Deprescribing antihypertensive drugs in frail older adults.

Antihypertensive drugs are commonly used by older adults because of the high prevalence of cardiovascular disease and its risk factors, and the increased absolute benefit of blood pressure reduction with increasing age. Clinical trials of blood pressure reduction in older adults have generally excluded older adults with multimorbidity, frailty and limited life expectancy. In this population, the benefit-harm ratio of aggressive blood pressure lowering may become unfavourable; a more relaxed blood pressure target may be appropriate; and deprescribing (cessation or dose reduction) of one or more antihypertensive drugs can be considered. Before deprescribing an antihypertensive drug, it is important to consider other indications for which it may have been prescribed (e.g. heart failure with reduced ejection fraction, diabetic nephropathy, atrial fibrillation). Evidence from randomised controlled deprescribing trials indicates that it is possible to deprescribe antihypertensives in frail older people. However, some patients may experience an increase in blood pressure that warrants restarting the drug. There are limited data on long-term outcomes (follow-up in deprescribing trials ranged from 4 to 56 weeks). The risk of adverse outcomes associated with deprescribing, such as withdrawal effects, can be minimised through appropriate planning, patient engagement, dose tapering and monitoring.

Deprescribing interventions in older adults: An overview of systematic reviews.

OBJECTIVE: The growing deprescribing field is challenged by a lack of consensus around evidence and knowledge gaps. The objective of this overview of systematic reviews was to summarize the review evidence for deprescribing interventions in older adults. METHODS: 11 databases were searched from 1st January 2005 to 16th March 2023 to identify systematic reviews. We summarized and synthesized the results in two steps. Step 1 summarized results reported by the included reviews (including meta-analyses). Step 2 involved a narrative synthesis of review results by outcome. Outcomes included medication-related outcomes (e.g., medication reduction, medication appropriateness) or twelve other outcomes (e.g., mortality, adverse events). We summarized outcomes according to subgroups (patient characteristics, intervention type and setting) when direct comparisons were available within the reviews. The quality of included reviews was assessed using A MeaSurement Tool to Assess systematic Reviews 2 (AMSTAR 2). RESULTS: We retrieved 3,228 unique citations and assessed 135 full-text articles for eligibility. Forty-eight reviews (encompassing 17 meta-analyses) were included. Thirty-one of the 48 reviews had a general deprescribing focus, 16 focused on specific medication classes or therapeutic categories and one included both. Twelve of 17 reviews meta-analyzed medication-related outcomes (33 outcomes: 25 favored the intervention, 7 found no difference, 1 favored the comparison). The narrative synthesis indicated that most interventions resulted in some evidence of medication reduction while for other outcomes we found primarily no evidence of an effect. Results were mixed for adverse events and few reviews reported adverse drug withdrawal events. Limited information was available for people with dementia, frailty and multimorbidity. All but one review scored low or critically low on quality assessment. CONCLUSION: Deprescribing interventions likely resulted in medication reduction but evidence on other outcomes, in particular relating to adverse events, or in vulnerable subgroups or settings was limited. Future research should focus on designing studies powered to examine harms, patient-reported outcomes, and effects on vulnerable subgroups. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178860.

Reducing potentially inappropriate polypharmacy at a national and international level: the impact of deprescribing networks.

INTRODUCTION: Over the past decade, polypharmacy has increased dramatically. Measurable harms include falls, fractures, cognitive impairment, and death. The associated costs are massive and contribute substantially to low-value health care. Deprescribing is a promising solution, but there are barriers. Establishing a network to address polypharmacy can help overcome barriers by connecting individuals with an interest and expertise in deprescribing and can act as an important source of motivation and resources. AREAS COVERED: Over the past decade, several deprescribing networks were launched to help tackle polypharmacy, with evidence of individual and collective impact. A network approach has several advantages; it can spark interest, ideas and enthusiasm through information sharing, meetings and conversations with the public, providers, and other key stakeholders. In this special report, the details of how four deprescribing networks were established across the globe are detailed. EXPERT OPINION: Networks create links between people who lead existing and/or budding deprescribing practices and policy initiatives, can influence people with a shared passion for deprescribing, and facilitate sharing of intellectual capital and tools to take initiatives further and strengthen impact.This report should inspire others to establish their own deprescribing networks, a critical step in accelerating a global deprescribing movement.

