Publications by authors named "Sarah N Hilmer"

225 Publications

Bridging geriatric medicine, clinical pharmacology and ageing biology to understand and improve outcomes of medicines in old age and frailty.

Authors:
Sarah N Hilmer

Ageing Res Rev 2021 Sep 3;71:101457. Epub 2021 Sep 3.

Kolling Institute, University of Sydney and Royal North Shore Hospital, St Leonards, NSW 2065, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.arr.2021.101457DOI Listing
September 2021

Consumer attitudes towards deprescribing: a systematic review and meta-analysis.

J Gerontol A Biol Sci Med Sci 2021 Aug 14. Epub 2021 Aug 14.

University of South Australia, UniSA: Clinical and Health Sciences, Quality Use of Medicines and Pharmacy Research Centre (QUMPRC), Adelaide, SA, Australia.

Background: Harmful and/or unnecessary medications use in older adults is common. This indicates deprescribing (supervised withdrawal of inappropriate medicines) is not happening as often as it should. This study aimed to synthesise the results of the Patients' Attitudes Towards Deprescribing (PATD) questionnaire (and revised versions).

Methods: Databases were searched from January 2013 to March 2020. Google Scholar was used for citation searching of the development and validation manuscripts to identify original research using the validated PATD, revised PATD (older adult and caregiver versions) and the version for people with cognitive impairment (rPATDcog).Two authors extracted data independently. A meta-analysis of proportions (random-effects model) was conducted with sub-group meta-analyses for setting and population.The primary outcome was the question: "If my doctor said it was possible, I would be willing to stop one or more of my medicines". Secondary outcomes were associations between participant characteristics and primary outcome and other (r)PATD results.

Results: We included 46 articles describing 40 studies (n = 10,816 participants). The meta-analysis found the proportion of participants who agreed or strongly agreed with this statement was 84% ((95% CI 81% - 88%) and 80% (95% CI 74% - 86%) in patients and caregivers respectively, with significant heterogeneity (I2 = 95% and 77%).

Conclusion: Consumers reported willingness to have a medication deprescribed although results should be interpreted with caution due to heterogeneity. The findings from this study moves towards understanding attitudes towards deprescribing, which could increase the discussion and uptake of deprescribing recommendations in clinical practice.
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http://dx.doi.org/10.1093/gerona/glab222DOI Listing
August 2021

Development, evaluation and use of COVID-19 vaccines in older adults: Preliminary principles for the pandemic and beyond.

Br J Clin Pharmacol 2021 09 2;87(9):3459-3461. Epub 2021 Aug 2.

Geriatric Subcommittee of the Clinical Division, IUPHAR (International Union of Basic and Clinical Pharmacology), Kansas, USA.

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http://dx.doi.org/10.1111/bcp.14967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444940PMC
September 2021

Considerations for systematic reviews of quantitative surveys: Learnings from a systematic review of the patients' Attitudes Towards Deprescribing questionnaire.

Res Social Adm Pharm 2021 Jul 30. Epub 2021 Jul 30.

University of South Australia, UniSA: Clinical and Health Sciences, Quality Use of Medicines and Pharmacy Research Centre (QUMPRC), Adelaide, SA, Australia; Dalhousie University and Nova Scotia Health Authority, Geriatric Medicine Research, Faculty of Medicine, and College of Pharmacy, Halifax, Australia.

This commentary looks at the process of conducting a systematic review of surveys and validated questionnaires. Surveys and other questionnaire style tools are often used in the field of social and administrative pharmacy, to capture beliefs, attitudes and experiences of patients and healthcare professionals (including pharmacists). Currently, there is little guidance available on how to conduct a systematic review of these types of studies. Considerations related to the process of a systematic review are highlighted, including identification of articles, data extraction, assessing quality of articles and synthesis and analysis of data.
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http://dx.doi.org/10.1016/j.sapharm.2021.07.024DOI Listing
July 2021

Deprescribing in the Older Patient: A Narrative Review of Challenges and Solutions.

Int J Gen Med 2021 24;14:3793-3807. Epub 2021 Jul 24.

Departments of Clinical Pharmacology and Aged Care, Faculty of Medicine and Health, The University of Sydney, Kolling Institute, Royal North Shore Hospital, Sydney, NSW, Australia.

Polypharmacy is a major challenge in healthcare for older people, and is associated with increased risks of adverse outcomes, such as delirium, falls, frailty, cognitive impairment and hospitalization. There is significant public and professional interest in the role of deprescribing in reducing medication-related harms in older people. We aim to provide a narrative review of 1) the safety and efficacy of deprescribing interventions, 2) the challenges and solutions of deprescribing research and implementation in clinical practice, and 3) the benefits of using Computerized Clinical Decision Support Systems (CCDSS) and Quality Indicators (QIs) in deprescribing research and practice. Deprescribing is an established management strategy to minimize polypharmacy and potentially inappropriate medications. There is limited clinical evidence for its efficacy on global and geriatric outcomes. Various challenges at patient, healthcare professional and healthcare system levels may impact on the success of deprescribing interventions in research and practice. Management strategies that target all levels of the healthcare system are required to overcome these challenges. Future studies may consider large multicenter prospective designs to establish the effects and sustainability of deprescribing interventions on clinical outcomes.
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http://dx.doi.org/10.2147/IJGM.S253177DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317936PMC
July 2021

Understanding the Role and Value of Process Quality Indicators in Older Vascular Surgery Inpatients.

J Surg Res 2021 Jun 23;267:91-101. Epub 2021 Jun 23.

