Assessment of the Quality of Reporting in Abstracts of Randomized Controlled Trials Published in Five Leading Chinese Medical Journals

Background

Clear, transparent and sufficiently detailed abstracts of randomized trials (RCTs), published in journal articles are important because readers will often base their initial assessment of a trial on such information. However, little is known about the quality of reporting in abstracts of RCTs published in medical journals in China.

Methods

We identified RCTs abstracts from 5 five leading Chinese medical journals published between 1998 and 2007 and indexed in MEDLINE. We assessed the quality of reporting of these abstracts based on the Consolidated Standards of Reporting Trials (CONSORT) abstract checklist. We also sought to identify whether any differences exist in reporting between the Chinese and English language version of the same abstract.

Results

We identified 332 RCT abstracts eligible for examination. Overall, the abstracts we examined reported 0–8 items as designated in the CONSORT checklist. On average, three items were reported per abstract. Details of the interventions (288/332; 87%), the number of participants randomized (216/332; 65%) and study objectives (109/332; 33%) were the top three items reported. Only two RCT abstracts reported details of trial registration, no abstracts reported the method of allocation concealment and only one mentioned specifically who was blinded. In terms of the proportion of RCT abstracts fulfilling a criterion, the absolute difference (percentage points) between the Chinese and English abstracts was 10% (ranging from 0 to 25%) on average, per item.

Conclusions

The quality of reporting in abstracts of RCTs published in Chinese medical journals needs to be improved. We hope that the introduction and endorsement of the CONSORT for Abstracts guidelines by journals reporting RCTs will lead to improvements in the quality of reporting.     

Reporting of Positive Results in Randomized Controlled Trials of Mindfulness-Based Mental Health Interventions

BackgroundA large proportion of mindfulness-based therapy trials report statistically significant results, even in the context of very low statistical power. The objective of the present study was to characterize the reporting of “positive” results in randomized controlled trials of mindfulness-based therapy. We also assessed mindfulness-based therapy trial registrations for indications of possible reporting bias and reviewed recent systematic reviews and meta-analyses to determine whether reporting biases were identified.MethodsCINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS databases were searched for randomized controlled trials of mindfulness-based therapy. The number of positive trials was described and compared to the number that might be expected if mindfulness-based therapy were similarly effective compared to individual therapy for depression. Trial registries were searched for mindfulness-based therapy registrations. CINAHL, Cochrane CENTRAL, EMBASE, ISI, MEDLINE, PsycInfo, and SCOPUS were also searched for mindfulness-based therapy systematic reviews and meta-analyses.Results108 (87%) of 124 published trials reported ≥1 positive outcome in the abstract, and 109 (88%) concluded that mindfulness-based therapy was effective, 1.6 times greater than the expected number of positive trials based on effect size d = 0.55 (expected number positive trials = 65.7). Of 21 trial registrations, 13 (62%) remained unpublished 30 months post-trial completion. No trial registrations adequately specified a single primary outcome measure with time of assessment. None of 36 systematic reviews and meta-analyses concluded that effect estimates were overestimated due to reporting biases.ConclusionsThe proportion of mindfulness-based therapy trials with statistically significant results may overstate what would occur in practice.     

The Effects of Perioperative Music Interventions in Pediatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective

Music interventions are widely used, but have not yet gained a place in guidelines for pediatric surgery or pediatric anesthesia. In this systematic review and meta-analysis we examined the effects of music interventions on pain, anxiety and distress in children undergoing invasive surgery.

Data Sources

We searched 25 electronic databases from their first available date until October 2014.

Study Selection

Included were all randomized controlled trials with a parallel group, crossover or cluster design that included pediatric patients from 1 month to 18 years old undergoing minimally invasive or invasive surgical procedures, and receiving either live music therapy or recorded music.

Data Extraction and Synthesis

4846 records were retrieved from the searches, 26 full text reports were evaluated and data was extracted by two independent investigators.

Main Outcome Measures

Pain was measured with the Visual Analogue Scale, the Coloured Analogue Scale and the Facial Pain Scale. Anxiety and distress were measured with an emotional index scale (not validated), the Spielberger short State Trait Anxiety Inventory and a Facial Affective Scale.