What do clinical practice guidelines say about deprescribing? A scoping review.

INTRODUCTION: Deprescribing (medication dose reduction or cessation) is an integral component of appropriate prescribing. The extent to which deprescribing recommendations are included in clinical practice guidelines is unclear. This scoping review aimed to identify guidelines that contain deprescribing recommendations, qualitatively explore the content and format of deprescribing recommendations and estimate the proportion of guidelines that contain deprescribing recommendations. METHODS: Bibliographic databases and Google were searched for guidelines published in English from January 2012 to November 2022. Guideline registries were searched from January 2017 to February 2023. Two reviewers independently screened records from databases and Google for guidelines containing one or more deprescribing recommendations. A 10% sample of the guideline registries was screened to identify eligible guidelines and estimate the proportion of guidelines containing a deprescribing recommendation. Guideline and recommendation characteristics were extracted and language features of deprescribing recommendations including content, form, complexity and readability were examined using a conventional content analysis and the SHeLL Health Literacy Editor tool. RESULTS: 80 guidelines containing 316 deprescribing recommendations were included. Deprescribing recommendations had substantial variability in their format and terminology. Most guidelines contained recommendations regarding for who (75%, n=60), what (99%, n=89) and when or why (91%, n=73) to deprescribe, however, fewer guidelines (58%, n=46) contained detailed guidance on how to deprescribe. Approximately 29% of guidelines identified from the registries sample (n=14/49) contained one or more deprescribing recommendations. CONCLUSIONS: Deprescribing recommendations are increasingly being incorporated into guidelines, however, many guidelines do not contain clear and actionable recommendations on how to deprescribe which may limit effective implementation in clinical practice. A co-designed template or best practice guide, containing information on aspects of deprescribing recommendations that are essential or preferred by end-users should be developed and employed. TRIAL REGISTRATION NUMBER: osf.io/fbex4.

A mixed-methods study on the pharmacological management of pain in Australian and Japanese nursing homes.

BACKGROUND: Understanding how analgesics are used in different countries can inform initiatives to improve the pharmacological management of pain in nursing homes. AIMS: To compare patterns of analgesic use among Australian and Japanese nursing home residents; and explore Australian and Japanese healthcare professionals' perspectives on analgesic use. METHODS: Part one involved a cross-sectional comparison among residents from 12 nursing homes in South Australia (N = 550) in 2019 and four nursing homes in Tokyo (N = 333) in 2020. Part two involved three focus groups with Australian and Japanese healthcare professionals (N = 16) in 2023. Qualitative data were deductively content analysed using the World Health Organization six-step Guide to Good Prescribing. RESULTS: Australian and Japanese residents were similar in age (median: 89 vs 87) and sex (female: 73% vs 73%). Overall, 74% of Australian and 11% of Japanese residents used regular oral acetaminophen, non-steroidal anti-inflammatory drugs or opioids. Australian and Japanese healthcare professionals described individualising pain management and the first-line use of acetaminophen. Australian participants described their therapeutic goal was to alleviate pain and reported analgesics were often prescribed on a regular basis. Japanese participants described their therapeutic goal was to minimise impacts of pain on daily activities and reported analgesics were often prescribed for short-term durations, corresponding to episodes of pain. Japanese participants described regulations that limit opioid use for non-cancer pain in nursing homes. CONCLUSION: Analgesic use is more prevalent in Australian than Japanese nursing homes. Differences in therapeutic goals, culture, analgesic regulations and treatment durations may contribute to this apparent difference.

Comparative Risk of Gout Flares When Initiating or Escalating Various Urate-Lowering Therapy: A Systematic Review With Network Meta-Analysis.

