantrone has been approved for secondary progressive MS (SPMS) treatment but data lacks the role of corticosteroid pulse therapy in SPMS. OBJECTIVES To evaluate the role of corticosteroid pulse therapy in patients with SPMS receiving mitoxantrone. PATIENTS AND METHODS A double blind randomized controlled clinical trial was performed on 71 patients with SPMS referred to Shahid Sadoughi Hospital (Yazd, Iran) for receiving mitoxantrone in two groups. The first group (35 patients) received 20 mg mitoxantrone plus 500 mg methylprednisolone monthly for six months. The second group (36 patients) received the same dosage of mitoxantrone plus 100 CC of 5% dextrose water monthly for six months. Expanded disability status scale (EDSS), MRI plaques in both groups before and after the treatment completion and six months after the end of trial were compared together. RESULTS 28 men and 43 women enrolled in the study. MRI plaques number reduced in groups significantly (2.29 vs. 2.17) without significant difference between the groups (P = 0.782). Six months after trial completion, plaques number increased in groups without significantly difference (0.72 vs. 0.77, P = 0.611). The mean value of EDSS showed significant reduction at the end of treatment in groups (0.79 and 0.53) without significant difference between the groups (P = 0.953). Six months after trial completion, EDSS increased in groups without significant difference (0.35 vs. 0.43, P = 0.624). CONCLUSIONS Corticosteroid pulse therapy in SPMS was effective in inflammatory process, but could not postpone or decline the neurodegenerative process and besides the imposing side effects could not result in significant improvement in EDSS and MRI plaques number in long term.

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STUDY QUESTION Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex(®)) non-inferior to vaginal progesterone (Endometrin(®)) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of -2.8% (95% confidence interval (CI) -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18-42 years, with a BMI of ≤ 30 kg/m(2), with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2-3) FSH of ≤ 15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS(®)). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Using a PP analysis, which included all patients who received an embryo transfer (Prolutex = 392; Endometrin = 390), the ongoing pregnancy rate per retrieval for subcutaneous versus vaginal progesterone was 41.6 versus 44.4%, with a difference between groups of -2.8% (95% CI -9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. In addition, rates of initial positive β-hCG (56.4% subcutaneous versus 59.0% vaginal; 95% CI -9.5, 4.3), clinical intrauterine pregnancy with fetal cardiac activity (42.6 versus 46.4%; 95% CI -10.8, 3.2), implantation defined as number of gestational sacs divided by number of embryos transferred (33.2 versus 35.1%; 95% CI -7.6, 4.0), live birth (41.1 versus 43.1%; 95% CI -8.9, 4.9) and take-home baby (41.1 versus 42.6%; 95% CI -8.4, 5.4) were comparable. Both formulations were well-tolerated, with no difference in serious adverse events. Analysis with the intention-to-treat population also demonstrated no difference for any outcomes between the treatment groups. LIMITATIONS, REASONS FOR CAUTION The conclusions are limited to the progesterone dosing regimen studied and duration of treatment for the patient population examined in this study. WIDER IMPLICATIONS OF THE FINDINGS Subcutaneous progesterone represents a novel option for luteal phase support in women undergoing IVF who for personal reasons prefer not to use a vaginal preparation or who wish to avoid the side effects of vaginal or i.m. routes of administration. STUDY FUNDING/COMPETING INTERESTS The study was funded by Institut Biochimique SA (IBSA). CAJ, BC, ST and CJ are employees of IBSA. FH currently consults for IBSA. TRIAL REGISTRATION NUMBER NCT00828191.

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BACKGROUND At present, diabetes is a chronic disease of great cost and heavy burdens. The International Diabetes Federation has repeatedly warned that by 2025, the global number of diabetics would rise to 333 million from 194 million in 2003. Although the occurrence of diabetes in developing countries is lower, China has a large population, so that the number of cases is increased. At the same time, more people have prediabetes, a growing health concern where a large percentage of the patients develop full type 2 diabetes. In addition, the patients of diabetes easily incur complications such as blindness, kidney failure, and cardiovascular diseases that can seriously affect the patients' quality of life and cause great economic burdens to family and society. Therefore, effective interventions for prediabetes are needed to prevent or delay the occurrence and development of diabetes. METHODS A randomized controlled trial that was assessed with pharmacoeconomic methods was undertaken in this study. The study term was 24 months (12 months for the intervention and 12 months for follow up). Four hundred participants, recruited from four cities in China: Beijing, Tianjin, Xian, and Naning, were randomized to the treatment group (JQJT tablets) and the control group (placebo). Participants included in this study had been diagnosed with prediabetes according to the criteria for western medicine and Traditional Chinese Medicine (TCM). The end-point effectiveness indexes included the incidence of diabetes and the reversion rate. The drug costs and lifestyle intervention costs were included in the total costs. The study used the cost-effectiveness analysis to discuss the economic advantage of the JQJT tablets. RESULTS The outcomes of the study contained 2 sections,namely clinical outcomes and cost-effectiveness analysis outcomes. The clinical outcomes: the treatment group and control group had no significant statistical difference P> 0.05) on the baseline of situation; Jinqi Jiangtang tablet effectively reduced the incidence of diabetes mellitus and enhanced reversion rate. compared with the control group (p< 0.05); the scores of SF-36 of two groups had no significant difference P> 0.05); finally the compliance of participants between the two groups had no significant difference. The cost-effectiveness analysis outcomes:in the intervention period of 12 months,on the aspect of reversion rate, the treatment group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio;on the aspect of the incidence of diabetes, the control group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio; in the follow-up period of 24 months, on the aspect of reversion rate, the treatment group had better economic advantage by using cost-effectiveness ratio and the incremental cost-effectiveness ratio, on the aspect of the incidence of diabetes, the control group had better economic advantage by using cost-effectivenes ratio and the incremental cost-effectiveness ratio.At the same time, these outcomes remained the same by sensitivity analysis. Assuming that prices and resident incomes rose 5%, the sensitiveness analysis shows that the two group affected by the paremeters changed little. CONCLUSION The importance and effectiveness of lifestyle education and JinQi Jiangtang tablets was proven. In both the intervention period and follow-up, JinQi Jiangtang tablets combined with lifestyle education had a greater cost advantage effect than the lifestyle education alone on the reversion rate; the lifestyle education had a greater cost advantage effect than the JinQi Jiangtang tablets combined with lifestyle education on the incidence of diabetes. TRIAL REGISTRATION Chinese Clinical Trials ChiCTR-TRC-09000401 ) , registered on 25 May 2009.