Results

Three RCTs were eligible for inclusion encompassing 196 orthopedic, cardiac and day surgery patients (age of 1 day to 18 years) receiving either live music therapy or recorded music. Overall a statistically significant positive effect was demonstrated on postoperative pain (SMD -1.07; 95%CI-2.08; -0.07) and on anxiety and distress (SMD -0.34 95% CI -0.66; -0.01 and SMD -0.50; 95% CI -0.84; - 0.16.

Conclusions and Relevance

This systematic review and meta-analysis indicates that music interventions may have a statistically significant effect in reducing post-operative pain, anxiety and distress in children undergoing a surgical procedure. Evidence from this review and other reviews suggests music therapy may be considered for clinical use.     

Post-Operative Auto-Transfusion in Total Hip or Knee Arthroplasty: A Meta-Analysis of Randomized Controlled Trials

Background

Total hip or knee arthroplasty is an elective procedure that is usually accompanied by substantial blood loss, which may lead to acute anemia. As a result, almost half of total joint arthroplasty patients receive allogeneic blood transfusions (ABT). Many studies have shown that post-operative auto-transfusion (PAT) significantly reduces the need for ABT, but other studies have questioned the efficacy of this method.

Methods

The protocol for this trial and supporting CONSORT checklist are available as supporting information; see Checklist S1. To evaluate the efficacy of PAT, we conducted a Cochrane systematic review that combined all available data from randomized controlled trials. Data from the six included trials were pooled for analysis. We then calculated relative risks with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences with 95% CIs for continuous outcomes.

Findings and Conclusion

To our knowledge, this is the first meta-analysis to compare the clinical results between PAT and a control in joint replacement patients. This meta-analysis has proven that the use of a PAT reinfusion system reduced significantly the demand for ABT, the number of patients who require ABT and the cost of hospitalization after total knee and hip arthroplasty. This study, together with other previously published data, suggests that PAT drains are beneficial. Larger, sufficiently powered studies are necessary to evaluate the presumed reduction in the incidence of infection as well as DVT after joint arthroplasty with the use of PAT.     

Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology

Background

Confidence that randomized controlled trial (RCT) results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP) is the primary trials journal amongst American Psychological Association (APA) journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1) adequacy of primary outcome analysis definitions; (2) registration status; and, (3) among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals.

Methods

Eligible RCTs were published in JCCP in 2013–2014. For each RCT, two investigators independently extracted data on (1) adequacy of outcome analysis definitions in the published report, (2) whether the RCT was registered prior to enrolling patients, and (3) adequacy of outcome registration.

Results

Of 70 RCTs reviewed, 12 (17.1%) adequately defined primary or secondary outcome analyses, whereas 58 (82.3%) had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7%) registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029). The proportion of registered trials in JCCP (55.7%) was comparable to behavioral medicine journals (52.6%; p = 0.709).

Conclusions

The quality of published outcome analysis definitions and trial registrations in JCCP is suboptimal. Greater attention to proper trial registration and outcome analysis definition in published reports is needed.     

Study Design and Quality of Reporting of Randomized Controlled Trials of Chronic Idiopathic or Autoimmune Urticaria: Review

Background

The recommended first-line therapy of chronic urticaria is second-generation antihistamines, but the modalities of treatment remains unclear. Numerous recommendations with heterogeneous conclusions have been published. We wondered whether such heterogeneous conclusions were linked to the quality of published studies and their reporting.

Objective

To review the study design and quality of reporting of randomized control trials investigating pharmacological treatment of autoimmune or idiopathic chronic urticaria.

Methodology/Principal Findings

MEDLINE and EMBASE were searched for pharmacological randomized controlled trials involving patients with chronic autoimmune or idiopathic urticaria, with the main outcome being treatment efficacy. Data were collected on general characteristics of the studies, internal validity, studied treatments, design of the trial, outcome measures and “spin” strategy in interpreting results. Spin was defined as use of specific reporting strategies to highlight that the experimental treatment is beneficial, despite statistically nonsignificant results. We evaluated 52 articles that met our criteria. Patients were reported as blinded in 42 articles (81%) and the outcome assessor was blinded in 37 (71%). A placebo was the only comparator in 13 (25%) studies. The study duration was <8 weeks in 39 articles (75%), with no follow-up after discontinuation of treatment in 37 (71%). In 4 articles (8%), blinding was clear because they described blinding of the outcome assessor, the treatment was not recognizable (identical or double-dummy) or had no major secondary effects, and computed randomization was centralized. The primary outcome was specified in 33 articles (63%) and was a score in 31. In total, 15 different scores were used. A spin strategy was used for 10 of 12 studies with a nonsignificant primary outcome.

