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Background Long-term preventive treatment such as treatment with statins should be reassessed among patients approaching end of life. The aim of the study was to describe the rate of discontinuation of statin treatment and factors associated with discontinuation in the 6 months before death. Methods This study is a retrospective cohort study using national registers and blood test results from primary health care patients. Patients in the Copenhagen municipality, Denmark who died between 1997 and 2018 and were statin users during the 10-year period before death were included. We calculated the proportion who remained statin users in the 6-month period before death. Factors associated with discontinuation were tested using logistic regression. Results A total of 55,591 decedents were included. More patients continued treatment (64%, n = 35,693) than discontinued (36%, n = 19,898) the last 6 months of life. The 70 and 80 age groups had the lowest odds of discontinuing compared to the 90 (OR 1.59, 95% CI 0.93–2.72) and 100 (OR 3.11, 95% CI 2.79–3.47) age groups. Increasing comorbidity score (OR 0.89, 95% CI 0.87; 0.90 per 1-point increase) and use of statins for secondary prevention (OR 0.89, 95% CI 0.85; 0.93) reduced the likelihood of discontinuation as did a diagnosis of dementia, heart failure, or cancer. Conclusion A substantial portion of patients continued statin treatment near end of life. Efforts to promote rational statin use and discontinuation are required among patients with limited life expectancy, including establishing clear, practical recommendations about statin discontinuation, and initiatives to translate recommendations into clinical practice.

Deprescribing is the planned and supervised process of stopping a medication when that medication may no longer be necessary, is causing more harm than good or does not align with a person's healthcare goals and treatment preferences. There has been an explosion of deprescribing research published over the last 10 years. Refereed/Peer-reviewed

It is no secret that proton pump inhibitor (PPI) use is common. Around 10% of the general population in some countries take a PPI. That number can climb up to 25% if we look at older people specifically. For most indications, PPIs are recommended for up to 8 weeks, though some people will need them beyond that period (eg, those with high risk of gastrointestinal bleeding, Barrett's esophagus, severe esophagitis, among other reasons). We know that PPIs are often taken for longer than needed or get started when they were never needed in the first place. Most studies looking at rates of unnecessary PPI use suggest around 50% of PPI users take them without ongoing need. Sometimes people stay on PPIs for years unnecessarily.

Contemporary guidelines suggest relaxed glycemic targets in populations with type 2 diabetes mellitus (T2DM) at risk of hypoglycemia, including people with multimorbidity, limited life expectancy or frailty. However, overtreatment remains commonplace. To inform safe deprescribing, a previous systematic review investigated the benefits and harms of deprescribing antihyperglycemics, but identified only limited, very low-quality evidence. We sought to update that review and identify and describe newly published literature on the effects of deprescribing antihyperglycemics in older adults with T2DM.We searched MEDLINE, EMBASE and the Cochrane Library (July 2015 to January 2021) for controlled studies published in English addressing the effects of deprescribing vs continuing antihyperglycemics in adults with T2DM. Two independent reviewers performed title, abstract and full-text screening, data extraction and risk-of-bias assessment. Cochrane's risk-of-bias tools, RoB 2 and ROBINS-I, were used. The findings were summarized narratively. GRADE (Grading of Recommendations, Assessment, Development and Evaluations) was used to evaluate the evidence.We identified 4 additional investigations-2 randomized controlled trials and 2 retrospective cohort studies. After deprescribing, 3 studies reported no clinically significant changes in glucose management and 2 studies reported reductions in adverse events (e.g. hypoglycemia, all-cause mortality and nonspine fractures). However, based on GRADE assessment, we found very low certainty of the evidence due to concerns of risk of bias (e.g. unmeasured confounding), imprecision, and indirectness.Deprescribing antihyperglycemic medications in older adults with T2DM is likely feasible and safe, and benefits may outweigh the harms. However, the evidence indicates very low certainty. Additional deprescribing studies are needed with rigorous methodologies and reporting.