Department of Geriatric Medicine, Concord Hospital, Concord, Sydney, Australia; Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Concord, Sydney, Australia; Centre for Education and Research on Ageing, and Ageing and Alzheimers Institute, Concord, Sydney, Australia.

Background: Despite the development of geriatrics surgery process quality indicators (QIs), few studies have reported on these QIs in routine surgical practice. Even less is known about the links between these QIs and clinical outcomes, and patient characteristics. We aimed to measure geriatrics surgery process QIs, and investigate the association between process QIs and outcomes, and QIs and patient characteristics, in hospitalized older vascular surgery patients.

Methods: This was a prospective cohort study of 150 consecutive patients aged ≥ 65 years admitted to a tertiary vascular surgery unit. Occurrence of geriatrics surgery process QIs as part of routine vascular surgery care was measured. Associations between QIs and high-risk patient characteristics, and QIs and clinical outcomes were assessed using clustered heatmaps.

Results: QI occurrence rate varied substantially from 2% to 93%. Some QIs, such as cognition and delirium screening, documented treatment preferences, and geriatrician consultation were infrequent and clustered with high-risk patient characteristcs. There were two major process-outcome clusters: (a) multidisciplinary consultations, communication and screening-based process QIs with multiple adverse outcomes, and (b) documentation and prescribing-related QIs with fewer adverse outcomes.

Conclusions: Clustering patterns of process QIs with clinical outcomes are complex, and there is a differential occurrence of QIs by patient characteristics. Prospective intervention studies that report on implemented QIs, outcomes and patient characteristics are needed to better understand the causal pathways between process QIs and outcomes, and to help prioritize targets for quality improvement in the care of older surgical patients.
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http://dx.doi.org/10.1016/j.jss.2021.05.003DOI Listing
June 2021

Optimising medication management during the COVID-19 pandemic.

J Pharm Pract Res 2020 Jun 4;50(3):186-189. Epub 2020 Jul 4.

Royal North Shore Hospital Sydney Australia.

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http://dx.doi.org/10.1002/jppr.1668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361261PMC
June 2020

Male-Female Differences In The Effects Of Age On Performance Measures Recorded For 23 Hours In Mice.

J Gerontol A Biol Sci Med Sci 2021 Jun 25. Epub 2021 Jun 25.

Laboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St Leonards, New South Wales, Australia.

Functional independence is an important aspect of successful aging and differs with age and by sex in humans. Physical performance often declines earlier than other age-associated functional impairments. Rodent models are used to study pharmacological/toxicological effects of human therapies. However, physical outcomes in mice are usually assessed for short periods, with limited information on the influence of age and sex. Here, we investigated how age and sex affected murine physical performance over 23 hours of continuous observation. Young (3 months) and old (22 months) C57BL/6JArc male and female mice were assessed using the Laboratory Animal Behavior Observation, Registration, and Analysis System. Mice were individually housed for recording of distance travelled, mean gait speed, and durations of different physical activities. Compared to young mice of the same sex, old mice travelled significantly shorter distances with slower gait speeds, shorter durations of locomotion, rearing, climbing and immobility. Older mice groomed significantly more than young mice. Old females reared more during the light cycle than old males. Young females climbed substantially more than young males. Significant age*sex interactions were detected for rearing and climbing, whereby an age-related decline was greater in males than females. Our results suggest that old age reduces exploratory activities and increases grooming in mice. Age-related declines vary between sexes and tend to be greater in males. This non-invasive assessment can be applied to investigate how different interventions affect rodents of different ages and sexes, through the day-night cycle.
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http://dx.doi.org/10.1093/gerona/glab182DOI Listing
June 2021

Attitudes to Drug Use in Residential Aged Care Facilities: A Cross-Sectional Survey of Nurses and Care Staff.

Drugs Aging 2021 Aug 25;38(8):697-711. Epub 2021 Jun 25.

Centre for Education and Research on Ageing, Concord Repatriation General Hospital and Concord Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.

Background: Residential aged care facility (RACF) staff are well placed to identify opportunities for more appropriate prescribing. However, little is known about their views of polypharmacy, deprescribing and specific medications.

Objective: The objective of this study was to establish the beliefs and attitudes of RACF staff towards polypharmacy and medication use in residents.

Methods: A cross-sectional survey was conducted on RACF staff in metropolitan New South Wales, Australia using a self-administered questionnaire. The questionnaire was drafted based on the available literature and research team expertise and then piloted by a mixed group of 13 RACF staff. The final version of the questionnaire consisted of 28 questions. A total of 38 RACFs were contacted about the study. The questionnaire was distributed to eligible RACF staff between October 2017 and October 2019. The RACF staff were eligible if they provided direct patient care to residents or worked as a facility manager. Participants were excluded if they had insufficient English language skills. The results were presented in two groups, the nursing and care staff, using descriptive statistics.

Results: A total of 176 individuals from nine RACFs completed the questionnaire of whom 160 were eligible for study inclusion. Most considered polypharmacy to be five or more different tablets and capsules per day (95% nursing and 82% care staff respectively). A wide range of beliefs about medication use and deprescribing that centred on what constitutes appropriate polypharmacy was identified. Most thought that preventive medications were essential for residents. Most nurses agreed that sleeping tablets and pharmacological management of verbal aggression and wandering behaviours should be used less frequently whilst most care staff agreed that medications should be used more frequently to manage physical aggression.

Conclusions: To successfully and sustainably optimise medication use in RACF residents, it is important to consider the variation in views of nurses and care staff.
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http://dx.doi.org/10.1007/s40266-021-00874-2DOI Listing
August 2021

Leveraging implementation science to increase the translation of deprescribing evidence into practice.