Conclusion

For establishing guidelines in treatment of chronic urticaria, studies should focus on choosing clinically relevant and reproducible primary outcomes, long-term follow-up, limited use of placebo and avoiding spin strategies.     

Characteristics of Randomized Trials Published in Latin America and the Caribbean According to Funding Source

Introduction

Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC).

Methods and Findings

The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author''s affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting.

Conclusion

Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems.     

Idraparinux or Idrabiotaparinux for Long-Term Venous Thromboembolism Treatment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Venous thromboembolism (VTE) is a prevalent disease with potential serious consequences. Idraparinux and idrabiotaparinux are two kinds of long-acting pentasaccharides. Evidence has shown that idraparinux and idrabiotaparinux are effective anticoagulants. However, up to now, there is no consensus on whether they are better than other anticoagulation methods for long-term VTE treatment.

Objective

To evaluate the effect of idraparinux or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment.

Methods

We searched Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of science, clinical trial registry web sites (clinical trials,WHO clinical trial registry), Googlescholar, PubMed related articles and companies'' web sites electronically up to Dec 30^th, 2012 and manually searched the reference lists and conference proceedings. Only randomized controlled trial (RCT) involving adult patients comparing idraparinux and/or idrabiotaparinux versus other anticoagulation methods for long-term VTE treatment was included. Two reviewers evaluated the studies and extracted data independently. Pooled risk ratios (RRs) were calculated as outcome measures and Revman 5.2 software was used to analyze data. Our primary efficacy and safety outcomes were the recurrent VTE and major bleeding rates.

Results

We included four RCTs and involved 8584 participants on idraparinux or idrabiotaparinux versus standard warfarin for VTE treatment from 9364 references. We did not perform meta-analysis on the VTE rate because of the significant heterogeneity. We used the fixed effect model to analyze the safety outcomes and demonstrated that idraparinux or idrabiotaparinux decreased major bleeding rate significantly (RR 0.73, 95% CI 0.54 to 0.98, P = 0.04) but had a trend to increase the all cause mortality (RR 1.26, 95% CI 1.00 to 1.57, P = 0.05) compared with warfarin.

Conclusions

Until now there is not sufficient evidence to clarify whether idraparinux or idrabiotaparinux is as effective and safe as the standard warfarin treatment for VTE treatment.     

Endoscopic Vascular Harvest in Coronary Artery Bypass Grafting Surgery: A Meta-Analysis of Randomized Trials and Controlled Trials

OBJECTIVE:: This meta-analysis sought to determine whether endoscopic vascular graft harvesting (EVH) improves clinical and resource outcomes compared with conventional open graft harvesting (OVH) in adults undergoing coronary artery bypass surgery. METHODS:: A comprehensive search was undertaken to identify all randomized and nonrandomized trials of EVH versus OVH up to April 2005. The primary outcome was wound complications. Secondary outcomes included any other clinical morbidity and resource utilization. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences (SMD) and their 95% confidence intervals (95% CI) were analyzed. RESULTS:: Thirty-six trials of 9,632 patients undergoing saphenous vein harvest met the inclusion criteria (13 randomized; 23 nonrandomized). Risk of wound complications was significantly reduced by EVH compared with OVH (OR 0.31, 95% CI 0.23-0.41). Similarly, the risk of wound infections was significantly reduced (OR 0.23, 95% CI 0.20-0.53; P < 0.0001). Need for surgical wound intervention was also significantly reduced (OR 0.16, 95% CI 0.08-0.29). The incidence of pain, neuralgia, and patient satisfaction was improved with EVH compared with OVH. Postoperative myocardial infarction, stroke, reintervention for ischemia or angina recurrence, and mortality were not significantly different. Operative time was significantly increased (WMD 15.26 minutes; 95% CI 0.01, 30.51), hospital length of stay was reduced (WMD -0.85 days; 95% CI -1.55, -0.15), and readmissions were reduced (OR 0.53, 95% CI 0.29-0.98). Costs were insufficiently reported to allow for aggregate analysis. CONCLUSIONS:: Endoscopic vascular graft harvesting of the saphenous vein reduces wound complications and improves patient satisfaction and resource utilization. Further research is required to determine the incremental cost-effectiveness of EVH versus OVH.     

