Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies

Aims/hypothesis The aim of this study was to investigate the association between routine vaccinations and the risk of childhood type 1 diabetes mellitus by systematically reviewing the published literature and performing meta-analyses where possible.

Methods A comprehensive literature search was performed of MEDLINE and EMBASE to identify all studies that compared vaccination rates in children who subsequently developed type 1 diabetes mellitus and in control children. ORs and 95% CIs were obtained from published reports or derived from individual patient data and then combined using a random effects meta-analysis.

Results In total, 23 studies investigating 16 vaccinations met the inclusion criteria. Eleven of these contributed to meta-analyses which included data from between 359 and 11,828 childhood diabetes cases. Overall, there was no evidence to suggest an association between any of the childhood vaccinations investigated and type 1 diabetes mellitus. The pooled ORs ranged from 0.58 (95% CI 0.24, 1.40) for the measles, mumps and rubella (MMR) vaccination in five studies up to 1.04 (95% CI 0.94, 1.14) for the haemophilus influenza B (HiB) vaccination in 11 studies. Significant heterogeneity was present in most of the pooled analyses, but was markedly reduced when analyses were restricted to study reports with high methodology quality scores. Neither this restriction by quality nor the original authors’ adjustments for potential confounding made a substantial difference to the pooled ORs.

Conclusions/interpretation This study provides no evidence of an association between routine vaccinations and childhood type 1 diabetes.

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central's Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols--PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.

Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.

Is hyperfiltration associated with the future risk of developing diabetic nephropathy? A meta-analysis.

Aims/hypothesis Glomerular hyperfiltration is a well established phenomenon occurring early in some patients with type 1 diabetes. However, there is no consistent answer regarding whether hyperfiltration predicts later development of nephropathy. We performed a systematic review and meta-analysis of observational studies that compared the risk of developing diabetic nephropathy in patients with and without glomerular hyperfiltration and also explored the impact of baseline GFR.

Methods A systematic review and meta-analysis was carried out. Cohort studies in type 1 diabetic participants were included if they contained data on the development of incipient or overt nephropathy with baseline measurement
of GFR and presence or absence of hyperfiltration.

Results We included ten cohort studies following 780 patients. After a study median follow-up of 11.2 years, 130 patients had developed nephropathy. Using a random effects model, the pooled odds of progression to a minimum
of microalbuminuria in patients with hyperfiltration was 2.71 (95% CI 1.20–6.11) times that of patients with normofiltration. There was moderate heterogeneity (heterogeneity test p=0.05, measure of degree of inconsistency=48%) and some evidence of funnel plot asymmetry, possibly due to publication bias. The pooled weighted mean difference in baseline GFR was 13.8 ml min-1 1.73 m-2 (95% CI 5.0–22.7) greater in the group progressing to nephropathy than in those not progressing (heterogeneity test p<0.01).

Conclusions/interpretation In published studies, individuals with glomerular hyperfiltration were at increased risk of progression to diabetic nephropathy using study level data. Further larger studies are required to explore this relationship and the role of potential confounding variables.

Systematic review and meta-analysis of the association between complement component 3 and age-related macular degeneration: A HUGE review and meta-analysis

We performed a meta-analysis to estimate the magnitude of C3 gene polymorphism effects, and their possible mode of action, on age-related macular degeneration (AMD). The meta-analysis included 16 studies for rs2230199 and 7 studies for rs1047286. Data extraction and risk of bias assessments were performed in duplicate, and heterogeneity and publication bias were explored. There was moderate evidence for association between both polymorphisms and AMD in individuals of European descent. For rs2230199, patients with CG and GG genotypes were 1.44 (95% CI: 1.33 – 1.56) and 1.88 (95% CI: 1.59 – 2.23) times more likely to have AMD than patients with CC genotype. For rs1047286, those with GA and AA genotypes had 1.27 (95% CI: 1.15 – 1.41) and 1.70 (95% CI: 1.27 – 2.11) times higher risk of AMD than those with GG genotypes. These gene effects suggested an additive model. The population attributable risks for the GG/GC and AA/GA genotypes are approximately 5-10%. Stratification of studies on the basis of ethnicity indicates that these variants are very infrequent in Asian populations and the significance of the effect observed is based largely on the high frequency of these variants within individuals of European descent. This meta-analysis supports the association between C3 and AMD and provides a robust estimate of the genetic risk.