OBJECTIVE: We systematically examined comparative gout flare risk after initiation or escalation of different urate-lowering therapies (ULTs), comparative flare risk with and without concomitant flare prophylaxis, adverse event rates associated with flare prophylaxis, and optimal duration of flare prophylaxis. METHODS: We searched the Medline, Embase, Web of Science, and Cochrane databases and clinical trial registries from inception to November 2021 for trials investigating adults with gout initiating or escalating ULT. We performed random effects network meta-analyses and calculated risk ratios (RRs) between treatments. Bias was assessed using the revised Cochrane risk-of-bias tool. RESULTS: We identified 3,775 records, of which 29 publications (27 trials) were included. When compared to placebo plus prophylaxis, the RR of flares ranged from 1.08 (95% confidence interval [CI] 0.87-1.33) for febuxostat 40 mg plus prophylaxis to RR 2.65 [95% CI 1.58-4.45] for febuxostat 80 mg plus lesinurad 400 mg plus prophylaxis. Compared to ULT alone, the RR of flares was lower for ULT plus rilonacept 160 mg (RR 0.35 [95% CI 0.25-0.50]), ULT plus rilonacept 80 mg (RR 0.43 [95% CI 0.31-0.60]) and ULT plus colchicine (RR 0.50 [95% CI 0.35-0.72]). There was limited evidence for other flare prophylaxis and on prophylaxis harms and optimal duration. Primarily because of missing outcome data and bias in the selection of reported results, 71.4% and 63.4% of studies were assessed as high risk of bias for flares and adverse events, respectively. CONCLUSION: The RR of flares when introducing ULT varies depending on ULT drug and dosing strategies. There were limited data on ULT escalation. Flare prophylaxis with colchicine and rilonacept reduces flare incidence. More research is required on the harms and optimal duration of prophylaxis.

Impact of arterial stiffness on cerebrovascular function: a review of evidence from humans and preclincal models.

With advancing age, the cerebral vasculature becomes dysfunctional, and this dysfunction is associated with cognitive decline. However, the initiating cause of these age-related cerebrovascular impairments remains incompletely understood. A characteristic feature of the aging vasculature is the increase in stiffness of the large elastic arteries. This increase in arterial stiffness is associated with elevated pulse pressure and blood flow pulsatility in the cerebral vasculature. Evidence from both humans and rodents supports that increases in large elastic artery stiffness are associated with cerebrovascular impairments. These impacts on cerebrovascular function are wide-ranging and include reductions in global and regional cerebral blood flow, cerebral small vessel disease, endothelial cell dysfunction, and impaired perivascular clearance. Furthermore, recent findings suggest that the relationship between arterial stiffness and cerebrovascular function may be influenced by genetics, specifically APOE and NOTCH genotypes. Given the strength of the evidence that age-related increases in arterial stiffness have deleterious impacts on the brain, interventions that target arterial stiffness are needed. The purpose of this review is to summarize the evidence from human and rodent studies, supporting the role of increased arterial stiffness in age-related cerebrovascular impairments.

Context matters: using an Evidence to Decision (EtD) framework to develop and encourage uptake of opioid deprescribing guideline recommendations at the point-of-care.

OBJECTIVES: To describe the development and use of an Evidence to Decision (EtD) framework when formulating recommendations for the Evidence-Based Clinical Practice Guideline for Deprescribing Opioid Analgesics. STUDY DESIGN AND SETTING: Evidence was derived from an overview of systematic reviews and qualitative studies conducted with healthcare professionals and people who take opioids for pain. A multidisciplinary guideline development group conducted extensive EtD framework review and iterative refinement to ensure that guideline recommendations captured contextual factors relevant to the guideline target setting and audience. RESULTS: The guideline development group considered and accounted for the complexities of opioid deprescribing at the individual and health system level, shaping recommendations and practice points to facilitate point-of-care use. Stakeholders exhibited diverse preferences, beliefs, and values. This variability, low certainty of evidence, and system-level policies and funding models impacted the strength of the generated recommendations, resulting in the formulation of four 'conditional' recommendations. CONCLUSION: The context within which evidence-based recommendations are considered, as well as the political and health system environment, can contribute to the success of recommendation implementation. Use of an EtD framework allowed for the development of implementable recommendations relevant at the point-of-care through consideration of limitations of the evidence and relevant contextual factors.

Evaluating the Safety of an Educational Deprescribing Intervention: Lessons from the Optimize Trial.