Mini-Incision versus Standard Incision Total Hip Arthroplasty Regarding Surgical Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Purpose

It remains controversial whether mini-incision (MI) benefits patients in total hip arthroplasty (THA). We performed a meta-analysis of randomized controlled trials (RCTs) to assess the effects of MI on surgical and functional outcomes in THA patients.

Methods

A systematic electronic literature search (up to May 2013) was conducted to identify RCTs comparing MI with standard incision (SI) THA. The primary outcome measures were surgical and functional outcomes. According to the surgical approach taken, MI THA patients were divided into four subgroups for sub-group meta-analysis. Standardized mean differences (SMDs) or risk differences (RDs) with accompanying 95% confidence intervals (CIs) were calculated and pooled using a fixed-effect or random-effect model according to the heterogeneity.

Results

A total of 14 RCTs involving THA 1,174 patients met the inclusion criteria. The trials were medium risk of bias. The overall meta-analysis showed MI THA reduced total blood loss (95% CI, -201.83 to -21.18; p=.02) and length of hospital stay ( 95% CI, -0.67 to -0.08; p=.01) with significant heterogeneity. However, subgroup meta-analysis revealed posterior MI THA had perioperative advantages of reduced surgical duration ( 95% CI, -8.45 to -2.67; P<.001), less blood loss ( 95% CI, -107.20 to -1.73; P=.04) and shorter hospital stay ( 95% CI, -0.74 to -0.06; p=.002) with low heterogeneity. There were no significant differences between MI and SI THA groups in term of pain medication dose, functional outcome (HHS), radiological outcome or complications (P>.05, respectively).

Conclusions

Although no definite overall conclusion can be arrived at on whether MI THA is superior to SI THA, posterior MI THA clearly result in a significant decrease in surgical duration, blood loss and hospital stay. It seems to be a safe minimally invasive surgical procedure without increasing the risk of component malposition or complications.     

Effects on Coronary Heart Disease of Increasing Polyunsaturated Fat in Place of Saturated Fat: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Reduced saturated fat (SFA) consumption is recommended to reduce coronary heart disease (CHD), but there is an absence of strong supporting evidence from randomized controlled trials (RCTs) of clinical CHD events and few guidelines focus on any specific replacement nutrient. Additionally, some public health groups recommend lowering or limiting polyunsaturated fat (PUFA) consumption, a major potential replacement for SFA.

Methods and Findings

We systematically investigated and quantified the effects of increased PUFA consumption, as a replacement for SFA, on CHD endpoints in RCTs. RCTs were identified by systematic searches of multiple online databases through June 2009, grey literature sources, hand-searching related articles and citations, and direct contacts with experts to identify potentially unpublished trials. Studies were included if they randomized participants to increased PUFA for at least 1 year without major concomitant interventions, had an appropriate control group, and reported incidence of CHD (myocardial infarction and/or cardiac death). Inclusions/exclusions were adjudicated and data were extracted independently and in duplicate by two investigators and included population characteristics, control and intervention diets, follow-up duration, types of events, risk ratios, and SEs. Pooled effects were calculated using inverse-variance-weighted random effects meta-analysis. From 346 identified abstracts, eight trials met inclusion criteria, totaling 13,614 participants with 1,042 CHD events. Average weighted PUFA consumption was 14.9% energy (range 8.0%–20.7%) in intervention groups versus 5.0% energy (range 4.0%–6.4%) in controls. The overall pooled risk reduction was 19% (RR = 0.81, 95% confidence interval [CI] 0.70–0.95, p = 0.008), corresponding to 10% reduced CHD risk (RR = 0.90, 95% CI = 0.83–0.97) for each 5% energy of increased PUFA, without evidence for statistical heterogeneity (Q-statistic p = 0.13; I² = 37%). Meta-regression identified study duration as an independent determinant of risk reduction (p = 0.017), with studies of longer duration showing greater benefits.

