The use of transvaginal synthetic mesh for anterior vaginal wall prolapse repair: a randomized controlled trial

The aim of the study was to compare the efficacy and safety of transvaginal trocar-guided polypropylene mesh insertion with traditional colporrhaphy for treatment of anterior vaginal wall prolapse.This is a randomized controlled trial in which women with advanced anterior vaginal wall prolapse, at least stage II with Ba a parts per thousand yenaEuro parts per thousand+1 cm according to the Pelvic Organ Prolapse Quantification (POP-Q) classification, were randomly assigned to have either anterior colporrhaphy (n = 39) or repair using trocar-guided transvaginal mesh (n = 40). the primary outcome was objective cure rate of the anterior compartment (point Ba) assessed at the 12-month follow-up visit, with stages 0 and I defined as anatomical success. Secondary outcomes included quantification of other vaginal compartments (POP-Q points), comparison of quality of life by the prolapse quality of life (P-QOL) questionnaire, and complication rate between the groups after 1 year. Study power was fixed as 80 % with 5 % cutoff point (p < 0.05) for statistical significance.The groups were similar regarding demographic and clinical preoperative parameters. Anatomical success rates for colporrhaphy and repair with mesh placement groups were 56.4 vs 82.5 % (95 % confidence interval 0.068-0.54), respectively, and the difference between the groups was statistically significant (p = 0.018). Similar total complication rates were observed in both groups, with tape exposure observed in 5 % of the patients. There was a significant improvement in all P-QOL domains as a result of both procedures (p < 0.001), but they were not distinct between groups (p > 0.05).Trocar-guided transvaginal synthetic mesh for advanced anterior POP repair is associated with a higher anatomical success rate for the anterior compartment compared with traditional colporrhaphy. Quality of life equally improved after both techniques. However, the trial failed to detect differences in P-QOL scores and complication rates between the groups.

Randomized, controlled trial investigating short-term health-related quality of life with doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: European Organization for Research and Treatment of Cancer Breast Cancer Group, Investigational Drug Branch for Breast Cancer and the New Drug Development Group Study.

PURPOSE: To compare health-related quality of life (HRQOL) in patients with metastatic breast cancer receiving the combination of doxorubicin and paclitaxel (AT) or doxorubicin and cyclophosphamide (AC) as first-line chemotherapy treatment. PATIENTS AND METHODS: Eligible patients (n = 275) with anthracycline-naive measurable metastatic breast cancer were randomly assigned to AT (doxorubicin 60 mg/m(2) as an intravenous bolus plus paclitaxel 175 mg/m(2) as a 3-hour infusion) or AC (doxorubicin 60 mg/m(2) plus cyclophosphamide 600 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation of paclitaxel (200 mg/m(2)) and cyclophosphamide (750 mg/m(2)) was planned at cycle 2 to reach equivalent myelosuppression in the two groups. HRQOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and the EORTC Breast Module at baseline and the start of cycles 2, 4, and 6, and 3 months after the last cycle. RESULTS: Seventy-nine percent of the patients (n = 219) completed a baseline measure. However, there were no statistically significant differences in HRQOL between the two treatment groups. In both groups, selected aspects of HRQOL were impaired over time, with increased fatigue, although some clinically significant improvements in emotional functioning were seen, as well as a reduction in pain over time. Overall, global quality of life was maintained in both treatment groups. CONCLUSION: This information is important when advising women patients of the expected HRQOL consequences of treatment regimens and should help clinicians and their patients make informed treatment decisions.

STAR 3 randomized controlled trial to compare sensor-augmented insulin pump therapy with multiple daily injections in the treatment of type 1 diabetes: research design, methods, and baseline characteristics of enrolled subjects.

BACKGROUND: Sensor-augmented pump therapy (SAPT) integrates real-time continuous glucose monitoring (RT-CGM) with continuous subcutaneous insulin infusion (CSII) and offers an alternative to multiple daily injections (MDI). Previous studies provide evidence that SAPT may improve clinical outcomes among people with type 1 diabetes. Sensor-Augmented Pump Therapy for A1c Reduction (STAR) 3 is a multicenter randomized controlled trial comparing the efficacy of SAPT to that of MDI in subjects with type 1 diabetes. METHODS: Subjects were randomized to either continue with MDI or transition to SAPT for 1 year. Subjects in the MDI cohort were allowed to transition to SAPT for 6 months after completion of the study. SAPT subjects who completed the study were also allowed to continue for 6 months. The primary end point was the difference between treatment groups in change in hemoglobin A1c (HbA1c) percentage from baseline to 1 year of treatment. Secondary end points included percentage of subjects with HbA1c < or =7% and without severe hypoglycemia, as well as area under the curve of time spent in normal glycemic ranges. Tertiary end points include percentage of subjects with HbA1c < or =7%, key safety end points, user satisfaction, and responses on standardized assessments. RESULTS: A total of 495 subjects were enrolled, and the baseline characteristics similar between the SAPT and MDI groups. Study completion is anticipated in June 2010. CONCLUSIONS: Results of this randomized controlled trial should help establish whether an integrated RT-CGM and CSII system benefits patients with type 1 diabetes more than MDI.

Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): study protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA. METHODS/DESIGN: COLKOA is a double-blind, placebo-controlled, randomized trial comparing a 16-week treatment with standard daily dose oral colchicine to placebo for KOA. A total of 120 participants with symptomatic KOA will be recruited from a single center in Singapore. The primary end point is 30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary end points include improvement in pain, physical function, and quality of life and change in serum, urine and synovial fluid biomarkers of cartilage metabolism and inflammation. A magnetic resonance imaging (MRI) substudy will be conducted in 20 participants to evaluate change in synovitis. Logistic regression will be used to compare changes between groups in an intention-to-treat analysis. DISCUSSION: The COLKOA trial is designed to evaluate whether commercially available colchicine is effective for improving signs and symptoms of KOA, and reducing synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. These biomarkers should provide insights into the underlying mechanism of therapeutic response. This trial will potentially provide data to support a new treatment option for KOA. TRIAL REGISTRATION: The trial has been registered at clinicaltrials.gov as NCT02176460 . Date of registration: 26 June 2014.

Randomized controlled trial of interferential therapy and manipulative therapy for acute low back pain.

Study Design. A multi-center assessor-blinded randomized clinical trial was conducted. Objectives. To investigate the relative effectiveness of interferential therapy and manipulative therapy for patients with acute low back pain when used as sole treatments and in combination. Summary of Background Data. Both manipulative therapy and interferential therapy are commonly used treatments for low back pain. Evidence for the effectiveness of manipulative therapy is available only for the short term. There is no evidence for interferential therapy and no study has investigated the effectiveness of interferential therapy combined with manipulative therapy. Methods. Consenting subjects (n=240) were randomly assigned to receive a copy of the Back Book and either manipulative therapy (MT; n=80), interferential therapy (IFT; n=80) or combined manipulative therapy and interferential therapy (CT; n=80). Follow-up outcome questionnaires were posted at discharge, 6 and 12 months. Results. The groups were balanced at baseline for low back pain and demographic characteristics. All interventions were found to significantly reduce functional disability and pain and increase quality of life at discharge and to maintain these improvements at 6 and 12 months. No significant differences were found between groups for reported LBP recurrence, work absenteeism, medication consumption, exercise participation and healthcare use at 12 months. Conclusions. For acute low back pain, interferential therapy whether used in isolation or in combination with manipulative therapy was as effective as manipulative therapy alone (in addition to the Back Book).

A randomized clinical trial of hydroxymethylglutaryl-Coenzyme A reductase inhibition for Acute Lung Injury (The HARP study)

Rationale: There is no effective pharmacological treatment for acute lung injury (ALI). Statins are a potential new therapy because they modify many of the underlying processes important in ALI.

Objectives: To test whether simvastatin improves physiological and biological outcomes in ALI.

Methods: We conducted a randomized, double-blinded, placebo-controlled trial in patients with ALI. Patients received 80 mg simvastatin or placebo until cessation of mechanical ventilation or up to 14 days. Extravascular lung water was measured using thermodilution. Measures of pulmonary and nonpulmonary organ function were assessed daily. Pulmonary and systemic inflammation was assessed by bronchoalveolar lavage fluid and plasma cytokines. Systemic inflammation was also measured by plasma C-reactive protein.

Measurements and Main Results: Sixty patients were recruited. Baseline characteristics, including demographics and severity of illness scores, were similar in both groups. At Day 7, there was no difference in extravascular lung water. By Day 14, the simvastatin-treated group had improvements in nonpulmonary organ dysfunction. Oxygenation and respiratory mechanics improved, although these parameters failed to reach statistical significance. Intensive care unit mortality was 30% in both groups. Simvastatin was well tolerated, with no increase in adverse events. Simvastatin decreased bronchoalveolar lavage IL-8 by 2.5-fold (P = 0.04). Plasma C-reactive protein decreased in both groups but failed to achieve significance in the placebo-treated group.