The term deprescribing first appeared in the English medical literature in 20031; however, use of the term did not catch on widely until about 2016 and it has had an exponential rise in use in academia since then. Deprescribing is the process of withdrawal of medications where the harms outweigh the benefits (in the individual), supervised by a healthcare professional. Refereed/Peer-reviewed

BACKGROUND: Discussing life expectancy helps inform decisions related to preventive medication, screening, and personal care planning. Our aim was to systematically review the literature on patient preferences for discussing life expectancy and to identify predictors for these preferences.METHODS: We searched PubMed, Cochrane Library, Embase, MEDLINE, PsycInfo, and gray literature from inception until 17 February 2021. Two authors screened titles/abstracts and full texts, and extracted data and one author assessed quality. The outcome of interest was the proportion of patients willing to discuss life expectancy. We reported descriptive statistics, performed a narrative synthesis, and explored sub-groups of patients according to patient characteristics.RESULTS: A total of 41 studies with an accumulated population of 27,570 participants were included, comprising quantitative survey/questionnaire studies (n=27) and qualitative interview studies (n=14). Willingness to discuss life expectancy ranged from 19 to 100% (median 61%, interquartile range (IQR) 50-73) across studies, with the majority (77%) reporting more than half of subjects willing to discuss. There was considerable heterogeneity in willingness to discuss life expectancy, even between studies from patients with similar ages, diseases, and cultural profiles. The highest variability in willingness to discuss was found among patients with cancer (range 19-100%, median 61%, IQR 51-81) and patients aged 50-64 years (range 19-97%, median 61%, IQR 45-87). This made it impossible to determine predictors for willingness to discuss life expectancy.DISCUSSION: Most patients are willing to discuss life expectancy; however, a substantial proportion is not. Heterogeneity and variability in preferences make it challenging to identify clear predictors of willingness to discuss. Variability in preferences may to some extent be influenced by age, disease, and cultural differences. These findings highlight the individual and complex nature in which patients approach this topic and stress the importance of clinicians considering eliciting patient's individual preferences when initiating discussions about life expectancy.

Background Deprescribing (planned, supervised discontinuation) of statins may be considered in some older persons. This should be carefully discussed between patients and GPs. Methods We examined GPs’ preferences for discussing statin deprescribing by conducting a discrete choice experiment (DCE) sent to a stratified random sample of 500 Danish GPs. Attributes were discussion topics (goals of therapy, evidence on statin use in older persons, adverse effects, uncertainty), and levels were the depth of the discussion topics (none, brief, detailed). We used mixed logistic regression for analysis. Results A total of 90 GPs (mean age 48, 54% female, mean 11 years in practice) completed the DCE. There was substantial variability in which topics GPs felt were most important to discuss; however, GPs generally preferred a brief discussion of topics to detailed ones. The most important discussion topic appeared to be goals of therapy. GPs felt a brief discussion of evidence was important but not a detailed one, while adverse effects and uncertainty were felt to be less important to discuss. Conclusion GPs prefer brief discussions on a range of topics when discussing statin deprescribing but have differing views on which topics are most important. For deprescribing communication tools to be useful to GPs in clinical practice, they may need to focus on brief coverage of the range of relevant topics. Future work should evaluate patient preferences, and opportunities for education and training for GPs on deprescribing communication.

Background Deprescribing of proton pump inhibitors (PPIs) can be considered in situations where the drug may no longer be necessary; however, this requires a careful discussion between patients and healthcare providers, often general practitioners (GPs). The aim of our study was to explore how GPs discuss PPI deprescribing with patients and compare that to how older patients would like to discuss this decision. Methods We conducted a qualitative study using semi-structured interviews with GPs (n = 11) and patients aged ≥65 years who were taking PPIs (n = 4). Analysis of interviews was based on systematic text condensation. Results We identified four main themes: (1) Reasons PPI deprescribing comes up, (2) Considering PPI deprescribing, (3) Discussion topics, and (4) Incorporating patient preferences into PPI deprescribing decisions. We found that PPI deprescribing often comes up during consultations for other problems or due to concern about medication burden in general. GPs discussed topics related to symptom control, such as the possibility of rebound symptoms, the need to taper PPIs, and what to do if symptoms returned. This aligned with what patients felt was important to discuss. Some GPs routinely incorporated patient preferences into decisions, whereas others did not. Conclusion When discussing PPI deprescribing, the GPs in our study generally focused on topics related to symptom control. There was variability in how and if patient preferences were discussed. Greater focus may be needed on developing mechanisms to elicit and incorporate patient preferences into PPI deprescribing decisions. Future research could also explore more systematic approaches to reassess ongoing PPI use in an effort to curb unnecessary long-term use of PPIs.

