Inpatient rehabilitation specifically designed for geriatric patients: systematic review and meta-analysis of randomised controlled trials

To assess the effects of inpatient rehabilitation specifically designed for geriatric patients compared with usual care on functional status, admissions to nursing homes, and mortality.

Body mass index, hormone replacement therapy, and endometrial cancer risk: a meta-analysis

Background: Body mass index (BMI) is a risk factor for endometrial cancer. We quantified the risk and investigated whether the association differed by use of hormone replacement therapy (HRT), menopausal status, and histologic type. Methods: We searched MEDLINE and EMBASE (1966 to December 2009) to identify prospective studies of BMI and incident endometrial cancer. We did random-effects meta-analyses, meta-regressions, and generalized least square regressions for trend estimations assuming linear, and piecewise linear, relationships. Results: Twenty-four studies (17,710 cases) were analyzed; 9 studies contributed to analyses by HRT, menopausal status, or histologic type, all published since 2003. In the linear model, the overall risk ratio (RR) per 5 kg/m2 increase in BMI was 1.60 (95% CI, 1.52–1.68), P < 0.0001. In the piecewise model, RRs compared with a normal BMI were 1.22 (1.19–1.24), 2.09 (1.94–2.26), 4.36 (3.75–5.10), and 9.11 (7.26–11.51) for BMIs of 27, 32, 37, and 42 kg/m2, respectively. The association was stronger in never HRT users than in ever users: RRs were 1.90 (1.57–2.31) and 1.18 (95% CI, 1.06–1.31) with P for interaction ¼ 0.003. In the piecewise model, the RR in never users was 20.70 (8.28–51.84) at BMI 42 kg/m2, compared with never users at normal BMI. The association was not affected by menopausal status (P ¼ 0.34) or histologic type (P ¼ 0.26). Conclusions: HRT use modifies the BMI-endometrial cancer risk association. Impact: These findings support the hypothesis that hyperestrogenia is an important mechanism underlying the BMI-endometrial cancer association, whilst the presence of residual risk in HRT users points to the role of additional systems. Cancer Epidemiol Biomarkers Prev; 19(12); 3119–30.

Efficacy of experimental treatments compared with standard treatments in non-inferiority trials: a meta-analysis of randomized controlled trials

Background There is concern that non-inferiority trials might be deliberately designed to conceal that a new treatment is less effective than a standard treatment. In order to test this hypothesis we performed a meta-analysis of non-inferiority trials to assess the average effect of experimental treatments compared with standard treatments. Methods One hundred and seventy non-inferiority treatment trials published in 121 core clinical journals were included. The trials were identified through a search of PubMed (1991 to 20 February 2009). Combined relative risk (RR) from meta-analysis comparing experimental with standard treatments was the main outcome measure. Results The 170 trials contributed a total of 175 independent comparisons of experimental with standard treatments. The combined RR for all 175 comparisons was 0.994 [95% confidence interval (CI) 0.978–1.010] using a random-effects model and 1.002 (95% CI 0.996–1.008) using a fixed-effects model. Of the 175 comparisons, experimental treatment was considered to be non-inferior in 130 (74%). The combined RR for these 130 comparisons was 0.995 (95% CI 0.983–1.006) and the point estimate favoured the experimental treatment in 58% (n = 76) and standard treatment in 42% (n = 54). The median non-inferiority margin (RR) pre-specified by trialists was 1.31 [inter-quartile range (IQR) 1.18–1.59]. Conclusion In this meta-analysis of non-inferiority trials the average RR comparing experimental with standard treatments was close to 1. The experimental treatments that gain a verdict of non-inferiority in published trials do not appear to be systematically less effective than the standard treatments. Importantly, publication bias and bias in the design and reporting of the studies cannot be ruled out and may have skewed the study results in favour of the experimental treatments. Further studies are required to examine the importance of such bias.

Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study

Objective To examine the presence and extent of small study effects in clinical osteoarthritis research. Design Meta-epidemiological study. Data sources 13 meta-analyses including 153 randomised trials (41 605 patients) that compared therapeutic interventions with placebo or non-intervention control in patients with osteoarthritis of the hip or knee and used patients’ reported pain as an outcome. Methods We compared estimated benefits of treatment between large trials (at least 100 patients per arm) and small trials, explored funnel plots supplemented with lines of predicted effects and contours of significance, and used three approaches to estimate treatment effects: meta-analyses including all trials irrespective of sample size, meta-analyses restricted to large trials, and treatment effects predicted for large trials. Results On average, treatment effects were more beneficial in small than in large trials (difference in effect sizes −0.21, 95% confidence interval −0.34 to −0.08, P=0.001). Depending on criteria used, six to eight funnel plots indicated small study effects. In six of 13 meta-analyses, the overall pooled estimate suggested a clinically relevant, significant benefit of treatment, whereas analyses restricted to large trials and predicted effects in large trials yielded smaller non-significant estimates. Conclusions Small study effects can often distort results of meta-analyses. The influence of small trials on estimated treatment effects should be routinely assessed.

Long-term antibiotic treatment for Crohn's disease: systematic review and meta-analysis of placebo-controlled trials

We investigated the effectiveness of long-term antibiotic treatment in patients with Crohn's disease.