The association between complement component 2/complement factor B polymorphisms and age-related macular degeneration: A HuGE review and meta-analysis

The authors performed a systematic review of the association of complement component 2(C2)/complement factor B (CFB) gene polymorphisms with age-related macular degeneration (AMD). In total, data from 19 studies published between 2006 and 2011 were pooled for 4 polymorphisms: rs9332739 and rs547154 in the C2 gene and rs4151667 and rs641153 in the CFB gene. Data extraction and assessments for risk of bias were independently performed by 2 reviewers. Allele frequencies and allele and genotypic effects were pooled. Heterogeneity and publication bias were explored. Pooled minor allele frequencies for all 4 SNPs were between 4.7% and 9.6% for all polymorphisms, except for an Indian population in which the C allele at rs9332739 was the major allele. For the C2 polymorphisms, the minor C allele at rs9332739 and the minor T allele at rs547154 carried estimated relative risks (odds ratios) of 0.55 (95% confidence interval (CI): 0.46, 0.65) and 0.47 (95% CI: 0.39, 0.57), respectively. For the CFB polymorphisms, the minor A alleles at rs4151667 and rs614153 carried estimated risks of 0.54 (95% CI: 0.45, 0.64) and 0.41 (95% CI: 0.34, 0.51), respectively. These allele effects contributed to an absolute lowering of the risk of all AMD in Caucasian populations by 2.0%-6.0%. This meta-analysis provides a robust estimate of the protective association of C2/CFB with AMD.

A systematic review and meta-analysis of the ethnic density effect in psychotic disorders

A number of studies have found an ethnic density effect in psychotic disorders, where the incidence for ethnic minorities increases as the neighbourhood proportional ethnic composition decreases [Morgan and Hutchinson, Psychol Med 40:705-709, (2010); Singh, Psychol Med 39:1402-1403, (2009); Schofield et al., Psychol Med 41:1263-1269, (2010)]. However, there is a mixed picture with some studies reporting no effect [Schofield et al., Psychol Med 41:1263-1269, (2010)]. This review aimed to establish the existence of the effect by answering the review question: is there an ethnic density dose effect in the prevalence of psychotic disorders?

How common are myeloproliferative neoplasms? A systematic review and meta-analysis

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera (PV), essential thrombocythemia (ET), and primary(idiopathic) myelofibrosis (PMF). In this systematic review, we provide a comprehensive report on the incidence and prevalence of MPNs across the globe. Electronic databases (PubMed, EMBASE, MEDLINE, and Web of Science) were searched from their inception to August 2012 for articles reporting MPN incidence or prevalence rates. A random effects meta-analysis was undertaken to produce combined incidence rates for PV, ET, and PMF. Both heterogeneity and small study bias were assessed. Thirty-four studies were included. Reported annual incidence rates ranged from 0.01 to 2.61, 0.21 to 2.27, and 0.22 to 0.99 per 100,000 for PV, ET, and PMF, respectively. The combined annual incidence rates for PV, ET, and PMF were 0.84, 1.03, and 0.47 per 100,000. There was high heterogeneity across disease entities (I(2) 97.1-99.8%) and evidence of publication bias for ET and PMF (Egger test, P = 50.007 and P ≤ 0.001, respectively).The pooled incidence reflects the rarity of MPNs. The calculated pooled incidence rates do not reflect MPN incidence across the globe due to the high unexplained heterogeneity. Improved, widespread registration of MPNs would provide better information for global comparison of the incidence and prevalence of MPNs.

