Evidence maps and evidence gaps: evidence review mapping as a method for collating and appraising evidence reviews to inform research and policy

Evidence reviews are a key mechanism for incorporating extensive, complex and specialised evidence into policy and practice, and in guiding future research. However, evidence reviews vary in scope and methodological rigour, creating several risks for decision-makers: decisions may be informed by less reliable reviews; apparently conflicting interpretations of evidence may obfuscate decisions; and low quality reviews may create the perception that a topic has been adequately addressed, deterring new syntheses (cryptic evidence gaps). We present a new approach, evidence review mapping, designed to produce a visual representation and critical assessment of the review landscape for a particular environmental topic or question. By systematically selecting and describing the scope and rigour of each review, this helps guide non-specialists to the most relevant and methodologically reliable reviews. The map can also direct future research through the identification of evidence gaps (whether cryptic or otherwise) and redundancy (multiple reviews on similar questions). We consider evidence review mapping a complementary approach to systematic reviews and systematic maps of primary literature and an important tool for facilitating evidence-based decision-making and research efficiency

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK

The evaluation and surgical management of cyclodialysis clefts that have failed to respond to conservative management

Purpose To investigate factors that may influence successful correction of hypotony in a consecutive series of patients with cyclodialysis clefts repaired surgically over a 10-year period. Design Retrospective interventional case series. Methods Interventional case series of consecutive patients with cyclodialysis clefts and hypotony treated surgically after failure of conservative treatment. Results Eighteen patients (18 eyes) of mean (SD) age 48.3 (15.8) years at the time of surgery were included (16 male, 2 female). All were diagnosed using gonioscopy, usually assisted with intracameral viscoelastic injection. Imaging used in three cases was not found to be sufficiently precise to plan surgical intervention, without prior gonioscopic cleft visualisation. The intraocular pressure (IOP) was restored in nine cases (50%) after one procedure with a postoperative IOP (mean±SD) of 13.6±4.5 mm Hg (6/11 who had cyclopexy as a first procedure and 3/6 who had cryopexy). 2?3 procedures were required in the remaining nine patients. There was a trend towards the use of cyclopexy for larger clefts and cryopexy for saller clefts (NS). We observed a trend for a lower likelihood of successful closure of larger clefts after one intervention. Two eyes that had cyclopexy required later IOP-lowering surgery to achieve IOP control. Conclusions Most clefts were closed with one procedure. A trend towards larger cleft size as a preoperative risk factor for failure to achieve closure with one procedure was observed. In this series, imaging was not found to be sufficiently precise to replace viscoelastic-Assisted gonioscopy in the diagnosis and evaluation of cyclodialysis clefts

Determinants of patient recruitment in a multicenter clinical trials group: trends, seasonality and the effect of large studies

BACKGROUND: We examined whether quarterly patient enrollment in a large multicenter clinical trials group could be modeled in terms of predictors including time parameters (such as long-term trends and seasonality), the effect of large trials and the number of new studies launched each quarter. We used the database of all clinical studies launched by the AIDS Clinical Trials Group (ACTG) between October 1986 and November 1999. Analyses were performed in two datasets: one included all studies and substudies (n = 475, total enrollment 69,992 patients) and the other included only main studies (n = 352, total enrollment 57,563 patients). RESULTS: Enrollment differed across different months of the year with peaks in spring and late fall. Enrollment accelerated over time (+27 patients per quarter for all studies and +16 patients per quarter for the main studies, p < 0.001) and was affected by the performance of large studies with target sample size > 1,000 (p < 0.001). These relationships remained significant in multivariate autoregressive modeling. A time series based on enrollment during the first 32 quarters could forecast adequately the remaining 21 quarters. CONCLUSIONS: The fate and popularity of large trials may determine the overall recruitment of multicenter groups. Modeling of enrollment rates may be used to comprehend long-term patterns and to perform future strategic planning

A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the Framingham Osteoporosis Study (FOS). We genotyped 1,206 male and 1,445 female participants of the FOS for four single-nucleotide polymorphism (SNPs) in PLIN1 and seven SNPs in PLIN4 and tested for associations with measures of BMD, bone ultrasound, hip geometry, and height. We found several gender-specific significant associations with the measured traits. The association of PLIN4 SNP rs8887, G>A with height in females trended toward significance after simulation testing (adjusted P = 0.07) and remained significant after simulation testing in the combined-sex model (adjusted P = 0.033). In a large study sample of men and women, we found a significant association between one SNP in PLIN4 and height but not with bone traits, suggesting that PATS family genes are not important in the regulation of bone. Identification of genes that influence human height may lead to a better understanding of the processes involved in growth and development

