In people with mild GERD, on-demand deprescribing may lead to an increase in GI symptoms (e.g. dyspepsia, regurgitation) and probably a reduction in pill burden. There was a decline in participant satisfaction, although heterogeneity was high. There were insufficient data to make a conclusion regarding long-term benefits and harms of PPI discontinuation, although two trials (one on-demand trial and one abrupt discontinuation trial) reported endoscopic findings in their intervention groups at study end.

BackgroundClass specific deprescribing guidelines could help clinicians taper and stop medications no longer needed or which may be causing more harm than benefit. We set out to develop methodology to create such guidelines using evidence-based methods for guideline development, evidence synthesis and recommendation rating.Methods and FindingsUsing a comprehensive checklist for a successful guideline enterprise, we conducted a national modified Delphi consensus process to identify priorities for deprescribing guidelines, then conducted scoping exercises to identify feasible topics, and sequentially developed three deprescribing guidelines. We selected guideline development team members for clinical expertise; a GRADE member worked with staff to ensure guideline development processes were followed. We conducted or used systematic searches and reviews of deprescribing trials of selected drug classes, reviews or systematic reviews of drug class effectiveness, reviews of reviews of drug class harm and narrative syntheses of contextual questions to inform recommendations and guideline development. Our 8 step process for guideline development included defining scope and purpose, developing a logic model to guide the process and generate key clinical questions, setting criteria for admissible evidence and conducting systematic reviews, synthesizing evidence considering additional contextual information and performing quality estimates, formulating recommendations and providing strength estimations, adding clinical considerations, conducting clinical and stakeholder review and finally updating content pre-publication. Innovative aspects of the guideline development process included synthesizing evidence for outcomes of tapering or stopping medication, and incorporating evidence for medication harm into the recommendation strength rating. Through the development of three deprescribing guidelines (for proton pump inhibitors, benzodiazepine receptor agonists and antipsychotics) and associated decision-support algorithms, we were able to gradually hone the methodology; each guideline will be published separately.ConclusionOur methodology demonstrates the importance of searching for short and long-term outcomes, showing the benefits of deprescribing and studying patient preferences. This publication will support development of future deprescribing guidelines.

sociatedcognitive impairment were only 0.1%, it would affect nearly 2500 people in Canada. Since cognitiveimpairment is a potentially debilitating adverse effect, it is importantto better understandthis risk to adequately assess the appropriateness of statinsfor individual patients. Additionally, although recent reports have highlighted

The National Lipid Association's Safety Task Force convened a consensus conference of experts to develop a position statement on cognitive function to revise and update that published originally by the Association in the 2006 assessment of statin safety by a panel of neurologists. The current expert panel was charged with addressing the specific issue of potential adverse cognitive effects attributable to statins. Search strategies recently used in systematic reviews were used to identify relevant evidence using keywords and topics via Medline searches from 1966 to December 2013. Manual searches of bibliographies were also conducted. Panel members were asked to use the evidence to formulate answers to a series of questions of relevance to the subject matter. The strength of recommendations and quality of evidence were graded using accepted contemporary definitions and procedures. Recommendations to patients, health professionals, and researchers were put forth by the panel to aid in daily clinical decision making, and in future research endeavors.

