Succinylcholine or rocuronium? A meta‐analysis of the effects on intubation conditions

This meta-analysis was undertaken to compare the effects of succinylcholine (SCH) and rocuronium (RCR) on endotracheal intubation (ETI) conditions. Eligible randomised controlled trials (RCTs) were identified via medline and a manual search of references. The frequencies of excellent and unacceptable ETI conditions in subjects receiving SCH 1.0-1.5 mg/kg and RCR 0.6-1.2 mg/kg were determined using standard statistical methods. Inclusion criteria were met by 16 RCTs, representing 1362 subjects. SCH was associated with a 17.7% increase (95% CI = 13-22) in the frequency of excellent ETI conditions and a 5.1% decrease (95% CI = -7.3 to -2.9) in the frequency of unacceptable ETI conditions, when compared with RCR. In the subgroup undergoing true rapid sequence intubation, SCH was associated with a 19.1% increase (95% CI = 13.7-24.5) in the frequency of excellent ETI conditions. SCH appears to be superior to RCR in creating excellent ETI conditions and avoiding unacceptable ETI conditions.     

Cell‐assisted lipotransfer: Friend or foe in fat grafting? Systematic review and meta‐analysis

Autologous fat grafting is a common procedure for soft‐tissue reconstruction but is associated with a graft resorption rate ranging from 20% to 80%. To improve the fat graft survival rate, a new technique, called cell‐assisted lipotransfer (CAL), was developed. With CAL, fat is injected along with adipose‐derived stromal cells that are assumed to improve fat survival rate. We conducted an evidence‐based meta‐analysis to evaluate the efficacy and safety of CAL as compared with conventional autologous fat grafting (non‐CAL). The databases MEDLINE (via PubMed), Cochrane Library, EBSCO, Web of Science, and EMBASE were searched for reports of clinical trials, case series, and cohorts available from 2008 to 2016. We conducted a meta‐analysis of the efficacy of CAL with data analysis concerning fat survival rate. The incidence of complications and the need for multiple procedures were evaluated to determine the safety of CAL. We identified 25 studies (696 patients) that were included in the systematic review; 16 studies were included in the meta‐analysis to evaluate the efficacy of CAL. The fat survival rate was significantly higher with CAL than non‐CAL (64% vs. 44%, p < .0001) independent of injection site (breast and face). This benefit of CAL was significant for only injection volumes <100 ml (p = .03). The two groups did not differ in frequency of multiple procedures after fat grafting, but the incidence of complications was greater with CAL than non‐CAL (8.4% vs. 1.5%, p = .0019). The CAL method is associated with better fat survival rate than with conventional fat grafting but only for small volumes of fat grafting (<100 ml). Nonetheless, the new technique is associated with more complications and did not reduce the number of surgical procedures needed after the first fat grafting. More prospective studies are required to draw clinical conclusions and to demonstrate the real benefit of CAL as compared with common autologous fat grafting.     

Is mental illness associated with placement into solitary confinement in correctional settings? A systematic review and meta‐analysis

The aim of this meta‐analysis was to examine the association between any mental health problem and the risk of being placed into solitary confinement in correctional settings. PubMed, PsycINFO, Web of Science and Google Scholar were searched from each database’s inception date to November 2019. All publications assessing both mental health problems and placement into solitary confinement in a sample of adult inmates in correctional settings were included. The meta‐analysis was performed using random‐effects models. Heterogeneity among study point estimates was assessed with Q statistics and quantified with I² index. Publication bias was assessed with funnel plots. Guidelines from Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) were followed throughout. After screening 2777 potential studies, 11 studies were included amounting to a total of 163 414 inmates. Included studies comprised of a mix of mental disorders rather than a specific diagnosis per se. The odds ratio (OR) from the pooled studies was 1.62 (confidence interval (CI) = 1.21–2.15). The observed relationship remained unchanged regardless of the removal of outliers (OR = 1.63, CI = 1.47–1.80) and regardless of the adjustment of confounders (OR = 1.58, CI = 1.32–1.88). The present study shows a moderate association between any mental health problem and placement into solitary confinement within a considerable sample of inmates. As more individuals suffering from mental illness enter the correctional system, it is essential that correction officials create new safe interventions to manage these inmates and offer them proper mental health care to limit the use of solitary confinement, which may have deleterious effects.     