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BACKGROUND Although the potential advantages of the Endocut mode (E-mode) of endoscopic sphincterotomy (EST) over the conventional blended cut mode (C-mode) have been reported, the problems, including the small sample size and retrospective analysis, that occurred in previous studies make it difficult to conclude the advantage of the E-mode regarding the safety and efficacy. We performed a prospective randomized controlled study to compare these modes. METHODS A total of 360 patients with choledocholithiasis or stenosis of the bile duct were randomly assigned to one of the modes. To avoid the technical bias due to multiple operators or institutions, the main operator and the institution were restricted to only one experienced doctor and 3 institutions at his place of employment, respectively. We defined pancreatitis, bleeding, and perforation as complications of EST. Besides, bleeding includes endoscopically evident bleeding that was defined as visible during the procedure of sphincterotomy and temporary slight oozing. RESULTS The complications occurred in 20 (11.2%) patients from the E-mode group: pancreatitis in 6 (3.4%) and endoscopically evident bleeding in 14 (7.8%). In contrast, the complications occurred in 25 (13.8%) patients from the C-mode group: pancreatitis in 7 (3.9%) and endoscopically evident bleeding in 18 (9.9%), although these findings were not statistically significant. Overall, there were no severe complications. There were no significant differences in completion ratio of EST and the time taken for the sphincterotomy between both groups. CONCLUSIONS The E-mode could not surpass the C-mode in safety and efficacy under the operation by a single endoscopist.

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BACKGROUND A large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection (CND) emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach (BABA), compared with conventional open procedure in papillary thyroid microcarcinoma. METHODS One-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People's Liberation Army (PLA) were randomly assigned to robotic group or conventional open approach group (n = 50 in each group). The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale (VAS), postoperative hospital stay time, complications, and numerical scoring system (NSS, used to assess cosmetic effect) were analyzed. RESULTS The robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group (118.8 ± 16.5 min vs. 90.7 ± 10.3 min, P < 0.05). The study showed significant differences between the two groups in terms of the VASs (2.1 ± 1.0 vs. 3.8 ± 1.2, P < 0.05) and NSS (8.9 ± 0.8 vs. 4.8 ± 1.7, P < 0.05). The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant (all P > 0.05). Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups. Postoperative cosmetic results were very satisfactory in the robotic group. CONCLUSIONS Robotic total thyroidectomy with CND via BABA is safe and effective for Chinese patients with papillary thyroid microcarcinoma who worry about the neck scars.

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INTRODUCTION Patients with metabolic syndrome (MetS) may have lower 25-hydroxyvitamin D (25(OH)VitD) serum levels compared with non-MetS individuals. Vitamin D (VitD) deficiency is associated with various cardiovascular disease (CVD) risk factors. Yet, the effect of VitD supplementation on MetS remains uncertain. Our aim was to examine the effect of VitD supplementation on CVD risk factors in MetS subjects. MATERIAL AND METHODS This pilot study had a PROBE (prospective, randomised, open-label, blinded end-point) design. Fifty patients with MetS were included and randomised either to dietary instructions ( n = 25) (control group) or dietary instructions plus VitD 2000 IU/day ( n = 25) (VitD group) for 3 months. This study is registered in ClinicalTrials.gov (NCT01237769). RESULTS In both groups a similar small weight reduction was achieved. In the VitD group serum 25(OH)VitD levels significantly increased by 91% (from 16.0 (3.0-35.0) to 30.6 (8.4-67.0) ng/ml, p < 0.001), while in the control group no significant change was observed (from 10.0 (4.0-39.6) to 13.0 (3.5-37.0) ng/ml). In both groups triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting glucose, haemoglobin A 1c , homeostasis model assessment index and diastolic blood pressure did not significantly change. Systolic blood pressure decreased by 3.7% (from 134 ±14 to 129 ±13 mm Hg, p = 0.05) in the VitD group, while it decreased by 1.5% (from 132 ±13 to 130 ±16 mm Hg, p = NS) in the control group ( p = NS between groups). In the VitD group serum 25(OH)VitD increase was negatively correlated with SBP decrease ( r = -0.398, p = 0.049). CONCLUSIONS VitD supplementation (2000 IU/day) did not affect various CVD risk factors in patients with MetS.

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BACKGROUND It is becoming increasingly evident that platelet chemokines are involved in distinct aspects of atherosclerosis. The aim of this study was to examine the effects of long-term supplementation with purified anthocyanins on platelet chemokines in hypercholesterolemic individuals and to identify correlations of decreased platelet chemokine levels with serum lipid and inflammatory marker levels. METHODS A total of 146 hypercholesterolemic individuals were recruited and treated with 320 mg of purified anthocyanins ( n  = 73) or a placebo ( n  = 73) daily for 24 weeks in this randomized, double-blind, placebo-controlled trial. RESULTS Anthocyanin supplementation for 24 weeks significantly decreased the plasma CXCL7 (-12.32% vs. 4.22%, P  = 0.001), CXCL5 (-9.95% vs. 1.93%, P  = 0.011), CXCL8 (-6.07% vs. 0.66%, P  = 0.004), CXCL12 (-8.11% vs. 5.43%, P  = 0.023) and CCL2 levels (-11.63% vs. 12.84%, P  = 0.001) compared with the placebo. Interestingly, the decreases in the CXCL7 and CCL2 levels were both positively correlated with the decreases in the serum low-density lipoprotein-cholesterol (LDL-C), high-sensitivity C-reactive protein (hsCRP) and interleukin-1β (IL-1β) levels after anthocyanin supplementation for 24 weeks. The decrease in the CXCL8 level was negatively correlated with the increase in the how-density lipoprotein-cholesterol (HDL-C) level and was positively correlated with the decrease in the soluble P-selectin (sP-selectin) level in the anthocyanin group. In addition, a positive correlation was observed between the decreases in the CXCL12 and tumornecrosis factor-α (TNF-α) levels after anthocyanin supplementation. However, the plasma CXCL4L1, CXCL1, macrophage migration inhibitory factor (MIF) and human plasminogen activator inhibitor 1 (PAI-1) levels did not significantly change following anthocyanin supplementation. CONCLUSIONS The present study supports the notion that platelet chemokines are promising targets of anthocyanins in the prevention of atherosclerosis. TRIAL REGISTRATION ChiCTR-TRC-08000240. Registered: 10 December 2008.