Conclusions

These findings provide evidence that consuming PUFA in place of SFA reduces CHD events in RCTs. This suggests that rather than trying to lower PUFA consumption, a shift toward greater population PUFA consumption in place of SFA would significantly reduce rates of CHD. Please see later in the article for the Editors'' Summary     

Risks and Benefits of Nalmefene in the Treatment of Adult Alcohol Dependence: A Systematic Literature Review and Meta-Analysis of Published and Unpublished Double-Blind Randomized Controlled Trials

Background

Nalmefene is a recent option in alcohol dependence treatment. Its approval was controversial. We conducted a systematic review and meta-analysis of the aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the harm/benefit of nalmefene versus placebo or active comparator in this indication.

Methods and Findings

Three reviewers searched for published and unpublished studies in Medline, the Cochrane Library, Embase, ClinicalTrials.gov, Current Controlled Trials, and bibliographies and by mailing pharmaceutical companies, the European Medicines Agency (EMA), and the US Food and Drug Administration. Double-blind randomized clinical trials evaluating nalmefene to treat adult alcohol dependence, irrespective of the comparator, were included if they reported (1) health outcomes (mortality, accidents/injuries, quality of life, somatic complications), (2) alcohol consumption outcomes, (3) biological outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors independently screened the titles and abstracts of the trials identified. Relevant trials were evaluated in full text. The reviewers independently assessed the included trials for methodological quality using the Cochrane Collaboration tool for assessing risk of bias. On the basis of the I2 index or the Cochrane’s Q test, fixed or random effect models were used to estimate risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% CIs. In sensitivity analyses, outcomes for participants who were lost to follow-up were included using baseline observation carried forward (BOCF); for binary measures, patients lost to follow-up were considered equal to failures (i.e., non-assessed patients were recorded as not having responded in both groups). Five randomized controlled trials (RCTs) versus placebo, with a total of 2,567 randomized participants, were included in the main analysis. None of these studies was performed in the specific population defined by the EMA approval of nalmefene, i.e., adults with alcohol dependence who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). No RCT compared nalmefene with another medication. Mortality at 6 mo (RR = 0.39, 95% CI [0.08; 2.01]) and 1 y (RR = 0.98, 95% CI [0.04; 23.95]) and quality of life at 6 mo (SF-36 physical component summary score: MD = 0.85, 95% CI [−0.32; 2.01]; SF-36 mental component summary score: MD = 1.01, 95% CI [−1.33; 3.34]) were not different across groups. Other health outcomes were not reported. Differences were encountered for alcohol consumption outcomes such as monthly number of heavy drinking days at 6 mo (MD = −1.65, 95% CI [−2.41; −0.89]) and at 1 y (MD = −1.60, 95% CI [−2.85; −0.35]) and total alcohol consumption at 6 mo (SMD = −0.20, 95% CI [−0.30; −0.10]). An attrition bias could not be excluded, with more withdrawals for nalmefene than for placebo, including more withdrawals for safety reasons at both 6 mo (RR = 3.65, 95% CI [2.02; 6.63]) and 1 y (RR = 7.01, 95% CI [1.72; 28.63]). Sensitivity analyses showed no differences for alcohol consumption outcomes between nalmefene and placebo, but the weight of these results should not be overestimated, as the BOCF approach to managing withdrawals was used.

Conclusions

The value of nalmefene for treatment of alcohol addiction is not established. At best, nalmefene has limited efficacy in reducing alcohol consumption.     

Comparison of Operative and Non-Operative Treatment of Acute Undisplaced or Minimally-Displaced Scaphoid Fractures: A Meta-Analysis of Randomized Controlled Trials

Background

Traditionally, acute undisplaced or minimally-displaced scaphoid fractures are treated by casting in short- or long-arm casts. Although reports have shown that operative treatment is safe, effective and produces satisfactory results, outcomes from current studies comparing these two methods are questionable. The aim of this meta-analysis was to evaluate the effects of operative versus non-operative treatment for acute undisplaced or minimally-displaced scaphoid fractures in adults.

Methods

Computerized searches were performed without language restrictions and all randomized controlled studies providing information on the effects of operative versus non-operative treatment on the outcomes of acute undisplaced or minimally-displaced scaphoid fractures were included. The weighted and standard mean difference (WMD and SMD) or the relative risk (RR) were calculated for continuous or dichotomous data respectively.