Can B‐domain deletion alter the immunogenicity of recombinant factor VIII? A meta‐analysis of prospective clinical studies

See also Iorio A, Marcucci M, Makris M. Concentrate‐related inhibitor risk: is a difference always real? This issue, pp 2176–9. Summary. Background: As a result of the infrequency of inhibitors in previously treated patients (PTPs) with hemophilia A and the small size of available clinical studies, the immunogenicity of factor (F)VIII products has been difficult to assess. Objectives: A meta‐analysis of prospective clinical studies was conducted to test the hypothesis that de novo inhibitor incidence differs between PTPs receiving full‐length recombinant FVIII (FL‐rFVIII) and B‐domain deleted recombinant FVIII (BDD‐rFVIII). Methods: Prospective studies with data on inhibitors in PTPs receiving FL‐rFVIII or BDD‐rFVIII were sought using systematic methods including bibliographic database searches. Data were secured from published study reports and inquiries to investigators. Between‐group differences in inhibitor incidence rates were evaluated using mixed effects Cox regression. Results: Twenty‐nine studies with 3012 total PTPs were included. Patients were at risk of de novo inhibitor development for a median of 79 exposure days. A total of 35 de novo inhibitors were observed. The cumulative hazard for all de novo inhibitors was 1.25% with a 95% confidence interval (CI) of 0.63–1.88%. The corresponding rate for high‐titer de novo inhibitors [> 5 Bethesda units (BU)] was 0.29% (CI, 0.01–0.57%). Exposure to BDD‐rFVIII was associated with an increased risk of all de novo inhibitors (hazard ratio, 7.26; CI, 2.12–24.9; P = 0.0016) and of high‐titer de novo inhibitors (hazard ratio, 10.8; CI, 2.17–53.7; P = 0.0037), compared with FL‐rFVIII. Conclusions: This meta‐analysis of prospective clinical studies suggests that recombinant FVIII products may differ in immunogenicity.     

Do selective COX‐2 inhibitors increase the risk of cerebrovascular events? A meta‐analysis of randomized controlled trials

ABSTRACT OBJECTIVES: To evaluate the risk of cerebrovascular events (CVEs) associated with selective cyclooxygenase-2 inhibitors (coxibs). METHOD: Systematic review and meta-analysis of randomized controlled trials (RCTs). A fixed-effect model was used to estimate the odds ratios (ORs) for risk of CVE associated with coxibs compared against placebo, non-selective non-steroidal anti-inflammatory drugs (NSAIDs) and other coxibs. RESULTS: Forty trials (88 116 patients) were included in the meta-analysis. The overall pooled OR for CVE for any coxib against placebo was 1.03 (95% CI: 0.71, 1.50). Comparing individual coxibs against placebo, we found that celecoxib, rofecoxib, etoricoxib and lumiracoxib were associated with higher CVE risks and valdecoxib was associated with a lower CVE risk, although there were no significant differences detected. There was also no significant difference in risk of CVE when comparing coxibs against any non-selective NSAIDs; the corresponding pooled OR was 0.86 (95% CI: 0.64, 1.16). CONCLUSION: On the basis of a detailed analysis of available RCTs, there does not appear to be any significant difference in risk of CVEs associated with coxibs when compared against placebo or non-selective NSAIDs. It is likely that the increased risk of thrombotic vascular events associated with coxibs is largely attributable to an increased risk of myocardial infarction, rather than CVEs.     

Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient‐level meta‐analysis

Summary. Aim: To determine if the mode of presentation of venous thromboembolism (VTE), as deep vein thrombosis (DVT) or pulmonary embolism (PE), predicts the likelihood and type of recurrence. Methods: We carried out a patient‐level meta‐analysis of seven prospective studies in patients with a first VTE who were followed after anticoagulation was stopped. We used Kaplan‐Meier analysis to determine the cumulative incidence of recurrent VTE according to mode of presentation, and multivariable Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for mode of and extent of DVT as potential risk factors for recurrence. Results: The 5‐year cumulative rate of recurrent VTE in 2554 patients was 22.6%. In 869 (36.1%) patients with PE, the 5‐year rate of any recurrence (DVT or PE) was 22.0%, and recurrence as PE was 10.6%. In 1365 patients with proximal DVT, the 5‐year recurrence rate was 26.4%, and recurrence with PE was 3.6%. The risk of recurrence as PE was 3.1‐fold greater in patients presenting with symptomatic PE than in patients with proximal DVT (HR, 3.1; 95% CI, 1.9–5.1). Patients with proximal DVT had a 4.8‐fold higher cumulative recurrence rate than those with distal DVT (HR, 4.8; 95% CI, 2.1–11.0). Conclusion: Whilst DVT and PE are manifestations of the same disease, the phenotypic expression is predetermined. Patients presenting with PE are three times more likely to suffer recurrence as PE than patients presenting with DVT. Patients presenting with calf DVT are at low risk of recurrence and at low risk of recurrence as PE.     

In or out? Methodological considerations for including and excluding findings from a meta‐analysis of predictors of antiretroviral adherence in HIV‐positive women

AIM: This paper is a discussion detailing the decisions concerning whether to include or exclude findings from a meta-analysis of report of quantitative studies of antiretroviral adherence in HIV-positive women. BACKGROUND: Publication constraints and the absence of reflexivity as a criterion for validity in, and reporting of, quantitative research preclude detailing the many judgements made in the course of a meta-analysis. Yet, such an accounting would assist researchers better to address the unique challenges to meta-analysis presented by the bodies of research they have targeted for review, and to show the subjectivity, albeit disciplined, that characterizes the meta-analytic process. DATA SOURCES: Data were 29 published and unpublished studies on antiretroviral adherence in HIV-positive women of any race/ethnicity, class, or nationality living in the United States of America. The studies were retrieved between June 2005 and January 2006 using 40 databases. REVIEW METHODS: Findings were included if they met the statistical assumptions of meta-analysis, including: (1) normal distribution of observations; (2) homogeneity of variances; and (3) independence of observations. RESULTS: Relevant studies and findings were excluded because of issues related to differences in study design, different operationalizations of dependent and independent variables, multiple cuts from common longitudinal data sets, and presentation of unadjusted and adjusted findings. These reasons led to the exclusion of 73% of unadjusted relationships and 87% of adjusted relationships from our data set, leaving few findings to synthesize. CONCLUSION: Decisions made during research synthesis studies may result in more information losses than gains, thereby obliging researchers to find ways to preserve findings that are potentially valuable for practice.     

Directly observed therapy and tuberculosis: how can a systematic review of qualitative research contribute to improving services? A qualitative meta‐synthesis

Title. Directly observed therapy and tuberculosis: how can a systematic review of qualitative research contribute to improving services? A qualitative meta‐synthesis Aim. This paper reports the findings from a qualitative meta‐synthesis concerning people with, or at risk of, tuberculosis, service providers and policymakers and their experiences and perceptions of tuberculosis and treatment. Background. Directly observed therapy is part of a package of interventions to improve tuberculosis treatment and adherence. A Cochrane systematic review of trials showed an absence of evidence for or against directly observed therapy compared with people treating themselves. Method. Qualitative systematic review methods were used to search, screen, appraise and extract data thematic analysis was used to synthesize data from 1990 to 2002, and an update of literature to December 2005. Two questions were addressed: ‘What does qualitative research tell us about the facilitators and barriers to accessing and complying with tuberculosis treatment?’ and ‘What does qualitative research tell us about the diverse results and effect sizes of the randomized controlled trials included in the Cochrane review?’ Findings help explain the diverse trial results in a Cochrane systematic review of directly observed therapy and tuberculosis and consider implications for research, policy and practice. Findings. Five themes emerged from the 1990 to 2002 synthesis: socio‐economic circumstances, material resources and individual agency; explanatory models and knowledge systems in relation to tuberculosis and its treatment; the experience of stigma and public discourses around tuberculosis; sanctions, incentives and support, and the social organization and social relationships of care. Two additional themes emerged from the 2005 update. Conclusion. The qualitative meta‐synthesis improved the relevance and scope of the Cochrane review of trials. The findings make a major contribution to the development of theory concerning global WHO‐branded disease control and the practicality of local delivery to people.     