Unnecessary polypharmacy continues to be a problem among older adults. The field of deprescribing (planned, supervised process of medication discontinuation) aims to address this problem. Deprescribing is a relatively new field despite having grown substantially in recent years. Much of the early research in this area focused on identifying barriers to and facilitators of deprescribing in clinical practice, which contributed to a large body of work on this topic. However, with continuing research around barriers and facilitators, we need to be mindful to undertake research that builds on existing knowledge, addresses known gaps, and advances the field. Additionally, there is a need in deprescribing research to shift focus to developing ways to address known barriers and harness knowledge of facilitators. That is, translating existing knowledge into strategies and tools that can impact clinical practice and lead to practical and sustained deprescribing efforts. Refereed/Peer-reviewed

Refereed/Peer-reviewed Background: Proton pump inhibitors (PPIs) are indicated for disorders including peptic ulcer disease and gastro-oesophageal reflux disease; however, they are often used for longer and at higher doses than recommended, or for indications that are not supported by evidence. Objective: The aim of this article is to outline evidence-based approaches to deprescribing PPIs. Discussion: PPIs are generally well tolerated; however, use beyond eight weeks is rarely indicated and increases the risk of adverse events. PPI deprescribing should be considered when there is no indication for long-term therapy. Evidence supports a patient-centred approach to PPI deprescribing involving stepping down the dose before ceasing or switching to pro re nata (PRN; ‘as needed’) use. Abrupt PPI discontinuation may result in short term rebound acid hypersecretion that can mimic symptom return. This can be minimised with gradual dose tapering prior to discontinuation and managed with PRN treatment. Prescribers should discuss the rationale for PPI deprescribing and involve patients in developing the deprescribing plan.

This cohort study uses registry data from Denmark to evaluate the association between discontinuation of long-term statin treatment and major adverse cardiovascular events among individuals aged 75 years or older., Key Points Question Is statin discontinuation associated with a higher rate of major adverse cardiovascular events than statin continuation among older people receiving long-term treatment with statins? Findings In this cohort study of 27 463 people treated with statins for primary prevention and 39 955 treated for secondary prevention, statin discontinuation was associated with a significantly higher rate of major adverse cardiovascular events for primary prevention and secondary prevention compared with treatment continuation. Meaning In this study, statin discontinuation was associated with a higher rate of cardiovascular events than statin continuation among older people receiving long-term statin treatment, but more definitive evidence is needed., Importance Statin use is common in older persons. Given uncertainties in ongoing benefit, changes in health status, and shifting goals of care and preferences, statin discontinuation may be considered in some older persons, although there is currently little evidence to guide this decision. Objective To evaluate the association between statin discontinuation and the rate of major adverse cardiovascular events (MACE) among people aged 75 years or older who receive long-term statin treatment. Design, Setting, and Participants This cohort study included all persons in Denmark aged 75 years or older who were treated with statins for at least 5 consecutive years as of January 1, 2011. Participants were followed up until December 31, 2016. Data were analyzed from July to November, 2020. Exposure Statin discontinuation. Main Outcomes and Measures Rate of occurrence of MACE and its components (myocardial infarction, ischemic stroke or transient ischemic attack, coronary revascularization, and death due to myocardial infarction or ischemic stroke) in persons continuing statins compared with those discontinuing statins. Confounding adjustment was done using inverse probability of treatment weighting. Analyses were conducted separately for primary prevention (no history of cardiovascular disease) and secondary prevention (history of cardiovascular disease). Results The study included 67 418 long-term statin users, including 27 463 in the primary prevention analysis (median age, 79 years [IQR, 77-83 years]; 18 134 [66%] female) and 39 955 in the secondary prevention analysis (median age, 80 years [IQR, 77-84 years]; 18 717 [47%] female). In both primary and secondary prevention analyses, the rate of MACE was higher among persons who discontinued statins compared with those who continued statins. In the primary prevention cohort, the weighted rate difference was 9 per 1000 person-years (95% CI, 5-12 per 1000 person-years) and the adjusted sub–hazard ratio was 1.32 (95% CI, 1.18-1.48), corresponding to 1 excess MACE per 112 persons who discontinued statins per year. In the secondary prevention cohort, the weighted rate difference was 13 per 1000 person-years (95% CI, 8-17 per 1000 person-years) and the adjusted sub–hazard ratio was 1.28 (95% CI, 1.18-1.39), corresponding to 1 excess MACE per 77 persons who discontinued statins per year. Conclusions and Relevance In this cohort study, among older adults receiving long-term statin treatment, discontinuation of statins was associated with a higher rate of MACE compared with statin continuation in both the primary and the secondary prevention cohorts. These findings suggest a need for robust evidence from randomized clinical trials.