Conclusions: Treatment with simvastatin appears to be safe and may be associated with an improvement in organ dysfunction in ALI. These clinical effects may be mediated by a reduction in pulmonary and systemic inflammation.

A Cluster Randomized Controlled Trial of an Adapted U.S. Model of Pharmaceutical Care for Nursing Home Residents in Northern Ireland (Fleetwood Northern Ireland Study): A Cost-Effectiveness Analysis

OBJECTIVES: To evaluate the cost-effectiveness of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Ireland (Fleetwood NI Study).
DESIGN: Economic evaluation alongside a cluster randomized controlled trial.
SETTING: Nursing homes in NI randomized to intervention (receipt of the adapted model of care; n511) or control (usual care continued; n511).
PARTICIPANTS: Residents aged 65 and older who provided informed consent (N5253; 128 intervention, 125 control) and who had full resource use data at 12 months.
INTERVENTION: Trained pharmacists reviewed intervention home residents’ clinical and prescribing information for 12 months, applied an algorithm that guided them in assessing the appropriateness of psychoactive medication, and worked with prescribers (general practitioners) to make changes. The control homes received usual care in which there was no pharmacist intervention.
MEASUREMENTS: The proportion of residents prescribed one or more inappropriate psychoactive medications (according to standardized protocols), costs, and a cost-effectiveness acceptability curve. The latter two outcomes are the focus for this article.
RESULTS: The proportions of residents receiving inappropriate psychoactive medication at 12 months in the intervention and control group were 19.5% and 50.4%, respectively. The mean cost of healthcare resources used per resident per year was $4,923 (95% con?dence interval.

A parenting intervenion for childhood behavioral problems: a randomised controlled trial in disadvantaged Community-based settings:A randomized controlled trial in disadvantaged community-based settings

Objective: A community-based randomized controlled trial (RCT) was conducted in urban areas characterized by high levels of disadvantage to test the effectiveness of the Incredible Years BASIC parent training program (IYBP) for children with behavioral problems. Potential moderators of intervention effects on child behavioral outcomes were also explored. Method: Families were included if the child (aged 32-88 months) scored above a clinical cutoff on the Eyberg Child Behavior Inventory (ECBI). Participants (n = 149) were randomly allocated on a 2:1 ratio to an intervention group (n = 103) or a waiting-list control group (n = 46). Child behavior, parenting skills, and parent well-being were assessed at baseline and 6 months later using parent-report and independent observations. An intention-to-treat analysis of covariance was used to examine postintervention differences between groups. Results: Statistically significant differences in child disordered behavior favored the intervention group on the ECBI Intensity (effect size = 0.7, p

Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease:LEADe

There is some evidence that statins may have a protective and symptomatic benefit in Alzheimer disease (AD). The LEADe study is a randomized controlled trial (RCT) evaluating the efficacy and safety of atorvastatin in patients with mild to moderate AD.

Effect of fruit and vegetable consumption on immune function in older people: A randomized controlled trial

Background: Fruit and vegetable (FV) intake, which is often low in older people, is associated with reduced chronic disease risk. Objective: We determined whether increased FV intake improves measures of immune function. Design: We conducted a randomized controlled trial (The Ageing and Dietary Intervention Trial) in 83 healthy volunteers aged 65-85 y with low FV intakes (=2 portions/d); 82 subjects completed the intervention. Participants were assigned to continue their normal diets or to consume =5 FV portions/d for 16 wk. At 12 wk, tetanus toxoid (0.5 mL intramuscular) and Pneumovax II vaccine (0.5 mL intramuscular; both vaccines from Sanofi Pasteur) were administered. FV intake was monitored by using diet histories, and biomarkers of nutritional status were assessed. The primary endpoint was the antibody response to vaccination. Specific antibodies binding to tetanus toxoid (total IgG) and pneumococcal capsular polysaccharide (total IgG and IgG2) were assessed at baseline and 16 wk. Participants were recruited between October 2006 and June 2008. Results: The change in FV consumption differed significantly between groups [mean change in number of portions (95% CI): in the 2-portion/d group, 0.4 portions/d (0.2, 0.7 portions/d); in the 5-portion/d group, 4.6 portions/d (4.1, 5.0 portions/d); P < 0.001)] and also in micronutrient status. Antibody binding to pneumococcal capsular polysaccharide (total IgG) increased more in the 5-portion/d group than in the 2-portion/d group [geometric mean (95% CI) of the week 16:baseline ratio: 3.1 (2.1, 4.4) and 1.7 (1.3, 2.1), respectively; P = 0.005)]. There was no significant difference in the increases in antibody binding to tetanus toxoid. Conclusion: Increased FV intake improves the Pneumovax II vaccination antibody response in older people, which links an achievable dietary goal with improved immune function. This trial was registered at clinicaltrials.gov as NCT00858728. © 2012 American Society for Nutrition.