Res Social Adm Pharm 2021 Jun 6. Epub 2021 Jun 6.

University of Washington, Department of Global Health, Seattle, WA, USA; University of Washington, Department of Epidemiology, Seattle, WA, USA.

Implementation science may address some of the limitations that impede the translation of deprescribing recommendations into practice and policy. Application of principles and standard terminologies from implementation science could improve understanding and interpretation of deprescribing research findings. As such, in this commentary we propose three main avenues to help achieve this. These include: The application of these concepts derived from implementation science could help inform future deprescribing needs for clinicians and researchers. Ultimately, this could help ensure the quality use of medications and examination of meaningful outcomes in deprescribing studies. This could result in more consistent and widespread translation of deprescribing evidence into practice and policy across various healthcare settings.
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http://dx.doi.org/10.1016/j.sapharm.2021.05.018DOI Listing
June 2021

Mortality trends of stroke and dementia: Changing landscapes and new challenges.

J Am Geriatr Soc 2021 Jun 16. Epub 2021 Jun 16.

Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

Background/importance: Stroke and dementia are important causes of death in the United States and may be interrelated as competing risks for mortality. No previous studies have simultaneously compared age- and sex-specific mortality trends between stroke and subtypes of dementia at a population level. Insights gained from this study can help identify high-risk populations and inform healthcare service requirements for managing stroke and dementia in the United States.

Objectives: To examine nationwide trends in mortality from stroke and subtypes of dementia in the United States by age group and sex.

Design: Population-based cross-sectional study.

Setting: U.S. mortality data from 2007 to 2016.

Participants: All U.S. residents whose primary cause of death was stroke, Alzheimer's disease, vascular dementia, or Lewy body dementia.

Measurements: Age-adjusted mortality, mortality trends among men and women were analyzed separately using joinpoint regression.

Results: From 2007 to 2016, age-adjusted stroke mortality fell by 21.6%. Age-adjusted mortality (per 1,000,000) for Alzheimer's disease, vascular dementia, and Lewy body dementia increased by 1.2-fold, 2-fold, and 3-fold, respectively. Annual age-adjusted stroke mortality decreased by an average rate of 2.67% per year, while annual age-adjusted mortality for Alzheimer's disease, vascular dementia, and Lewy body dementia increased by an average rate of 2.06%, 4.90%, and 12.13% per year, respectively. Mortality from stroke and dementia increased with age. Greater reductions in stroke mortality and greater increases in dementia mortality were seen in women than men; and in older than younger (<65 years) people.

Conclusions: There has been a striking rising trend in dementia mortality coincident with a reduction in stroke mortality in the United States. There are persistent age and sex disparities in stroke and dementia mortality trends. Our findings support the pathophysiological relationship between stroke and dementia, and have important implications for future research, healthcare planning, and provision.
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http://dx.doi.org/10.1111/jgs.17322DOI Listing
June 2021

Translational Gerontology Research to Understand the Effects of Medications in Older Adults.

J Gerontol A Biol Sci Med Sci 2021 05;76(6):1007-1009

Laboratory of Ageing and Pharmacology, Kolling Institute, Royal North Shore Hospital and Faculty of Medicine and Health, University of Sydney, St Leonards, New South Wales, Australia.

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http://dx.doi.org/10.1093/gerona/glab031DOI Listing
May 2021

Attitudes toward deprescribing among adults with heart failure with preserved ejection fraction.

J Am Geriatr Soc 2021 Jul 12;69(7):1948-1955. Epub 2021 May 12.

Department of Medicine, Weill Cornell Medicine, New York, New York, USA.

Background/objectives: Attitudes toward deprescribing could vary among subpopulations. We sought to understand patient attitudes toward deprescribing among patients with heart failure with preserved ejection fraction (HFpEF).

Design: Retrospective cohort study.

Setting: Academic medical center in New York City.

Participants: Consecutive patients with HFpEF seen in July 2018-December 2019 at a program dedicated to providing care to older adults with HFpEF.

Measurements: We assessed the prevalence of vulnerabilities outlined in the domain management approach for caring for patients with heart failure and examined data on patient attitudes toward having their medicines deprescribed via the revised Patient Attitudes Toward Deprescribing (rPATD).

Results: Among 134 patients with HFpEF, median age was 75 (interquartile range 69-82), 60.4% were women, and 35.8% were nonwhite. Almost all patients had polypharmacy (94.0%) and 56.0% had hyperpolypharmacy; multimorbidity (80.6%) and frailty (78.7%) were also common. Overall, 90.3% reported that they would be willing to have one or more of their medicines deprescribed if told it was possible by their doctors; and 26.9% reported that they would like to try stopping one of their medicines to see how they feel without it. Notably, 91.8% of patients reported that they would like to be involved in decisions about their medicines. In bivariate logistic regression, nonwhite participants were less likely to want to try stopping one of their medicines to see how they feel without it (odds ratio 0.25, 95% confidence interval [0.09-0.62], p = 0.005).

Conclusions: Patients with HFpEF contend with many vulnerabilities that could prompt consideration for deprescribing. Most patients with HFpEF were amenable to deprescribing. Race may be an important factor that impacts patient attitudes toward deprescribing.
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http://dx.doi.org/10.1111/jgs.17204DOI Listing
July 2021

Supporting deprescribing in hospitalised patients: formative usability testing of a computerised decision support tool.

BMC Med Inform Decis Mak 2021 04 5;21(1):116. Epub 2021 Apr 5.