IntroductionSeveral new oral drug classes for type 2 diabetes (T2DM) have been introduced in the last 20 years accompanied by developments in clinical evidence and guidelines. The uptake of new therapies and contemporary use of blood glucose-lowering drugs has not been closely examined in Canada. The objective of this project was to describe these treatment patterns and relate them to changes in provincial practice guidelines.Research design and methodsWe conducted a longitudinal drug utilization study among persons with T2DM aged ≥18 years from 2001 to 2020 in British Columbia (BC), Canada. We used dispensing data from community pharmacies with linkable physician billing and hospital admission records. Laboratory results were available from 2011 onwards. We identified incident users of blood glucose-lowering drugs, then determined sequence patterns of medications dispensed, with stratification by age group, and subgroup analysis for patients with a history of cardiovascular disease.ResultsAmong a cohort of 362 391 patients (mean age 57.7 years old, 53.5% male) treated for non-insulin-dependent diabetes, the proportion who received metformin monotherapy as first-line treatment reached a maximum of 90% in 2009, decreasing to 73% in 2020. The proportion of patients starting two-drug combinations nearly doubled from 3.3% to 6.4%. Sulfonylureas were the preferred class of second-line agents over the course of the study period. In 2020, sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists accounted for 21% and 10% of second-line prescribing, respectively. For patients with baseline glycated hemoglobin (A1C) results prior to initiating diabetic treatment, 41% had a value ≤7.0% and 27% had a value over 8.5%.ConclusionsOral diabetic medication patterns have changed significantly over the last 20 years in BC, primarily in terms of medications used as second-line therapy. Over 40% of patients with available laboratory results initiated T2DM treatment with an A1C value ≤7.0%, with the average A1C value trending lower over the last decade.

Background Deprescribing literature has been increasing rapidly. Our aim was to develop and validate search filters to identify articles on deprescribing in Medline via PubMed and in Embase via Embase.com. Methods Articles published from 2011 to 2020 in a core set of eight journals (covering fields of interest for deprescribing, such as geriatrics, pharmacology and primary care) formed a reference set. Each article was screened independently in duplicate and classified as relevant or non-relevant to deprescribing. Relevant terms were identified by term frequency analysis in a 70% subset of the reference set. Selected title and abstract terms, MeSH terms and Emtree terms were combined to develop two highly sensitive filters for Medline via Pubmed and Embase via Embase.com. The filters were validated against the remaining 30% of the reference set. Sensitivity, specificity and precision were calculated with their 95% confidence intervals (95% CI). Results A total of 23,741 articles were aggregated in the reference set, and 224 were classified as relevant to deprescribing. A total of 34 terms and 4 MeSH terms were identified to develop the Medline search filter. A total of 27 terms and 6 Emtree terms were identified to develop the Embase search filter. The sensitivity was 92% (95% CI: 83–97%) in Medline via Pubmed and 91% (95% CI: 82–96%) in Embase via Embase.com. Conclusions These are the first deprescribing search filters that have been developed objectively and validated. These filters can be used in search strategies for future deprescribing reviews. Further prospective studies are needed to assess their effectiveness and efficiency when used in systematic reviews.

Purpose: To examine use of sedating medications around the time of nursing home admission in Denmark. Methods: We conducted a register-based drug utilization study, describing patterns of commonly used medications with sedative effects leading up to and after nursing home admission using data from 94 Danish nursing homes between 2015 and 2017. Results: We identified 5179 residents (median age 84 years, 63% female) and described monthly incidence and total use of benzodiazepines (BZDs), Z drugs, mirtazapine/mianserin, quetiapine, promethazine, and melatonin. The proportion of unique users of sedating medications was similar before and after admission (42% before vs. 40% after) despite an increase in total use after admission. The overall incidence of sedating medications peaked in the 6 months before and 6 months after admission (peaking at 4.6 per 100 person-months 1 month after admission). The most commonly initiated medications were mirtazapine/mianserin, followed by BZDs and Z drugs. Total use of sedating medications increased leading up to admission (peaking at 1001 defined daily doses per 100 residents per month 1 month after admission) and decreased gradually after admission. Conclusions: Sedative medication initiation increases sharply leading up to admission in Danish nursing homes. Mirtazapine/mianserin is a commonly used agent in nursing homes, despite limited evidence on benefits and harms. Efforts to promote rational use of these medications in nursing homes remain warranted.

