Background

There are both theoretical and empirical reasons to believe that design and execution factors are associated with bias in controlled trials. Statistically significant moderator effects, such as the effect of trial quality on treatment effect sizes, are rarely detected in individual meta-analyses, and evidence from meta-epidemiological datasets is inconsistent. The reasons for the disconnect between theory and empirical observation are unclear. The study objective was to explore the power to detect study level moderator effects in meta-analyses.

Methods

We generated meta-analyses using Monte-Carlo simulations and investigated the effect of number of trials, trial sample size, moderator effect size, heterogeneity, and moderator distribution on power to detect moderator effects. The simulations provide a reference guide for investigators to estimate power when planning meta-regressions.

Results

The power to detect moderator effects in meta-analyses, for example, effects of study quality on effect sizes, is largely determined by the degree of residual heterogeneity present in the dataset (noise not explained by the moderator). Larger trial sample sizes increase power only when residual heterogeneity is low. A large number of trials or low residual heterogeneity are necessary to detect effects. When the proportion of the moderator is not equal (for example, 25% 'high quality', 75% 'low quality' trials), power of 80% was rarely achieved in investigated scenarios. Application to an empirical meta-epidemiological dataset with substantial heterogeneity (I(2) = 92%, τ(2) = 0.285) estimated >200 trials are needed for a power of 80% to show a statistically significant result, even for a substantial moderator effect (0.2), and the number of trials with the less common feature (for example, few 'high quality' studies) affects power extensively.

Conclusions

Although study characteristics, such as trial quality, may explain some proportion of heterogeneity across study results in meta-analyses, residual heterogeneity is a crucial factor in determining when associations between moderator variables and effect sizes can be statistically detected. Detecting moderator effects requires more powerful analyses than are employed in most published investigations; hence negative findings should not be considered evidence of a lack of effect, and investigations are not hypothesis-proving unless power calculations show sufficient ability to detect effects.

BACKGROUND: The problem of loneliness has garnered increased attention from policymakers, payors, and providers due to higher rates during the pandemic, particularly among seniors. Prior systematic reviews have in general not been able to reach conclusions about effectiveness of interventions. METHODS: Computerized databases were searched using broad terms such as loneliness or lonely or social isolation or social support from Jan 1, 2011 to June 23, 2021. We reference mined existing systematic reviews for additional and older studies. The Social Interventions Research & Evaluation Network database and Google were searched for gray literature on Feb 4, 2022. Eligible studies were RCTs and observational studies of interventions to reduce loneliness in community-living adults that used a validated loneliness scale; studies from low- or middle-income countries were excluded, and studies were excluded if restricted to populations where all persons had the same disease (such as loneliness in persons with dementia). RESULTS: A total of 5971 titles were reviewed and 60 studies were included in the analysis, 36 RCTs and 24 observational studies. Eleven RCTs and 5 observational studies provided moderate certainty evidence that group-based treatment was associated with reduced loneliness (standardized mean difference for RCTs =  - 0.27, 95% CI - 0.48, - 0.08). Five RCTs and 5 observational studies provided moderate certainty evidence that internet training was associated with reduced loneliness (standardized mean difference for RCTs =  - 0.22, 95% CI - 0.30, - 0.14). Low certainty evidence suggested that group exercises may be associated with very small reductions in loneliness. Evidence was insufficient to reach conclusions about group-based activities, individual in-person interactions, internet-delivered interventions, and telephone-delivered interventions. DISCUSSION: Low-to-moderate certainty evidence exists that group-based treatments, internet training, and possibly group exercises are associated with modest reductions in loneliness in community-living older adults. These findings can inform the design of supplemental benefits and the implementation of evidence-based interventions to address loneliness. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ( CRD42021272305 ).