Preferred Reporting Items for a Systematic Review and Meta-analysis of Individual Participant Data The PRISMA-IPD Statement

IMPORTANCE Systematic reviews and meta-analyses of individual participant data (IPD) aim to collect, check, and reanalyze individual-level data from all studies addressing a particular research question and are therefore considered a gold standard approach to evidence synthesis. They are likely to be used with increasing frequency as current initiatives to share clinical trial data gain momentum and may be particularly important in reviewing controversial therapeutic areas.

OBJECTIVE To develop PRISMA-IPD as a stand-alone extension to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, tailored to the specific requirements of reporting systematic reviews and meta-analyses of IPD. Although developed primarily for reviews of randomized trials, many items will apply in other contexts, including reviews of diagnosis and prognosis.

DESIGN Development of PRISMA-IPD followed the EQUATOR Network framework guidance and used the existing standard PRISMA Statement as a starting point to draft additional relevant material. A web-based survey informed discussion at an international workshop that included researchers, clinicians, methodologists experienced in conducting systematic reviews and meta-analyses of IPD, and journal editors. The statement was drafted and iterative refinements were made by the project, advisory, and development groups. The PRISMA-IPD Development Group reached agreement on the PRISMA-IPD checklist and flow diagram by consensus.

FINDINGS Compared with standard PRISMA, the PRISMA-IPD checklist includes 3 new items that address (1) methods of checking the integrity of the IPD (such as pattern of randomization, data consistency, baseline imbalance, and missing data), (2) reporting any important issues that emerge, and (3) exploring variation (such as whether certain types of individual benefit more from the intervention than others). A further additional item was created by reorganization of standard PRISMA items relating to interpreting results. Wording was modified in 23 items to reflect the IPD approach.

CONCLUSIONS AND RELEVANCE PRISMA-IPD provides guidelines for reporting systematic reviews and meta-analyses of IPD.

A systematic review and meta-analysis of the survival of non-feldspathic porcelain veneers over 5 and 10 years

PURPOSE: This systematic review aimed to report and explore the survival of dental veneers constructed from non-feldspathic porcelain over 5 and 10 years.

MATERIALS AND METHODS: A total of 4,294 articles were identified through a systematic search involving all databases in the Cochrane Library, MEDLINE (OVID), EMBASE, Web of Knowledge, specific journals (hand-search), conference proceedings, clinical trials registers, and collegiate contacts. Articles, abstracts, and gray literature were sought by two independent researchers. There were no language limitations. One hundred sixteen studies were identified for full-text assessment, with 10 included in the analysis (5 qualitative, 5 quantitative). Study characteristics and survival (Kaplan-Meier estimated cumulative survival and 95% confidence interval [CI]) were extracted or recalculated. A failed veneer was one which required an intervention that disrupted the original marginal integrity, had been partially or completely lost, or had lost retention more than twice. A meta-analysis and sensitivity analysis of Empress veneers was completed, with an assessment of statistical heterogeneity and publication bias. Clinical heterogeneity was explored for results of all veneering materials from included studies.

RESULTS: Within the 10 studies, veneers were fabricated with IPS Empress, IPS Empress 2, Cerinate, and Cerec computer-aided design/computer-assisted manufacture (CAD/CAM) materials VITA Mark I, VITA Mark II, Ivoclar ProCad. The meta-analysis showed the pooled estimate for Empress veneers to be 92.4% (95% CI: 89.8% to 95.0%) for 5-year survival and 66% to 94% (95% CI: 55% to 99%) for 10 years. Data regarding other non-feldspathic porcelain materials were lacking, with only a single study each reporting outcomes for Empress 2, Cerinate, and various Cerec porcelains over 5 years. The sensitivity analysis showed data from one study had an influencing and stabilizing effect on the 5-year pooled estimate.

