Wade Thompson

Methodology for Developing Deprescribing Guidelines: Using Evidence and GRADE to Guide Recommendations for Deprescribing.

Background Class 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 Findings Using 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. Conclusion Our 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.

Atypical antipsychotics for insomnia: a systematic review

BACKGROUND Observational evidence suggests that atypical antipsychotics such as quetiapine are increasingly being used to manage insomnia. This is concerning given the uncertain efficacy and potential adverse effects associated with these medications. OBJECTIVES The objectives of this study are to evaluate the benefits and adverse effects of atypical antipsychotics used specifically for insomnia. METHODS The methods used in this study are systematic review and narrative synthesis. DATA SOURCES The data were collected from PubMed; EMBASE; Cochrane Library; PsycINFO; grey literature; and the manufacturers of risperidone, quetiapine and olanzapine. PARTICIPANTS AND INTERVENTIONS Adult patients ≥18 years of age using atypical antipsychotics specifically for primary or co-morbid insomnia for ≥ 1 week were compared to those receiving active intervention or placebo. APPRAISAL AND SYNTHESIS METHODS Two independent reviewers screened titles, abstracts and full-text articles; extracted data; and conducted risk-of-bias analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was completed. RESULTS One double-blind randomized controlled trial (n = 13) met the eligibility criteria. Statistically significant differences were not observed from baseline between quetiapine and placebo after 2 weeks for primary insomnia in terms of total sleep time (mean difference (MD) 52.68 min, 95% CI -27.27 to 132.6), reduction in sleep latency (MD 72.44 min, 95% CI -2.65 to 147.5) or improved sleep satisfaction measured with a visual analogue scale out of 100 (MD 6.16, 95% CI -12.32 to 24.64), despite a trend towards improved sleep parameters. The study was rated as very low quality. CONCLUSIONS AND IMPLICATIONS Very low quality evidence suggests that quetiapine does not significantly improve sleep parameters compared with placebo in primary insomnia, despite a trend towards clinical improvements. Atypical antipsychotics should be avoided in the first-line treatment of primary insomnia until further evidence is available.

Revisiting medication use in a frail 93-year-old man experiencing possible adverse effects.

See also the practice article by Farrell and colleagues at [www.cmaj.ca/lookup/doi/10.1503/cmaj.122012][1] (Oct. 1 issue) and the commentary by Frank at [www.cmaj.ca/lookup/doi/10.1503/cmaj.131568][2] (page [407][3], this issue) A 93-year-old man was referred to a geriatric day hospital for

Managing polypharmacy in a 77-year-old woman with multiple prescribers

A 77-year-old woman was referred to a geriatric day hospital with concerns about mobility and falls, pain, constipation, cognition and polypharmacy. Comorbidities included cerebrovascular disease, coronary artery disease, hypertension, dementia, fibromyalgia, myositis, bipolar disorder, arthritis,

Lack of Evidence to Guide Deprescribing of Antihyperglycemics: A Systematic Review

IntroductionIndividualizing glycemic targets to goals of care and time to benefit in persons with type 2 diabetes is good practice, particularly in populations at risk of hypoglycemia and adverse outcomes relating to the use of antihyperglycemics. Guidelines acknowledge the need for relaxed targets in frail older adults, but there is little guidance on how to safely deprescribe (i.e. stop, reduce or substitute) antihyperglycemics.MethodsThe purpose of this study was to synthesize evidence from all studies evaluating the effects of deprescribing versus continuing antihyperglycemics in older adults with type 2 diabetes. To this end, we searched MEDLINE, EMBASE, and Cochrane Library (July 2015) for controlled studies evaluating the effects of deprescribing antihyperglycemics in adults with type 2 diabetes. All such studies were eligible for inclusion in our study, and two independent reviewers screened titles, abstracts and full-text articles, extracted data, and evaluated risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment and a narrative summary were completed.ResultsWe identified two controlled before-and-after studies, both of very low quality. One study found that an educational intervention decreased glyburide use while not compromising glucose control. The other reported that cessation of antihyperglycemics in elderly nursing home patients resulted in a non-significant increase in glycated hemoglobin (HbA1C). No significant change in hypoglycemia rate was found in the only study with this outcome measure.ConclusionsThere is limited evidence available regarding deprescribing antihyperglycemic medications. Adequately powered, high-quality studies, particularly in the elderly and with clinically important outcomes, are required to support evidence-based decision-making.Protocol registration numberCRD42015017748.

