Economic evaluation of adult rehabilitation: a systematic review and meta-analysis of randomized controlled trials in a variety of settings

Objectives:
To report if there is a difference in costs from a societal perspective between adults receiving rehabilitation in an inpatient rehabilitation setting versus an alternative setting. If there are cost differences, to report whether opting for the least expensive program setting adversely affects patient outcomes.

Data Sources:
Electronic databases from the earliest possible date until May 2011. All languages were included.

Study Selection
Multiple reviewers identified randomized controlled trials with a full economic evaluation that compared adult inpatient rehabilitation with an alternative. There were 29 included trials with 6746 participants.

Data Extraction
Multiple observers extracted data independently. Trial appraisal included a risk of bias assessment and a checklist to report the strength of the economic evaluation.

Data Synthesis:
Results were synthesized using standardized mean differences (SMDs) and meta-analyses for the primary outcome of cost. The Grading of Recommendations Assessment, Development, and Evaluation was applied to assess for risk of bias across studies for meta-analyses. There was high-quality evidence that cost was significantly reduced for rehabilitation in the home versus inpatient rehabilitation in a meta-analysis of 732 patients poststroke (pooled SMD [δ]=−.28; 95% confidence interval [CI], −.47 to −.09), without compromise to patient outcomes. Results of individual trials in other patient groups (orthopedic, rheumatoid arthritis, and geriatric) receiving rehabilitation in the home or community were generally consistent with the meta-analysis. There was moderate quality evidence that cost was significantly reduced for inpatient rehabilitation (stroke unit) versus general acute care in a meta-analysis of 463 patients poststroke (δ=.31; 95% CI, .15–.48), with improvement to patient outcomes. These results were not replicated in 2 individual trials with a geriatric and a mixed cohort, where costs did not differ between general acute care and inpatient rehabilitation. Three of the 4 individual trials, inclusive of a stroke or orthopedic population, reported less cost for an intensive inpatient rehabilitation program compared with usual inpatient rehabilitation. Sensitivity analysis included a health service perspective and varied inflation rates with no change to the significant findings of the meta-analyses.

Conclusions:
Based on this systematic review and meta-analyses, a single rehabilitation service may not provide health economic benefits for all patient groups and situations. For some patients, inpatient rehabilitation may be the most cost-effective method of providing rehabilitation; yet, for other patients, rehabilitation in the home or community may be the most cost-effective model of care. To achieve cost-effective outcomes, the ideal combination of rehabilitation services and patient inclusion criteria, as well as further data for nonstroke populations, warrants further research.

Family-based interventions for reducing sedentary time in youth: a systematic review of randomized controlled trials

Family involvement in interventions to reduce sedentary time may help foster appropriate long-term screen-based habits in children. This review systematically synthesized evidence from randomized controlled trials of interventions with a family component that targeted reduction of sedentary time, including TV viewing, video games and computer use, in children. MEDLINE, PubMed, PsycInfo, CINAHL and Embase were searched from inception through March 2012. Seventeen articles were considered eligible and included in the review. Studies were judged to be at low-to-moderate risk of bias. Despite inconsistent study results, level of parental involvement, rather than the setting itself, appeared an important determinant of intervention success. Studies including a parental component of medium-to-high intensity were consistently associated with statistically significant changes in sedentary behaviours. Participant age was also identified as a determinant of intervention outcomes; all three studies conducted in pre-school children demonstrated significant decreases in sedentary time. Finally, TV exposure appeared to be related to changes in energy intake rather than physical activity. Future studies should assess the effects of greater parental involvement and child age on success of sedentary behaviour interventions. More research is required to better understand the relationship between screen time and health behaviours, particularly energy intake.

Small-scale randomized controlled trials need more powerful methods of mediational analysis than the Baron-Kenny method

Objective: To devise more-effective physical activity interventions, the mediating mechanisms yielding behavioral change need to be identified. The Baron–Kenny method is most commonly used, but has low statistical power and may not identify mechanisms of behavioral change in small-to-medium size studies. More powerful statistical tests are available.
Study Design and Setting: Inactive adults (N = 52) were randomized to either a print or a print-plus-telephone intervention. Walking and exercise-related social support were assessed at baseline, after the intervention, and 4 weeks later. The Baron–Kenny and three alternative methods of mediational analysis (Freedman–Schatzkin; MacKinnon et al.; bootstrap method) were used to examine the effects of social support on initial behavior change and maintenance. Results: A significant mediational effect of social support on initial behavior change was indicated by the MacKinnon et al., bootstrap, and, marginally, Freedman–Schatzkin methods, but not by the Baron–Kenny method. No significant mediational effect of social support on maintenance of walking was found. Conclusions:  Methodologically rigorous intervention studies to identify mediators of change in physical activity are costly and labor ntensive, and may not be feasible with large samples. The use of statistically powerful tests of mediational effects in small-scale studies can inform the development of more effective interventions.