BACKGROUND: Mobilization and manipulation therapies are widely used by patients with chronic nonspecific neck pain; however, questions remain around efficacy, dosing, and safety, as well as how these approaches compare to other therapies. OBJECTIVES: Based on published trials, to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic nonspecific neck pain. STUDY DESIGN: A systematic literature review and meta-analysis. METHODS: We identified studies published between January 2000 and September 2017, by searching multiple electronic databases, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation and/or mobilization therapies to sham, no treatment, each other, and other active therapies, or when combined as multimodal therapeutic approaches. We assessed risk of bias by using the Scottish Intercollegiate Guidelines Network criteria. When possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation was applied to determine the confidence in effect estimates. This project was funded by the National Center for Complementary and Integrative Health under award number U19AT007912 and ultimately used to inform an appropriateness panel. RESULTS: A total of 47 randomized trials (47 unique trials in 53 publications) were included in the systematic review. These studies were rated as having low risk of bias and included a total of 4,460 patients with nonspecific chronic neck pain who were being treated by a practitioner using various types of manipulation and/or mobilization interventions. A total of 37 trials were categorized as unimodal approaches and involved thrust or nonthrust compared with sham, no treatment, or other active comparators. Of these, only 6 trials with similar intervention styles, comparators, and outcome measures/timepoints were pooled for meta-analysis at 1, 3, and 6 months, showing a small effect in favor of thrust plus exercise compared to an exercise regimen alone for a reduction in pain and disability. Multimodal approaches appeared to be effective at reducing pain and improving function from the 10 studies evaluated. Health-related quality of life was seldom reported. Some 22/47 studies did not report or mention adverse events. Of the 25 that did, either no or minor events occurred. LIMITATIONS: The current evidence is heterogeneous, and sample sizes are generally small. CONCLUSIONS: Studies published since January 2000 provide low-moderate quality evidence that various types of manipulation and/or mobilization will reduce pain and improve function for chronic nonspecific neck pain compared to other interventions. It appears that multimodal approaches, in which multiple treatment approaches are integrated, might have the greatest potential impact. The studies comparing to no treatment or sham were mostly testing the effect of a single dose, which may or may not be helpful to inform practice. According to the published trials reviewed, manipulation and mobilization appear safe. However, given the low rate of serious adverse events, other types of studies with much larger sample sizes would be required to fully describe the safety of manipulation and/or mobilization for nonspecific chronic neck pain. KEY WORDS: Chronic neck pain, nonspecific, chiropractic, manipulation, mobilization, systematic review, meta-analysis, appropriateness.

Objective

Little evidence exists about effective and scalable methods for meaningful stakeholder engagement in research. We explored patient/caregiver experiences with a high-tech online engagement approach for patient-centered research prioritization, compared their experiences with those of professional stakeholders, and identified factors associated with favorable participant experiences.

Methods

We conducted 8 online modified-Delphi (OMD) panels. Panelists participated in 2 rating rounds with a statistical feedback/online discussion round in between. Panels focused on weight management/obesity, heart failure, and Kawasaki disease. We recruited a convenience sample of adults with any of the 3 conditions (or parents/guardians of Kawasaki disease patients), clinicians, and researchers. Measures included self-reported willingness to use OMD again, the panelists' study participation and online discussion experiences, the system's perceived ease of use, and active engagement metrics.

Results

Out of 349 panelists, 292 (84%) completed the study. Of those, 46% were patients, 36% were clinicians, and 19% were researchers. In multivariate models, patients were not significantly more actively engaged (Odds ratio (OR) = 1.69, 95% confidence interval (CI), 0.94-3.05) but had more favorable study participation (β = 0.49; P  ≤ .05) and online discussion (β = 0.18; P  ≤ .05) experiences and were more willing to use OMD again (β = 0.36; P  ≤ .05), compared to professional stakeholders. Positive perceptions of the OMD system's ease of use (β = 0.16; P  ≤ .05) and favorable study participation (β = 0.26; P  ≤ .05) and online discussion (β = 0.57; P  ≤ .05) experiences were also associated with increased willingness to use OMD in the future. Active engagement was not associated with online experience indices or willingness to use OMD again.

Conclusion

Online approaches to engaging large numbers of stakeholders are a promising and efficient adjunct to in-person meetings.

BACKGROUND: Obesity is a major threat to public health and traditional bariatric surgery continues to have low utilization. Endoscopic treatments for obesity have emerged that offer less risk, but questions remain regarding efficacy, durability, and safety. We compared the efficacy of endoscopic bariatric procedures as compared to other existing treatments. METHODS: A literature search of Embase, Cochrane Central, and Pubmed was conducted from January 1, 2014 to December 7, 2021, including endoscopic bariatric therapies that were FDA or CE approved at the time of search to non-endoscopic treatments. Thirty-seven studies involving 15,639 patients were included. Primary outcomes included % total body weight loss (%TBWL), % excess body weight loss (%EBWL), and adverse events. Secondary outcomes included quality of life data and differences in hemoglobin A1C levels. Strength of clinical trial and observational data were graded according to the Cochrane methods. RESULTS: Intragastric balloons achieved greater %TBWL with a range of 7.6-14.1% compared to 3.3-6.7% with lifestyle modification at 6 months, and 7.5-14.0% compared to 3.1-7.9%, respectively, at 12 months. When endoscopic sleeve gastroplasty (ESG) was compared to laparoscopic sleeve gastrectomy (LSG), ESG had less %TBWL at 4.7-14.4% compared to 18.8-26.5% after LSG at 6 months, and 4.5-18.6% as compared to 28.4-29.3%, respectively, at 12 months. For the AspireAssist, there was greater %TBWL with aspiration therapy compared to lifestyle modification at 12 months, 12.1-18.3% TBWL versus 3.5-5.9% TBWL, respectively. All endoscopic interventions had higher adverse events rates compared to lifestyle modification. CONCLUSION: This review is the first to evaluate various endoscopic bariatric therapies using only RCTs and observational studies for evaluation of weight loss compared with conservative management, lifestyle modification, and bariatric surgery. Endoscopic therapies result in greater weight loss compared to lifestyle modification, but not as much as bariatric surgery. Endoscopic therapies may be beneficial as an alternative to bariatric surgery.