Results

A total of six studies reported in seven publications were included, representing data on 340 fractures. Meta-analysis indicated that operative treatment resulted in significantly better functional outcomes in the short term when compared with non-operative treatment. Consistently, patients who accepted surgery had a more rapid return to work. Further, surgery was advantageous in preventing delayed union of the fractures, a finding supported by the results of analysis of the time to fracture union. A number-needed-to-treat analysis revealed that more than 20 patients would have to undergo operative treatment to prevent one delayed union.

Conclusion

Acute undisplaced or minimally-displaced scaphoid fractures demonstrate faster recovery with operative treatment; however, the current meta-analysis does not provide evidence supporting the routine use of operative treatment for all acute undisplaced or minimally-displaced scaphoid fractures.     

Aliskiren and Amlodipine in the Management of Essential Hypertension: Meta-Analysis of Randomized Controlled Trials

Background

Aliskiren is a novel renin-angiotensin aldosterone system (RAAS) inhibitor, the combination therapy of aliskiren and amlodipine for blood pressure control have been reported recently. The primary objective of this analysis is to review recently reported randomized controlled trials (RCTs) to compare antihypertensive effects and adverse events between mono (amlodipine or aliskiren alone) and combination therapy of both medicines.

Methods

Databases for the search included Pubmed, Embase and the Cochrane Central Register of Controlled Trials. Revman v5.0 statistical program was used to analyze the data. Weighted mean differences (WMD) with a 95% confidence interval (CI) were used for the calculation of continuous data, and relative risk (RR) with a 95% CI was used for dichotomous data.

Results

We analyzed the data from 7 RCTs for a total of 6074 participants in this meta-analysis. We found that the aliskiren/amlodipine combination therapy had a stronger effect in lowering blood pressure as compared with the monotherapy using aliskiren (SBP: WMD = −10.42, 95% CI −13.03∼−7.82, P<0.00001; DBP: WMD = −6.60, 95% CI −7.22∼−5.97, P<0.00001) or amlodipine (SBP: WMD = −4.85, 95% CI −6.88∼−2.81, P<0.00001; DBP: WMD = −2.91, 95% CI −3.85∼−1.97, P<0.00001). No differences were found in terms of adverse events between combination therapy and monotherapy, except for the rates of peripheral edema and hypokalaemia which were significantly lower in the combination therapy than in the amlodipine monotherapy (RR = 0.78, 0.66∼0.92, P = 0.004; RR = 0.51, 0.27∼0.97, P = 0.04). Similar antihypertensive effects were found in both obese (body mass index > = 30 kg/m²) hypertensive and non-obese (body mass index <30 kg/m²) hypertensive patients. Moreover, there was no difference with the blood pressure lowering or adverse effects with regards to the combination therapy in both subgroups.

Conclusion

We found that aliskiren/amlodipine combination therapy provided a more effective blood pressure reduction than monotherapy with either drug without increase in the occurrence of adverse events.     

Misrepresentation of Randomized Controlled Trials in Press Releases and News Coverage: A Cohort Study

Background

Previous studies indicate that in published reports, trial results can be distorted by the use of “spin” (specific reporting strategies, intentional or unintentional, emphasizing the beneficial effect of the experimental treatment). We aimed to (1) evaluate the presence of “spin” in press releases and associated media coverage; and (2) evaluate whether findings of randomized controlled trials (RCTs) based on press releases and media coverage are misinterpreted.

Methods and Findings

We systematically searched for all press releases indexed in the EurekAlert! database between December 2009 and March 2010. Of the 498 press releases retrieved and screened, we included press releases for all two-arm, parallel-group RCTs (n = 70). We obtained a copy of the scientific article to which the press release related and we systematically searched for related news items using Lexis Nexis.“Spin,” defined as specific reporting strategies (intentional or unintentional) emphasizing the beneficial effect of the experimental treatment, was identified in 28 (40%) scientific article abstract conclusions and in 33 (47%) press releases. From bivariate and multivariable analysis assessing the journal type, funding source, sample size, type of treatment (drug or other), results of the primary outcomes (all nonstatistically significant versus other), author of the press release, and the presence of “spin” in the abstract conclusion, the only factor associated, with “spin” in the press release was “spin” in the article abstract conclusions (relative risk [RR] 5.6, [95% CI 2.8–11.1], p<0.001). Findings of RCTs based on press releases were overestimated for 19 (27%) reports. News items were identified for 41 RCTs; 21 (51%) were reported with “spin,” mainly the same type of “spin” as those identified in the press release and article abstract conclusion. Findings of RCTs based on the news item was overestimated for ten (24%) reports.