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BACKGROUND Tracheal intubation can be associated with considerable hemodynamic changes, particularly in patients with uncontrolled hypertension. The GlideScope(®) video-laryngoscope (GVL) is a novel video laryngoscope that does not need direct exposure of the vocal cords, and it can also produce lower hemodynamic changes due to lower degrees of trauma and stimuli to the oropharynx than a Macintosh direct laryngoscope (MDL). OBJECTIVES The aim of this clinical trial was to compare hemodynamic alterations following tracheal intubation with a GVL and MDL in patients with uncontrolled hypertension. PATIENTS AND METHODS Sixty patients who had uncontrolled hypertension and scheduled for elective surgery requiring tracheal intubation, were randomly assigned to receive intubated with either a GVL (n = 30) or a MDL (n = 30). Intubation time, heart rate, rate pressure product (RPP), and mean arterial blood pressure (MAP), were compared between the two groups at; baseline, following induction of anesthesia, after intubation, and at one minute intervals for 5 minutes. RESULTS A total of 59 patients finished the study. Intubation time was longer in the GVL group (9.80 ± 1.27 s) than in the MDL group (8.20 ± 1.17 s) (P < 0.05). MAP, pulse rate, and RPP were lower in the GVL than the MDL group after endotracheal intubation (P < 0.05). MAP, heart rate, and RPP returned to pre-intubation values at 3 and 4 minutes after intubation in the GVL and MDL groups, respectively (P < 0.05). CONCLUSIONS Hemodynamic fluctuations in patients with uncontrolled hypertension after endotracheal intubation were lower with the GVL than the MDL technique.

1significant effect

BACKGROUND Potentially avoidable risk factors continue to cause unnecessary disability and premature death in older people. Health risk assessment (HRA), a method successfully used in working-age populations, is a promising method for cost-effective health promotion and preventive care in older individuals, but the long-term effects of this approach are unknown. The objective of this study was to evaluate the effects of an innovative approach to HRA and counselling in older individuals for health behaviours, preventive care, and long-term survival. METHODS AND FINDINGS This study was a pragmatic, single-centre randomised controlled clinical trial in community-dwelling individuals aged 65 y or older registered with one of 19 primary care physician (PCP) practices in a mixed rural and urban area in Switzerland. From November 2000 to January 2002, 874 participants were randomly allocated to the intervention and 1,410 to usual care. The intervention consisted of HRA based on self-administered questionnaires and individualised computer-generated feedback reports, combined with nurse and PCP counselling over a 2-y period. Primary outcomes were health behaviours and preventive care use at 2 y and all-cause mortality at 8 y. At baseline, participants in the intervention group had a mean ± standard deviation of 6.9 ± 3.7 risk factors (including unfavourable health behaviours, health and functional impairments, and social risk factors) and 4.3 ± 1.8 deficits in recommended preventive care. At 2 y, favourable health behaviours and use of preventive care were more frequent in the intervention than in the control group (based on z-statistics from generalised estimating equation models). For example, 70% compared to 62% were physically active (odds ratio 1.43, 95% CI 1.16-1.77, p = 0.001), and 66% compared to 59% had influenza vaccinations in the past year (odds ratio 1.35, 95% CI 1.09-1.66, p = 0.005). At 8 y, based on an intention-to-treat analysis, the estimated proportion alive was 77.9% in the intervention and 72.8% in the control group, for an absolute mortality difference of 4.9% (95% CI 1.3%-8.5%, p = 0.009; based on z-test for risk difference). The hazard ratio of death comparing intervention with control was 0.79 (95% CI 0.66-0.94, p = 0.009; based on Wald test from Cox regression model), and the number needed to receive the intervention to prevent one death was 21 (95% CI 12-79). The main limitations of the study include the single-site study design, the use of a brief self-administered questionnaire for 2-y outcome data collection, the unavailability of other long-term outcome data (e.g., functional status, nursing home admissions), and the availability of long-term follow-up data on mortality for analysis only in 2014. CONCLUSIONS This is the first trial to our knowledge demonstrating that a collaborative care model of HRA in community-dwelling older people not only results in better health behaviours and increased use of recommended preventive care interventions, but also improves survival. The intervention tested in our study may serve as a model of how to implement a relatively low-cost but effective programme of disease prevention and health promotion in older individuals. TRIAL REGISTRATION International Standard Randomized Controlled Trial Number: ISRCTN 28458424.

1significant effect

AIMS To investigate the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes. METHODS In a double-blind placebo-controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100,000 IU vitamin D2 (ergocalciferol) or 100,000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4 months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4 months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C-reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation. RESULTS The mean [standard deviation (s.d.)] 25-hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: -0.05% [95% confidence interval (CI) -0.11, 0.02] or -0.51 mmol/mol (95% CI -1.16, 0.14; p = 0.13); D3 versus placebo: 0.02% (95% CI -0.04, 0.08) or 0.19 mmol/mol (95% CI -0.46, 0.83; p = 0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: -0.68 m/s (95% CI -1.31, -0.05); D3 versus placebo -0.73 m/s (95% CI -1.42, -0.03)]. No important safety issues were identified. CONCLUSIONS Short-term supplementation with vitamin D2 or D3 had no effect on HbA1c. The modest reduction in PWV with both D2 and D3 relative to placebo suggests that vitamin D supplementation has a beneficial effect on arterial stiffness.

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METHODS Two hundred and forty patients were randomly allocated into six groups: Group I, anesthesia was maintained with sevoflurane; Group II, anesthesia was maintained with sevoflurane and 8 mg of ondansetron; Group III, anesthesia was maintained with propofol; Group IV, anesthesia was maintained with propofol and 8 mg of ondansetron; Group V, anesthesia was maintained with sevoflurane and propofol; Group VI, anesthesia was maintained with sevoflurane combined with propofol and 8 mg of ondansetron. RESULTS We found that the incidence of vomiting was lower in group II (17.5%), group IV (7.5%), and group VI (10%) compared with group I (55%), group III (27.5%), and group V (30%), respectively (P < 0.05). The incidence of vomiting was also lower in group III (27.5%) and group V (30%) when compared with group I (55%) (P < 0.05). The incidence of nausea was 55% in group I, 42.5% in group II, 30% in group III, 27.5% in group IV, 30% in group V, and 30% in group VI. Groups III and V had a lower incidence of nausea than group I (P < 0.05). CONCLUSIONS We conclude that compared with sevoflurane anesthesia alone, anesthesia with either propofol alone or propofol combined with sevoflurane resulted in a reduced incidence of vomiting and nausea during the first 24 h after surgery. Administration of ondansetron effectively reduced the incidence of vomiting but not that of nausea for all three types of general anesthesia.