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BackgroundFew studies have examined the effectiveness of community-based self-management interventions in older adults with type 2 diabetes mellitus (T2DM) and multiple chronic conditions (MCC). The objectives of this study were to examine the feasibility of implementation in practice (primary) and the feasibility of study methods and potential effectiveness (secondary) of the Aging, Community and Health—Community Partnership Program, a new 6-month interprofessional, nurse-led program to promote diabetes self-management in older adults (>65 years) with T2DM and MCC.MethodsThis study used a prospective one-group pre-test/post-test design. Participants were recruited from a specialized diabetes clinic. They received a median of three in-home/clinic visits by certified diabetes educators (CDEs) and attended a median of three group wellness sessions provided by the CDEs in partnership with a community-based seniors’ association. The primary outcome was the feasibility of the program (acceptability, fidelity, implementation barriers/facilitators). Secondary outcomes included the feasibility of the study methods (recruitment/retention rates and procedures, eligibility criteria, data collection and analysis methods) and potential effectiveness of the program based on 6-month changes in self-reported outcomes including self-management behavior (diet, exercise, self-monitoring), health status (quality of life, mental health), and costs of service use. Analysis of feasibility outcomes was primarily based on descriptive statistics. The potential effectiveness of the program was explored using different tests, with the results expressed using descriptive statistics and effect estimates (95 % confidence intervals).ResultsIn total, 45 (88 %) of 51 eligible persons consented to participate. Of these, 37 (82 %) completed the 6-month follow-up. Participants and providers viewed the program as acceptable and feasible. Participants had a higher SF-12 physical component summary score at 6 months compared with baseline (mean score difference 3.0, 95 % CI 0.2–5.8). Median costs for diabetes care increased over 6 months (reflecting inclusion of program costs), while other service costs either decreased or remained unchanged.ConclusionsThis study offers preliminary evidence that the program was feasible to deliver and acceptable to participants and providers. Initial results suggest that the program may improve physical functioning. A randomized controlled trial is feasible, with some adaptations to the program and study methods that were identified from this feasibility study.Trial registrationClinicaltrials.gov identifier: NCT01880476 Electronic supplementary materialThe online version of this article (doi:10.1186/s40814-016-0063-1) contains supplementary material, which is available to authorized users.

A number of cytochrome P450 (CYP)3A phenotyping probes have been used to characterize the drug interaction potential of new molecular entities; of these, midazolam has emerged as the gold standard. Recently, plasma 4β-hydroxycholesterol (4β-OHC), the metabolite of CYP3A-mediated cholesterol metabolism, has been championed as an endogenous biomarker for CYP3A, particularly during chronic conditions where CYP3A activity is altered by disease and in long-term treatment studies where midazolam administration is not optimal. Multiple studies in humans have shown that 4β-OHC can qualitatively differentiate among weak, moderate, and potent CYP3A induction when an inducer, typically rifampin, is administered for up to 2 weeks. Conversely, longer durations of CYP3A inhibitor administration (ࣙ1 month) appear to be necessary to differentiate among weak, moderate, and potent CYP3A inhibitors. A number of studies have reported statistically significant linear relationships between 4β-OHC plasma concentrations (and 4β-OHC:cholesterol ratios) and midazolam clearance. However, sufficiently powered studies assessing the ability of 4β-OHC or 4β-OHC:cholesterol ratios to measure CYP3A activity (ie, predictive performance) have not been conducted to date. Additional limitations associated with 4β-OHC phenotyping include inability to detect acute changes in CYP3A activity, uncertainty with regard to its intestinal formation, ambiguity surrounding the role of CYP3A5 in its metabolism, and lack of clarity regarding the role of transporters in its disposition. As such, the data do not support the use of 4β-OHC or 4β-OHC:cholesterol ratios as an endogenous biomarker for CYP3A activity. Keywords4β-hydroxycholesterol, biomarker, cytochrome P450 (CYP)3A, drug interaction the European Medicines Agency as a sensitive index substrate for CYP3A metabolism. 8,9 Recently, plasma 4β-hydroxycholesterol (4β-OHC), which is the metabolite of CYP3A4/5-mediated cholesterol metabolism, has been championed as an endogenous biomarker for CYP3A. 10,11 Further, 4β-OHC and 4β-OHC:cholesterol ratios have been suggested as a probe for CYP3A in the drug development process. 11 This review critically examines the use of 4β-OHC as a marker for CYP3A activity and assesses its potential utility for this purpose. Cholesterol and 4β-OHCCholesterol is biotransformed into oxysterols via several pathways including auto-oxidation and

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