Kolling Institute of Medical Research, Faculty of Medicine and Health, University of Sydney and Royal North Shore Hospital, Sydney, Australia.

Background: Despite growing evidence that deprescribing can improve clinical outcomes, quality of life and reduce the likelihood of adverse drug events, the practice is not widespread, particularly in hospital settings. Clinical risk assessment tools, like the Drug Burden Index (DBI), can help prioritise patients for medication review and prioritise medications to deprescribe, but are not integrated within routine care. The aim of this study was to conduct formative usability testing of a computerised decision support (CDS) tool, based on DBI, to identify modifications required to the tool prior to trialling in practice.

Methods: Our CDS tool comprised a DBI MPage in the electronic medical record (clinical workspace) that facilitated review of a patient's DBI and medication list, access to deprescribing resources, and the ability to deprescribe. Two rounds of scenario-based formative usability testing with think-aloud protocol were used. Seventeen end-users participated in the testing, including junior and senior doctors, and pharmacists.

Results: Participants expressed positive views about the DBI CDS tool but testing revealed a number of clear areas for improvement. These primarily related to terminology used (i.e. what is a DBI and how is it calculated?), and consistency of functionality and display. A key finding was that users wanted the CDS tool to look and function in a similar way to other decision support tools in the electronic medical record. Modifications were made to the CDS tool in response to user feedback.

Conclusion: Usability testing proved extremely useful for identifying components of our CDS tool that were confusing, difficult to locate or to understand. We recommend usability testing be adopted prior to implementation of any digital health intervention. We hope our revised CDS tool equips clinicians with the knowledge and confidence to consider discontinuation of inappropriate medications in routine care of hospitalised patients. In the next phase of our project, we plan to pilot test the tool in practice to evaluate its uptake and effectiveness in supporting deprescribing in routine hospital care.
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http://dx.doi.org/10.1186/s12911-021-01484-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022373PMC
April 2021

Polypharmacy Results in Functional Impairment in Mice: Novel Insights Into Age and Sex Interactions.

J Gerontol A Biol Sci Med Sci 2021 Sep;76(10):1748-1756

Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, New South Wales, Australia.

Males and females may respond differently to medications, yet knowledge about sexual dimorphisms in the effects of polypharmacy remains limited, particularly in aging. This study aimed to assess the effect of high Drug Burden Index (DBI) polypharmacy treatment compared to control on physical function and behavior in young and old, male and female mice. We studied whether age and sex play a role in physical function and behavior following polypharmacy treatment and whether they are paralleled by differences in serum drug levels. Young (2.5 months) and old (21.5 months), C57BL/6 mice were randomized to control or high DBI polypharmacy treatment (simvastatin, metoprolol, oxybutynin, oxycodone, and citalopram; n = 6-8/group) for 4-6 weeks. Compared to control, polypharmacy reduced physical function (grip strength, rotarod latency, gait speed, and total distance), middle zone distance (increased anxiety), and nesting score (reduced activities of daily living) in mice of both ages and sexes (p < .001). Old animals had a greater decline in nesting score (p < .05) and midzone distance (p < .001) than young animals. Grip strength declined more in males than females (p < .05). Drug levels at steady state were not significantly different between polypharmacy-treated animals of both ages and sexes. We observed polypharmacy-induced functional impairment in both age and sex groups, with age and sex interactions in the degree of impairment, which were not explained by serum drug levels. Studies of the pathogenesis of functional impairment from polypharmacy may improve management strategies in both sexes.
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http://dx.doi.org/10.1093/gerona/glab088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8436985PMC
September 2021

New Horizons in the impact of frailty on pharmacokinetics: latest developments.

Age Ageing 2021 06;50(4):1054-1063

Centre for Medicine Use and Safety, Monash University, Parkville, VIC, Australia.

Frail older people have a high prevalence of drug use and are susceptible to adverse drug reactions. The physiological changes of frailty are likely to affect pharmacokinetics and pharmacodynamics. We reviewed the methods and findings of published studies of pharmacokinetics in frailty. Nine studies describing pharmacokinetics and an additional three of pharmacokinetic pathways in frail older people were identified. Most pharmacokinetic studies investigated a single administration of a medication, dose or formulation, in small populations, often with limited representation of males or females, and applied variable definitions of frailty. Pharmacokinetic sampling designs generally utilised saturated sampling followed by analysis based on the trapezoidal rule for area under the curve, with more recent studies using sparser sampling and more sophisticated modelling to obtain individual and population values of all pharmacokinetic parameters. Overall, the pharmacokinetic studies reported only small changes in some parameters for some drugs with frailty, with the most consistent change reduced hepatic clearance in frail older people. Recommendations for future studies of pharmacokinetics in frailty include (i) standard objective definitions of frailty; (ii) larger studies including people with mild, moderate and severe frailty; (iii) population pharmacokinetic modelling to allow sparser sampling and consideration of multiple influences on pharmacokinetics; (iv) physiologically based modelling as the physiology of frailty emerges and (v) longitudinal pharmacokinetic studies of chronic drug therapy from middle to old age and from robust to pre-frail to frail, including pre-clinical studies. These data, accompanied by pharmacodynamics data in frailty, will inform safe, effective prescribing for frail older people.
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http://dx.doi.org/10.1093/ageing/afab003DOI Listing
June 2021

Nationwide mortality trends of delirium in Australia and the United States from 2006 to 2016.

Australas J Ageing 2021 Mar 9. Epub 2021 Mar 9.

Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, NSW, Australia.