INTRODUCTION: Cholinesterase inhibitors (ChEIs) and memantine are medications used to treat the symptoms of specific types of dementia. Their benefits and harms can change over time, particularly during long term use. Therefore, appropriate use of ChEIs and memantine involves both prescribing these medications to individuals who are likely to benefit, and deprescribing (withdrawing) them from individuals when the risks outweigh the benefits. We recently developed an evidence-based clinical practice guideline for deprescribing ChEIs and memantine, using robust international guideline development processes. MAIN RECOMMENDATIONS: Our recommendations aim to assist clinicians to: identify individuals who may be suitable for a trial of deprescribing ChEIs and memantine (such as those who do not have an appropriate indication, those who have never experienced a benefit, those who appear to be no longer benefitting, and those who have severe or end-stage dementia); and taper treatment and monitor individuals during the deprescribing process. CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE: Deprescribing ChEIs and memantine through shared decision making with individuals and their caregivers by: determining their treatment goals; discussing benefits and harms of continuing and ceasing medication, from the start of therapy and throughout; and engaging them in monitoring after discontinuation, while informing carers that the individual will continue to decline after discontinuation. This approach may reduce adverse drug reactions and medication burden, leading to improved quality of life in people with dementia. Refereed/Peer-reviewed

Background and objective There is limited evidence on the clinical effects of statins in older persons. We aimed to explore statin use and discontinuation patterns in Danes age 70 and older. Design Register-based drug utilisation study. Setting Danish nationwide health registries. Subjects All Danish persons aged ≥70 years between 2011 and 2016. Measurements (1) Monthly prevalence and (2) quarterly incidence of statin use, (3) characteristics of new users, (4) total amount of statin redeemed, (5) statin discontinuation rate between 2014 and 2016 in long-term statin users and (6) factors associated with discontinuation. Results We identified 395,279 unique older statin users between 2011 and 2016. The prevalence increased from 30% in 2011 to 33% in 2016 (23% for primary prevention and 56% for secondary prevention in 2016). The quarterly incidence fell from 11 per 1,000 persons in 2011 to 7 per 1,000 persons in 2016. The prevalence was generally stable in those 70 to 79 years. In those aged ≥80 years, the prevalence increased despite decreasing incidence. The proportion of persons initiating for primary prevention decreased from 58% in 2011 to 52% in 2016. Approximately 19% of long-term statin users discontinued therapy between 2014 and 2016. Increasing age was the strongest predictor of statin discontinuation. Conclusions Approximately one in three Danes age ≥ 70 years were taking statins in 2016. The characteristics of incident users shifted between 2011 and 2016, with less people age 80 and older starting on statins and fewer people starting for primary prevention.

Acute upper respiratory tract infections (URTIs) result from viral or bacterial pathogens that infect the upper airways.1 URTIs comprise a range of conditions and symptoms such as cough, sore throat, acute otitis media (AOM), pharyngitis, tonsillitis, rhinitis, common cold, influenza, and sinusitis.1 While serious complications are rare, patients can develop pneumonia and associated adverse sequelae.1 A substantial proportion of health care visits to primary care and other family medicine settings are due to suspected URTIs.2 Most URTIs are viral in origin, meaning they are unlikely to benefit from antibiotics and can often be effectively managed remotely with supportive treatments. Despite this knowledge, antibiotics are often inappropriately prescribed.3 , 4 A descriptive analysis in Ontario estimated unnecessary antibiotic prescribing in primary care at rates of 48.4% for acute sinusitis and 52.6% for acute bronchitis.5 Further, more than 80% of unnecessary antibiotic prescriptions were attributed to respiratory tract conditions and infections.5 Overprescribing contributes to excessive use, unwanted side effects (e.g., allergic reactions, gastrointestinal symptoms, emergency department visits),6 and antibiotic resistance.7 Antibiotic resistance is a global public health threat and its reduction is a priority.8 Initiatives such as Choosing Wisely aim to reduce antibiotic overuse and advise against using antibiotics for URTIs that are viral in origin.7 However, while the risks of inappropriate and overuse are established, antibiotic prescribing is challenging and providers must balance the pressure of diagnostic uncertainty, time constraints, and patient expectations and preferences against the undesirable consequences of overprescribing.8 Thus, there is interest in management approaches that aid decision-making and reduce excessive prescribing and use. Various interventions are available that address inappropriate antibiotic prescribing and the pressures of providing in-person care for patients with URTIs. These include delayed (post-dated) antibiotic prescriptions9 and different interventions to guide the use of antibiotics (e.g., clinical decision support tools, rapid point-of-care testing [POCT], viral prescription pads). 10 The desired outcome is to reduce the overprescribing of antibiotics and antibiotic resistance, and potentially to improve clinical outcomes (e.g., reduce harms from antibiotics) and reduce health care utilization such as hospital and emergency department visits. Changes to health care service delivery and organization due to the COVID-19 pandemic mean providers in primary care face difficulty in caring for patients with URTIs.7 Practical guidance and interventions continue to be required to assist clinicians in making care decisions for patients with upper respiratory tract symptoms. Resources such as the Using Antibiotics Wisely campaign's updated The Cold Standard toolkit provide resources for clinicians to support virtual and in-person management.11 However, there continues to be an interest and need for evaluating contemporary evidence to identify which interventions might be most effective for supporting shared decision-making and optimizing the care of people with URTIs. This report aims to summarize the evidence regarding the clinical effectiveness of delayed antibiotic prescription-filling interventions and other family medicine interventions to influence the use of antibiotics for suspected acute URTIs.