BACKGROUND: Patients, family members, and clinicians express concerns about potential adverse drug withdrawal events (ADWEs) following medication discontinuation or fears of upsetting a stable medical equilibrium as key barriers to deprescribing. Currently, there are limited methods to pragmatically assess the safety of deprescribing and ascertain ADWEs. We report the methods and results of safety monitoring for the OPTIMIZE trial of deprescribing education for patients, family members, and clinicians. METHODS: This was a pragmatic cluster randomized trial with multivariable Poisson regression comparing outcome rates between study arms. We conducted clinical record review and adjudication of sampled records to assess potential causal relationships between medication discontinuation and outcomes. This study included adults aged 65+ with dementia or mild cognitive impairment, one or more additional chronic conditions, and prescribed 5+ chronic medications. The intervention included an educational brochure on deprescribing that was mailed to patients prior to primary care visits, a clinician notification about individual brochure mailings, and an educational tip sheets was provided monthly to primary care clinicians. The outcomes of the safety monitoring were rates of hospitalizations and mortality during the 4 months following brochure mailings and results of record review and adjudication. The adjudication process was conducted throughout the trial and included classifications: likely, possibly, and unlikely. RESULTS: There was a total of 3012 (1433 intervention and 1579 control) participants. There were 420 total hospitalizations involving 269 (18.8%) people in the intervention versus 517 total hospitalizations involving 317 (20.1%) people in the control groups. Adjusted risk ratios comparing intervention to control groups were 0.92 [95% confidence interval (CI) 0.72, 1.16] for hospitalization and 1.19 (95% CI 0.67, 2.11) for mortality. Both groups had zero deaths "likely" attributed to a medication change prior to the event. A total of 3 out of 30 (10%) intervention group hospitalizations and 7 out of 35 (20%) control group hospitalizations were considered "likely" due to a medication change. CONCLUSIONS: Population-based deprescribing education is safe in the older adult population with cognitive impairment in our study. Pragmatic methods for safety monitoring are needed to further inform deprescribing interventions. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia.

Importance: Physicians endorse deprescribing of risky or unnecessary medications for older adults (aged ≥65 years) with dementia, but there is a lack of information on what influences decisions to deprescribe in this population. Objective: To understand how physicians make decisions to deprescribe for older adults with moderate dementia and ethical and pragmatic concerns influencing those decisions. Design, Setting, and Participants: A cross-sectional national mailed survey study of a random sample of 3000 primary care physicians from the American Medical Association Physician Masterfile who care for older adults was conducted from January 15 to December 31, 2021. Main Outcomes and Measures: The study randomized participants to consider 2 clinical scenarios in which a physician may decide to deprescribe a medication for older adults with moderate dementia: 1 in which the medication could cause an adverse drug event if continued and the other in which there is no evidence of benefit. Participants ranked 9 factors related to possible ethical and pragmatic concerns through best-worst scaling methods (from greatest barrier to smallest barrier to deprescribing). Conditional logit regression quantified the relative importance for each factor as a barrier to deprescribing. Results: A total of 890 physicians (35.0%) returned surveys; 511 (57.4%) were male, and the mean (SD) years since graduation was 26.0 (11.7). Most physicians had a primary specialty in family practice (50.4% [449 of 890]) and internal medicine (43.5% [387 of 890]). A total of 689 surveys were sufficiently complete to analyze. In both clinical scenarios, the 2 greatest barriers to deprescribing were (1) the patient or family reporting symptomatic benefit from the medication (beneficence and autonomy) and (2) the medication having been prescribed by another physician (autonomy and nonmaleficence). The least influential factor was ease of paying for the medication (justice). Conclusions and Relevance: Findings from this national survey study of primary care physicians suggests that understanding ethical aspects of physician decision-making can inform clinician education about medication management and deprescribing decisions for older adults with moderate dementia.

Revisiting systematic reviews on deprescribing trials to better inform future practice and research.

Deprescribing aims to address the problem of medication overuse in older adults. There has been an increasing number of systematic reviews of 'deprescribing'. We aimed to describe the categories of trials included in recent systematic reviews, and to make recommendations for future research. We categorized 122 trials included in eight recent deprescribing systematic reviews into: discontinuation, deprescribing implementation, medication optimisation (including medication initiation) and non-initiation trials. We identified heterogeneity and inconsistency in the categories of trials included in deprescribing systematic reviews. For example, 39 trials (32.0%) involved medication initiation in addition to the deprescribing component. It is now time for international researchers to develop and validate terminology used for trials involving discontinuation/deprescribing of medications, and to provide recommendations for evidence synthesis that will better inform future research, and translation into practice and policy.