CONCLUSION: The long-term outcome (> 5 years) of non-feldspathic porcelain veneers is sparsely reported in the literature. This systematic review indicates that the 5-year cumulative estimated survival for etchable non-feldspathic porcelain veneers is over 90%. Outcomes may prove clinically acceptable with time, but evidence remains lacking and the use of these materials for veneers remains experimental.

Dyslipidemia and Diabetic Macular Edema: A Systematic Review and Meta-Analysis

Topic: A systematic review and meta-analysis of dyslipidemia and diabetic macular edema (DME). 

Clinical Relevance: Diabetic macular edema causes impairment of vision in patients with diabetes, and dyslipidemia has been reported as a risk factor for its development. A systematic review with a meta-analysis was undertaken to examine the evidence of an association between dyslipidemia and DME. 

Methods: We defined eligibility criteria as randomized controlled trials (RCTs) and cohort, case-control, and cross-sectional studies reporting on the relationship between blood lipid levels and DME. We performed a literature search in MEDLINE, PubMed, and Embase from inception to September 2014. We used the NewcastleeOttawa scale to assess the quality of case-control, cross-sectional, and cohort studies, and the Cochrane risk of bias tool for RCTs. 

Results: The search strategy identified 4959 publications. After screening, we selected 21 articles for review (5 cross-sectional, 5 cohort, 7 case-control, and 4 RCTs). Meta-analysis of case-control studies revealed that mean levels of total serum cholesterol (TC), low-density lipoproteins (LDLs), and serum triglycerides (TGs) were significantly higher in patients with DME compared with those without DME (TC: 30.08; 95% confidence interval [CI], 21.14e39.02; P < 0.001; LDL: 18.62; 95% CI, 5.80e31.43; P < 0.05; TG: 24.82; 95% CI, 9.21e40.42; P < 0.05). Meta-analysis of RCTs did not show significant risk in worsening of hard exudates and severity of DME in the lipid-lowering group compared with placebo (hard exudates: relative risk, 1.00; 95% CI, 0.47e2.11; P ¼ 1.00; DME: relative risk, 1.18; 95% CI, 0.75e1.86; P ¼ 0.48). 

Conclusions: Despite evidence from the cohort studies and meta-analysis of the case-control studies suggesting a strong relationship between lipid levels and DME, this was not confirmed by the meta-analysis that included only prospective RCTs. Therefore, given the significant public health relevance of the topic, the relationship between lipid levels and DME deserves further investigation.