ObjectiveProton pump inhibitor (PPI) use has risen substantially, primarily driven by ongoing use over months to years. However, there is no consensus on how to define long-term PPI use. Our objectives were to review and compare definitions of long-term PPI use in existing literature and describe the rationale for each definition. Moreover, we aimed to suggest generally applicable definitions for research and clinical use.DesignThe databases PubMed and Cochrane Library were searched for publications concerning long-term use of PPIs and ClinicalTrials.gov was searched for registered studies. Two reviewers independently screened the titles, abstracts, and full texts in two series and subsequently extracted data.ResultsA total of 742 studies were identified, and 59 met the eligibility criteria. In addition, two ongoing studies were identified. The definition of long-term PPI use varied from >2 weeks to >7 years. The most common definition was ≥1 year or ≥6 months. A total of 12/61 (20%) of the studies rationalised their definition.ConclusionThe definitions of long-term PPI treatment varied substantially between studies and were seldom rationalised.In a clinical context, use of PPI for more than 8 weeks could be a reasonable definition of long-term use in patients with reflux symptoms and more than 4 weeks in patients with dyspepsia or peptic ulcer. For research purposes, 6 months could be a possible definition in pharmacoepidemiological studies, whereas studies of adverse effects may require a tailored definition depending on the necessary exposure time. We recommend to always rationalise the choice of definition.

BACKGROUND: Hypertension is an important risk factor for subsequent cardiovascular events, including ischaemic and haemorrhagic stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death. Overall, the use of antihypertensive medications has led to reduction in cardiovascular disease, morbidity rates and mortality rates. However, the use of antihypertensive medications is also associated with harms, especially in older people, including the development of adverse drug reactions, drug-drug interactions and can contribute to increasing medication-related burden. As such, discontinuation of antihypertensives may be considered and appropriate in some older people.OBJECTIVES: To investigate whether withdrawal of antihypertensive medications is feasible, and evaluate the effects of withdrawal of antihypertensive medications on mortality, cardiovascular outcomes, hypertension and quality of life in older people.SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to April 2019: the Cochrane Hypertension Specialised Register, CENTRAL (2019, Issue 3), Ovid MEDLINE, Ovid Embase, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also conducted reference checking, citation searches and, when appropriate, contacted study authors to identify any additional studies. The searches had no language restrictions.SELECTION CRITERIA: We included randomised controlled trials (RCTs) of withdrawal versus continuation of antihypertensive medications used for hypertension or primary prevention of cardiovascular disease in older adults (defined as 50 years and over). Participants were eligible if they lived in the community, residential aged care facilities, or were based in hospital settings. We sought to include trials looking at the complete withdrawal of the antihypertensive medication, and those focusing on a dose reduction of the antihypertensive medicine.DATA COLLECTION AND ANALYSIS: We compared the intervention of discontinuing or reducing antihypertensive medication to usual treatment using mean differences (MD) and 95% confidence intervals (95% CIs) for continuous variables and we used Peto odds ratios (ORs) and 95% CI for binary variables. Our primary outcomes included: mortality, myocardial infarction, development of adverse drug reactions or adverse drug withdrawal reactions. Secondary outcomes included: blood pressure, hospitalisation, stroke, success of withdrawing from antihypertensives, quality of life, and falls. Two authors independently, and in duplicate, conducted all stages of study selection, data extraction and quality assessment.MAIN RESULTS: Six RCTs met the inclusion criteria and were included in the review (1073 participants). Study duration and follow-up ranged from 4 weeks to 56 weeks. Meta-analysis of studies showed that, in the discontinuation group compared to continuation, the odds for all-cause mortality were 2.08 (95% CI 0.79 to 5.46; low certainty of evidence), for myocardial infarction 1.86 (95% CI 0.19 to 17.98; very low certainty of evidence) and for stroke 1.44 (95% CI 0.25 to 8.35; low certainty of evidence). Blood pressure was higher in the discontinuation group than the continuation group (systolic blood pressure: MD = 9.75 mmHg, 95% CI 7.33 to 12.18; and diastolic blood pressure: MD = 3.5 mmHg, 95% CI 1.82 to 5.18; low certainty of evidence). For the development of adverse events, meta-analysis was not possible; antihypertensive discontinuation did not appear to increase the risk of adverse events and may lead to resolution of adverse drug reactions, although eligible studies had limited reporting of adverse effects of drug withdrawal (very low certainty of evidence). One study reported hospitalisation with an odds ratio of 0.83 for discontinuation compared to continuation (95% CI 0.33 to 2.10; low certainty of evidence). No studies were identified which reported falls. Between 10.5% and 33.3% of participants in the discontinuation group compared to 9% to 15% in the continuation group experienced raised blood pressure or other clinical criteria (as pre-defined by the studies) that would require restarting of therapy/removal from the study. The sources of bias included selective reporting (reporting bias), lack of blinding of outcome assessment (detection bias), incomplete outcome data (attrition bias), and lack of blinding of participants and personnel (performance bias).AUTHORS' CONCLUSIONS: There is no evidence of an effect of discontinuing compared with continuing antihypertensives used for hypertension or primary prevention of cardiovascular disease in older adults on all-cause mortality and myocardial infarction. The evidence was low to very low certainty mainly due to small studies and low event rates. These limitations mean that we cannot make any firm conclusions about the effect of deprescribing antihypertensives on these outcomes. Future research should focus on populations with the greatest uncertainty of the benefit:risk ratio for use of antihypertensive medications, such as those with frailty, older age groups and those taking polypharmacy, and measure clinically important outcomes such as falls, quality of life and adverse drug events.