Objectives: To examine nationwide trends in delirium mortality in Australia and the United States between 2006 and 2016.

Methods: Delirium mortality data for Australian and United States populations were obtained from World Health Organization Mortality Database. Mortality trends were assessed using joinpoint regression.

Results: Age-adjusted delirium mortality increased by 16.35%/year and 4.04%/year in Australia and the United States, respectively. Average annual age-adjusted delirium mortality rate (per 1 000 000 population) was 2.90 in Australia, and 1.06 in the United States. Death rates from delirium increased with age. Mortality was consistently higher in men than women, but the rate of annual increase was greater in women.

Conclusions: Our study provided important population-level data on delirium and its outcomes in Australia and the United States. Reported death rates attributed to delirium increased over the 11-year period in both countries and were consistently higher in Australia than the United States. There were distinct age and sex differences in mortality trends.
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http://dx.doi.org/10.1111/ajag.12926DOI Listing
March 2021

Multicentre stepped-wedge cluster randomised controlled trial of an antimicrobial stewardship programme in residential aged care: protocol for the START trial.

BMJ Open 2021 03 2;11(3):e046142. Epub 2021 Mar 2.

Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Victoria, Australia

Introduction: Antimicrobial resistance is a growing global health threat, driven by increasing inappropriate use of antimicrobials. High prevalence of unnecessary use of antimicrobials in residential aged care facilities (RACFs) has driven demand for the development and implementation of antimicrobial stewardship (AMS) programmes. The Stepped-wedge Trial to increase antibiotic Appropriateness in Residential aged care facilities and model Transmission of antimicrobial resistance (START) will implement and evaluate the impact of a nurse-led AMS programme on antimicrobial use in 12 RACFs.

Methods And Analysis: The START trial will implement and evaluate a nurse-led AMS programme via a stepped-wedge cluster randomised controlled trial design in 12 RACFs over 16 months. The AMS programme will incorporate education, aged care-specific treatment guidelines, documentation forms, and audit and feedback strategies that will target aged care staff, general practitioners, pharmacists, and residents and their families. The intervention will primarily focus on urinary tract infections, lower respiratory tract infections, and skin and soft tissue infections. RACFs will transition from control to intervention phases in random order, two at a time, every 2 months, with a 2-month transition, wash-in period. The primary outcome is the cumulative proportion of residents within each facility prescribed an antibiotic during each month and total days of antibiotic use per 1000 occupied bed days. Secondary outcomes include the number of courses of systemic antimicrobial therapy, antimicrobial appropriateness, antimicrobial resistant organisms, infection, change in antimicrobial susceptibility profiles, hospitalisations and all-cause mortality. Analyses will be conducted according to the intention-to-treat principle.

Ethics And Dissemination: Ethics approval has been granted by the Alfred Hospital Human Research Ethics Committee (HREC/18/Alfred/591). Research findings will be disseminated through peer-reviewed publications, conferences and summarised reports provided to participating RACFs.

Trial Registration Number: NCT03941509.
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http://dx.doi.org/10.1136/bmjopen-2020-046142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929827PMC
March 2021

Caregivers' experiences of medication management advice for people living with dementia at discharge.

J Eval Clin Pract 2021 Feb 15. Epub 2021 Feb 15.

School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.

Rationale, Aims, And Objectives: Caregivers of people living with dementia play an essential role in managing medications across transitions of care. Adequate caregiver medication management guidance at hospital discharge is important to ensure optimal outcomes from medication use. This qualitative study explores the experiences and perspectives of caregivers about the medication management guidance provided at hospital discharge.

Methods: A qualitative approach using semi-structured, telephone interviews was conducted with 31 caregivers of people with dementia across Australia. Purposive sampling was used to ensure maximum variation of diverse experiences and perspectives.

Results: Caregivers' experiences of medication guidance for people with dementia at discharge were described in three themes including: (a) inadequate information about medication management at discharge; (b) limited caregiver engagement in medication management decisions; and (c) difficulties ensuring medication supply post discharge. Most participants indicated they would like to be included in discussions at discharge. However, participation was influenced by caregivers being overwhelmed by discharge processes; proactively seeking information on medication-related harm; and belief in advocacy as part of their caregiver role. Caregivers reported they would like to receive a tailored medication list for people with dementia which included information on medications that may impact on the patient's cognition, and for hospital staff to communicate with both the community pharmacist and primary care physician, to improve co-ordination post transition.

Discussion: In our study of caregivers of people with dementia, we identified key recommendations to facilitate regular participation of people living with dementia and their caregiver around medication guidance at discharge.
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http://dx.doi.org/10.1111/jep.13551DOI Listing
February 2021

Development and dissemination of the national strategic action plan for reducing inappropriate polypharmacy in older Australians.

Intern Med J 2021 Jan;51(1):111-115

NHMRC Cognitive Decline Partnership Centre, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia.

A cohesive, national approach is needed to address inappropriate polypharmacy in older adults and promote deprescribing. We describe the dissemination of the Quality Use of Medicines to Optimise Ageing in Older Australians: Recommendations for a National Strategic Action Plan to Reduce Inappropriate Polypharmacy, and the initiatives taken to date that align with, and assist in operationalising this plan.
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http://dx.doi.org/10.1111/imj.15155DOI Listing
January 2021

Communicating deprescribing decisions made in hospital with general practitioners in the community.

Intern Med J 2021 Sep;51(9):1473-1478

Kolling Institute of Medical Research, Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, Sydney, New South Wales, Australia.

Background: Deprescribing, the supervised withdrawal of inappropriate medications, intends to manage polypharmacy, which is prevalent in older patients.

