Else Marie Bartels

Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials

BACKGROUND Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. METHODS We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo. FINDINGS Patients given rimonabant had a 4.7 kg (95% CI 4.1-5.3 kg; p<0.0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1.4; p=0.0007; number needed to harm=25 individuals [95% CI 17-58]), and 1.4 times more serious adverse events (OR=1.4; p=0.03; number needed to harm=59 [27-830]). Patients given rimonabant were 2.5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2.5; p=0.01; number needed to harm=49 [19-316]). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3.0; p=0.03; number needed to harm=166 [47-3716]). INTERPRETATION Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events--ie, depressed mood disorders and anxiety-despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.

Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis

This review aims to assess by meta-analysis of randomised controlled trials (RCTs) changes in pain and function when overweight patients with knee osteoarthritis (OA) achieve a weight loss. Systematic searches were performed and reference lists from the retrieved trials were searched. RCTs were enclosed in the systematic review if they explicitly stated diagnosis of knee OA and reported a weight change as the only difference in intervention from the control group. Outcome Measures for Arthritis Clinical Trials III outcome variables were considered for analysis. Effect size (ES) was calculated using RevMan, and meta-regression analyses were performed using weighted estimates from the random effects analyses. Among 35 potential trials identified, four RCTs including five intervention/control groups met our inclusion criteria and provided data from 454 patients. Pooled ES for pain and physical disability were 0.20 (95% CI 0 to 0.39) and 0.23 (0.04 to 0.42) at a weight reduction of 6.1 kg (4.7 to 7.6 kg). Meta-regression analysis showed that disability could be significantly improved when weight was reduced over 5.1%, or at the rate of >0.24% reduction per week. Clinical efficacy on pain reduction was present, although not predictable after weight loss. Meta-regression analysis indicated that physical disability of patients with knee OA and overweight diminished after a moderate weight reduction regime. The analysis supported that a weight loss of >5% should be achieved within a 20-week period—that is, 0.25% per week.

Consumption of industrial and ruminant trans fatty acids and risk of coronary heart disease: a systematic review and meta-analysis of cohort studies

The aim of this systematic review and meta-analysis was to summarize the evidence from observational studies assessing the association between intake of trans fatty acids (TFA) and the risk of coronary heart disease (CHD), with a specific emphasis on distinguishing between TFA of industrial and ruminant origin. By searching five bibliographic databases, analyses from six published and two unpublished prospective cohort studies, assessing the association of intake of TFA with fatal and/or non-fatal CHD, were identified. Four and three studies reported separate associations for intake of ruminant or industrial-TFA, respectively. The pooled relative risk estimates for comparison of extreme quintiles of total-TFA intake (corresponding to intake increments ranging from 2.8 to ∼10 g/day) were 1.22 (95% confidence interval: 1.08–1.38; P=0.002) for CHD events and 1.24 (1.07–1.43; P=0.003) for fatal CHD. Ruminant-TFA intake (increments ranging from 0.5 to 1.9 g/day) was not significantly associated with risk of CHD (risk ratio (RR)=0.92 (0.76–1.11); P=0.36), and neither was industrial-TFA intake, although there was a trend towards a positive association (RR=1.21 (0.97–1.50); P=0.09). In conclusion, our analysis suggests that industrial-TFA may be positively related to CHD, whereas ruminant-TFA is not, but the limited number of available studies prohibits any firm conclusions concerning whether the source of TFA is important. The null association of ruminant-TFA with CHD risk may be due to lower intake levels.

A RANDOMIZED CONTROLLED TRIAL OF AQUATIC AND LAND-BASED EXERCISE IN PATIENTS WITH KNEE OSTEOARTHRITIS*

OBJECTIVE To compare the efficacy of aquatic exercise and a land-based exercise programme vs control in patients with knee osteoarthritis. METHODS Primary outcome was change in pain, and in addition Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS). Standing balance and strength was also measured after and at 3-month follow-up. Seventy-nine patients (62 women), with a mean age of 68 years (age range 40-89 years) were randomized to aquatic exercise (n = 27), land-based exercise (n = 25) or control (n = 27). RESULTS No effect was observed immediately after exercise cessation (8 weeks). At 3-month follow-up a reduction in pain was observed only in the land-based exercise group compared with control (-8.1 mm, (95% confidence interval -15.4 to -0.4; p = 0.039), but no differences between groups were observed for KOOS; and no improvement following aquatic exercise. Eleven patients reported adverse events (i.e. discomfort) in land-based exercise, while only 3 reported adverse events in the aquatic exercise. CONCLUSION Only land-based exercise showed some improvement in pain and muscle strength compared with the control group, while no clinical benefits were detectable after aquatic exercise compared with the control group. However, aquatic exercise has significantly less adverse effects compared with a land-based programme.