BackgroundGiven uncertainty surrounding benefits and harms, shifts in patient health status, and changing patient goals and preferences, statin deprescribing may be considered in some older people. This decision should be carefully discussed between GPs and patients.AimTo explore how GPs discuss deprescribing of statins with their older patients.Design & settingA qualitative study was undertaken using face-to-face, semi-structured interviews with Danish GPs from the regions of Southern Demark and Zealand.MethodThe GP participants belonged to group practices and were identified from personal networks and snowballing. The interviews lasted approximately 30 minutes and were conducted in English. They were analysed using systematic text condensation.ResultsA total of 11 GPs were interviewed and three themes were identified. (1) Reason for initiating a discussion: statin deprescribing mainly came up when GPs reviewed medication lists. There were differences between GPs regarding when or if they brought up deprescribing. (2) Discussion topics: GPs often discussed their interpretation of evidence surrounding statin use in older people. There were differences in how and if GPs discussed patient preferences. GPs viewed uncertainty and life expectancy as difficult to discuss. (3) Depth of discussion: the perceived level of patient engagement, and clinical context, could influence the extent of discussion.ConclusionGPs identified a range of topics that could be discussed with patients surrounding statin deprescribing. The depth and content of discussions varied according to the situation, and between GPs. Challenges may exist in communicating around certain topics, such as uncertainty and life expectancy. Further understanding of how to best communicate around challenging topics, and development of structured frameworks, may help facilitate statin deprescribing discussions. Identifying what patients think is important to discuss would provide necessary insight to promote quality discussions and shared understanding of the decision.

OBJECTIVES 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. DESIGN Systematic review and narrative synthesis. SETTING We searched MEDLINE (via Ovid SP), EMBASE (via Ovid SP), and CINAHL from inception to December 2017, along with grey literature. We included articles that described a tool to guide deprescribing of medications. PARTICIPANTS Frail older persons and older persons with limited life expectancy. MEASUREMENTS Narrative description of tools. RESULTS We identified 15 tools and organized them into three main categories: tools (n = 2) that described a model or framework for approaching deprescribing, tools (n = 9) that outlined a deprescribing approach for the entire medication list, and tools (n = 4) that provided medication‐specific advice. The complexity of the tools ranged from simple lists to detailed, step‐wise protocols. The development methodology varied widely, and the methods used to synthesize the tools were generally not well described. Most tools were based on expert opinion. Only four of the 15 tools have been tested in clinical practice (in very low‐quality studies). CONCLUSION Tools exist to help clinicians deprescribe in frail older persons and those with limited life expectancy. These tools may assist clinicians at various stages in the deprescribing process. However, it remains to be investigated whether use of such tools in practice is likely to improve clinical outcomes or reduce inappropriate medication use. J Am Geriatr Soc 67:172–180, 2019.

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.