The effect of tai chi on psychosocial well-being : a systematic review of randomized controlled trials

Objective : This systematic review aimed to critically appraise published clinical trials designed to assess the effect of Tai Chi on psychosocial well-being.

Data Sources : Databases searched included MEDLINE, CINAHL, EMBASE, HEALT, PsycINFO, CISCOM, the Cochrane Central Register of Controlled Trials of the Cochrane Library, and dissertations and conference proceedings from inception to August 2008.

Review Methods : Methodological quality was assessed using a modified Jadad scale. A total of 15 studies met the inclusion criteria (i.e. English publications of randomized controlled trials with Tai Chi as an intervention and psychological well-being as an outcome measure), of which eight were high quality trials. The psychosocial outcomes measured included anxiety (eight studies), depression (eight studies), mood (four studies), stress (two studies), general mental health three studies), anger, positive and negative effect, self-esteem, life satisfaction, social interaction and self-rated health (one study each).

Results : Tai Chi intervention was found to have a significant effect in 13 studies, especially in the management of depression and anxiety. Although the results seemed to suggest Tai Chi is effective, they should be interpreted cautiously as the quality of the trials varied substantially. Furthermore, significant findings were shown in only six high quality studies. Moreover, significant between group differences after Tai Chi intervention was demonstrated in only one high quality study (the other three significant results were observed in non-high quality studies). Two high quality studies in fact found no significant Tai Chi effects.

Conclusion : It is still premature to make any conclusive remarks on the effect of Tai Chi on psychosocial well-being.

Oiling the brain : a review of randomized controlled trials of omega-3 fatty acids in psychopathology across the lifespan

Around one in four people suffer from mental illness at some stage in their lifetime. There is increasing awareness of the importance of nutrition, particularly omega-3 polyunsaturated fatty acids (n-3 PUFA), for optimal brain development and function. Hence in recent decades, researchers have explored effects of n-3 PUFA on mental health problems over the lifespan, from developmental disorders in childhood, to depression, aggression, and schizophrenia in adulthood, and cognitive decline, dementia and Alzheimer’s disease in late adulthood. This review provides an updated overview of the published and the registered clinical trials that investigate effects of n-3 PUFA supplementation on mental health and behavior, highlighting methodological differences and issues.

Multivitamin-multimineral supplementation and mortality: a meta-analysis of randomized controlled trials

BACKGROUND: Multivitamins are the most commonly used supplement in the developed world. Recent epidemiologic findings suggest that multivitamin use increases the risk of mortality. OBJECTIVE: We aimed to determine whether multivitamin-multimineral treatment, used for primary or secondary prevention, increases the risk of mortality in independently living adults. DESIGN: We performed a meta-analysis of randomized controlled trials. Multiple electronic databases were systematically searched from March to October 2012. Randomized controlled primary or secondary prevention trials were considered for inclusion. Eligible trials investigated daily multivitamin-multimineral supplementation for ≥1 y. Cohorts described as institutionalized or as having terminal illness (tertiary prevention) were excluded. The number of deaths and the sample size of each study arm were extracted independently by 2 researchers. Twenty-one articles were included in the analysis, which generated a total pooled sample of 91,074 people and 8794 deaths. These trials were pooled in a meta-analysis, and the outcomes were expressed as RRs and 95% CIs. RESULTS: The average age of the pooled sample was 62 y, and the average duration of supplementation was 43 mo. Across all studies, no effect of multivitamin-multimineral treatment on all-cause mortality (RR: 0.98; 95% CI: 0.94, 1.02) was observed. There was a trend for a reduced risk of all-cause mortality across primary prevention trials (RR: 0.94; 95% CI: 0.89, 1.00). Multivitamin-multimineral treatment had no effect on mortality due to vascular causes (RR: 1.01; 95% CI: 0.93, 1.09) or cancer (RR: 0.96; 95% CI: 0.88, 1.04). No statistical evidence of heterogeneity or publication bias was observed. CONCLUSION: Multivitamin-multimineral treatment has no effect on mortality risk.

