Comparisons of Interventions for Preventing Falls in Older Adults

Question  What types of fall-prevention programs may be effective for reducing injurious falls in older people?

Findings  In a network meta-analysis including 54 studies and 41 596 participants, exercise (odds ratio [OR], 0.51), combined exercise, vision assessment and treatment, and environmental assessment and modification (OR, 0.30), combined exercise, and vision assessment and treatment (OR, 0.17), and combined clinic-level quality-improvement strategies, multifactorial assessment and treatment, calcium supplementation, and vitamin D supplementation (OR, 0.12) were significantly associated with reductions in injurious falls.

Meaning  The analysis identified combinations of interventions likely to be more effective than usual care for preventing injurious falls.

Reference: JAMA. 2017;318(17):1687-1699.

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Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis

Objective To assess whether weight loss interventions for adults with obesity affect all cause, cardiovascular, and cancer mortality, cardiovascular disease, cancer, and body weight.

Design Systematic review and meta-analysis of randomised controlled trials (RCTs) using random effects, estimating risk ratios, and mean differences. Heterogeneity investigated using Cochran’s Q and I2 statistics. Quality of evidence assessed by GRADE criteria.

Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, and full texts in our trials’ registry for data not evident in databases. Authors were contacted for unpublished data.

Eligibility criteria for selecting studies RCTs of dietary interventions targeting weight loss, with or without exercise advice or programmes, for adults with obesity and follow-up ≥1 year.

Results 54 RCTs with 30 206 participants were identified. All but one trial evaluated low fat, weight reducing diets. For the primary outcome, high quality evidence showed that weight loss interventions decrease all cause mortality (34 trials, 685 events; risk ratio 0.82, 95% confidence interval 0.71 to 0.95), with six fewer deaths per 1000 participants (95% confidence interval two to 10). For other primary outcomes moderate quality evidence showed an effect on cardiovascular mortality (eight trials, 134 events; risk ratio 0.93, 95% confidence interval 0.67 to 1.31), and very low quality evidence showed an effect on cancer mortality (eight trials, 34 events; risk ratio 0.58, 95% confidence interval 0.30 to 1.11). Twenty four trials (15 176 participants) reported high quality evidence on participants developing new cardiovascular events (1043 events; risk ratio 0.93, 95% confidence interval 0.83 to 1.04). Nineteen trials (6330 participants) provided very low quality evidence on participants developing new cancers (103 events; risk ratio 0.92, 95% confidence interval 0.63 to 1.36).

Conclusions Weight reducing diets, usually low in fat and saturated fat, with or without exercise advice or programmes, may reduce premature all cause mortality in adults with obesity.

Systematic review registration PROSPERO CRD42016033217.

Reference: BMJ 2017;359:j4849

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Objective To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat.

Design Systematic review and meta-analysis of randomised control trials.

Data sources Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews.

Study selection Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status.

Review methods Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach.

Results 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval −1.9 to −7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (−0.4 to −21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups.

Conclusion Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat.

Systematic review registration PROSPERO CRD42017067808.

Reference: BMJ 2017;358:j3887

Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials

Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy.

Design Systematic review and meta-analyses of relapse prevention trials.

Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016).

Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse.

Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool.

Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies).

Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients’ preferences.

Reference: BMJ 2017;358:j3927

Effect of diet and physical activity based interventions in pregnancy on gestational weight gain and pregnancy outcomes: meta-analysis of individual participant data from randomised trials

Objective To synthesise the evidence on the overall and differential effects of interventions based on diet and physical activity during pregnancy, primarily on gestational weight gain and maternal and offspring composite outcomes, according to women’s body mass index, age, parity, ethnicity, and pre-existing medical condition; and secondarily on individual complications.

Design Systematic review and meta-analysis of individual participant data (IPD).

Data sources Major electronic databases from inception to February 2017 without language restrictions.

Eligibility criteria for selecting studies Randomised trials on diet and physical activity based interventions in pregnancy.

Data synthesis Statistical models accounted for clustering of participants within trials and heterogeneity across trials leading to summary mean differences or odds ratios with 95% confidence intervals for the effects overall, and in subgroups (interactions).

Results IPD were obtained from 36 randomised trials (12 526 women). Less weight gain occurred in the intervention group than control group (mean difference −0.70 kg, 95% confidence interval −0.92 to −0.48 kg, I2=14.1%; 33 studies, 9320 women). Although summary effect estimates favoured the intervention, the reductions in maternal (odds ratio 0.90, 95% confidence interval 0.79 to 1.03, I2=26.7%; 24 studies, 8852 women) and offspring (0.94, 0.83 to 1.08, I2=0%; 18 studies, 7981 women) composite outcomes were not statistically significant. No evidence was found of differential intervention effects across subgroups, for either gestational weight gain or composite outcomes. There was strong evidence that interventions reduced the odds of caesarean section (0.91, 0.83 to 0.99, I2=0%; 32 studies, 11 410 women), but not for other individual complications in IPD meta-analysis. When IPD were supplemented with study level data from studies that did not provide IPD, the overall effect was similar, with stronger evidence of benefit for gestational diabetes (0.76, 0.65 to 0.89, I2=36.8%; 59 studies, 16 885 women).

Conclusion Diet and physical activity based interventions during pregnancy reduce gestational weight gain and lower the odds of caesarean section. There is no evidence that effects differ across subgroups of women.

Reference: BMJ 2017;358:j3119

Screening for Obesity and Intervention for Weight Management in Children and Adolescents

Importance  Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood.

Objective  To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force.

Data Sources  MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016.

Study Selection  English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings.

Data Extraction and Synthesis  Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin.

Main Outcomes and Measures  Weight or excess weight (eg, body mass index [BMI]; BMI zscore, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms.

Results  There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: −0.86 (95% CI, −1.44 to −0.29; 6 studies; I2 = 0%) for metformin and −0.50 to −0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: −6.4 mm Hg (95% CI, −8.6 to −4.2; 6 studies; I2 = 51%) for systolic blood pressure and −4.0 mm Hg (95% CI, −5.6 to −2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%.

Conclusions and Relevance  Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Reference: JAMA. 2017;317(23):2427-2444.

Association of Gestational Weight Gain With Maternal and Infant Outcomes

Question  What is the association between gestational weight gain above or below the Institute of Medicine guidelines and maternal and infant outcomes?

Findings  In this systematic review and meta-analysis of 1 309 136 pregnancies, gestational weight gain below recommendations (in 23% of women) was associated with higher risk of small for gestational age (odds ratio [OR], 1.53) and preterm birth (OR, 1.70) and lower risk of large for gestational age (OR, 0.59) and macrosomia (OR, 0.60). Gestational weight gain above recommendations (47%) was associated with lower risk of small for gestational age (OR, 0.66) and preterm birth (OR, 0.77) and higher risk of large for gestational age (OR, 1.85), macrosomia (OR, 1.95), and cesarean delivery (OR, 1.30).

Meaning  Gestational weight gain below or above the Institute of Medicine guidelines was associated with higher risk of some adverse maternal and infant outcomes.

Reference: JAMA. 2017;317(21):2207-2225.