Conclusion

“Spin” was identified in about half of press releases and media coverage. In multivariable analysis, the main factor associated with “spin” in press releases was the presence of “spin” in the article abstract conclusion.     

Investigating Sources of Heterogeneity in Randomized Controlled Trials of the Effects of Pharmacist Interventions on Glycemic Control in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis

Objective

To assess the effect of pharmacist interventions on glycemic control in type 2 diabetic patients and to examine factors that could explain the variation across studies.

Methods

A comprehensive literature search was performed in PubMed, Scopus, and LILACS databases for randomized controlled trials (RCTs) published up to July 2015. The search strategy included the use of MeSH terms or text words related to pharmacist interventions, type 2 diabetes, and randomized controlled trials. RCTs published in English, Portuguese, or Spanish that evaluated the effect of pharmacist intervention on glycemic control in type 2 diabetic outpatients were included. Two independent authors executed study selection, data extraction, and risk of bias assessment. Mean differences in glycosylated hemoglobin (HbA1c) were estimated using random-effect models, and heterogeneity was evaluated by subgroup and meta-regression analyses.

Results

The literature search yielded 963 records of potential interest, of which 30 were included in the systematic review and 22 in the meta-analysis. Most of these RCTs were conducted in the United States in patients in outpatient clinics using face-to-face contact only. All RCTs performed patient education, and most executed the medication review. The appraised sample showed uncertain or high risk of bias in most of the items evaluated, resulting in low-quality studies. In comparison with usual care, pharmacist interventions were associated with significant reductions in HbA1c levels (-8.5% [95% CI: -1.06, -0.65]; P < 0.0001; I² = 67.3%). Subgroup analysis indicated differences of heterogeneity by country, baseline HbA1c levels, setting, intervention frequency, and random allocation. Age and HbA1c levels partly explained the variability across studies by meta-regression.

Conclusions

Our findings confirmed that pharmacist interventions improve glycemic control in patients with type 2 diabetes compared with usual care and suggest that younger patients or with higher baseline HbA1c levels may be the main beneficiaries of pharmacist care.

Protocol PROSPERO Registration Number

CRD42014007457     

Acute Endovascular Reperfusion Therapy in Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background

Randomized controlled trials (RCTs) of endovascular therapy for acute ischemic stroke have had inconsistent results. We evaluated the efficacy and safety of endovascular therapy in published RCTs.

Methods

We performed a systematic review of RCTs of endovascular therapy with thrombolytic or mechanical reperfusion compared with interventions without endovascular therapy. Primary outcome was the frequency of good functional outcome (modified Rankin scale (mRS) of 0-2 at 90 days) and secondary outcomes were mortality at 90 days and symptomatic intracranial hemorrhage (sICH). Random-effects meta-analysis was performed and the Cochrane risk of bias assessment was used to evaluate quality of evidence.

Results

Ten studies involving 1,612 subjects were included. Endovascular therapy was not significantly associated with good functional outcome (Relative Risk [RR] =1.17; 95% CI, 0.97 to 1.42; p=0.10 and Absolute Risk Difference [ARD] =7%; 95%CI -0.1% to 14%; p=0.05); heterogeneity was moderate among studies (I²=30%). Mortality was unchanged with endovascular therapy (RR=0.92; 95 % CI, 0.75 to 1.13; p=0.45) and there was no difference in sICH (RR=1.20; 95 % CI, 0.79 to 1.82; p=0.39). The quality of evidence was low for all outcomes and the recommendation is weak for the use of endovascular therapy as per GRADE methodology.

Conclusions

Intra-arterial therapy did not show significant increase in good outcomes and no changes in either mortality or sICH in patients with acute ischemic stroke. We need further RCTs with better design and quality to evaluate the true efficacy of endovascular therapy.