Cross-age tutoring in kindergarten and elementary school settings: A systematic review and meta-analysis

This systematic review summarizes effects of peer tutoring delivered to children between 5 and 11 years old by non-professional tutors, such as classmates, older children and adult community peer volunteers. Inclusion criteria for the review included tutoring studies with a randomized controlled trial design, reliable measures of academic outcomes, and duration of at least 12 weeks. Searches of electronic databases, previous reviews, and contacts with researchers yielded 11,564 titles. After screening, 15 studies were included in the analysis. Cross-age tutoring showed small significant effects for tutees on the composite measure of reading (g = 0.18, 95% CI: 0.08, 0.27, N = 8251), decoding skills (g = 0.29, 95% CI: 0.13, 0.44, N = 7081), and reading comprehension (g = 0.11, 95% CI: 0.01, 0.21, N = 6945). No significant effects were detected for other reading sub-skills or for mathematics. The benefits to tutees of non-professional cross-age peer tutoring can be given a positive, but weak recommendation. Effect Sizes were modest and in the range −0.02 to 0.29. Questions regarding study limitations, lack of cost information, heterogeneity of effects, and the relatively small number of studies that have used a randomized controlled trial design means that the evidence base is not as strong as it could be. Subgroup analyses of included studies indicated that highly-structured reading programmes were of more benefit than those that were loosely-structured. Large-scale replication trials using factorial designs, reliable outcome measures, process evaluations and logic models are needed to better understand under what conditions, and for whom, cross-age non-professional peer tutoring may be most effective.

Recipient obesity and outcomes after kidney transplantation: a systematic review and meta-analysis

BACKGROUND: The prevalence of obesity is increasing globally and is associated with chronic kidney disease and premature mortality. However, the impact of recipient obesity on kidney transplant outcomes remains unclear. This study aimed to investigate the association between recipient obesity and mortality, death-censored graft loss and delayed graft function (DGF) following kidney transplantation.

METHODS: A systematic review and meta-analysis was conducted using Medline, Embase and the Cochrane Library. Observational studies or randomized controlled trials investigating the association between recipient obesity at transplantation and mortality, death-censored graft loss and DGF were included. Obesity was defined as a body mass index (BMI) of ≥30 kg/m(2). Obese recipients were compared with those with a normal BMI (18.5-24.9 kg/m(2)). Pooled estimates of hazard ratios (HRs) for patient mortality or death-censored graft loss and odds ratios (ORs) for DGF were calculated.

RESULTS: Seventeen studies including 138 081 patients were analysed. After adjustment, there was no significant difference in mortality risk in obese recipients [HR = 1.24, 95% confidence interval (CI) = 0.90-1.70, studies = 5, n = 83 416]. However, obesity was associated with an increased risk of death-censored graft loss (HR = 1.06, 95% CI = 1.01-1.12, studies = 5, n = 83 416) and an increased likelihood of DGF (OR = 1.68, 95% CI = 1.39-2.03, studies = 4, n = 28 847).

CONCLUSIONS: Despite having a much higher likelihood of DGF, obese transplant recipients have only a slightly increased risk of graft loss and experience similar survival to recipients with normal BMI.

A systematic review investigating the effectiveness of Complementary and Alternative Medicine (CAM) for the management of low back and/or pelvic pain (LBPP) in pregnancy

Aim: To evaluate and summarize the current evidence on the effectiveness of complementary and alternative medicine for the management of low back pain and/or pelvic pain in pregnancy.

Background: International research demonstrates that 25-30% of women use complementary and alternative medicine to manage low back and pelvic pain in pregnancy without robust evidence demonstrating its effectiveness.

Design: A systematic review of randomized controlled trials to determine the effectiveness of complementary and alternative medicine for low back and/or pelvic pain in pregnancy.

Data Sources: Cochrane library (1898-2013), PubMed (1996-2013), MEDLINE (1946-2013), AMED (1985-2013), Embase (1974-2013), Cinahl (1937-2013), Index to Thesis (1716-2013) and Ethos (1914-2013).

Review Methods: Selected studies were written in English, randomized controlled trials, a group 1 or 2 therapy and reported pain reduction as an outcome measure. Study quality was reviewed using Risk of Bias and evidence strength the Cochrane Grading of Recommendations and Development Evaluation Tool.

Results: Eight studies were selected for full review. Two acupuncture studies with low risk of bias showed both clinically important changes and statistically significant results. There was evidence of effectiveness for osteopathy and chiropractic. However, osteopathy and chiropractic studies scored high for risk of bias. Strength of the evidence across studies was very low.