Effects of glucosamine, chondroitin, or placebo in patients with osteoarthritis of hip or knee: network meta-analysis

OBJECTIVE: To determine the effect of glucosamine, chondroitin, or the two in combination on joint pain and on radiological progression of disease in osteoarthritis of the hip or knee. Design Network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points. MAIN OUTCOME MEASURE: Pain intensity. Secondary outcome was change in minimal width of joint space. The minimal clinically important difference between preparations and placebo was prespecified at -0.9 cm on a 10 cm visual analogue scale. DATA SOURCES: Electronic databases and conference proceedings from inception to June 2009, expert contact, relevant websites. Eligibility criteria for selecting studies Large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head. Results 10 trials in 3803 patients were included. On a 10 cm visual analogue scale the overall difference in pain intensity compared with placebo was -0.4 cm (95% credible interval -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference. Industry independent trials showed smaller effects than commercially funded trials (P=0.02 for interaction). The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero. Conclusions Compared with placebo, glucosamine, chondroitin, and their combination do not reduce joint pain or have an impact on narrowing of joint space. Health authorities and health insurers should not cover the costs of these preparations, and new prescriptions to patients who have not received treatment should be discouraged.

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Ear canal cholesteatoma: meta-analysis of clinical characteristics with update on classification, staging and treatment

We present an update on clinical evaluation, staging, classification and treatment of canal cholesteatoma, including a meta-analysis of clinical data of the last 30 years.

Does land-based exercise reduce pain and disability associated with hip osteoarthritis? A meta-analysis of randomized controlled trials

Objective To determine if clinical guidelines recommending therapeutic exercise for people with hip osteoarthritis (OA) are supported by rigorous scientific evidence. Methods A meta-analysis of randomized controlled trials (RCTs) recruiting people with hip OA and comparing some form of land-based exercise program (as opposed to exercises conducted in the water) with a non-exercise group in terms of hip pain and/or self-reported physical function. Results Thirty-two RCTs were identified, but only five met the inclusion criteria. Only one of the five included RCTs restricted recruitment to people with hip OA, the other four RCTs also recruiting participants with knee OA. The five included studies provided data on 204 and 187 hip OA participants for pain and physical function, respectively. Combining the results of the five included RCTs using a fixed-effects model demonstrated a small treatment effect for pain (standardized mean difference (SMD) −0.38; 95% confidence interval (CI) −0.67 to −0.09). No significant benefit in terms of improved self-reported physical function was detected (SMD −0.02; 95% CI −0.31 to 0.28). Conclusion Currently there is only silver level evidence (one small RCT) supporting the benefit of land-based therapeutic exercise for people with symptomatic hip OA in terms of reduced pain and improved physical function. The limited number and small sample size of the included RCTs restricts the confidence that can be attributed to these results.

Sacral neuromodulation for neurogenic lower urinary tract dysfunction: systematic review and meta-analysis

Context Treatment of neurogenic lower urinary tract dysfunction (LUTD) is a challenge, because conventional therapies often fail. Sacral neuromodulation (SNM) has become a well-established therapy for refractory non-neurogenic LUTD, but its value in patients with a neurologic cause is unclear. Objective To assess the efficacy and safety of SNM for neurogenic LUTD. Evidence acquisition Studies were identified by electronic search of PubMed, EMBASE, and ScienceDirect (on 15 April 2010) and hand search of reference lists and review articles. SNM articles were included if they reported on efficacy and/or safety of tested and/or permanently implanted patients suffering from neurogenic LUTD. Two reviewers independently selected studies and extracted data. Study estimates were pooled using Bayesian random-effects meta-analysis. Evidence synthesis Of the 26 independent studies (357 patients) included, the evidence level ranged from 2b to 4 according to the Oxford Centre for Evidence-Based Medicine. Half (n = 13) of the included studies reported data on both test phase and permanent SNM; the remaining studies were confined to test phase (n = 4) or permanent SNM (n = 9). The pooled success rate was 68% for the test phase (95% credibility interval [CrI], 50–87) and 92% (95% CrI, 81–98%) for permanent SNM, with a mean follow-up of 26 mo. The pooled adverse event rate was 0% (95% CrI, 0–2%) for the test phase and 24% (95% CrI, 6–48%) for permanent SNM. Conclusions There is evidence indicating that SNM may be effective and safe for the treatment of patients with neurogenic LUTD. However, the number of investigated patients is low with high between-study heterogeneity, and there is a lack of randomised, controlled trials. Thus, well-designed, adequately powered studies are urgently needed before more widespread use of SNM for neurogenic LUTD can be recommended.

Safety and Functional Outcome of Thrombolysis in Dissection-Related Ischemic Stroke: A Meta-Analysis of Individual Patient Data

The safety and efficacy of thrombolysis in cervical artery dissection (CAD) are controversial. The aim of this meta-analysis was to pool all individual patient data and provide a valid estimate of safety and outcome of thrombolysis in CAD.

Functional parkin promoter polymorphism in Parkinson's disease: new data and meta-analysis

A functional SNP (rs9347683) in the promoter region of the parkin gene had been implicated as a risk factor in older Parkinson's disease (PD) patients.

Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysis

Unexplained differences between classes of antihypertensive drugs in their effectiveness in preventing stroke might be due to class effects on intraindividual variability in blood pressure. We did a systematic review to assess any such effects in randomised controlled trials.