Study objectives

To characterize the nature and impact of sleep disturbances on quality of life (QOL) in women with interstitial cystitis/bladder pain syndrome (IC/BPS).

Methods

Participants were 3,397 women from a telephone probability survey who met IC/BPS symptom criteria. Sleep quality, duration, and IC/BPS nocturnal symptoms (i.e., trouble sleeping due to bladder pain, urgency, or needing to use the bathroom), general QOL (mental and physical health and sexual functioning), and IC/BPS QOL impairment were assessed via self-report during telephone interview.

Results

Over half of the sample reported poor sleep quality, sleep duration ≤ 6 hours, or trouble sleeping due to IC/BPS symptoms. After covariate adjustment, short sleep duration was significantly associated with greater IC/BPS QOL impairment (β = -0.04; p < 0.001) and poorer self-reported physical health (β = 1.86; p < 0.001). Poor sleep quality was significantly associated with greater IC/BPS QOL impairment (β = 0.06; p < 0.001), poorer self-reported physical health (β = -2.86; p < 0.001), and greater sexual dysfunction (β = -0.04; p < 0.05). IC/BPS nocturnal symptoms were significantly associated with greater IC/BPS impairment (β = 0.14; p < 0.001), poorer physical health (β = -2.76; p < 0.001) and mental health (β = 0.52; p < 0.01), and greater sexual dysfunction (β = -0.10; p < 0.001), after covariate adjustment. After further adjustment for IC/BPS nocturnal symptoms, we found that poor sleep quality and short sleep duration were independent correlates of poor self-reported physical health.

Conclusions

Poor sleep quality and short sleep duration, as well as disorder-specific sleep disturbances, are highly prevalent in women with IC/BPS and are associated with poorer disease-specific and general QOL.

Background context

Mobilization and manipulation therapies are widely used to benefit patients with chronic low back pain. However, questions remain about their efficacy, dosing, safety, and how these approaches compare with other therapies.

Purpose

The present study aims to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic low back pain.

Study design/setting

This is a systematic literature review and meta-analysis.

Outcome measures

The present study measures self-reported pain, function, health-related quality of life, and adverse events.

Methods

We identified studies by searching multiple electronic databases from January 2000 to March 2017, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation or mobilization therapies with sham, no treatment, other active therapies, and multimodal therapeutic approaches. We assessed risk of bias using Scottish Intercollegiate Guidelines Network criteria. Where possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was applied to determine the confidence in effect estimates. This project is funded by the National Center for Complementary and Integrative Health under Award Number U19AT007912.

Results

Fifty-one trials were included in the systematic review. Nine trials (1,176 patients) provided sufficient data and were judged similar enough to be pooled for meta-analysis. The standardized mean difference for a reduction of pain was SMD=-0.28, 95% confidence interval (CI) -0.47 to -0.09, p=.004; I²=57% after treatment; within seven trials (923 patients), the reduction in disability was SMD=-0.33, 95% CI -0.63 to -0.03, p=.03; I²=78% for manipulation or mobilization compared with other active therapies. Subgroup analyses showed that manipulation significantly reduced pain and disability, compared with other active comparators including exercise and physical therapy (SMD=-0.43, 95% CI -0.86 to 0.00; p=.05, I²=79%; SMD=-0.86, 95% CI -1.27 to -0.45; p<.0001, I²=46%). Mobilization interventions, compared with other active comparators including exercise regimens, significantly reduced pain (SMD=-0.20, 95% CI -0.35 to -0.04; p=.01; I²=0%) but not disability (SMD=-0.10, 95% CI -0.28 to 0.07; p=.25; I²=21%). Studies comparing manipulation or mobilization with sham or no treatment were too few or too heterogeneous to allow for pooling as were studies examining relationships between dose and outcomes. Few studies assessed health-related quality of life. Twenty-six of 51 trials were multimodal studies and narratively described.

Conclusion

There is moderate-quality evidence that manipulation and mobilization are likely to reduce pain and improve function for patients with chronic low back pain; manipulation appears to produce a larger effect than mobilization. Both therapies appear safe. Multimodal programs may be a promising option.

Background

The prevalence of knee osteoarthritis (OA)/degenerative joint disease (DJD) is increasing in the USA. Systematic reviews of treatment efficacy and adverse events (AEs) of hyaluronic acid (HA) injections report conflicting evidence about the balance of benefits and harms. We review evidence on efficacy and AEs of intraarticular viscosupplementation with HA in older individuals with knee osteoarthritis and account for differences in these conclusions from another systematic review.