1significant effect

AIM Recent research has shown that adopting strong (i.e. high fear) visual health-warning messages can increase the perceived health risks and intentions to reduce alcohol consumption. Separately, it is known that the speed at which alcohol is consumed has dramatic effects on the level of intoxication. In the present study we aimed to combine these two separate areas to understand whether the speed of alcohol consumption is influenced by the type of alcohol health warning contained on the beverage. SUBJECT AND METHODS In the present study, female participants ( N  = 45) consumed an alcoholic beverage in a relaxed environment in one of three conditions: no health-warning label, a text-only health-warning label or a pictorial health-warning label with text. RESULTS We found that compared with the control condition, the beverage was consumed at a slower rate in the two health-warning conditions, which surprisingly did not differ from each other. Despite these effects, product acceptability did not differ between the text-only and control conditions. CONCLUSION These are the first set of results to demonstrate how the use of strong health warnings on alcoholic beverages can influence actual drinking rate and further suggest that the beneficial effects of slowed consumption are possible in the absence of any reduction in consumer acceptability.

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BACKGROUND AND OBJECTIVE RESPIRE, a randomized trial of an improved cookstove, was conducted in Guatemala to assess health effects of long-term reductions in wood smoke exposure. Given the evidence that ambient particles increase blood pressure, we hypothesized that the intervention would lower blood pressure. METHODS TWO STUDY DESIGNS WERE USED: a) between-group comparisons based on randomized stove assignment, and b) before-and-after comparisons within subjects before and after they received improved stoves. From 2003 to 2005, we measured personal fine particle (particulate matter with aerodynamic diameter < 2.5 microm; PM(2.5)) exposures and systolic (SBP) and diastolic blood pressure (DBP) among women > 38 years of age from the chimney woodstove intervention group (49 subjects) and traditional open wood fire control group (71 subjects). Measures were repeated up to three occasions. RESULTS Daily average PM(2.5) exposures were 264 and 102 microg/m(3) in the control and intervention groups, respectively. After adjusting for age, body mass index, an asset index, smoking, secondhand tobacco smoke, apparent temperature, season, day of week, time of day, and a random subject intercept, the improved stove intervention was associated with 3.7 mm Hg lower SBP [95% confidence interval (CI), -8.1 to 0.6] and 3.0 mm Hg lower DBP (95% CI, -5.7 to -0.4) compared with controls. In the second study design, among 55 control subjects measured both before and after receiving chimney stoves, similar associations were observed. CONCLUSION The between-group comparisons provide evidence, particularly for DBP, that the chimney stove reduces blood pressure, and the before-and-after comparisons are consistent with this evidence.

1significant effect

BACKGROUND Ischemic brain strokes consisttwo-thirdsof strokesand their complications bear a lot of disability for patient and society. In this study, we seek for effect of Erythropoietin on ischemic brain stroke's outcomes according to National Institutes of Health Stroke Scale (NIHSS) changes. METHODS This study is a RCT (randomized clinical trial). All patients with focal neurologic deficit with primary suspicion of brain stroke undergone neuroimaging evaluations. After confirmation of new ischemic brain stroke, the patients with inclusion criteria'srandomized into two groups of cases and controls. NIHSS was defined for each patient and all patients received a routine treatment protocol. Erythropoietin 16,000 IU as a bolus intravenous dose was given to case patients as soon as neuroimaging study confirmed new ischemic stroke and continued as 8000 IU each 12 h up to total dose of 56,000 IU during 3 days. Patients re-evaluated at days 14 and 28 and NIHSS was assessed by another neurologist blinded to patient's group. Finally, NIHSS changes of both groups compared with each other's. RESULTS Evaluations revealed that in days14 and 28 during follow-up, Erythropoietin was effective in NIHSS (P= 0.0001). This effect was of value in level of consciousness Commands (P= 0.024), facial palsy (P= 0.003), motor arm (P= 0.0001), motor leg (P= 0.0001), sensory (P= 0.009), and best language (P= 0.023). CONCLUSIONS Administration of high-dose erythropoietin in first 24 h can be effective on reduction of ischemic stroke complication. A larger scale clinical trial is warranted.

1significant effect

BACKGROUND Depression is prevalent in people with type 2 diabetes and affects both glycemic control and overall quality of life. The aim of this trial was to evaluate the effect of the antidepressant paroxetine on metabolic control, quality of life and mental well-being in mildly depressed women with type 2 diabetes. METHODS We randomised 15 mildly depressed women with non-optimally controlled type 2 diabetes to a 10-week single-blind treatment with either paroxetine 20 mg per day or placebo. Primary efficacy measurements were glycemic control and quality of life. Glycosylated hemoglobin A1c (GHbA1c) was used as a measure of glycemic control. Quality of life was evaluated using RAND-36. Mental state was assessed using two clinician-rated scoring instruments, Hamilton's Anxiety Scale (HAM-A) and Montgomery-Asberg's Depression Rating Scale (MADRS), and a patient-rated scoring instrument, Beck's Depression Inventory (BDI). RESULTS At the end of the study no significant difference between groups in improvement of quality of life was found. A trend towards a superior improvement in glycemic control was found in the paroxetine group (p = 0.08). A superior increase in sex-hormone-binding-globuline (SHBG) levels was evidenced in the paroxetine group (p = 0.01) as a sign of improved insulin sensitivity. There was also a trend for superior efficacy of paroxetine in investigator-rated anxiety and depression. This notion was supported by a trend for superior decrease of serum cortisol levels in the paroxetine group (p = 0.06). CONCLUSION Paroxetine has a beneficial effect on measures of insulin sensitivity and may improve glycemic control. Larger studies of longer duration are needed to verify the benefits of paroxetine in type 2 diabetes. While waiting for more conclusive evidence it seems sensible to augment standard care of type 2 diabetes with paroxetine even in patients who do not fulfil routine psychiatric criteria for initiation of antidepressant drug treatment.

