Citations

Abstract Physical activity may be associated with reduced risk of gastric cancer. We performed a systematic review and meta-analysis to evaluate the magnitude of the association and the quality of supporting evidence. After a comprehensive search of bibliographic databases and conference proceedings through February 2013 for observational studies that examined associations between recreational and/or occupational physical activity and gastric cancer risk, we identified 16 studies (seven cohort, nine case control) reporting 11,111 cases of gastric cancer among 1,606,760 patients. Summary adjusted-OR estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Meta-analysis demonstrated that the risk of gastric cancer was 21% lower among the most physically active people as compared with the least physically active people (OR = 0.79; 95% CI, 0.71–0.87) with moderate heterogeneity among studies (I2 = 55%). This protective effect was seen for gastric cancers in the cardia (four studies; OR = 0.80; 95% CI, 0.63–1.00) and distal stomach (five studies; OR = 0.63; 95% CI, 0.52–0.76). The effect size was significantly smaller in high-quality studies (six studies; OR = 0.86; 95% CI, 0.75–0.99), as compared with low-quality studies (10 studies; OR = 0.74; 95% CI, 0.69–0.81). The results were consistent across sex, study quality, study design, and geographic location. In conclusion, meta-analysis of published observational studies indicates that physical activity is associated with reduced risk of gastric cancer. Lifestyle interventions focusing on increasing physical activity may decrease the global burden of gastric cancer, in addition to a myriad of other health benefits. Cancer Prev Res; 7(1); 12–22. ©2013 AACR.

Abstract Background: Antidiabetic medications (ADM) may modify colorectal cancer risk in patients with diabetes mellitus. We performed a systematic review and meta-analysis, evaluating the effect of metformin, thiazolidinediones (TZD), sulfonylureas, and insulin on colorectal cancer risk in diabetic patients. Methods: We conducted a systematic search of multiple bibliographic databases, up to September 2012, for articles that evaluated exposure to metformin, TZD, sulfonylureas, and insulin, reported colorectal cancer risk in patients with diabetes mellitus, and reported OR or provided data for their estimation. Summary OR estimates with 95% confidence intervals (CI) were estimated using the random-effects model. Results: Fifteen studies reporting 13,871 cases of colorectal cancer in 840,787 patients with diabetes mellitus were included. Meta-analysis of observational studies showed an 11% reduction in colorectal cancer risk associated with metformin use (n = 9 studies; OR, 0.89; 95% CI, 0.81–0.99), whereas TZD use was not associated with colorectal cancer risk (n = 5 studies; OR, 0.96; 95% CI, 0.87–1.05). Conversely, a trend toward higher colorectal cancer risk was observed with sulfonylurea (n = 7 studies; OR, 1.11; 95% CI, 0.97–1.26) and insulin (n = 9 studies; OR, 1.33; 95% CI, 0.91–1.94) use, although these associations were not statistically significant. There was considerable heterogeneity across studies, partly explained by study location and adjustment for concomitant use of other ADMs. Post-hoc analysis of randomized controlled trials did not reveal any significant association between ADM and colorectal cancer risk. Conclusions: Meta-analysis of published studies supports a protective association between metformin use and colorectal cancer risk in patients with diabetes mellitus. Impact: Clinical trials on the chemopreventive effect of metformin against colorectal cancer are warranted. Cancer Epidemiol Biomarkers Prev; 22(12); 2258–68. ©2013 AACR.

Background In 2005, the Endocrine Society (TES) adopted the GRADE system of developing clinical practice guidelines. This system facilitates the formulation of evidence-based recommendations by explicitly describing the confidence in estimates (quality of evidence) and strength of each recommendation. Objectives To describe and characterise the relationship between confidence in estimates and strength of recommendation in TES guidelines. Methods We included all published TES guidelines between 2005 (when TES started using GRADE) and 2011. Independently and in duplicate, reviewers extracted, for each recommendation: disease area, confidence in estimates and design of the studies considered, and strength of recommendation. In strong recommendations with low quality of we developed and applied a taxonomy of appropriate recommendations and identified those we considered inappropriate. Results Most of the 357 recommendations issued were supported by evidence warranting low or very low confidence in estimates (256, 72%). Evidence cited in support of these recommendations came exclusively from observational studies in 233 recommendations (65%). Most recommendations were strong (206, 58%); of these, 121 (59%) were supported by evidence warranting low or very low confidence in estimates. In 101/121 (83%), we identified a compelling rationale for the recommendations; in 20 (17%), we did not. Conclusions Most TES strong recommendation based on low quality evidence are justified and appropriate, but a substantial proportion are not. Implications for Guideline Developers Guideline developers should carefully justify any strong recommendations based on low confidence in effect estimates.