Validity, reliability and responsiveness of patient-reported outcome questionnaires when assessing hip and groin disability: a systematic review

Background Novel treatment interventions are advancing rapidly in the management of hip and groin disability in the physically active young to middle-aged population. Objective To recommend the most suitable patient-reported outcome (PRO) questionnaires for the assessment of hip and groin disability based on a systematic review of evidence of validity, reliability and responsiveness of these instruments. Methods MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO, SportsDiscus and Web of Science were all searched up to January 2009. Two reviewers independently rated measurement properties of the PRO questionnaires in the included studies, according to a standardised criteria list. Results The computerised search identified 2737 publications. Forty-one publications investigating measurement properties of PRO questionnaires assessing hip or groin disability were included in the study. Twelve different questionnaires designed for patients with hip disability and one questionnaire for patients with groin disability were identified. Hip dysfunction and Osteoarthritis Outcome Score (HOOS) contains adequate measurement qualities to evaluate patients with hip osteoarthritis (OA) or total hip replacement (THR). Hip Outcome Score (HOS) is the best available questionnaire for evaluating hip arthroscopy, but the Inguinal Pain Questionnaire, the only identified questionnaire evaluating groin disability, does not contain adequate measurement qualities. Conclusions HOOS is recommended for evaluating patients with hip OA undergoing non-surgical treatment and surgical interventions such as THR. HOS is recommended for evaluating patients undergoing hip arthroscopy. Current and new PRO questionnaires should also be evaluated in younger patients (age <50) with hip and/or groin disability, including surgical and non-surgical patients.

Comparative Effectiveness of Injection Therapies in Lateral Epicondylitis A Systematic Review and Network Meta-analysis of Randomized Controlled Trials

Background: Injection therapy with glucocorticoids has been used since the 1950s as a treatment strategy for lateral epicondylitis (tennis elbow). Lately, several novel injection therapies have become available. Purpose: To assess the comparative effectiveness and safety of injection therapies in patients with lateral epicondylitis. Study Design: Systematic review and meta-analysis. Methods: Randomized controlled trials comparing different injection therapies for lateral epicondylitis were included provided they contained data for change in pain intensity (primary outcome). Trials were assessed using the Cochrane risk of bias tool. Network (random effects) meta-analysis was applied to combine direct and indirect evidence within and across trial data using the final end point reported in the trials, and results for the arm-based network analyses are reported as standardized mean differences (SMDs). Results: Seventeen trials (1381 participants; 3 [18%] at low risk of bias) assessing injection with 8 different treatments—glucocorticoid (10 trials), botulinum toxin (4 trials), autologous blood (3 trials), platelet-rich plasma (2 trials), and polidocanol, glycosaminoglycan, prolotherapy, and hyaluronic acid (1 trial each)—were included. Pooled results (SMD [95% confidence interval]) showed that beyond 8 weeks, glucocorticoid injection was no more effective than placebo (−0.04 [−0.45 to 0.35]), but only 1 trial (which did not include a placebo arm) was at low risk of bias. Although botulinum toxin showed marginal benefit (−0.50 [−0.91 to −0.08]), it caused temporary paresis of finger extension, and all trials were at high risk of bias. Both autologous blood (−1.43 [−2.15 to −0.71]) and platelet-rich plasma (−1.13 [−1.77 to −0.49]) were also statistically superior to placebo, but only 1 trial was at low risk of bias. Prolotherapy (−2.71 [−4.60 to −0.82]) and hyaluronic acid (−5.58 [−6.35 to −4.82]) were both more efficacious than placebo, whereas polidocanol (0.39 [−0.42 to 1.20]) and glycosaminoglycan (−0.32 [−1.02 to 0.38]) showed no effect compared with placebo. The criteria for low risk of bias were only met by the prolotherapy and polidocanol trials. Conclusion: This systematic review and network meta-analysis of randomized controlled trials found a paucity of evidence from unbiased trials on which to base treatment recommendations regarding injection therapies for lateral epicondylitis.