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BACKGROUND Immunization quality improvement programs are often limited by the cost and inconvenience associated with delivering face-to-face consultations to primary care providers. To investigate a more efficient mode of intervention delivery, we conducted a process evaluation that compared in-person consultations to those delivered via interactive webinar. METHODS The Centers for Disease Control and Prevention's Assessment, Feedback, Incentives, and eXchange (AFIX) Program is an immunization quality improvement program implemented in all 50 states. In 2011, we randomly assigned 61 high-volume primary care clinics in North Carolina to receive an in-person or webinar AFIX consultation focused on adolescent immunization. We used surveys of participating vaccine providers and expense tracking logs to evaluate delivery modes on participation, satisfaction, and cost. Clinics served 71,874 patients, ages 11 to 18. RESULTS Clinics that received in-person and webinar consultations reported similar levels of participation on key programmatic activities with one exception: more webinar clinics reported improving documentation of previously administered, 'historical' vaccine doses. Both in-person and webinar clinics showed sustained improvement in confidence to use reminder/recall systems (both p < 0.05). Participants rated delivery modes equally highly on satisfaction measures such as convenience (mean = 4.6 of 5.0). Delivery cost per clinic was $152 for in-person consultations versus $100 for webinar consultations. CONCLUSIONS In-person and webinar delivery modes were both well received, but webinar AFIX consultations cost substantially less. Interactive webinar delivery shows promise for considerably extending the reach of immunization quality improvement programs. TRIAL REGISTRATION Clinicaltrials.gov, NCT01544764.

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OBJECTIVE The aim of this study was to evaluate the cleaning effectiveness achieved with two reciprocating single-file systems in severely curved root canals: Reciproc and WaveOne. MATERIALS AND METHODS Twenty-five mesial roots of mandibular molars were randomly separated into two groups, according to the instrumentation system used. The negative control group consisted of five specimens that were not instrumented. The mesial canals (buccal and lingual) in Reciproc Group were instrumented with file R25 and the WaveOne group with the Primary file. The samples were submitted to histological processing and analyzed under a digital microscope. RESULTS The WaveOne group presented a larger amount of debris than the Reciproc Group, however, without statistically significant difference (P > 0.05). A larger amount of debris in the control group was observed, with statistically significant difference to Reciproc and WaveOne groups (P < 0.05). CONCLUSIONS The two reciprocating single-file instrumentation systems presented similar effectiveness for root canal cleaning.

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BACKGROUND The aim of this study was to compare the intravenous (IV) and caudal routes of administration of sufentanil for children undergoing orchidopexy and also to evaluate the effects on addition of caudal adrenaline and neostigmine. MATERIALS AND METHODS SIXTY PATIENTS SCHEDULED FOR ORCHIDOPEXY WERE DIVIDED INTO THE FOLLOWING GROUPS: 1) Group IVSu received IV 0.5 μg/kg sufentanil and caudal saline; 2) Group CSu received caudal 0.5 μg/kg sufentanil and IV saline; 3) Group CSuAdr received caudal sufentanil plus adrenaline 5 μg/ml (1:200,000) and IV saline; 4) Group CSuNeo received caudal sufentanil plus neostigmine, and IV saline; and 5) Group CSuNeoAdr received caudal sufentanil plus neostigmine plus adrenaline, and IV saline. Heart rate and mean blood pressure >15% was treated with increasing isoflurane concentration. Consumption of isoflurane, side effects, quality of sleep, time to first administration of analgesic, and number of doses of 24-h rescue analgesic were recorded. RESULTS Groups were demographically similar. Isoflurane consumption showed the following association: Group IVSu = Group CSuNeo = Group CSuNeoAdr < Group CSu = Group CSuAdr (P < 0.02). VAS for sedation on reversal of anesthesia showed the following association: Group CSuNeo = Group CSuNeoAdr < Group CSu = Group CSuAdr = Group IVSu (P < 0.005). Time to the first administration of dipyrone showed the following association: Group IVSu = Group CSu = Group CSuAdr (3-4 h) < Group CSuNeo = Group CSuNeoAdr (10-11 h) (P < 0.05). Number of doses of rescue analgesic showed the following association: Group IVSu = Group CSu = Group CSuAdr > Group CSuNeo = Group CSuNeoAdr (P < 0.005). Incidence of adverse effects was similar among groups. CONCLUSION Caudal sufentanil alone was no better than when administered in the IV route, and would just be justified by the association of neostigmine, but not adrenaline. Neostigmine association resulted in better perioperative analgesia.

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BACKGROUND A2143G mutation of 23S rRNA gene of H. pylori results in clarithromycin (CLR) resistance. To investigate the prevalence of the CLR resistance-related A2143G mutation of the H. pylori-specific 23S rRNA gene in Chinese subjects with and without CLR use history, 307 subjects received the treatment with amoxicillin and omeprazole (OA) and 310 subjects received a placebo in 1995, and 153 subjects received a triple therapy with OA and CLR (OAC) in 2000. DNA was extracted from fasting gastric juice at the end of the intervention trial in 2003. H. pylori infection was determined by H. pylori-specific 23S rRNA PCR, ELISA, and13C-urea breath test assays. Mutations of the 23S rRNA gene were detected by RFLP assays. RESULTS The presence of 23S rRNA due to H. pylori infection in the OA group remained lower than that in the placebo group 7.3 yrs after OA-therapy [51.1% (157/307) vs. 83.9% (260/310), p = 0.0000]. In the OAC group, the 23S rRNA detection rate was 26.8% (41/153) three yrs after OAC-treatment. The A2143G mutation rate among the 23S rRNA-positive subjects in the OAC group [31.7% (13/41)] was significantly higher than that in the OA group [10.2% (16/157)] and the placebo group [13.8% (36/260)]. The frequency of the AAGGG --> CTTCA (2222-2226) and AACC --> GAAG (2081-2084) sequence alterations in the OAC group was also significantly higher than those in the OA group and the placebo group. CONCLUSION Primary prevalence of the A2143G mutation was 10~14% among Chinese population without history of CLR therapy. Administration of CLR to eliminate H. pylori infection increased the prevalence of the A2143G mutation in Chinese subjects (32%) significantly.