SYSTEMATIC REVIEW AND META-ANALYSIS: EFFECTS OF WALKING EXERCISE IN CHRONIC MUSCULOSKELETAL PAIN

SYSTEMATIC REVIEW AND META-ANALYSIS: EFFECTS OF WALKING EXERCISE IN CHRONIC MUSCULOSKELETAL PAIN O'Connor S.R.1, Tully M.A.2, Ryan B.3, Baxter D.G.3, Bradley J.M.1, McDonough S.M.11University of Ulster, Health & Rehabilitation Sciences Research Institute, Newtownabbey, United Kingdom, 2Queen's University, UKCRC Centre of Excellence for Public Health (NI), Belfast, United Kingdom, 3University of Otago, Centre for Physiotherapy Research, Dunedin, New ZealandPurpose: To examine the effects of walking exercise on pain and self-reported function in adults with chronic musculoskeletal pain.Relevance: Chronic musculoskeletal pain is a major cause of morbidity, exerting a substantial influence on long-term health status and overall quality of life. Current treatment recommendations advocate various aerobic exercise interventions for such conditions. Walking may represent an ideal form of exercise due to its relatively low impact. However, there is currently limited evidence for its effectiveness.Participants: Not applicable.Methods: A comprehensive search strategy was undertaken by two independent reviewers according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) and the recommendations of the Cochrane Musculoskeletal Review Group. Six electronic databases (Medline, CINAHL, PsychINFO, PEDro, Sport DISCUS and the Cochrane Central Register of Controlled Trials) were searched for relevant papers published up to January 2010 using MeSH terms. All randomised or non-randomised studies published in full were considered for inclusion. Studies were required to include adults aged 18 years or over with a diagnosis of chronic low back pain, osteoarthritis or fibromyalgia. Studies were excluded if they involved peri-operative or post-operative interventions or did not include a comparative, non exercise or non-walking exercise control group. The U.S. Preventative Services Task Force system was used to assess methodological quality. Data for pain and self-reported function were extracted and converted to a score out of 100.Analysis: Data were pooled and analyzed using RevMan (v.5.0.24). Statistical heterogeneity was assessed using the X2 and I2 test statistics. A random effects model was used to calculate the mean differences and 95% CIs. Data were analyzed by length of final follow-up which was categorized as short (≤8 weeks post randomisation), mid (2-12 months) or long-term (>12 months).Results: A total of 4324 articles were identified and twenty studies (1852 participants) meeting the inclusion criteria were included in the review. Overall, studies were judged to be of at least fair methodological quality. The most common sources of likely bias were identified as lack of concealed allocation and failure to adequately address incomplete data. Data from 12 studies were suitable for meta-analysis. Walking led to reductions in pain at short (<8 weeks post randomisation) (-8.44 [-14.54, -2.33]) and mid-term (>8 weeks - 12 month) follow-up (-9.28 [-16.34, -2.22]). No effect was observed for long-term (>12 month) data (-2.49 [-7.62, 2.65]). For function, between group differences were observed for short (-11.57 [-16.06, -7.08]) and mid-term data (-13.26 [-16.91, -9.62]). A smaller effect was also observed at long-term follow-up (-5.60 [-7.70, -3.50]).Conclusions: Walking interventions were associated with statistically significant improvements in pain and function at short and mid-term follow-up. Long-term data were limited but indicated that these effects do not appear to be maintained beyond twelve months.Implications: Walking may be an effective form of exercise for individuals with chronic musculoskeletal pain. However, further research is required which examines longer term follow-up and dose-response issues in this population.Key-words: 1. Walking exercise 2. Musculoskeletal pain 3. Systematic reviewFunding acknowledgements: Department of Employment and Learning, Northern Ireland.Ethics approval: Not applicable.

Homocysteine, Methylenetetrahydrofolate Reductase C677T Polymorphism, and Risk of Retnal Vein Occlusion: A Meta-analysis

Objective: To assess the role of plasma total homocysteine (tHcy) concentrations and homozygosity for the thermolabile variant of the methylenetetrahydrofolate reductase (MTHFR) C677T gene as risk factors for retinal vascular occlusive disease.

Design: Retinal vein occlusion (RVO) is an important cause of vision loss. Early meta-analyses showed that tHcy was associated with an increased risk of RVO, but a significant number of new studies have been published. Participants and/or Controls: RVO patients and controls.

Methods: Data sources included MEDLINE, Web of Science, and PubMed searches and searching reference lists of relevant articles and reviews. Reviewers searched the databases, selected the studies, and then extracted data. Results were pooled quantitatively using meta-analytic methods.

Main Outcome Measures: tHcy concentrations and MTHFR genotype.

Results: There were 25 case-control studies for tHcy (1533 cases and 1708 controls) and 18 case-control studies for MTHFR (1082 cases and 4706 controls). The mean tHcy was on average 2.8 mol/L (95% confidence
interval [CI], 1.8 –3.7) greater in the RVO cases compared with controls, but there was evidence of between-study heterogeneity (P0.001, I2 93%). There was funnel plot asymmetry suggesting publication bias. There was no evidence of association between homozygosity for the MTHFR C677T genotype and RVO (odds ratio [OR] 1.20; 95% CI, 0.84–1.71), but again marked heterogeneity (P 0.004, I2 53%) was observed.

Conclusions: There was some evidence that elevated tHcy was associated with RVO, but not homozygosity for the MTHFR C677T genotype. Both analyses should be interpreted cautiously because of marked heterogeneity between the study estimates and possible effect of publication bias on the tHcy findings.

Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.