Methods

We searched PubMed and eight other databases and gray literature sources from 1990 to December 12, 2014. Double-blind placebo-controlled randomized controlled trials (RCTs) reporting functional outcomes or quality-of-life; RCTs and observational studies on delay/avoidance of arthroplasty; RCTs, case reports, and large cohort studies and case series assessing safety; and systematic reviews reporting on knee pain were considered for inclusion. A standardized, pre-defined protocol was applied by two independent reviewers to screen titles and abstracts, review full text, and extract details on study design, interventions, outcomes, and quality. We compared our results with those of a prior systematic review and found them to be discrepant; our analysis of why this discrepancy occurred is the focus of this manuscript.

Results

Eighteen RCTs reported functional outcomes: pooled analysis of ten placebo-controlled, blinded trials showed a standardized mean difference of -0.23 (95 % confidence interval (CI) -0.45 to -0.01) favoring HA at 6 months. Studies reported few serious adverse events (SAEs) and no significant differences in non-serious adverse events (NSAEs) (relative risk (RR) [95 % CI] 1.03 [0.93-1.15] or SAEs (RR [95 % CI] 1.39 [0.78-2.47]). A recent prior systematic review reported similar functional outcomes, but significant SAE risk. Differences in SAE inclusion and synthesis accounted for the disparate conclusions.

Conclusions

Trials show a small but significant effect of HA on function on which recent systematic reviews agree, but lack of AE synthesis standardization leads to opposite conclusions about the balance of benefits and harms. A limitation of the re-analysis of the prior systematic review is that it required imputation of missing data.

Background

The purpose of this review is to study the effect of school-based interventions on smoking prevention for girls.

Methods

We performed a systematic review of articles published since 1992 on school-based tobacco-control interventions in controlled trials for smoking prevention among children. We searched the databases of PubMed, Embase, Web of Science, The Cochrane Databases, CINAHL, Social Science Abstracts, and PsycInfo. Two reviewers independently assessed trials for inclusion and quality and extracted data. A pooled random-effects estimate was estimated of the overall relative risk.

Results

Thirty-seven trials were included, of which 16 trials with 24,210 girls were included in the pooled analysis. The overall pooled effect was a relative risk (RR) of 0.96 (95 % confidence interval (CI) 0.86-1.08; I (2)=75 %). One study in which a school-based intervention was combined with a mass media intervention showed more promising results compared to only school-based prevention, and four studies with girl-specific interventions, that could not be included in the pooled analysis, reported statistically significant benefits for attitudes and intentions about smoking and quit rates.

Conclusions

There was no evidence that school-based smoking prevention programs have a significant effect on preventing adolescent girls from smoking. Combining school-based programs with mass media interventions, and developing girl-specific interventions, deserve additional study as potentially more effective interventions compared to school-based-only intervention programs.

Systematic review registration

PROSPERO CRD42012002322.

Objectives

To systematically document the implementation, components, comparators, adherence, and effectiveness of published fall prevention approaches in U.S. acute care hospitals.

Design

Systematic review. Studies were identified through existing reviews, searching five electronic databases, screening reference lists, and contacting topic experts for studies published through August 2011.

Setting

U.S. acute care hospitals.

Participants

Studies reporting in-hospital falls for intervention groups and concurrent (e.g., controlled trials) or historic comparators (e.g., before-after studies).

Intervention

Fall prevention interventions.

Measurements

Incidence rate ratios (IRR, ratio of fall rate postintervention or treatment group to the fall rate preintervention or control group) and ratings of study details.

Results

Fifty-nine studies met inclusion criteria. Implementation strategies were sparsely documented (17% not at all) and included staff education, establishing committees, seeking leadership support, and occasionally continuous quality improvement techniques. Most interventions (81%) included multiple components (e.g., risk assessments (often not validated), visual risk alerts, patient education, care rounds, bed-exit alarms, and postfall evaluations). Fifty-four percent did not report on fall prevention measures applied in the comparison group, and 39% neither reported fidelity data nor described adherence strategies such as regular audits and feedback to ensure completion of care processes. Only 45% of concurrent and 15% of historic control studies reported sufficient data to compare fall rates. The pooled postintervention incidence rate ratio (IRR) was 0.77 (95% confidence interval = 0.52-1.12, P = .17; eight studies; I(2) : 94%). Meta-regressions showed no systematic association between implementation intensity, intervention complexity, comparator information, or adherence levels and IRR.

Conclusion

Promising approaches exist, but better reporting of outcomes, implementation, adherence, intervention components, and comparison group information is necessary to establish evidence on how hospitals can successfully prevent falls.