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PurposeTo determine whether intraocular pressure (IOP) lowering with fixed-combination brinzolamide/brimonidine (BBFC) adjunctive to a prostaglandin analog (PGA) was superior to that of vehicle+PGA in patients with open-angle glaucoma or ocular hypertension who were inadequately controlled with PGA monotherapyMethodsThis 6-week, multicenter, randomized, double-masked, parallel-group trial was conducted at 30 clinical sites in the United States between October 2013 and May 2014. Eligible patients were adults with open-angle glaucoma or ocular hypertension and with mean IOP ≥21 and <32 mm Hg, whereas receiving an open-label PGA (latanoprost, bimatoprost, or travoprost). Patients instilled a PGA once-daily in a run-in phase before randomization to masked BBFC or vehicle adjunctive treatment. Masked treatments were instilled 3 times daily for 6 weeks, and patients continued once-daily use of their PGA. The primary efficacy end point was the between-group difference in mean diurnal IOP (average of 0800, 1000, 1500, and 1700 hours time points) at week 6.ResultsAt week 6, mean diurnal IOP with BBFC+PGA was lower than with vehicle+PGA (17.1±0.4 mm Hg vs 20.5±0.4 mm Hg; between-group difference, -3.4±0.5 mm Hg; P<0.0001; 95% confidence interval, -4.5 to -2.4 mm Hg). BBFC+PGA reduced mean diurnal IOP by 5.7 mm Hg (25%) from the baseline IOP achieved with PGA monotherapy.ConclusionsTherapy with BBFC produced an additive IOP-lowering effect compared with a PGA alone or in conjunction with vehicle. BBFC may provide an effective treatment option for patients receiving PGA monotherapy who require additional IOP reduction.

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PURPOSE Two individual phase 3 conjunctival allergen challenge (CAC) studies of similar design have assessed the efficacy and safety of olopatadine hydrochloride (HCl) 0.77% for the treatment of allergic conjunctivitis. The purpose of this study is to evaluate the integrated efficacy and safety of olopatadine HCl 0.77% from a larger dataset by pooling data from the two individual CAC studies. METHODS Data were pooled from two phase 3, randomized, multicenter, double-masked, active- and vehicle-controlled CAC studies. The primary comparison was on ocular itching scores between olopatadine HCl 0.77% versus vehicle (at onset and 24 hours) and olopatadine HCl 0.77% versus olopatadine 0.2% (at 24 hours). Additional end points included conjunctival redness, total redness, and proportion of itching responders at onset and 24-hour duration of CAC. For both primary and secondary analysis, mixed model repeated measures analysis was used, except for proportion of ocular itching responders. Sensitivity analyses were carried out using a two-sample t -test. RESULTS This analysis included 448 patients. Olopatadine HCl 0.77% was superior to vehicle ( P <0.0001) at onset and 24-hour duration of action (difference in means: -1.14 to -1.52) and to olopatadine 0.2% ( P =0.0009) at 24-hour duration of action in relieving ocular itch. Additionally, olopatadine HCl 0.77% substantially reduced conjunctival redness and total redness over vehicle and olopatadine 0.2% at onset and 24-hour duration of action. At 24 hours CAC, there were a higher proportion of itching responders with olopatadine HCl 0.77% compared to vehicle or olopatadine 0.2% (difference in proportion of responders: 43.17%, P <0.0001, and 17.25%, P =0.0012, respectively). No safety concerns were identified. CONCLUSION This analysis confirms the findings from the individual studies. The rapid onset and prolonged duration of action (for 24 hours) of olopatadine HCl 0.77% supports once-daily dosing in the treatment of allergic conjunctivitis.

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BACKGROUND Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. METHODS Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. RESULTS Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35-0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33-3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96-2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84-2.49). CONCLUSION Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens.

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BACKGROUND The aim of the study was to determine the influence of lead shielding on the dose to female breasts in conventional x-ray lumbar spine imaging. The correlation between the body mass index and the dose received by the breast was also investigated. MATERIALS AND METHODS Breast surface dose was measured by thermoluminescent dosimeters (TLD). In the first phase measurements of breast dose with and without shielding from lumbar spine imaging in two projections were conducted on an anthropomorphic phantom. In the second stage measurements were performed on 100 female patients, randomly divided into two groups of 50, with breast shielding only used in one group. RESULTS On average, breast exposure dose in lumbar spine imaging in both projections (anteroposterior (AP) and lateral) was found reduced by approximately 80% (p < 0,001) when shielding with 0.5 mm lead equivalent was used (from 0.45±0.25 mGy to 0.09±0.07 mGy on the right and from 0.26±0.14 mGy to 0.06±0.04 mGy on the left breast). No correlation between the body mass index (BMI) and the breast surface radiation dose was observed. CONCLUSIONS Although during the lumbar spine imaging breasts receive low-dose exposure even when shielding is not used, the dose can be reduced up to 80% by breast shielding with no influence on the image quality.

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OBJECTIVES Biological disease-modifying antirheumatic drugs (bDMARDs) have shown diminished clinical response following an inadequate response (IR) to ≥1 previous bDMARD. Here, tofacitinib was compared with placebo in patients with an IR to conventional synthetic DMARDs (csDMARDs; bDMARD-naive) and in patients with an IR to bDMARDs (bDMARD-IR). METHODS Data were taken from phase II and phase III studies of tofacitinib in patients with rheumatoid arthritis (RA). Patients received tofacitinib 5 or 10 mg twice daily, or placebo, as monotherapy or with background methotrexate or other csDMARDs. Efficacy endpoints and incidence rates of adverse events (AEs) of special interest were assessed. RESULTS 2812 bDMARD-naive and 705 bDMARD-IR patients were analysed. Baseline demographics and disease characteristics were generally similar between treatment groups within subpopulations. Across subpopulations, improvements in efficacy parameters at month 3 were generally significantly greater for both tofacitinib doses versus placebo. Clinical response was numerically greater with bDMARD-naive versus bDMARD-IR patients (overlapping 95% CIs). Rates of safety events of special interest were generally similar between tofacitinib doses and subpopulations; however, patients receiving glucocorticoids had more serious AEs, discontinuations due to AEs, serious infection events and herpes zoster. Numerically greater clinical responses and incidence rates of AEs of special interest were generally reported for tofacitinib 10 mg twice daily versus tofacitinib 5 mg twice daily (overlapping 95% CIs). CONCLUSIONS Tofacitinib demonstrated efficacy in both bDMARD-naive and bDMARD-IR patients with RA. Clinical response to tofacitinib was generally numerically greater in bDMARD-naive than bDMARD-IR patients. The safety profile appeared similar between subpopulations. TRIAL REGISTRATION NUMBERS (NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385).