Pedometer-driven walking for chronic low back pain:A feasibility randomized controlled trial

OBJECTIVES: To evaluate the feasibility of an RCT of a pedometer-driven walking program and education/advice to remain active compared with education/advice only for treatment of chronic low back pain (CLBP). METHODS: Fifty-seven participants with CLBP recruited from primary care were randomly allocated to either: (1) education/advice (E, n=17) or (2) education/advice plus an 8-week pedometer-driven walking program (EWP, n=40). Step targets, actual daily step counts, and adverse events were recorded in a walking diary over the 8 weeks of intervention for the EWP group only. All other outcomes (eg, functional disability using the Oswestry Disability Questionnaire (ODQ), pain scores, physical activity (PA) measurement etc.) were recorded at baseline, week 9 (immediately post-intervention), and 6 months in both groups. RESULTS: The recruitment rate was 22% and the dropout rate was lower than anticipated (13% to 18% at 6 mo). Adherence with the EWP was high, 93% (n=37/40) walked for =6 weeks, and increased their steps/day [mean absolute increase in steps/d, 2776, 95% confidence interval (CI), 1996-3557] by 59% (95% CI, 40.73%-76.25%) from baseline. Mean percentage adherence with weekly step targets was 70% (95% CI, 62%-77%). Eight (20%) minor-related adverse events were observed in 13% (5/40) of the participants. The EWP group participants demonstrated an 8.2% point improvement [95% CI, -13 to -3.4] on the ODQ at 6 months compared with 1.6% points [95% CI, -9.3 to 6.1) for the E group (between group d=0.44). There was also a larger mean improvement in pain (d=0.4) and a larger increase in PA (d=0.59) at 6 months in EWP. DISCUSSION: This preliminary study demonstrated that a main RCT is feasible. EWP was safe and produced a real increase in walking; CLBP function and pain improved, and participants perceived a greater improvement in their PA levels. These improvements require confirmation in a fully powered RCT.

Visual outcomes in the subfoveal radiotherapy study:A randomized controlled trial of teletherapy for age-related macular degeneration

Objective: To determine whether teletherapy with 6-mV photons can reduce visual loss in patients with subfoveal choroidal neovascularization in age-related macular degeneration. Design: A multicenter, single-masked, randomized controlled trial of 12 Gy of external beam radiation therapy delivered to the macula of an affected eye vs observation only. Setting: Three United Kingdom-based hospital units. Participants: Patients with age-related macular degeneration, aged 60 years and older, who had subfoveal choroidal neovascularization and a visual acuity of 20/200 (logMAR 1.0) or better. Methods: Two hundred three patients were randomly assigned to radiotherapy or observation. Treatment was undertaken at designated radiotherapy centers, and patients assigned to the treatment group received a total dosage of 12 Gy of 6-mV photons in 6 fractions. Follow-up was scheduled at 3, 6, 12, and 24 months. After excluding protocol violators, the data from 199 patients were analyzed. Main Outcome Measures: The primary outcome measure was mean loss of distance visual acuity in the study eye at 12 and 24 months. Other outcome variables analyzed were near visual acuity and contrast sensitivity. The proportions of patients losing 3 or more or 6 or more lines of distance and near acuity and 0.3 or more or 0.6 or more log units of contrast sensitivity at each follow-up were also analyzed. Results: At all time points, mean distance visual acuity was better in the radiotherapy-treated group than in the control group, but the differences did not reach statistical significance. At 24 months, analysis of the proportions of patients with loss of 3 or more (moderate) (P=.08) or 6 or more (severe) (P=.29) lines of distance vision showed that fewer treated patients had severe losses, but there was no statistically significant difference between groups. For near visual acuity, although there was no evidence of treatment benefit at 12 and 24 months, a significant difference in favor of treatment was present at 6 months (P=.048). When analyzed by the proportions of patients losing 3 lines of contrast sensitivity, there was a significant difference in favor of treatment at 24 months (P=.02). No adverse retinal effects were observed during the study, but transient disturbance of the precorneal tear film was noted in treated patients. Conclusion: The results of the present trial do not support the routine clinical use of external beam radiation therapy in subjects with subfoveal choroidal neovascularization in age-related macular degeneration.

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): Study protocol for a randomized controlled trial

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care.

METHODS/DESIGN: EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate.

TRIAL REGISTRATION: ISRCTN44464607.