Aims: To examine general practitioner (GP) perceptions of communication processes between clinicians in hospital and GP in the community about deprescribing decisions made in hospital.

Methods: Focus groups and interviews were held with 15 GP, exploring deprescribing in hospitals, communication of deprescribing information and the format of communications. Sessions were audiotaped, transcribed and analysed using an inductive approach.

Results: GP stated that they should be involved in deprescribing decisions, especially for older complex patients, because of their good knowledge of their patients. Barriers to effective communication included the acute nature of hospital stays and lack of time. Facilitators included long-term relationships of GP with their patients and engaged patients. GP preferred communication of deprescribing decisions to be over the telephone while the patient was still in hospital, and with a concise, electronic discharge summary at the time of discharge. GP indicated that rationale for medication changes and recommended follow-up actions were crucial in a discharge summary to enable care post-discharge.

Conclusions: GP welcome increased communication with hospital clinicians regarding deprescribing decisions made while patients are in hospital. Communication needs to be timely, transparent, succinct and accessible. Lack of time and difficulties contacting hospital clinicians challenge this process.
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http://dx.doi.org/10.1111/imj.15208DOI Listing
September 2021

Development and validation of a frailty index based on data routinely collected across multiple domains in NSW hospitals.

Australas J Ageing 2021 Jun 19;40(2):184-194. Epub 2020 Dec 19.

Laboratory of Ageing and Pharmacology, Faculty of Medicine and Health, Kolling Institute of Medical Research, Royal North Shore Hospital and Northern Clinical School, University of Sydney, Sydney, NSW, Australia.

Objective(s): To develop and validate a frailty index (FI) that covers multiple domains, using routine hospital data. To investigate the FI's validity, after excluding medication-related items (FI-ExMeds), for studies of frailty and polypharmacy.

Methods: A FI was derived from routine NSW hospital data following standard published guidance. In a development cohort (151 inpatients ≥ 70 years), the FI was correlated with the Reported Edmonton Frail Scale (REFS) using Pearson's R. Validity and distribution of FI and FI-ExMeds, and correlation with each other, were evaluated in a validation cohort (999 inpatients ≥ 75 years).

Results: The mean FI for the development cohort was 0.27 (SD 0.09). The FI showed moderate linear correlation with the REFS (n = 148, R = 0.52, P < .001). In the validation cohort, mean FI (n = 993) and FI-ExMeds (n = 990) were both 0.28 (SD 0.11). FI-ExMeds showed high linear correlation with the FI (n = 990, R = 0.99, P < .001).

Conclusion: This multi-domain FI is comparable to REFS, with adequate redundancy to exclude deficits for specific analyses.
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http://dx.doi.org/10.1111/ajag.12888DOI Listing
June 2021

Fall-related mortality trends in Australia and the United Kingdom: Implications for research and practice.

Maturitas 2020 Dec 26;142:68-72. Epub 2020 Jul 26.

Departments of Clinical Pharmacology and Aged Care, Royal North Shore Hospital, St Leonards, NSW, Australia; Laboratory of Ageing and Pharmacology, Kolling Institute of Medical Research, St Leonards, NSW, Australia; Faculty of Medicine and Health, University of Sydney, NSW, Australia. Electronic address:

Objectives: To characterise changes in nationwide fall-related mortality rates in Australia and the United Kingdom (UK) between 2006 and 2016 by age group and sex.

Study Design: Trend analysis of falls mortality data from World Health Organization (WHO) Mortality Database for the Australian and UK population.

Main Outcome Measures: We assessed age-specific, sex-specific and age-adjusted mortality rates. Mortality trends were assessed via the annual percentage change (APC) using joinpoint regression.

Results: The annual average age-adjusted falls mortality rate was 38.63 per 1,000,000 population in Australia, and 34.12 per 1,000,000 population in the UK. From 2006 to 2016, age-adjusted mortality rate due to falls increased in Australia and the UK by an average annual rate of 3.77% (95% CI 2.91% to 4.64%; p<0.01) and 2.11% (95% CI 1.43% to 2.80%; p<0.01) respectively. Death rates from falls increased with age. People aged ≥95 years had the highest mortality rate from falls in Australia and the UK. Men had a higher annual average age-adjusted mortality rate from falls than women (1.6 times higher in Australia and 1.7 times higher in the UK). Women had a larger annual percentage increase in falls mortality rate compared to men over the study period.

Conclusions: There was a major increase in reported fall-related deaths in Australia and the UK between 2006 and 2016, especially in the very elderly. Men had a higher mortality rate from falls than women. Factors contributing to the apparent increases in fall-related mortality may include reduced cancer and cardiovascular mortality and better ascertainment of cause of death.
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http://dx.doi.org/10.1016/j.maturitas.2020.07.008DOI Listing
December 2020

The Prognostic Performance of Frailty for Delirium and Functional Decline in Vascular Surgery Patients.

J Am Geriatr Soc 2021 03 5;69(3):688-695. Epub 2020 Nov 5.

Department of Geriatric Medicine, Concord Hospital, Concord, Australia.

Background: Frailty in older vascular surgery patients is associated with increased mortality, hospital stay, and morbidity. The association of frailty with hospital-acquired geriatric syndromes such as delirium and functional decline has not been well studied.

Objectives: To investigate the association between frailty and hospital-acquired geriatric syndromes in older hospitalized vascular surgery patients, and to evaluate the prognostic performance of the frailty index (FI) and the Clinical Frailty Scale (CFS) for delirium and functional decline.