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BACKGROUND Myrtle (Myrtus communis L.) has been used in the Iranian Traditional Medicine as a treatment for abnormal uterine bleeding-menometrorrhagia. The main aim of this study is to evaluate the effect of myrtle fruit syrup on abnormal uterine bleeding-menometrorrhagia. METHODS A randomized, double-blind, placebo-controlled pilot study was conducted on 30 women suffering from abnormal uterine bleeding-menometrorrhagia. Treatment comprised of giving 15 ml oral myrtle syrup daily (5 ml three times a day) for 7 days starting from the onset of bleeding. The myrtle syrup along with placebo was repeated for 3 consecutive menstrual periods. Menstrual duration and number of used pads were recorded by the Pictorial Blood loss Assessment Chart at the end of each menstrual period. The quality of life was also evaluated using the menorrhagia questionnaire. RESULTS The mean number of bleeding days significantly declined from 10.6 ± 2.7 days to 8.2 ± 1.9 days after 3 months treatment with the syrup (p = 0.01) and consequently the participants in the intervention group used fewer pads after 3 months (16.4 ± 10.7) compared with the number of pads used at the beginning of the treatment (22.7 ± 12.0, p = 0.01). Bleeding days and number of pads used by the participants in the placebo group did not change significantly. Also significant changes of quality of life scores were observed in the intervention group after 3 months compared to the baseline. CONCLUSION Myrtle syrup is introduced as a potential remedy for abnormal uterine bleeding-menometrorrhagia.

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INTRODUCTION Roux-en-Y gastric bypass (RYGB) is considered the gold standard bariatric procedure with documented safety and effectiveness. Laparoscopic sleeve gastrectomy (LSG) is a newer procedure being done with increasing frequency. Randomized comparisons of LSG and other bariatric procedures are limited. We present the results of the first prospective randomized trial comparing LSG and RYGB in the Polish population. AIM To assess the efficacy and safety of LSG versus RYGB in the treatment of morbid obesity and obesity-related comorbidities. MATERIAL AND METHODS Seventy-two morbidly obese patients were randomized to RYGB (36 patients) or LSG (36 patients). Both groups were comparable regarding age, gender, body mass index (BMI) and comorbidities. The follow-up period was at least 12 months. Baseline and 6 and 12 month outcomes were analyzed including assessment of percent excess weight lost (%EWL), reduction in BMI, morbidity (minor, major, early and late complications), mortality, reoperations, comorbidities and nutritional deficiencies. RESULTS There was no 30-day mortality and no significant difference in major complication rate (0% after RYGB and 8.3% after LSG, p > 0.05) or minor complication rate (16.6% after RYGB and 10.1% after LSG, p > 0.05). There were no early reoperations after RYGB and 2 after LSG (5.5%) (p > 0.05). Weight loss was significant after RYGB and LSG but there was no difference between both groups at 6 and 12 months of follow-up. At 12 months %EWL in RYGB and LSG groups reached 64.2% and 67.6% respectively (p > 0.05). There was no significant difference in the overall prevalence of comorbidities and nutritional deficiencies. CONCLUSIONS Both LSG and RYGB produce significant weight loss at 6 and 12 months after surgery. The procedures are equally effective with regard to %EWL, reduction in BMI and amelioration of comorbidities at 6 and 12 months of follow-up. Laparoscopic sleeve gastrectomy and RYGB are comparably safe techniques with no significant differences in minor and major complication rates at 6 and 12 months.

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BACKGROUND AND AIM Intrathecal (IT) neostigmine has been used as an adjunct to spinal anesthesia. The purpose of this study was to determine whether a combination of low-dose neostigmine IT would enhance analgesia of a fixed dose of fentanyl IT, in patients undergoing unilateral total knee replacement (TKR) surgery with spinal anesthesia. SETTINGS AND DESIGN Forty-five patients scheduled for unilateral TKR were randomized to one of the three groups (n = 15) and prospectively studied using placebo-controlled, double-blinded design. MATERIALS AND METHODS A 19-G epidural catheter was introduced through the L3-L4 interspace with patient in the sitting position, followed by spinal anesthesia administration through the L3-L4 interspace. Fifteen milligrams of hyperbaric bupivacaine (3 ml) plus the test drug (0.5 ml) was administered IT. The test drug was normal saline (0.5 ml) in group I; fentanyl 20 mcg (0.4 ml) and normal saline (0.1 ml) in group II; and fentanyl 20 mcg (0.4 ml) and neostigmine 1 mcg (0.1 ml) in group III. Characteristics of sensory and motor block, heart rate, and blood pressure were recorded intraoperatively. Postoperatively, pain scores, postoperative nausea and vomiting (PONV) scores, and sedation scores, and postoperative analgesic dose were recorded. RESULTS Forty-five patients were enrolled in this study and 43 patients were subjected to statistical analysis. Overall 24-h visual analog score in group III was significantly less than in those who received fentanyl alone (P = 0.00). The durations of complete analgesia and effective analgesia were longer for all patients in group III compared with group II (P < 0.05) and group I (P < 0.005) patients. The total number of epidural top ups (rescue analgesia) required was less in group II (P < 0.05) and group III (P < 0.005) patients, compared with the control group. The incidence of nausea and vomiting was not increased in group III patients. CONCLUSIONS The addition of 1 mcg neostigmine IT increased the duration of analgesia and decreased the analgesic consumption in 24 h in TKR. There was no increase in the incidence of adverse effects.