Conclusion: There is limited evidence supporting the use of general CAM for managing pregnancy-related low back and/or pelvic pain. However, the restricted availability of high-quality studies, combined with the very low evidence strength, makes it impossible to make evidence-based recommendations for practice.

Online health information - what the newspapers tell their readers: a systematic content analysis

Background: This study investigated the nature of newspaper reporting about online health information in the UK and US. Internet users frequently search for health information online, although the accuracy of the information retrieved varies greatly and can be misleading. Newspapers have the potential to influence public health behaviours, but information has been lacking in relation to how newspapers portray online health information to their readers.

Methods: The newspaper database Nexis (R) UK was searched for articles published from 2003 - 2012 relating to online health information. Systematic content analysis of articles published in the highest circulation newspapers in the UK and US was performed. A second researcher coded a 10% sample to establish inter-rater reliability of coding.

Results: In total, 161 newspaper articles were included in the analysis. Publication was most frequent in 2003, 2008 and 2009, which coincided with global threats to public health. UK broadsheet newspapers were significantly more likely to cover online health information than UK tabloid newspapers (p = 0.04) and only one article was identified in US tabloid newspapers. Articles most frequently appeared in health sections. Among the 79 articles that linked online health information to specific diseases or health topics, diabetes was the most frequently mentioned disease, cancer the commonest group of diseases and sexual health the most frequent health topic. Articles portrayed benefits of obtaining online health information more frequently than risks. Quotations from health professionals portrayed mixed opinions regarding public access to online health information. 108 (67.1%) articles directed readers to specific health-related web sites. 135 (83.9%) articles were rated as having balanced judgement and 76 (47.2%) were judged as having excellent quality reporting. No difference was found in the quality of reporting between UK and US articles.

Conclusions: Newspaper coverage of online health information was low during the 10-year period 2003 to 2012. Journalists tended to emphasise the benefits and understate the risks of online health information and the quality of reporting varied considerably. Newspapers directed readers to sources of online health information during global epidemics although, as most articles appeared in the health sections of broadsheet newspapers, coverage was limited to a relatively small readership.

Early childhood neurodevelopment after intrauterine growth restriction: a systematic review

BACKGROUND AND OBJECTIVE: Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR.

METHODS: PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines.

RESULTS: Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR.

CONCLUSIONS: Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies.

A systematic review of population based epidemiological studies in Myasthenia Gravis

Background: The aim was to collate all myasthenia gravis (MG) epidemiological studies including AChR MG and MuSK MG specific studies. To synthesize data on incidence rate (IR), prevalence rate (PR) and mortality rate (MR) of the condition and investigate the influence of environmental and technical factors on any trends or variation observed.

Methods: Studies were identified using multiple sources and meta-analysis performed to calculate pooled estimates for IR, PR and MR.

Results: 55 studies performed between 1950 and 2007 were included, representing 1.7 billion population-years. For All MG estimated pooled IR (eIR): 5.3 per million person-years (C.I.: 4.4, 6.1), range: 1.7 to 21.3; estimated pooled PR: 77.7 per illion persons (C.I.: 64.0, 94.3), range 15 to 179; MR range 0.1 to 0.9 per millions person-years. AChR MG eIR: 7.3 (C.I.: 5.5, 7.8), range: 4.3 to 18.0; MuSK MG IR range: 0.1 to 0.32. However marked variation persisted between populations studied with similar methodology and in similar areas.

Conclusions: We report marked variation in observed frequencies of MG. We show evidence of increasing frequency of MG with year of study and improved study quality. This probably reflects improved case ascertainment. But other factors must also influence disease onset resulting in the observed variation in IR across geographically and genetically similar populations.

Patience, Persistence and Pragmatism: Experiences and Lessons Learnt from the Implementation of Clinically Integrated Teaching and Learning of Evidence-Based Health Care - A Qualitative Study

Background

Clinically integrated teaching and learning are regarded as the best options for improving evidence-based healthcare (EBHC) knowledge, skills and attitudes. To inform implementation of such strategies, we assessed experiences and opinions on lessons learnt of those involved in such programmes.