Clinical practice guideline for deprescribing opioid analgesics: summary of recommendations.

INTRODUCTION: Long term opioids are commonly prescribed to manage pain. Dose reduction or discontinuation (deprescribing) can be challenging, even when the potential harms of continuation outweigh the perceived benefits. The Evidence-based clinical practice guideline for deprescribing opioid analgesics was developed using robust guideline development processes and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology, and contains deprescribing recommendations for adults prescribed opioids for pain. MAIN RECOMMENDATIONS: Eleven recommendations provide advice about when, how and for whom opioid deprescribing should be considered, while noting the need to consider each person's goals, values and preferences. The recommendations aim to achieve: implementation of a deprescribing plan at the point of opioid initiation; initiation of opioid deprescribing for persons with chronic non-cancer or chronic cancer-survivor pain if there is a lack of overall and clinically meaningful improvement in function, quality of life or pain, a lack of progress towards meeting agreed therapeutic goals, or the person is experiencing serious or intolerable opioid-related adverse effects; gradual and individualised deprescribing, with regular monitoring and review; consideration of opioid deprescribing for individuals at high risk of opioid-related harms; avoidance of opioid deprescribing for persons nearing the end of life unless clinically indicated; avoidance of opioid deprescribing for persons with a severe opioid use disorder, with the initiation of evidence-based care, such as medication-assisted treatment of opioid use disorder; and use of evidence-based co-interventions to facilitate deprescribing, including interdisciplinary, multidisciplinary or multimodal care. CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: To our knowledge, these are the first evidence-based guidelines for opioid deprescribing. The recommendations intend to facilitate safe and effective deprescribing to improve the quality of care for persons taking opioids for pain.

Barriers and Enablers in the Use of Parenteral Methotrexate in Rheumatoid Arthritis Patients: A Scoping Review.

OBJECTIVE: Methotrexate (MTX) is effective in controlling disease activity in rheumatoid arthritis (RA). Parenteral MTX may have benefits over oral MTX, but it is rarely used in practice. To better understand this low usage rate, it is necessary to explore the barriers and enablers of therapy from the perspective of RA patients. The objectives of this scoping review were to describe RA patients' perspectives on the barriers and enablers in the use of parenteral MTX and to identify the research gaps in this field. METHODS: The search was performed in Medline, Embase, Scopus, and Cochrane Library from inception to May 2021. Data synthesis was conducted using the Theoretical Framework of Acceptability. This scoping review included any type of study that explored the use of parenteral MTX by adult RA patients from the patients' perspective, written in English. RESULTS: Fifteen studies were included; findings related to the constructs "affective attitude," "burden," "intervention coherence," and "self-efficacy" were explored the most, while some were rarely ("opportunity cost" and "perceived effectiveness") or not ("ethicality") reported. RA patients were generally satisfied with MTX injections ("affective attitude"). From the burden construct, the requirement for dexterity for administering MTX by injection was considered a barrier, whereas the lack of significant pain from MTX injection was considered an enabler. CONCLUSION: The findings suggested that patients generally preferred parenteral MTX formulations with attributes that facilitate self-administration. However, much of the identified research focused on prefilled pen devices, and significant gaps were identified, such as a lack of qualitative research.

Impact of a Comprehensive Intervention Bundle Including the Drug Burden Index on Deprescribing Anticholinergic and Sedative Drugs in Older Acute Inpatients: A Non-randomised Controlled Before-and-After Pilot Study.