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BACKGROUND Cognitive remediation therapy (CRT) is one of the promising new non-drug approaches to reducing cognitive deficits of patients with schizophrenia that has not yet been fully evaluated in China. AIM Assess the efficacy of CRT in improving the cognitive functioning, social functioning and insight of patients with chronic schizophrenia. METHODS 126 clinically stable inpatients with chronic schizophrenia were randomly allocated to an intervention group (with CRT) and a treatment as usual group (TAU) (which used standard occupational and recreational therapy methods). The treatment frequency and duration were the same for the two groups: five times per week for three months. The Wisconsin Card Sorting Test (WCST) was used to evaluate before versus after changes in cognitive function, the Scale of Social Skills of chronic schizophrenia Inpatients (SSSI) was used to assess social functioning, and the Insight and Treatment Attitude Questionnaire (ITAQ) was use to assess insight. RESULTS Four patients dropped out during the study leaving 60 in the CRT group and 62 in the TAU group in the final analysis. Both groups showed significant improvement in WCST measures over the three-month trial but the improvement in the CRT group was significantly greater than that for the TAU group on all of the WCST measures assessed. The total SSSI score improved significantly in both groups over the three months, but the improvement in the two groups was not significantly different. The total ITAQ score also showed significant improvement in both groups over the three months and the degree of improvement was significantly greater in the CRT group than in the TAU group. CONCLUSION As an adjunctive treatment to antipsychotic medication, a three month course of CRT is more effective at improving the cognitive functioning and insight of hospitalized patients with chronic schizophrenia than routine occupational and recreational therapy.

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OBJECTIVES To investigate the effectiveness of oxycodone compared with fentanyl for attenuating the hemodynamic response during endotracheal intubation. METHODS This study was conducted from June 2014 to February 2015 on healthy adults undergoing general anesthesia at the Yeungnam University Hospital, Daegu, Republic of Korea. Ninety-five patients were randomly assigned to one of 3 groups to receive the following drugs; Group F: fentanyl 2 μg/kg; Group O/70: oxycodone 140 μg/kg; Group O/100: oxycodone 200 μg/kg. Five minutes after injection of the study drug, general anesthesia was induced with propofol 1.5 mg/kg and rocuronium 0.8 mg/kg. The mean blood pressure (MBP), heart rate (HR), peripheral oxygen saturation (SpO2), and bispectral index (BIS) were compared before administration of the study drug (T1), just before endotracheal intubation (T2), one minute after endotracheal intubation (T3), and 7.5 minutes after endotracheal intubation (T4). Complications were assessed. RESULTS The 2 oxycodone groups showed no significant differences in MBP, HR, SpO2, and BIS compared to Group F at the time points assessed. The incidence of complications was comparable among the groups. CONCLUSIONS Oxycodone could successfully be used to attenuate the sympathetic response during anesthetic induction. The hemodynamic profiles and incidence of complications were clinically similar among the groups, but Group O/70 tended to show a lower rate of complications of apnea.

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BACKGROUND Untreated procedural pain leads to long-term and short-term complications in neonates. Preventing pain in sick infants and neonates, whose conditions are getting worse, not only is a professional and legal duty but also a prevention measure to decrease future psychological and even neurological complications. Therefore, nurses should prevent newborns' pain. The aim of this study was to compare the effects of massage and breastfeeding on the pain of the neonates. MATERIALS AND METHODS This was a clinical trial conducted among 75 full-term and near-term infants who underwent venipuncture. The newborns were randomly allocated to the following groups ( n = 25 for each): group 1, breastfeeding; group 2, massage; and group 3, control. In the first group, venipuncture was done 2 minutes after breastfeeding. In the second group, massage was done with effleurage technique for 3 minutes and venipuncture was done 2 minutes after massage. The Neonatal Infant Pain Scale (NIPS) was used for pain measurement in the first 30 seconds of venipuncture. Data were analyzed by t -test and one-way analysis of variance (ANOVA). RESULTS The lowest mean pain score recorded in the massage group (0.92) whereas it was 4.84 in the breastfeeding group and 6.16 in the control group. ANOVA test and post-hoc statistics revealed that both interventions resulted in a significant reduction of the pain scores. CONCLUSIONS According to the findings of this study, the lowest pain score was in massage group, then in breastfeeding group and control group accordingly. Considering the fact that massage and breastfeeding are natural, useful, and cost free interventions and do not need any special facility, these methods are suggested in pain management and pain control during painful procedures administrated for infants.

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BACKGROUND Low-dose dextromethorphan (DM) might have anti-inflammatory and neurotrophic effects mechanistically remote from an NMDA receptor. In a randomized, double-blind, controlled 12 week study, we investigated whether add-on dextromethorphan reduced cytokine levels and benefitted opioid-dependent patients undergoing methadone maintenance therapy (MMT). METHODS Patients were randomly assigned to a group: DM60 (60mg/day dextromethorphan; n = 65), DM120 (120mg/day dextromethorphan; n = 65), or placebo (n = 66). Primary outcomes were the methadone dose required, plasma morphine level, and retention in treatment. Plasma tumor necrosis factor (TNF)-α, C-reactive protein, interleukin (IL)-6, IL-8, transforming growth factor-β1, and brain-derived neurotrophic factor (BDNF) levels were examined during weeks 0, 1, 4, 8, and 12. Multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. RESULTS After 12 weeks, the DM60 group had significantly longer treatment retention and lower plasma morphine levels than did the placebo group. Plasma TNF-α was significantly decreased in the DM60 group compared to the placebo group. However, changes in plasma cytokine levels, BDNF levels, and the methadone dose required in the three groups were not significantly different. CONCLUSIONS We provide evidence-decreased concomitant heroin use-of low-dose add-on DM's efficacy for treating opioid-dependent patients undergoing MMT.

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BACKGROUND There are no studies regarding 4% articaine infiltration injection into the retro-molar area for an impacted lower third molar (LITM) surgery. This study aimed to evaluate the efficacy of infiltration using 1.7 ml (single cartridge: SC) of 4% articaine versus 3.4 ml (double cartridges: DC) of 4% articaine with 1:100,000 epinephrine in LITM surgery. METHOD This study involved 30 healthy patients with symmetrical LITM. The patients were assigned to receive either a DC or SC of 4% articaine with 1:100,000 epinephrine as a local anesthetic for each operation. Onset, duration, profoundness, need for additional anesthetic administration, total volume of anesthetic used, vitality of the tooth, and pain score during operation were recorded. RESULTS The DC of 4 % articaine had a significantly higher success rate (83.3%) than did the SC (53.3%; P < 0.05). The duration of soft tissue anesthesia was longer in the DC group. The intra-operative pain was higher in the SC group with a significant (P < 0.05) requirement for a supplementary local anesthetic. CONCLUSION We concluded that using DC for the infiltration injection had a higher success rate, longer duration of anesthesia, less intra-operative pain, and a lower amount of additional anesthesia than SC in the surgical removal of LITM. We recommend that a DC of 4% articaine and a 1:100,000 epinephrine infiltration in the retro-molar region can be an alternative anesthetic for LITM surgery.

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