Design: Prospective cohort study.

Setting: Acute care academic hospital.

Participants: Patients aged 65 years or more admitted to a tertiary vascular surgery unit (N=150).

Measurements: Frailty was assessed using the FI and CFS. The adjusted association of frailty status with delirium and functional decline was assessed using logistic regression analysis. The prognostic performance of FI and CFS was determined by assessing C-statistic and positive and negative predictive values (PPV and NPV).

Results: Of 150 participants, FI identified 34 (23%) and CFS identified 45 (30%) as frail. Frailty was an independent predictor of delirium (FI adjusted odds ratio, odds ratio (OR) = 5.66, 95% confidence interval (CI) = 1.53-21.03; CFS adjusted OR = 4.07, 95% CI = 1.14-14.50), but not functional decline. FI and CFS showed acceptable prognostic performance for delirium (C-statistic 0.74), but not functional decline (C-statistic 0.63-0.64). For both outcomes, the FI and CFS had high NPV (86-96%), and low PPV (22-29%).

Conclusion: Frail older vascular surgery patients are more likely to develop hospital-acquired geriatric syndromes. The FI and CFS have acceptable prognostic performance for predicting delirium but not all individuals who are identified as frail develop delirium. Ongoing research is needed to identify interventions that improve outcomes in patients who screen positive for frailty.
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http://dx.doi.org/10.1111/jgs.16907DOI Listing
March 2021

Correction to: Implementation of the goal-directed medication review electronic decision support system (G-MEDSS)© into home medicines review: a protocol for a clusterrandomised clinical trial in older adults.

BMC Geriatr 2020 Oct 2;20(1):378. Epub 2020 Oct 2.

NHMRC Cognitive Decline Partnership Centre, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12877-020-01681-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532095PMC
October 2020

Impact of the Goal-directed Medication Review Electronic Decision Support System on Drug Burden Index: A cluster-randomised clinical trial in primary care.

Br J Clin Pharmacol 2021 03 2;87(3):1499-1511. Epub 2020 Nov 2.

NHMRC Cognitive Decline Partnership Centre, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, St Leonards, New South Wales, Australia.

Aims: The Goal-directed Medication Review Electronic Decision Support System (G-MEDSS) assesses and reports a patient's goals, attitudes to deprescribing and Drug Burden Index (DBI) score, a measure of cumulative exposure to anticholinergic and sedative medications. This study evaluated the effect of implementing G-MEDSS in home medicines reviews (HMRs) on DBI exposure and clinical outcomes.

Methods: A cluster-randomised clinical trial was performed across Australia. Accredited clinical pharmacists were randomised into intervention (G-MEDSS with usual care HMR) or comparison groups (usual care HMR alone). Patients were recruited by pharmacists from those routinely referred by general practitioners for HMR. The primary outcome was the proportion of patients with any reduction in DBI at 3-months follow-up. Secondary outcomes included change in DBI continuous score at 3-months, HMR recommendations to change DBI and clinical outcomes.

Results: There were 201 patient participants at baseline (n = 88 intervention, n = 113 comparison), with 159 followed-up at 3-months (n = 63 intervention, n = 96 comparison). The proportion of patients with a reduction in DBI was not significantly different at 3-months (intervention 17%, comparison 11%; adjusted odds ratio 1.44, 95% confidence interval 0.56-3.80). Regarding secondary outcomes, there was no difference in change in DBI score at 3-months. However, the HMR report made recommendations to reduce DBI for a significantly greater proportion of patients in the intervention than in the comparison group (intervention 37%, comparison 14%; adjusted odds ratio 3.20, 95% confidence interval 1.50-6.90). No changes were observed in clinical outcomes.

Conclusion: Implementation of G-MEDSS within HMR did not reduce patients' DBI at 3 months compared with usual care HMR.
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http://dx.doi.org/10.1111/bcp.14557DOI Listing
March 2021

Quantification of serum levels in mice of seven drugs (and six metabolites) commonly taken by older people with polypharmacy.

Fundam Clin Pharmacol 2021 Apr 14;35(2):410-422. Epub 2020 Oct 14.

Kolling Institute of Medical Research, Royal North Shore Hospital, 10 Westbourne St, Sydney, NSW, 2065, Australia.

Polypharmacy (use of ≥ 5 drugs) is common in older people but has minimal preclinical or clinical evidence of safety or efficacy and is associated with adverse outcomes in older people. Drug-drug interactions are poorly understood beyond drug pairs. An efficient and sensitive method to measure multiple serum drugs and metabolites could inform drug dosing in polypharmacy. Development of a sensitive liquid chromatography - tandem mass spectrometry method to simultaneously measure seven drugs and their respective metabolites in serum in a preclinical model of polypharmacy. This method was validated for optimal recovery, matrix effect, limit of quantification (LOQ), inter- and intra-day variability, and carry over. Serum samples from mice (n = 5-6/group) treated with chronic oral doses of three polypharmacy regimens and five monotherapies were screened for drug and metabolite levels (metoprolol, α-hydroxymetoprolol, O-desmethylmetoprolol, omeprazole, 5-hydroxyomeprazole, omeprazole sulphone, acetaminophen, irbesartan, citalopram, oxybutynin, oxycodone, noroxycodone, oxymorphone and tenivastatin). The LOQ for the compounds ranged from 0.05 to 0.1 ng/mL in serum. Recovery, matrix effect, and inter- and intra-day variability peak response were acceptable. No carry over was observed at the concentrations tested. Analytes were detectable in mice treated with these drugs, and differences in drug levels were observed with different polypharmacy and monotherapy regimens. The method is sensitive and robust to measure parent drugs and metabolites simultaneously in the context of polypharmacy. Polypharmacy appeared to affect drug levels in a preclinical model. This model can be used to understand pharmacokinetics of chronic polypharmacy, which could inform prescribing and improve outcomes for older people.
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http://dx.doi.org/10.1111/fcp.12602DOI Listing
April 2021

The utility of a computerised clinical decision support system intervention in home medicines review: A mixed-methods process evaluation.