Deprescribing guidelines: An international symposium on development, implementation, research and health professional education

Deprescribing is a clinically important and feasible innovation that ensures medication efficacy, reduces harms, and mitigates polypharmacy. It involves reducing doses or stopping medications that are not useful, no longer needed, or which may be causing harm. It may also involve changing to a safer agent or using non-pharmacological approaches for care instead. Clinical guidelines combined with behaviour changes (of health care providers (HCPs), the public, and health care decision-makers) are needed to integrate deprescribing into routine practice. Using rigorous international standards, the Bruyère Research Institute Deprescribing Guidelines research team validated a ground-breaking deprescribing guideline methodology and developed or co-developed 5 evidence-based deprescribing guidelines. In March 2018, the team hosted an international symposium convening HCPs, researchers, public agencies, policymakers, and patient advocates in Ottawa, Ontario, Canada. This 3-day symposium aimed to facilitate knowledge exchange amongst guideline developers, users, and the public; initiate partnerships and collaborations for new deprescribing guideline recommendations and effectiveness research; and to continue work on HCP deprescribing education activities. An interprofessional planning committee developed an overall agenda, and small groups worked on session objectives and formats for different components: methods for rigorous deprescribing guideline development, implementation experiences, research/evaluation experiences and educational needs. Through a series of keynote speakers, panel discussions, and small working groups, the symposium provided a forum for participants to meet one another, learn about their different experiences with deprescribing guidelines, and develop collaborations for future initiatives. One hundred thirty participants, from 10 countries and representing over 100 institutions and organizations took part. Symposium proceedings are presented in this issue of RSAP for sharing with the wider community engaged in the care of patients with problematic polypharmacy.

Deprescribing: Future directions for research

A World Café workshop was held at the Bruyère Evidence-Based Deprescribing Guidelines Symposium in March 2018 with 30 participants (researchers, clinicians, policy makers, stakeholders). This workshop explored priorities for future work in the field of deprescribing and deprescribing guidelines through group discussion. The discussions were guided by the following questions: (1) What are deprescribing research priorities (to inform guideline development), (2) What outcome measures are important for developing deprescribing guidelines, and (3) How do we evaluate the implementation and effectiveness of deprescribing guidelines? Discussion from all 3 questions identified 6 main priority areas: (1) conducting high-quality and long-term clinical trials that measure patient-important outcomes, (2) focusing on patient involvement and perspectives, (3) investigating the pharmacoeconomics of deprescribing interventions, (4) understanding deprescribing interventions in different populations, (5) generating evidence on clinical management during deprescribing (e.g. managing adverse drug withdrawal effects, subsequent re-prescribing), and (6) implementing interventions in clinical practice. These topics represent what a group of experienced researchers, clinicians, and stakeholders in the field collectively felt was important to consider for design and implementation of future deprescribing studies. The aim is for these findings to stimulate future discussions and be considered by granting agencies, policy makers, deprescribing research networks, and individual researchers planning future deprescribing studies.

Tools for Deprescribing in Frail Older Persons and Those with Limited Life Expectancy: A Systematic Review: Deprescribing tools

To summarize available tools that can assist clinicians in identifying and reducing or stopping (deprescribing) potentially inappropriate medications and that specifically consider frailty or limited life expectancy.

Health care providers’ roles and responsibilities in management of polypharmacy: Results of a modified Delphi

Background: Little is known about the roles that allow interprofessional teams to effectively manage older patients experiencing polypharmacy. Objectives: To identify and examine the consensus on salient interprofessional roles, responsibilities and competencies required in managing polypharmacy. Methods: Four focus groups with 35 team members practising in geriatrics were generated to inform survey development. The sessions generated 63 competencies, roles or responsibilities, which were categorized into 4 domains defined by the Canadian Interprofessional Health Collaborative. The resulting survey was administered nationally to geriatric health care professionals who were asked to rate the importance of each item in managing polypharmacy; we sought agreement within and across professions using a confirmatory 2-round Delphi method. Results: Round 1 was completed by 98 survey respondents and round 2 by 72. There was high intra-professional and interprofessional consensus regarding the importance of competencies among physicians, nurses and pharmacists; though pharmacists rated fewer competencies as important. Less consensus was observed among other health care professionals or they indicated the nonimportance of competencies despite focus group discussion to the contrary. Discussion: Although there is a strong consensus of polypharmacy management competencies across team members who have been more traditionally involved in medication management, there continue to be health care providers with differing understandings of competencies that may contribute to reduced reliance on medication. Lower importance ratings suggest pharmacists may not acknowledge or recognize their own potential roles in interprofessional polypharmacy management. Conclusion: Further exploration to understand the underutilization of professional expertise in managing polypharmacy will contribute to refining role clarity and translating competencies in practical settings, as well as guiding educators regarding curricular content.

Side Effects of Long-Term Proton Pump Inhibitor Use: A Review

Proton pump inhibitors (PPIs) are widely used, and concerns about overuse have been raised. Therefore, side effects are important to be aware of and several suggested side effects of long-term use have been studied. In this MiniReview, we sum up the evidence of side effects related to long-term PPI treatment. Suspected side effects are mainly related to increased susceptibility to infections, secondary hypergastrinaemia, impeded absorption of micronutrients or idiosyncratic reactions. Most of the potential side effects have only been evaluated in observational studies demonstrating conflicting and weak associations with a substantial risk of confounding. However, a high probability of causality seems to be established for the side effects increased risk of gastrointestinal infections and rebound acid hypersecretion following discontinuation of treatment due to secondary hypergastrinaemia. The risk of side effects should not be a reason to withhold PPIs from patients with a true indication, and worry about poorly proven side effects should not lead to unnecessary discontinuation. The most important safety issue regarding PPI therapy is to critically evaluate the indication when initiating treatment and reconsidering the indication in long-term-treated patients.