Methods and Findings

We conducted semi-structured interviews with 24 EBHC programme coordinators from around the world, selected through purposive sampling. Following data transcription, a multidisciplinary group of investigators carried out analysis and data interpretation, using thematic content analysis. Successful implementation of clinically integrated teaching and learning of EBHC takes much time. Student learning needs to start in pre-clinical years with consolidation, application and assessment following in clinical years. Learning is supported through partnerships between various types of staff including the core EBHC team, clinical lecturers and clinicians working in the clinical setting. While full integration of EBHC learning into all clinical rotations is considered necessary, this was not always achieved. Critical success factors were pragmatism and readiness to use opportunities for engagement and including EBHC learning in the curriculum; patience; and a critical mass of the right teachers who have EBHC knowledge and skills and are confident in facilitating learning. Role modelling of EBHC within the clinical setting emerged as an important facilitator. The institutional context exerts an important influence; with faculty buy-in, endorsement by institutional leaders, and an EBHC-friendly culture, together with a supportive community of practice, all acting as key enablers. The most common challenges identified were lack of teaching time within the clinical curriculum, misconceptions about EBHC, resistance of staff, lack of confidence of tutors, lack of time, and negative role modelling.

Conclusions

Implementing clinically integrated EBHC curricula requires institutional support, a critical mass of the right teachers and role models in the clinical setting combined with patience, persistence and pragmatism on the part of teachers.

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.

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

PURPOSE: This systematic review reports on the survival of feldspathic porcelain veneers.

MATERIALS AND METHODS: The Cochrane Library, MEDLINE (OVID), Embase, Web of Knowledge, selected journals, clinical trials registers, and conference proceedings were searched independently by two reviewers. Academic colleagues were also contacted to identify relevant research. Inclusion criteria were human cohort studies (prospective and retrospective) and controlled trials assessing outcomes of feldspathic porcelain veneers in more than 15 patients and with at least some of the veneers in situ for 5 years. Of 4,294 articles identified, 116 studies underwent full-text screenings and 69 were further reviewed for eligibility. Of these, 11 were included in the qualitative analysis and 6 (5 cohorts) were included in meta-analyses. Estimated cumulative survival and standard error for each study were assessed and used for meta-, sensitivity, and post hoc analyses. The I2 statistic and the Cochran Q test and its associated P value were used to evaluate statistical heterogeneity, with a random-effects meta-analysis used when the P value for heterogeneity was less than .1. Galbraith, forest, and funnel plots explored heterogeneity, publication patterns, and small study biases.

RESULTS: The estimated cumulative survival for feldspathic porcelain veneers was 95.7% (95% confidence interval [CI]: 92.9% to 98.4%) at 5 years and ranged from 64% to 95% at 10 years across three studies. A post hoc meta-analysis indicated that the 10-year best estimate may approach 95.6% (95% CI: 93.8% to 97.5%). High levels of statistical heterogeneity were found.

CONCLUSIONS: When bonded to enamel substrate, feldspathic porcelain veneers have a very high 10-year survival rate that may approach 95%. Clinical heterogeneity is associated with differences in reported survival rates. Use of clinically relevant survival definitions and careful reporting of tooth characteristics, censorship, clustering, and precise results in future research would improve metaanalytic estimates and aid treatment decisions.

Physical rehabilitation interventions for adult intensive care patients across the continuum of recovery (i.e. within the intensive care unit (ICU) and following ICU and hospital discharge): an overview of systematic reviews

Background
Patients admitted to the intensive care unit with critical illness often experience significant physical impairments, which typically persist for many years following resolution of the original illness. Physical rehabilitation interventions that enhance restoration of physical function have been evaluated across the continuum of recovery following critical illness including within the intensive care unit, following discharge to the ward and beyond hospital discharge. Multiple systematic reviews have been published appraising the expanding evidence investigating these physical rehabilitation interventions, although there appears to be variability in review methodology and quality. We aim to conduct an overview of existing systematic reviews of physical rehabilitation interventions for adult intensive care patients across the continuum of recovery.

Methods/design
This protocol has been developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. We will search the Cochrane Systematic Review Database, Database of Abstracts of Reviews of Effectiveness, Cochrane Central Register of Controlled Trials, MEDLINE, Excerpta Medica Database and Cumulative Index to Nursing and Allied Health Literature databases. We will include systematic reviews of randomised controlled trials of adult patients, admitted to the intensive care unit and who have received physical rehabilitation interventions at any time point during their recovery. Data extraction will include systematic review aims and rationale, study types, populations, interventions, comparators, outcomes and quality appraisal method. Primary outcomes of interest will focus on findings reflecting recovery of physical function. Quality of reporting and methodological quality will be appraised using the PRISMA checklist and the Assessment of Multiple Systematic Reviews tool.