Abstract Background There is growing attention towards increasing patient and service user engagement ( PSUE ) in biomedical and health services research. Existing variations in language and design inhibit reporting and indexing, which are crucial to comparative effectiveness in determining best practices. Objective This paper utilizes a systematic review and environmental scan to derive an evidence‐based framework for PSUE . Design A metanarrative systematic review and environmental scan/manual search using scientific databases and other search engines, along with feedback from a patient advisory group ( PAG ). Eligible sources English‐language studies, commentaries, grey literature and other sources (including systematic and non‐systematic reviews) pertaining to patient and public involvement in biomedical and health services research. Data extracted Study description (e.g. participant demographics, research setting) and design, if applicable; frameworks, conceptualizations or planning schemes for PSUE ‐related endeavours; and methods for PSUE initiation and gathering patients'/service users' input or contributions. Results Overall, 202 sources were included and met eligibility criteria; 41 of these presented some framework or conceptualization of PSUE . Sources were synthesized into a two‐part framework for PSUE: (i) integral PSUE components include patient and service user initiation, reciprocal relationships, colearning and re‐assessment and feedback, (ii) sources describe PSUE at several research stages, within three larger phases: preparatory, execution and translational. Discussion and Conclusions Efforts at developing a solid evidence base on PSUE are limited by the non‐standard and non‐empirical nature of much of the literature. Our proposed two‐part framework provides a standard structure and language for reporting and indexing to support comparative effectiveness and optimize PSUE .

Background and Purpose— Use of endovascular coiling for treatment of ruptured and unruptured intracranial aneurysms (IAs) in the elderly is increasing. We performed a meta-analysis of the literature examining clinical and angiographic outcomes for treatment of IAs in the elderly. Methods— We performed a comprehensive review of the literature from 1995 to 2012, reporting series of patients ≥65 years of age with ruptured or unruptured IAs treated with endovascular approach. Event rates were pooled across studies using random effects meta-analysis. Results— A total of 21 studies reporting on 1511 patients were included. Long-term aneurysm occlusion rates were 79% (95% confidence interval [CI], 70%–85%). Perioperative stroke occurred in 4% (95% CI, 3%–6%), with similar rates between patients with ruptured (5%; 95% CI, 3%–7%) and unruptured aneurysms (4%; 95% CI, 1%–14%; P =0.68). Intraprocedural rupture occurred in 1% (95% CI, 0%–3%) and 4% (95% CI, 2–6%; P =0.04) of patients with unruptured and ruptured aneurysms, respectively. Perioperative mortality rate for patients with ruptured aneurysms was 23% (95% CI, 17%–30%) and 1% (95% CI, 0%–6%) for patients with unruptured aneurysms ( P <0.01). Rates of good clinical outcome at 1 year were 93% (95% CI, 88%–96%) and 66% (95% CI, 59%–72%) in patients with unruptured and ruptured aneurysms, respectively. Conclusions— This study suggests that endovascular treatment of IAs in the elderly is associated with high long-term occlusion rates. Given the morbidity and mortality associated with endovascular treatment of IAs in the elderly, careful patient selection, especially in the case of patients with unruptured aneurysm, is recommended.

AimTreatment of hepatitis C genotype 4 (HCV‐G4) with pegylated interferon (PEG IFN) has not been adequately studied and is considered to be challenging. The aim of this meta‐analysis is to systematically review and evaluate the effectiveness of 48 weeks of combined PEG IFN plus ribavirin (RBV) compared to standard interferon (IFN) plus RBV. The outcome of interest is sustained virological response (SVR).MethodsWe searched for eligible randomized controlled trials (RCT) through May 2012. Random effects meta‐analysis was used to pool the risk ratio (RR) of achieving SVR across trials.ResultsFive RCT enrolling 386 patients were included. The PEG IFN/RBV group had increased likelihood of achieving SVR (RR = 1.51, 95% confidence interval [CI] = 1.08–2.10). SVR was significantly higher in PEG IFN‐α‐2a compared to the ‐α‐2b group (P = 0.02). There was no statistically significant effect of ribavirin dosage on SVR (P = 0.55). The quality of evidence was moderate overall and limited by heterogeneity.ConclusionIn treatment‐naive patients with HCV‐G4, treatment with PEG IFN plus RBV achieves higher SVR rate than treatment with IFN plus RBV.