Understanding heterogeneity in meta‐analysis: the role of meta‐regression

Background: Meta‐regression has grown in popularity in recent years, paralleling the increasing numbers of systematic reviews and meta‐analysis published in the biomedical literature. However, many clinicians and decision‐makers may be unfamiliar with the underlying principles and assumptions made within meta‐regression leading to incorrect interpretation of their results. Aims: This paper reviews the appropriate use and interpretation of meta‐regression in the medical literature, including cautions and caveats to its use. Materials & Methods: A literature search of MEDLINE (OVID) from 1966‐February 2009 was conducted to identify literature relevant to the topic of heterogeneity and/or meta‐regression in systematic reviews and meta‐analysis. Results: Meta‐analysis, a statistical method of pooling data from studies included in a systematic review, is often compromised by heterogeneity of its results. This could include clinical, methodological or statistical heterogeneity. Meta‐regression, said to be a merging of meta‐analytic and linear regression principles, is a more sophisticated tool for exploring heterogeneity. It aims to discern whether a linear relationship exists between an outcome measure and on or more covariates. The associations found in a meta‐regression should be considered hypothesis generating and not regarded as proof of causality. Conclusions: The current review will enable clinicians and healthcare decision‐makers to appropriately interpret the results of meta‐regression when used within the constructs of a systematic review, and be able to extend it to their clinical practice.     

Evidence synthesis and meta‐analysis: a practical approach

A systematic review (SR) is an explicit and clear assessment of the literature, derived from a clearly articulated research question, along with a critical analysis and according to different tools and a summary of the evidence. If researchers find clear and homogeneous data, then it is possible to perform a meta‐analysis (MA). SRs must include the following: a clear question based on the PICO (patient or population, intervention, comparison and outcome) strategy, a reproducible search strategy, appropriate selection of studies along with data extraction, assessment of the quality of evidence and a MA if it is appropriate. SRs and meta‐analyses are fundamental supports for decision‐making in the clinical area, in public health and government policies in a wide arena of knowledge generation. Understanding the role of SRs and their conduct that can be an important skill to practitioners such as urology nurses, particularly those involved in research studies.     

Homoarginine and all‐cause mortality: A systematic review and meta‐analysis

Background

Homoarginine, a basic amino acid and analogue of L‐arginine, has been shown to exert salutary effects on vascular homoeostasis, possibly through interaction with the enzymes nitric oxide synthase and arginase. This might translate into improved survival outcomes, particularly in subjects with moderate‐high cardiovascular risk. We conducted a systematic review and meta‐analysis to investigate the association between circulating homoarginine concentrations and all‐cause mortality in observational studies of human cohorts.

Materials and methods

Studies reporting baseline circulating homoarginine concentrations and all‐cause mortality as outcome were searched using the MEDLINE, Scopus and Cochrane databases until January 2018. Hazard ratios (HRs) with 95% confidence intervals (CIs) derived from multivariate Cox's proportional‐hazards analysis were extracted from individual studies.

Results

A total of 13 studies in 11 964 participants were included in the final analysis. Homoarginine concentrations were inversely associated with all‐cause mortality (HR 0.64, 95% CI 0.57‐0.73). This association remained significant in participant sub‐groups with predominant cardiovascular disease (HR 0.64, 95% CI 0.55‐0.76) and renal disease (HR 0.60, 95% CI 0.46‐0.68).

Conclusions

This meta‐analysis of observational studies showed an inverse association between circulating homoarginine concentrations and all‐cause mortality. Further research is warranted to investigate the direct effects of homoarginine on cardiovascular homoeostasis, the associations between homoarginine and all‐cause mortality in other population groups, and the effects of interventions on homoarginine concentrations on clinical outcomes.     

Acupuncture for schizophrenia: a systematic review and meta‐analysis

Background: Acupuncture is one of the most popular types of complementary/alternative medicine. It is sometimes used as a treatment for schizophrenia. Aims: The objective of this review is to assess systematically the clinical evidence for or against acupuncture as a treatment for schizophrenia. Methods: We searched 20 databases from their inception to May 2009 without language restrictions. All randomised clinical trials (RCTs) of acupuncture, with or without electrical stimulation or moxibustion for patients with schizophrenia were considered for inclusion. Results: Thirteen RCTs, all originating from China, met the inclusion criteria. One RCT reported significant effects of electroacupuncture (EA) plus drug therapy for improving auditory hallucunations and positive symptom compared with sham EA plus drug therapy. Four RCTs showed significant effects of acupuncture for response rate compared with antipsychotic drugs [n = 360, relative risk (RR): 1.18, 95% confidence interval (CI): 1.03–1.34, p = 0.01; heterogeneity: τ² = 0.00, χ² = 2.98, p = 0.39, I² = 0%]. Seven RCTs showed significant effects of acupuncture plus antipsychotic drug therapy for response rate compared with antipsychotic drug therapy (n = 457, RR: 1.15, 95% CI: 1.04–1.28, p = 0.008, heterogeneity: τ² = 0.00, χ² = 6.56, p = 0.36, I² = 9%). Two RCTs tested laser acupuncture against sham laser acupuncture. One RCT found beneficial effects of laser acupuncture on hallucination and the other RCT showed significant effects of laser acupuncture on response rate, Brief Psychiatric Rating Scale and clinical global index compared with sham laser. The methodological quality was generally poor and there was not a single high quality trial. Conclusion: These results provide limited evidence for the effectiveness of acupuncture in treating the symptoms of schizophrenia. However, the total number of RCTs, the total sample size and the methodological quality were too low to draw firm conclusions. As all studies originated from China, international studies are needed to test whether there is any effect.     