Adding a new anticoagulant or antiplatelet agent for patient receiving aspirin after an acute coronary syndrome? - Results from a pairwise and network meta-analysis of randomized-controlled trials

 Objectives: To synthesize the efficacy and safety outcomes from randomized-controlled trials (RCTs) regarding new oral anticoagulant, protease-activated receptor-1 (PAR-1) antagonist, and warfarin adjunctive to aspirin for patients after acute coronary syndrome (ACS) via pair-wise and network meta-analyses.
Methods: A comprehensive literature search was performed in Embase, Medline, Cochrane Library Web of Knowledge, and Scopus. The pair-wise meta-analysis was undertaken respectively to each agent/treatment category via Revmen 5.1. In order to estimate the relative efficacy of each agent/treatment category whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in WinBUGS using both fixed- and random-effects model. Covariate analysis was performed to explore the effects of length of follow-up and age of subject on the final results.
Results: In total, 23 RCTs were included in the meta-analysis. As shown by the results (OR,95%CI) for the pair-wise meta-analysis, new oral anticoagulants (0.85, [0.78, 0.93] and 3.04, [2.21, 4.19]), PAR-1 antagonists (0.80, [0.52, 1.22] and 1.55, [1.25, 1.93]) and warfarin (0.87, [0.74, 1.02] and 1.77, [1.46, 2.14]) might be able to provide better outcome in the incidences of major adverse events (MAE) but with higher bleeding risk comparing to aspirin treatment alone. Based on the model fit assessment, the random-effects model was adopted. The network meta-analysis (treatment effect comparing to aspirin lone) identified ximelagatran (-0.3044, [-0.8601, 0.2502]), dabigatran (-0.2144, [-0.8666, 0.4525]), rivoroxaban (-0.2179, [-0.5986, 0.1628]) and vorapaxar (-0.2272, [-0.81, 0.1664]) produced better improvements in MAE incidences whereas vorapaxar (0.3764, [-0.4444, 1.124]), warfarin (0.663, [0.3375, 1.037]), ximelagatran (0.7509, [-0.4164, 2.002]) and apixaban (0.8594, [-0.0049, 1.7]) produced less major bleeding events. The indirect comparisons among drug category (difference in incidence comparing to aspirin lone) showed new oral anticoagulants (-0.1974, [-0.284, -0.111]) and PAR-1 antagonists (-0.1239, [-0.215, -0.033]) to besuperior to warfarin (-0.1004, [-0.166, -0.035]) in the occurrences of MAE whereas PAR-1 antagonists (0.4292, [0.2123, 0.6476]) afforded better outcomes in major bleeding events against warfarin (0.5742, [0.3889, 0.7619]) and new oral anticoagulants (1.169, [0.8667, 1.485]).
Conclusion: Based on the study results, we cannot recommend the routine administration of new oral anticoagulant as add-on treatment for patients after ACS. However, for ACS patients comorbid with atrial fibrillation, new oral anticoagulant might be superior to warfarin in both efficacy and safety outcomes.

Efficacy and safety of thrombin-receptor antagonist (atopaxar and vorapaxar) in patients with acute coronary syndrome or coronary artery disease-a meta-analysis of randomized controlled trials

Background: Meta-analysis for the efficacy and safety data of thrombin-receptor antagonist (TRA) based on patients with acute coronary syndrome (ACS) or coronary artery disease (CAD) and indirect comparisons between TRAs were not available. Objectives: We intended to synthesize the primary end points based on different patient populations (ACS or CAD) as well as perform indirect comparison between two newly invented antiplatelet agents atopaxar and vorapaxar. Methods: A literature search was performed in MEDLINE, Embase, and Cochrane Library. Incidences of major adverse cardiovascular events (MACEs) and bleeding events according to thrombolysis in myocardial infarction were selected as primary outcomes, whereas adverse effects were considered as secondary outcomes. Corresponding results were synthesized using Revman 5.1 according to ACS or CAD cohorts. Results: Among the seven included randomized controlled trials, the efficacy end points in the TRA treatment group were favorable compared with placebo. Specifically, the odds ratio (OR) of MACEs was 0.80 (95% confidence interval [CI] 0.52-1.22) for patients with ACS and 0.74 (95% CI 0.53-1.05) for the cohort with CAD. The events of bleeding were unanimously superior in the placebo arm for both cohorts. The indirect comparison showed a superior trend in favor of atopaxar over vorapaxar in occurrences of MACEs (OR 0.93; 95% CI 0.38-1.32), myocardial infarction (OR 0.52; 95% CI 0.13-0.95), and cardiovascular death (OR 0.82; 95% CI 0.12-4.24) and caused less incidence of bleeding. Conclusions: Besides being more effective than placebo in improving the incidence of MACEs but with a higher risk of bleeding, TRAs may exert different effects in patients with ACS and CAD. Indirect comparisons also suggested that atopaxar might be better than vorapaxar in lowering the incidence of MACEs, myocardial infarction, and cardiovascular death and at the same time with lower risks of bleeding.

mHealth technologies to influence physical activity and sedentary behaviors: behavior change techniques, systematic review and meta-analysis of randomized controlled trials

BACKGROUND: mHealth programs offer potential for practical and cost-effective delivery of interventions capable of reaching many individuals.