How high should total pain‐relief score be to obviate the need for analgesic remedication in acute pain? Estimation using signal detection theory and individual‐patient meta‐analysis

BACKGROUND: A pain relief score 50% of the maximum is often used as a clinically meaningful outcome in meta-analyses of analgesic trials. This arbitrary value requires validation. OBJECTIVE: To determine the optimum pain relief score for predicting pain relief sufficient to obviate the need for analgesic remedication in acute post-surgical pain. DESIGN: Individual-patient meta-analysis of randomized controlled trials and use of signal detection theory to identify the optimum cut-off point on the total pain relief score (TOTPAR). Analgesic remedication was used as the clinical outcome. DATA SOURCES: Seven parallel-group, active and placebo-controlled trials of minor analgesics. RESULTS: The predictive value of the TOTPAR score [expressed as a percentage of the maximum score (%maxTOTPAR)] for remedication was excellent for all the trials. The pooled estimate of the area under the receiver operating curve, an index of discriminative power, was outstanding 0.96 (95% CI 0.95-0.97). The pooled estimate of the optimal %maxTOTPAR for predictive purposes was 44.11 (95% CI 44.00-44.23). CONCLUSION: The analysis suggests that the arbitrary 50% cut-off point TOTPAR score often used in meta-analyses of analgesic trials in dental pain is reasonably acceptable. This is different to the 33% cut-off point reported for analgesic trials of acute breakthrough cancer pain and some chronic pain states such as diabetic neuropathy and postherpetic neuralgia. These differences deserve careful consideration when reading reports of analgesic trials and meta-analyses. Remedication itself should be considered as the preferred outcome measure for analgesic trials.     

Are Nonpharmacologic Pain Interventions Effective at Reducing Pain in Adult Patients Visiting the Emergency Department? A Systematic Review and Meta‐analysis

Objectives

Pain is a common complaint in the emergency department (ED). Its management currently depends heavily on pharmacologic treatment, but evidence suggests that nonpharmacologic interventions may be beneficial. The purpose of this systematic review and meta‐analysis was to assess whether nonpharmacologic interventions in the ED are effective in reducing pain.

Methods

We conducted a systematic review of the literature on all types of nonpharmacologic interventions in the ED with pain reduction as an outcome. We performed a qualitative summary of all studies meeting inclusion criteria and meta‐analysis of randomized controlled studies measuring postintervention changes in pain. Interventions were divided by type into five categories for more focused subanalyses.

Results

Fifty‐six studies met inclusion criteria for summary analysis. The most studied interventions were acupuncture (10 studies) and physical therapy (six studies). The type of pain most studied was musculoskeletal pain (34 studies). Most (42 studies) reported at least one improved outcome after intervention. Of these, 23 studies reported significantly reduced pain compared to control, 24 studies showed no difference, and nine studies had no control group. Meta‐analysis included 22 qualifying randomized controlled trials and had a global standardized mean difference of –0.46 (95% confidence interval = –0.66 to –0.27) in favor of nonpharmacologic interventions for reducing pain.

Conclusion

Nonpharmacologic interventions are often effective in reducing pain in the ED. However, most existing studies are small, warranting further investigation into their use for optimizing ED pain management.