INTRODUCTION: Implementation of the Drug Burden Index (DBI) as a risk assessment tool in clinical practice may facilitate deprescribing. OBJECTIVE: The purpose of this study is to evaluate how a comprehensive intervention bundle using the DBI impacts (i) the proportion of older inpatients with at least one DBI-contributing medication stopped or dose reduced on discharge, compared with admission; and (ii) the changes in deprescribing of different DBI-contributing medication classes during hospitalisation. METHODS: This before-and-after study was conducted in an Australian metropolitan tertiary referral hospital. Patients aged ≥ 75 years admitted to the acute aged care service for ≥ 48 h from December 2020 to October 2021 and prescribed DBI-contributing medication were included. During the control period, usual care was provided. During the intervention, access to the intervention bundle was added, including a clinician interface displaying DBI score in the electronic medical record. In a subsequent 'stewardship' period, a stewardship pharmacist used the bundle to provide clinicians with patient-specific recommendations on deprescribing of DBI-contributing medications. RESULTS: Overall, 457 hospitalisations were included. The proportion of patients with at least one DBI-contributing medication stopped/reduced on discharge increased from 29.9% (control period) to 37.5% [intervention; adjusted risk difference (aRD) 6.5%, 95% confidence intervals (CI) -3.2 to 17.5%] and 43.1% (stewardship; aRD 12.1%, 95% CI 1.0-24.0%). The proportion of opioid prescriptions stopped/reduced rose from 17.9% during control to 45.7% during stewardship (p = 0.04). CONCLUSION: Integrating a comprehensive intervention bundle and accompanying stewardship program is a promising strategy to facilitate deprescribing of sedative and anticholinergic medications in older inpatients.

Blood pressure surge with alarm is reduced after exercise and diet intervention in firefighters.

BACKGROUND: Cardiac-related incidents are a public health concern for tactical occupations, and cardiovascular disease rates are higher in these populations compared with civilians. Research is needed to examine blood pressure (BP) responses in firefighters. The pager alert is one occupational hazard, and it is unknown if lifestyle change can reduce the systolic surge response. PURPOSE: To measure BP surge with alarm in firefighters to determine whether the magnitude is lower after a 6-week tactical exercise and Mediterranean-diet intervention. METHODS: SBP and DBP and BP surge levels, circulating markers, vascular health, and fitness were analyzed. BP surge with alarm was captured during a 12-hour workshift. Exercise and diet were self-reported. Diet was tracked with diet scores based on number of servings. RESULTS: Twenty five firefighters (43.4 ±â€…13.9 years) participated. We found changes in the magnitude of BP surge with alarm (SBP surge from16.7 ±â€…12.9 to 10.5 ±â€…11.7 mmHg, P < 0.05; DBP surge from 8.2 ±â€…10.8 to 4.9 ±â€…5.6 mmHg, P > 0.05) after intervention. We confirm that clinical (127.6 ±â€…9.1 to 120 ±â€…8.2 mmHg) and central (122.7 ±â€…11.3 to 118.2 ±â€…10.7 mmHg) SBP levels improve with exercise and diet. We report for the first time in firefighters that oxidative stress markers superoxide dismutase (9.1 ±â€…1.5 to 11.2 ±â€…2.2 U/ml) and nitric oxide (40.4 ±â€…7 to 48.9 ±â€…16.9 µmol/l) levels improve with an exercise and diet intervention. CONCLUSION: These findings have implications toward the benefit that short-term lifestyle changes make toward reducing the alarm stress response in first responders.

Willingness of older people living with dementia and mild cognitive impairment and their caregivers to have medications deprescribed.

BACKGROUND: people living with cognitive impairment commonly take multiple medications including potentially inappropriate medications (PIMs), which puts them at risk of medication related harms. AIMS: to explore willingness to have a medication deprescribed of older people living with cognitive impairment (dementia or mild cognitive impairment) and multiple chronic conditions and assess the relationship between willingness, patient characteristics and belief about medications. METHODS: cross-sectional study using results from the revised Patients' Attitudes Towards Deprescribing questionnaire (rPATDcog) collected as baseline data in the OPTIMIZE study, a pragmatic, cluster-randomised trial educating patients and clinicians about deprescribing. Eligible participants were 65+, diagnosed with dementia or mild cognitive impairment, and prescribed at least five-long-term medications. RESULTS: the questionnaire was mailed to 1,409 intervention patients and 553 (39%) were returned and included in analysis. Participants had a mean age of 80.1 (SD 7.4) and 52.4% were female. About 78.5% (431/549) of participants said that they would be willing to have one of their medications stopped if their doctor said it was possible. Willingness to deprescribe was negatively associated with getting stressed when changes are made and with previously having a bad experience with stopping a medication (P < 0.001 for both). CONCLUSION: most older people living with cognitive impairment are willing to deprescribe. Addressing previous bad experiences with stopping a medication and stress when changes are made to medications may be key points to discuss during deprescribing conversations.