Melanocortin-1 Receptor, Skin Cancer and Phenotypic Characteristics (M-SKIP) Project: Study Design and Methods for Pooling Results of Genetic Epidemiological Studies

Background: For complex diseases like cancer, pooled-analysis of individual data represents a powerful tool to investigate the joint contribution of genetic, phenotypic and environmental factors to the development of a disease. Pooled-analysis of epidemiological studies has many advantages over meta-analysis, and preliminary results may be obtained faster and with lower costs than with prospective consortia. Design and methods: Based on our experience with the study design of the Melanocortin-1 receptor (MC1R) gene, SKin cancer and Phenotypic characteristics (M-SKIP) project, we describe the most important steps in planning and conducting a pooled-analysis of genetic epidemiological studies. We then present the statistical analysis plan that we are going to apply, giving particular attention to methods of analysis recently proposed to account for between-study heterogeneity and to explore the joint contribution of genetic, phenotypic and environmental factors in the development of a disease. Within the M-SKIP project, data on 10,959 skin cancer cases and 14,785 controls from 31 international investigators were checked for quality and recoded for standardization. We first proposed to fit the aggregated data with random-effects logistic regression models. However, for the M-SKIP project, a two-stage analysis will be preferred to overcome the problem regarding the availability of different study covariates. The joint contribution of MC1R variants and phenotypic characteristics to skin cancer development will be studied via logic regression modeling. Discussion: Methodological guidelines to correctly design and conduct pooled-analyses are needed to facilitate application of such methods, thus providing a better summary of the actual findings on specific fields

Socio-cultural determinants of physical activity across the life course: a 'Determinants of Diet and Physical Activity' (DEDIPAC) umbrella systematic literature review

Objective Regular physical activity (PA) reduces the risk of disease and premature death. Knowing factors associated with PA might help reducing the disease and economic burden caused by low activity. Studies suggest that socio-cultural factors may affect PA, but systematic overviews of findings across the life course are scarce. This umbrella systematic literature review (SLR) summarizes and evaluates available evidence on socio-cultural determinants of PA in children, adolescents, and adults. Methods This manuscript was drafted following the recommendations of the ‘Preferred Reporting Items for Systematic reviews and Meta-Analyses’ (PRISMA) checklist. The MEDLINE, Web of Science, Scopus, and SPORTDiscus databases were searched for SLRs and meta-analyses (MAs) on observational studies published in English that assessed PA determinants between January 2004 and April 2016. The methodological quality was assessed and relevant information on socio-cultural determinants and any associations with PA was extracted. The available evidence was evaluated based on the importance of potential determinants and the strength of the evidence. Results Twenty SLRs and three MAs encompassing 657 eligible primary studies investigated potential socio-cultural PA determinants, with predominantly moderate methodological quality. Twenty-nine potential PA determinants were identified that were primarily assessed in children and adolescents and investigated the micro-environmental home/household level. We found probable evidence that receiving encouragement from significant others and having a companion for PA were associated with higher PA in children and adolescents, and that parental marital status (living with partner) and experiencing parental modeling were not associated with PA in children. Evidence for the other potential determinants was limited, suggestive, or non-conclusive. In adults, quantitative and conclusive data were scarce. Conclusions A substantial number of SLRs and MAs investigating potential socio-cultural determinants of PA were identified. Our data suggest that receiving social support from significant others may increase PA levels in children and adolescents, whereas parental marital status is not a determinant in children. Evidence for other potential determinants was limited. This was mainly due to inconsistencies in results on potential socio-cultural determinants of PA across reviews and studies

The Value of p-Value in Biomedical Research

Significance tests and the corresponding p-values play a crucial role in decision making. In this commentary the meaning, interpretation and misinterpretation of p-values is presented. Alternatives for evaluating the reported evidence are also discussed

Common variation near CDKN1A, POLD3 and SHROOM2 influences colorectal cancer risk

We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.Swedish Research Council et al.Manuscrip

Cardiovascular and renal outcomes of renin-angiotensin system blockade in adult patients with diabetes mellitus: a systematic review with network meta-analyses

Medications aimed at inhibiting the renin-angiotensin system (RAS) have been used extensively for preventing cardiovascular and renal complications in patients with diabetes, but data that compare their clinical effectiveness are limited. We aimed to compare the effects of classes of RAS blockers on cardiovascular and renal outcomes in adults with diabetes