Discussion
We anticipate the findings from this novel overview of systematic reviews will contribute to the synthesis and interpretation of existing evidence regarding physical rehabilitation interventions and physical recovery in post-critical illness patients across the continuum of recovery.

Pan-retinal photocoagulation and other forms of laser treatment and drug therapies for non-proliferative diabetic retinopathy: systematic review and economic evaluation

BACKGROUND: Diabetic retinopathy is an important cause of visual loss. Laser photocoagulation preserves vision in diabetic retinopathy but is currently used at the stage of proliferative diabetic retinopathy (PDR).

OBJECTIVES: The primary aim was to assess the clinical effectiveness and cost-effectiveness of pan-retinal photocoagulation (PRP) given at the non-proliferative stage of diabetic retinopathy (NPDR) compared with waiting until the high-risk PDR (HR-PDR) stage was reached. There have been recent advances in laser photocoagulation techniques, and in the use of laser treatments combined with anti-vascular endothelial growth factor (VEGF) drugs or injected steroids. Our secondary questions were: (1) If PRP were to be used in NPDR, which form of laser treatment should be used? and (2) Is adjuvant therapy with intravitreal drugs clinically effective and cost-effective in PRP?

ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) for efficacy but other designs also used.

REVIEW METHODS: Systematic review and economic modelling.

RESULTS: The Early Treatment Diabetic Retinopathy Study (ETDRS), published in 1991, was the only trial designed to determine the best time to initiate PRP. It randomised one eye of 3711 patients with mild-to-severe NPDR or early PDR to early photocoagulation, and the other to deferral of PRP until HR-PDR developed. The risk of severe visual loss after 5 years for eyes assigned to PRP for NPDR or early PDR compared with deferral of PRP was reduced by 23% (relative risk 0.77, 99% confidence interval 0.56 to 1.06). However, the ETDRS did not provide results separately for NPDR and early PDR. In economic modelling, the base case found that early PRP could be more effective and less costly than deferred PRP. Sensitivity analyses gave similar results, with early PRP continuing to dominate or having low incremental cost-effectiveness ratio. However, there are substantial uncertainties. For our secondary aims we found 12 trials of lasers in DR, with 982 patients in total, ranging from 40 to 150. Most were in PDR but five included some patients with severe NPDR. Three compared multi-spot pattern lasers against argon laser. RCTs comparing laser applied in a lighter manner (less-intensive burns) with conventional methods (more intense burns) reported little difference in efficacy but fewer adverse effects. One RCT suggested that selective laser treatment targeting only ischaemic areas was effective. Observational studies showed that the most important adverse effect of PRP was macular oedema (MO), which can cause visual impairment, usually temporary. Ten trials of laser and anti-VEGF or steroid drug combinations were consistent in reporting a reduction in risk of PRP-induced MO.

LIMITATION: The current evidence is insufficient to recommend PRP for severe NPDR.

CONCLUSIONS: There is, as yet, no convincing evidence that modern laser systems are more effective than the argon laser used in ETDRS, but they appear to have fewer adverse effects. We recommend a trial of PRP for severe NPDR and early PDR compared with deferring PRP till the HR-PDR stage. The trial would use modern laser technologies, and investigate the value adjuvant prophylactic anti-VEGF or steroid drugs.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005408.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Traumatic brain injury and co-occurring problems in prison populations: a systematic review.

Background: A growing body of epidemiological research suggests high rates of traumatic brain injury (TBI) in prisoners. The aim of this review is to systematically explore the literature surrounding the rates of TBI and their co-occurrences in a prison population.
Methods: Six electronic databases were systematically searched for articles published between 1980 and 2014. Studies were screened for inclusion based on predetermined criteria by two researchers who independently performed data extraction. Study quality was appraised based on a modified quality assessment tool.
Results: Twenty six studies were included in this review. Quality assessment ranged from 20% (poor) to 80% (good) with an overall average of 60%. Twenty four papers included TBI prevalence rates, which ranged from 5.69%-88%. Seventeen studies explored co-occurring factors including rates of aggression (n=7), substance abuse (n=9), anxiety and depression (n=5), neurocognitive deficits (n=4), and psychiatric conditions (n=3).
Conclusions: The high degree of variation in TBI rates may be attributed to the inconsistent way in which TBI was measured with only seven studies using valid and reliable screening tools. Additionally, gaps in the literature surrounding personality outcomes in prisoners with TBI, female prisoners with TBI, and qualitative outcomes were found.

Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review

Objective: To summarise the findings of an updated Cochrane review of interventions aimed at improving the appropriate use of polypharmacy in older people. Design: Cochrane systematic review. Multiple electronic databases were searched including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (from inception to November 2013). Hand searching of references was also performed. Randomised controlled trials (RCTs), controlled clinical trials, controlled before-and-after studies and interrupted time series analyses reporting on interventions targeting appropriate polypharmacy in older people in any healthcare setting were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation).
Setting: All healthcare settings. 
Participants: Older people (≥65 years) with ≥1 long-term condition who were receiving polypharmacy (≥4 regular medicines).
Primary and secondary outcome measures: Primary outcomes were the change in prevalence of appropriate polypharmacy and hospital admissions. Medication-related problems (eg, adverse drug reactions), medication adherence and quality of life were included as secondary outcomes.
Results: 12 studies were included: 8 RCTs, 2 cluster RCTs and 2 controlled before-and-after studies. 1 study involved computerised decision support and 11 comprised pharmaceutical care approaches across various settings. Appropriateness was measured using validated tools, including the Medication Appropriateness Index, Beers’ criteria and Screening Tool of Older Person’s Prescriptions (STOPP)/ Screening Tool to Alert doctors to Right Treatment (START). The interventions demonstrated a reduction in inappropriate prescribing. Evidence of effect on hospital admissions and medication-related problems was conflicting. No differences in health-related quality of life were reported.
Conclusions: The included interventions demonstrated improvements in appropriate polypharmacy based on reductions in inappropriate prescribing. However, it remains unclear if interventions resulted in clinically significant improvements (eg, in terms of hospital admissions). Future intervention studies would benefit from available guidance on intervention development, evaluation and reporting to facilitate replication in clinical practice.

Risk factors (excluding hormone therapy) for endometrial hyperplasia: a systematic review.

Objective: To conduct a systematic review of risk factors associated with the development of Endometrial Hyperplasia (EH).

Data sources: Ovid MEDLINE, EMBASE and Web of Science databases were searched from inception to 30 June 2015.

Study eligibility: Fifteen observational studies that reported on EH risk in relation to lifestyle factors (n=14), medical history (n=11), reproductive and menstrual history (n=9) and measures of socio-economic status (n=2) were identified. Pooled relative risk estimates and corresponding 95% confidence intervals (CI) were able to be derived for EH and Body Mass Index (BMI), smoking, diabetes and hypertension, using random effects models comparing high versus low categories.

Results: The pooled relative risk for EH when comparing women with the highest versus lowest BMI was 1.82 (95% CI 1.22–2.71; n=7 studies, I2=90.4%). No significant associations were observed for EH risk for smokers compared with non-smokers (RR 0.88, 95% CI 0.66-1.17; n=3, I2=0.0%), hypertensive versus normotensive women (RR 1.51, 95% CI 0.72–3.15; n=5 studies, I2=79.1%), or diabetic versus non-diabetic women (RR 1.77, 95% CI 0.79–3.96; n=5 studies, I2=31.8%) respectively although the number of included studies was limited. There were mixed reports on the relationship between age and risk of EH. Too few studies reported on other factors to reach any conclusions in relation to EH risk.

Conclusions: A high BMI was associated with an increased risk of EH, providing additional rationale for women to maintain a normal body weight. No significant associations were detected for other factors and EH risk, however relatively few studies have been conducted and few of the available studies adequately adjusted for relevant confounders. Therefore, further aetiological studies of endometrial hyperplasia are warranted.

Markers of vitamin D exposure and oesophageal cancer risk: a systematic review and meta-analysis.

Vitamin D has been associated with reduced risk of many cancers, but evidence for oesophageal cancer is mixed. To clarify the role of Vitamin D, we performed a systematic review and meta-analysis to evaluate the association of Vitamin D exposures and oesophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's oesophagus and squamous dysplasia. Ovid MEDLINE, EMBASE and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D (n=3), Vitamin D intake (n=4), UVB exposure (n=1), and genetic factors (n=7) were retrieved. Higher 25-OHD was associated with increased risk of cancer (adenocarcinoma or SCC, OR=1.39;95%CI:1.04-1.74), with the majority of participants coming from China. No association was observed between Vitamin D intake and risk of cancer overall (OR=1.03;0.65-1.42); however, a non-significantly increased risk for adenocarcinoma (OR=1.45;0.65-2.24) and non-significantly decreased risk for SCC (OR=0.80;0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers, OR=0.45;0.00-0.91, and a suggestive association was observed for rs2107301. No consistent associations were observed between Vitamin D exposures and occurrence of oesophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made.