Res Social Adm Pharm 2021 04 10;17(4):715-722. Epub 2020 Jun 10.

NHMRC Cognitive Decline Partnership Centre, Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, NSW, Australia; Clinical Pharmacology and Aged Care, Kolling Institute of Medical Research, Royal North Shore Hospital, New South Wales, Australia.

Background: Use of high-risk medications is common and associated with adverse effects in older adults, including those living with dementia. A Computerised Clinical Decision Support System (CCDSS) called G-MEDSS© (Goal-directed Medication Review Electronic Decision Support System) contains tools that identify medications with anticholinergic and sedative effects and align older adult's health and medication goals of care with medication management strategies.

Objectives: To describe the utility of a CCDSS called G-MEDSS in Home Medicines Review (HMR) by an accredited clinical pharmacist (ACP) using a mixed-methods process evaluation method.

Methods: A mixed-methods process evaluation was conducted as part of a nation-wide cluster-randomised clinical trial evaluating the effectiveness of implementing G-MEDSS in HMR. Data were collected from ACPs and HMR recipients (the patient) using a feedback survey (ACPs and HMR recipients) and one-on-one telephone interviews (HMR recipients). Quantitative and qualitative data were combined at the start of analysis. Content analysis of the qualitative data was conducted, and emerging categories were linked to quantitative data.

Results: Feedback surveys were completed by eight ACPs and 26 HMR recipients; 11 HMR recipients completed one-on-one telephone interviews. Overall, ACPs and HMR recipients who received the intervention reported a positive attitude towards the utility of G-MEDSS in HMR. ACPs reported that G-MEDSS enhanced their ability to make evidence-based recommendations about anticholinergic and sedative medications, and to better align HMR recommendations with HMR recipients' goals of care. However, ACPs described that it was difficult to obtain goals of care from HMR recipients. HMR recipients gave mixed reports about the ACPs consultations: some HMR recipients reported that they were engaged in discussions about their views on medications, whilst other participants reported that discussions about their concerns towards medications and goals was limited.

Conclusions: This study suggests that a CCDSS, such as G-MEDSS, demonstrates good utility to assist ACPs to identify and assess anticholinergic and sedative medications. Given the mixed feedback from the ACPs on the different components of the G-MEDSS, further refinement of these tools and their use in combination in practice may be needed.
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http://dx.doi.org/10.1016/j.sapharm.2020.06.010DOI Listing
April 2021

Drug Burden Index and Cognitive and Physical Function in Aged Care Residents: A Longitudinal Study.

J Am Med Dir Assoc 2020 08;21(8):1086-1092.e1

Department of PharmacoTherapy, PharmacoEpidemiology & PharmacoEconomics, University of Groningen, Groningen Research Institute of Pharmacy, Groningen, the Netherlands.

Objectives: Anticholinergic/antimuscarinic and sedative medications (eg, benzodiazepines) have been found to be associated with poorer cognitive and physical function and mobility impairment in older age. However, previous studies were mostly conducted among community-dwelling older individuals and had often a cross-sectional design. Accordingly, our aim was to examine longitudinal associations between cumulative exposure to anticholinergic and sedative medications and cognitive and physical function among residents from aged care homes.

Design: Longitudinal study.

Setting And Participants: A total of 4624 residents of Dutch aged care homes of whom data were collected between June 2005 and April 2014.

Methods: Outcome measures were collected with the Long-Term Care Facilities assessment from the international Residential Assessment Instrument (interRAI-LTCF) and included the Cognitive Performance Scale, the Activities of Daily Living (ADL) Hierarchy scale, a timed 4-meter walk test, distance walked, hours of physical activity, and days being outside. Cumulative exposure to anticholinergic and sedative medications was calculated with the Drug Burden Index (DBI), a linear additive pharmacological dose-response model. Associations were examined with linear mixed models to take the potential dependence of observations into account (ie, data were collected at repeated assessment occasions of residents who were clustered in aged care homes). Analyses were adjusted for sex, age, dementia, comorbidity (neurological, psychiatric, cardiovascular, oncological, and pulmonary), fractures, depressive symptoms, and medications excluded from the DBI.

Results: We observed significant longitudinal associations between a higher DBI and poorer ADLs, fewer hours of physical activity, and fewer days being outside. We found no significant longitudinal association between a higher DBI and poorer cognitive function.

Conclusions And Implications: Over time, cumulative exposure to anticholinergic and sedative medications is associated with poorer physical but not cognitive function in aged care residents. Careful monitoring of aged care residents with high cumulative anticholinergic and sedative medication exposure is needed.
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http://dx.doi.org/10.1016/j.jamda.2020.05.037DOI Listing
August 2020

Withdrawal of antihypertensive drugs in older people.

Cochrane Database Syst Rev 2020 06 10;6:CD012572. Epub 2020 Jun 10.

School of Pharmacy, Faculty of Medicine and Health, and Charles Perkins Centre, University of Sydney, Sydney, Australia.

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.
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http://dx.doi.org/10.1002/14651858.CD012572.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387859PMC
June 2020
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