Learning effect of isokinetic measurements in healthy subjects, and reliability and comparability of Biodex and Lido dynamometers

The aim of this study was to examine the learning effect during a set of isokinetic measurements, to evaluate the reliability of the Biodex System 3 PRO dynamometer, and to compare the Biodex System 3 PRO and the Lido Active dynamometers on both extension and flexion over the elbow and the knee at 60° s−1. Thirteen (nine women, four men) healthy participants were measured five times using the Biodex and once using the Lido dynamometer. The intervals between the first four tests were 20 min, and 1 week between tests 4 and 5. Between Biodex and Lido measurements there was a 20 min time interval. When comparing the first five measurements (Biodex), no systematic effect over time and an excellent reliability were found with respect to elbow and knee flexion and extension. No difference in muscle strength (Nm) between the Biodex and Lido was observed for knee flexion (P = 0·59), knee extension (P = 0·18) and elbow extension (P = 0·63). However, elbow flexion showed a 14·8% (95% CI: 11·2–18·4%; P = 0·0001) higher peak torque on Biodex. In conclusion, no learning effect was observed and the Biodex proved to be a highly reliable isokinetic dynamometer. A difference was observed when comparing Biodex and Lido on elbow flexion, but the difference did not outrange the expected variation found with a typical isokinetic measurement, which is why both sets of equipment seem applicable in clinical practice.

Isokinetic and isometric muscle strength in a healthy population with special reference to age and gender

Aim:  Muscle strength is an excellent indicator of general health when based on reliable measurements. Muscle strength data for a healthy population are rare or non‐existent. The aim of the present study was to measure a set of normal values for isometric and isokinetic muscle strength for all the major joint movements of the body and, from these data, to create a basis for comparison of the muscle strength of an individual with the expected value in a normal population.

Knee Injury and Osteoarthritis Outcome Score (KOOS): systematic review and meta-analysis of measurement properties

OBJECTIVE To conduct a systematic review and meta-analysis to synthesize evidence regarding measurement properties of the Knee injury and Osteoarthritis Outcome Score (KOOS). DESIGN A comprehensive literature search identified 37 eligible papers evaluating KOOS measurement properties in participants with knee injuries and/or osteoarthritis (OA). Methodological quality was evaluated using the COSMIN checklist. Where possible, meta-analysis of extracted data was conducted for all studies and stratified by age and knee condition; otherwise narrative synthesis was performed. RESULTS KOOS has adequate internal consistency, test-retest reliability and construct validity in young and old adults with knee injuries and/or OA. The ADL subscale has better content validity for older patients and Sport/Rec for younger patients with knee injuries, while the Pain subscale is more relevant for painful knee conditions. The five-factor structure of the original KOOS is unclear. There is some evidence that the KOOS subscales demonstrate sufficient unidimensionality, but this requires confirmation. Although measurement error requires further evaluation, the minimal detectable change for KOOS subscales ranges from 14.3 to 19.6 for younger individuals, and ≥20 for older individuals. Evidence of responsiveness comes from larger effect sizes following surgical (especially total knee replacement) than non-surgical interventions. CONCLUSIONS KOOS demonstrates adequate content validity, internal consistency, test-retest reliability, construct validity and responsiveness for age- and condition-relevant subscales. Structural validity, cross-cultural validity and measurement error require further evaluation, as well as construct validity of KOOS Physical function Short form. Suggested order of subscales for different knee conditions can be applied in hierarchical testing of endpoints in clinical trials. SYSTEMATIC REVIEW REGISTRATION PROSPERO (CRD42011001603).

Does the hip powder of Rosa canina (rosehip) reduce pain in osteoarthritis patients? – a meta-analysis of randomized controlled trials

OBJECTIVE Meta-analysis of randomized controlled trials (RCTs)--of a hip powder of Rosa canina (rosehip) preparation for symptomatic treatment of osteoarthritis (OA), in order to estimate the empirical efficacy as a pain reducing compound. METHOD RCTs from systematic searches were included if they explicitly stated that OA patients were randomized to either rosehip or placebo. The primary outcome was reduction in pain calculated as effect size (ES), defined as the standardized mean difference (SMD). As secondary analysis the number of responders to therapy was analyzed as Odds Ratios (OR), and expressed as the Number Needed to Treat (NNT). Restricted Maximum Likelihood (REML) methods were applied for the meta-analyses using mixed effects models. RESULTS The three studies (287 patients and a median trial-duration of 3 months)--all supported by the manufacturer (Hyben-Vital International)--showed a reduction in pain scores by rosehip powder (145 patients) compared to placebo (142 patients): ES of 0.37 [95% confidence interval (CI): 0.13-0.60], P=0.002. Test for homogeneity seemed to support that the efficacy was consistent across trials (I(2)=0%). Thus it seems reasonable to assume that the three studies were measuring the same overall effect. It seemed twice as likely that a patient allocated to rosehip powder would respond to therapy, compared to placebo (OR=2.19; P=0.0009); corresponding to a NNT of six (95% CI: 4-13) patients. CONCLUSIONS Although based on a sparse amount of data, the results of the present meta-analysis indicate that rosehip powder does reduce pain; accordingly it may be of interest as a nutraceutical, although its efficacy and safety need evaluation and independent replication in a future large-scale/long-term trial.