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Observational studies have suggested that metformin decreases the incidence of several common cancers. However, findings regarding breast cancer have been mixed. In order to explore this issue, a systematic literature review and meta-analysis were performed with a focus on potential biases. We conducted a comprehensive literature search for all pertinent studies addressing metformin use and breast cancer risk by searching PubMed, Cochrane Library, and Scopus (which includes Embase, ISI Web of Science) using the Mesh terms: “metformin” or “biguanides” or “diabetes mellitus, type 2/therapy” and “cancer” or “neoplasms.” When multiple hazard ratios (HR) or odds ratio (OR) were reported, the most adjusted estimate was used in the base-case analysis. We pooled the adjusted HR and performed sensitivity analyses on duration of metformin use (> or ≤3 years use), study quality (assessed using the GRADE system), and initial observation year of the cohort (before vs after 1997). From a total of 443 citations, 18 full-text articles were considered, and seven independent studies were included. All were observational (four cohort and three case control). Our combined OR of all seven studies was 0.83 (0.71–0.97). Stronger associations were found when analyses were limited to studies estimating the impact of longer metformin use (OR = 0.75. 95 % CI 0.62, 0.91) or among studies that began observing their cohort before 1997 (OR = 0.68. 95 % CI 0.55–0.084). Stratification according to study quality did not affect the combined OR but higher quality studies had smaller CI and achieved statistical significance. Interpretation is limited by the observational nature of reports and different comparison groups. Our analyses support a protective effect of metformin on breast cancer risk among postmenopausal women with diabetes. Clinical trials are needed for definitive determination of the role of metformin in breast cancer risk reduction.

Background Chronic pain has emerged as a disease in itself, affecting a growing number of people. Effective patient-provider communication is central to good pain management because pain can only be understood from the patient’s perspective. We aimed to develop a user-centered tool to improve patient-provider communication about chronic pain and assess its feasibility in real-world settings in preparation for further evaluation and distribution. Methods To identify and prioritize patient treatment goals for chronic pain, strategies to improve patient-provider communication about chronic pain, and facilitate implementation of the tool, we conducted nominal group technique meetings and card sorting with patients with chronic pain and experienced providers ( n  = 12). These findings informed the design of the PainAPP tool. Usability and beta-testing with patients ( n  = 38) and their providers refined the tool and assessed its feasibility, acceptability, and preliminary impact. Results Formative work revealed that patients felt neither respected nor trusted by their providers and focused on transforming providers’ negative attitudes towards them, whereas providers focused on gathering patient information. PainAPP incorporated areas prioritized by patients and providers: assessing patient treatment goals and preferences, functional abilities and pain, and providing patients tailored education and an overall summary that patients can share with providers. Beta-testing involved 38 patients and their providers. Half of PainAPP users shared their summaries with their providers. Patients rated PainAPP highly in all areas. All users would recommend it to others with chronic pain; nearly all trusted the information and said it helped them think about my treatment goals (94%), understand my chronic pain (82%), make the most of my next doctor’s visit (82%), and not want to use opioids (73%) . Beta-testing revealed challenges delivering the tool and summary report to patients and providers in a timely manner and obtaining provider feedback. Conclusions PainAPP appears feasible for use, but further adaptation and testing is needed to assess its impact on patients and providers. Trial registration This study was approved by the University of New England Independent Review Board for the Protection of Human Subjects in Research (012616–019) and was registered with ClinicalTrials.gov (protocol ID: NCT03425266) prior to enrollment. The trial was prospectively registered and was approved on February 7, 2018.

Background. Most people with multiple sclerosis (MS) want to be involved in medical decision making about disease-modifying therapies (DMTs), but new approaches are needed to overcome barriers to participation. Objectives. We sought to develop a shared decision-making (SDM) tool for MS DMTs, evaluate patient and provider responses to the tool, and address challenges encountered during development to guide a future trial. Methods. We created a patient-centered design process informed by image theory to develop the MS-SUPPORT SDM tool. Development included semistructured interviews and alpha and beta testing with MS patients and providers. Beta testing assessed dissemination and clinical integration strategies, decision-making processes, communication, and adherence. Patients evaluated the tool before and after a clinic visit. Results. MS-SUPPORT combines self-assessment with tailored feedback to help patients identify their treatment goals and preferences, correct misperceptions, frame decisions, and promote adherence. MS-SUPPORT generates a personal summary of their responses that patients can share with their provider to facilitate communication. Alpha testing (14 patients) identified areas needing improvement, resulting in reorganization and shortening of the tool. MS-SUPPORT was highly rated in beta testing (15 patients, 4 providers) on patient-provider communication, patient preparation, adherence, and other endpoints. Dissemination through both patient and provider networks appeared feasible. All patient testers wanted to share the summary report with their provider, but only 60% did. Limitations. Small sample size, no comparison group. Conclusions. The development process resulted in a patient-centered SDM tool for MS that may facilitate patient involvement in decision making, help providers understand their patients’ preferences, and improve adherence, though further testing is needed. Beta testing in real-world conditions was critical to prepare the tool for future testing and inform the design of future studies.

Recent experimental data show that exposure to microbes during early childhood can confer immunological tolerance and protect against Crohn's disease (CD). Epidemiological evidence for this link, however, remains controversial. Using prospective data, we examined the link between this hypothesis and risk for CD in children and young adults.MethodsA case-control study design was used. CD cases (diagnosed before age 20 years) were recruited from a tertiary-care pediatric hospital in Montreal, and population-based controls matched for age, gender and, geographical location were selected. Infection data were ascertained from physician-billing records. These records, which use International Classification of Diseases, Ninth Revision diagnostic codes, were consulted retrospectively but provide prospectively collected diagnostic information. Conditional logistic regression analysis was used to study potential associations. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated.ResultsFour hundred nine cases and 1621 controls were included. Regression analysis adjusting for potential confounding variables suggested that any recorded infection before the diagnosis of CD was associated with reduced risk of CD (OR, 0.67; 95% CI, 0.48–0.93). The protective effect was restricted to infections occurring mainly before 5 years of age, with increasing number of infections resulting in greater protection (1–5 infections: OR, 0.74; ≥6 infections: OR, 0.61; P value for trend = 0.039). Infections affecting the oral and upper respiratory tracts, cellulitis, and, enteric infections seemed most protective.ConclusionsOur study provides support for the hygiene hypothesis, whereby exposure to infections in early childhood could potentially reduce risks of CD.