Murad, M. Hassan

SummaryBackgroundHighly selective 5‐HT4agonists have been suggested for the treatment of chronic constipation (CC).AimTo assess the effects of highly selective 5‐HT4agonists (prucalopride, velusetrag or naronapride) on patient‐important clinical efficacy outcomes and safety in adults withCC.MethodsWe searched the medical literature in January 2013 usingMEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5‐HT4agonists in adults withCC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention‐to‐treat analyses, pooled using a random‐effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI).ResultsMain outcomes included stool frequency, Patient‐Assessment of Constipation Quality of Life (PAC‐QOL),PACof symptoms (PAC‐SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5‐HT4agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95%CI1.23–2.79); mean ≥1SCBMover baseline (RR = 1.57; 95%CI1.19, 2.06); ≥1 point improvement inPAC‐QOLandPAC‐SYMscores. The only active comparator trial of prucalopride andPEG3350 suggestedPEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5‐HT4agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride.ConclusionDemonstration of efficacy on patient‐important outcomes and a favourable safety profile support the continued use and development of highly selective 5–HT4agonists in the treatment of chronic constipation.

Abstract Objective Our objective was to formulate a clinical practice guideline for the management of the pregnant woman with diabetes. Participants The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee of The Endocrine Society, 5 additional experts, a methodologist, and a medical writer. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. Consensus Process One group meeting, several conference calls, and innumerable e-mail communications enabled consensus for all recommendations save one with a majority decision being employed for this single exception. Conclusions Using an evidence-based approach, this Diabetes and Pregnancy Clinical Practice Guideline addresses important clinical issues in the contemporary management of women with type 1 or type 2 diabetes preconceptionally, during pregnancy, and in the postpartum setting and in the diagnosis and management of women with gestational diabetes during and after pregnancy.

AbstractBackgroundVarious components of the skin biopsy requisition form (SBRF) may contribute to accurate dermatopathologic interpretation.MethodsA search of electronic databases, including those of Ovid MEDLINE In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE, Ovid EMBASE, the Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, and Scopus, was conducted from inception to October 2011. Two authors independently screened all articles for eligibility. Inclusion criteria required material to represent original studies on skin biopsy and pathology requisition forms. Data abstracted from each article that met the inclusion criteria included details of the study characteristics, including the study location, type of pathology practice, specimen type, type of dermatoses, medical specialty of the requesting provider, suggested clinical components, and format of the SBRF.ResultsOf 32 titles and abstracts reviewed, seven articles were included. From these, we determined that dermatologists, general practitioners and surgeons completed SBRFs. Commonly included components were patient demographics and requesting clinician characteristics. Clinical information and differential diagnosis were provided in 4% (two of 48 surgeons) to 36% (18 of 50 dermatologists) of requisitions. Most SBRFs did not include information on specimen type, clinical morphology, photographs or clinical history.ConclusionsThe limited medical literature demonstrates variation in the content of SBRFs across clinicians and practices, and suggests an important target for improvement in the quality of communication and dermatologic care by requesting clinicians and pathologists.

Context: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. Objective: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. Data Sources: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). Study Selection: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. Data Extraction: Two authors performed the data extraction independently. Data Synthesis: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, −2.3 mg/dL; 95% confidence interval, −4.5 to −0.1, I2 = 72%, P = .04) and fasting blood insulin (weighted mean difference, −2.1 μU/mL, 95% confidence interval, −3.3 to −1.0, I2 = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. Conclusions: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

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.