PURPOSE: To (1) compare the effectiveness of mHealth interventions to promote physical activity (PA) and reduce sedentary behavior (SB) in free-living young people and adults with a comparator exposed to usual care/minimal intervention; (2) determine whether, and to what extent, such interventions affect PA and SB levels and (3) use the taxonomy of behavior change techniques (BCTs) to describe intervention characteristics.

METHODS: A systematic review and meta-analysis following PRISMA guidelines was undertaken to identify randomized controlled trials (RCTs) comparing mHealth interventions with usual or minimal care among individuals free from conditions that could limit PA. Total PA, moderate-to-vigorous intensity physical activity (MVPA), walking and SB outcomes were extracted. Intervention content was independently coded following the 93-item taxonomy of BCTs.

RESULTS: Twenty-one RCTs (1701 participants-700 with objectively measured PA) met eligibility criteria. SB decreased more following mHealth interventions than after usual care (standardised mean difference (SMD) -0.26, 95 % confidence interval (CI) -0.53 to -0.00). Summary effects across studies were small to moderate and non-significant for total PA (SMD 0.14, 95 % CI -0.12 to 0.41); MVPA (SMD 0.37, 95 % CI -0.03 to 0.77); and walking (SMD 0.14, 95 % CI -0.01 to 0.29). BCTs were employed more frequently in intervention (mean = 6.9, range 2 to 12) than in comparator conditions (mean = 3.1, range 0 to 10). Of all BCTs, only 31 were employed in intervention conditions.

CONCLUSIONS: Current mHealth interventions have small effects on PA/SB. Technological advancements will enable more comprehensive, interactive and responsive intervention delivery. Future mHealth PA studies should ensure that all the active ingredients of the intervention are reported in sufficient detail.

Zinc for treating of children and adolescents with attention-deficit hyperactivity disorder : a systematic review of randomized controlled clinical trials

This study systematically reviews the randomized clinical trials examining the effect of zinc on attention-deficit hyperactivity disorder (ADHD), searching the PubMed/Medline and Scholar Google databases. All randomized controlled trials that examined zinc as the intervention, and ADHD as the primary outcome were included. Only three randomized controlled trials, one which included a community sample and two that included clinical samples, met inclusion criteria. The only trial that was well controlled and randomized according to the baseline zinc level showed that using zinc, either alone or in combination with stimulants, did not improve ADHD. Considering the lack of clear evidence for the effect of zinc on ADHD and the possible effect of zinc on the nervous system, more clinical studies are needed to prove or disprove the effect of zinc as a monotherapy or adjuvant therapy.

Statins for the treatment of depression: a meta-analysis of randomized, double-blind, placebo-controlled trials

BACKGROUND: In epidemiological studies, statins appear to benefit mood, and there are now some randomized controlled trials examining the efficacy of statins. However, the role of statins in depression remains uncertain. Thus the aim of this paper was to assess the effect of statins on depressive symptoms by performing a meta-analysis of all double-blind, randomized, placebo controlled clinical trials (RCT) conducted in subjects with depression. METHODS: A systematic search was executed using PubMed and ClinicalTrials.gov in November 30th, 2015 for all double-blind, RCT of statins versus placebo in persons with depressive symptoms. Sixty-seven potential articles were identified through search of electronic databases, of those three met inclusion criteria and were included in the meta-analysis. The outcome measure was change in Hamilton Depression Rating Scale (HDRS) scores associated with statin use. A meta-analysis was conducted and standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated. GRADE was used to assess study quality. RESULTS: The three articles included provided data on 165 participants with moderate to severe depression. Of these, 82 were randomized to statins as an adjuvant therapy to antidepressant treatment (i.e., citalopram or fluoxetine) and 83 to the placebo arm. All studies were double-blind RCTs, with a follow-up of 6-12 weeks. The statin agents evaluated were lovastatin, atorvastatin, and simvastatin. When compared to placebo, statins, as add-on to treatment as usual, largely improved depressive symptoms as assessed by the HDRS (SMD=-0.73, 95% IC -1.04 to -0.42, p<0.001, 3 between-group comparisons, n=165). No serious adverse effects were reported. CONCLUSIONS: Our results suggest that adjunctive treatment with statins could be useful for the treatment of depressive symptoms. Additional double-blind, randomised, placebo-controlled trials are necessary to settle the matter.

Feasibility of conducting a palliative care randomized controlled trial in children with advanced cancer: assessment of the PediQUEST study

Pediatric palliative care randomized controlled trials (PPC-RCTs) are uncommon.