Background: Deprescribing of preventive medications may be considered in some nursing home residents. It is important to understand how to effectively communicate around this complex decision, from both a physician and resident perspective. Objective: The objective of this study was to explore how nursing home residents would like to discuss deprescribing of preventive medications with their physicians. Methods: We conducted a qualitative study with face-to-face, semi-structured interviews. Participants were Danish nursing home residents aged ≥70 years deemed cognitively able to participate by nursing staff. They were taking one or more of statins, antihypertensives, antihyperglycemics, or antiplatelets. Interviews were audio recorded and transcribed verbatim. Analysis was conducted based on systematic text condensation. Results: Nine nursing home residents (median age 85 years, seven female) were interviewed. Participants were generally aware of their overall number of medications but unaware of specific medications and why they were taking them. All participants displayed a high degree of trust in their physicians, preferring to defer decisions to them, and generally believed their medication was necessary if their physician had prescribed it. Residents would be open to deprescribing if their physician suggested it but were not aware of the possibility to be involved in the decision (e.g., discuss goals of care and treatment preferences) and had difficulty imagining what they could discuss with their physician about a deprescribing decision. Conclusion: The interviewed nursing home residents could not imagine how they might discuss potential deprescribing of preventive medications with their physician, and what topics would be important. Future work should explore how nursing home residents can be encouraged to be part of such discussions and investigate ways to have residents share their goals and preferences regarding deprescribing.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: 1. To assess the benefits and harms of deprescribing benzodiazepine receptor agonists (BZRAs) in comparison with continued BZRA use. 2. To assess the benefits and harms of deprescribing benzodiazepine receptor agonists (BZRAs) in comparison with usual care.

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. Refereed/Peer-reviewed

BACKGROUND AND OBJECTIVE: Use of statins is considerable among older persons. We investigated factors associated with statin discontinuation in new statin users aged 70 years or older within the first 4 years of use.DESIGN: Register-based descriptive drug utilization study using data from 2008 to 2016.POPULATION/SETTING: All Danish persons, aged 70 years or older, initiating statin treatment.MEASUREMENTS: Rates and predictors of statin discontinuation after 1 year (early), 2 years, and 4 years. Predictors of discontinuation were estimated using logistic regression.RESULTS: We included 83 788 statin initiators. At 1 year, 13% had discontinued their treatment, while another 12% and 13% discontinued after 2 and 4 years, respectively. The overall discontinuation rate over 4 years was 32%. Increasing age was associated with discontinuation at all time points (adjusted odds ratio [OR] = 2.06 [95% confidence interval {CI} = 1.35-3.16] at 1 year, adjusted OR = 3.94 [95% CI, 1.83-8.49] at 4 years, comparing those aged >95 years to those aged 70-74 years). Further, higher comorbidity scores and use of more than 10 medications were modestly associated with discontinuation. Use of statins for secondary prevention was associated with decreased odds of discontinuation compared to primary prevention at 1 year (adjusted OR = 0.74; 95% CI, 0.65-0.83) and at 4 years (adjusted OR = 0.83; 95% CI, 0.72-0.95), along with concomitant use of cardiovascular (CV) therapies. The annual proportion of early discontinuers ranged from 14% to 17% for primary prevention and from 9% to 12% for secondary prevention between 2008 and 2015.DISCUSSION: Statin discontinuation within the first 4 years after initiation appeared to be influenced most strongly by age, and may also be influenced by comorbidity, polypharmacy, use for secondary prevention, and concomitant CV medication use. Future research should clarify reasons for, and discussions about, statin discontinuation and initiation among older persons, to provide additional insight on this topic.

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.

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.

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.Systematic review and narrative synthesis.We searched MEDLINE (via Ovid SP), EMBASE (via Ovid SP), and CINAHL from inception to December 2017, along with grey literature. We included articles that described a tool to guide deprescribing of medications.Frail older persons and older persons with limited life expectancy.Narrative description of tools.We identified 15 tools and organized them into three main categories: tools (n = 2) that described a model or framework for approaching deprescribing, tools (n = 9) that outlined a deprescribing approach for the entire medication list, and tools (n = 4) that provided medication-specific advice. The complexity of the tools ranged from simple lists to detailed, step-wise protocols. The development methodology varied widely, and the methods used to synthesize the tools were generally not well described. Most tools were based on expert opinion. Only four of the 15 tools have been tested in clinical practice (in very low-quality studies).Tools exist to help clinicians deprescribe in frail older persons and those with limited life expectancy. These tools may assist clinicians at various stages in the deprescribing process. However, it remains to be investigated whether use of such tools in practice is likely to improve clinical outcomes or reduce inappropriate medication use. J Am Geriatr Soc 67:172-180, 2019.

Galen's De indolentia, a recently discovered letter-treatise, provides salient evidence for culture, literature, medicine, and philosophy at Rome in the late second century CE. Galen's vast oeuvre offers an important—although often neglected—source for the study of early Christian literature.