Polypoidal choroidal vasculopathy treatment options: A meta‐analysis

Background

Combined treatment with intravitreal anti‐vascular endothelial growth factor (anti‐VEGF) and verteporfin photodynamic therapy (PDT) is widely used for patients with polypoidal choroidal vasculopathy (PCV), although clinical evidence regarding the therapeutic efficacy and safety of such treatment remains lacking.

Design/Methods

We performed a meta‐analysis of previously reported studies comparing combination treatment, PDT monotherapy, and anti‐VEGF monotherapy. Primary outcome measures included changes in best‐corrected visual acuity (BCVA) and central retinal thickness (CRT). The proportion of patients with polyp regression was regarded as the secondary outcome measure.

Results

Twenty studies (three RCTs and 19 retrospective studies) involving 1,178 patients with PCV were selected. Significant differences in the proportion of patients with polyps were observed between the PDT and anti‐VEGF monotherapy groups at 3 and ≥6 months (P < .00001; and P = .0001, respectively). Significantly greater reductions in CRT were observed in the anti‐VEGF than in the PDT group at the 3‐month follow‐up (P = .04). Significantly greater improvements in BCVA were observed in the combined therapy group than in the PDT monotherapy group at 3, 6, 12, and 24 months (P = .03; P = .005; P = .02; and P < .00001, respectively). Combined treatment also resulted in significantly greater improvements in BCVA than monotherapy with anti‐VEGF at 6 and 24 months (P = .001; P < .00001, respectively), and significantly greater polyp regression than that observed following anti‐VEGF treatment at 3 and ≥6 months (P < .00001; P < .0001, respectively).

Conclusions

Combined therapy involving anti‐VEGF agents and PDT may be more effective in improving long‐term outcomes for patients with PCV than monotherapy.     

Self‐management education interventions for persons with schizophrenia: A meta‐analysis

Although self‐management education programs for persons with schizophrenia are being developed and advocated, uncertainty about their overall effectiveness remains. The purpose of this meta‐analysis was to examine outcomes of self‐management education interventions in persons with schizophrenia. Six electronic databases were searched. Manual searches were conducted of the reference lists of the identified studies and major psychiatric journals. Randomized controlled trials of self‐management education interventions aimed at reducing relapse and hospital readmissions, as well as improving symptoms, psychosocial functioning, and adherence to medication treatment were identified. Data were extracted and the quality of included studies were rated by two authors independently. Finally, 13 studies with 1404 patients were included. Self‐management education interventions were associated with a significant reduction of relapse events and re‐hospitalizations. Patients who received self‐management education were more likely to improve adherence to medication and symptoms compared to patients receiving other care. However, a benefit on psychosocial functioning was not confirmed in the current meta‐analysis. The study concludes that self‐management education intervention is a feasible and effective method for persons with schizophrenia and should be routinely offered to all persons with schizophrenia.     

Effectiveness of pharmacist‐participated warfarin therapy management: a systematic review and meta‐analysis

Summary. Objective: Although pharmacist‐participated warfarin therapy management (PWTM) has been accepted and implemented in various parts of the world, the evidence demonstrating the effects of PWTM compared with usual care on clinical outcomes is lacking. We performed a systematic review and meta‐analysis to compare the effects of PWTM with usual care on bleeding and thromboembolic outcomes. Methods: We searched MEDLINE, SCOPUS, EMBASE, IPA, CINAHL, Cochrane CENTRAL, Thai Index Medicus and Thai Medical Index, and reference lists of studies, without language restriction. Databases were searched from their inception to July 2009. The studies using warfarin as an anticoagulant with sufficient data for compilation of 2 × 2 tables were included. Both randomized controlled trials (RCTs) and non‐RCTs were considered. Two authors independently reviewed each study, assigned quality scores and extracted data for all outcomes using a standardized form. Pooled effect estimates (risk ratio; RR) were obtained using a random effects model. Result: Of 661 articles identified, 24 studies with 728,377 patients were included. In the random‐effects meta‐analysis of RCTs, the PWTM group had statistically significant effects on the prevention of total bleeding [RR, 0.51; 95% confidence interval (CI), 0.28–0.94]. However, the effects on major bleeding (RR, 0.64; 95% CI, 0.18–2.36), thromboembolic events (RR, 0.79; 95% CI, 0.33–1.93), all‐cause mortality (RR, 0.93; 95% CI, 0.41–2.13) and warfarin‐related mortality (RR, 0.65; 95% CI, 0.18–2.42) were not significant. Conclusion: Pharmacist’s participation in the management of warfarin therapy significantly reduces total bleeding, with a non‐significant trend towards decreases in other warfarin‐related complications.