Hospital pharmacists' opinions on a risk prediction tool for medication-related harm in older people.

AIM: Older adults are particularly affected by medication-related harm (MRH) during transitions of care. There are no clinical tools predicting those at highest risk of MRH post hospital discharge. The PRIME study (prospective study to develop a model to stratify the risk of MRH in hospitalized patients) developed and internally validated a risk-prediction tool (RPT) that provides a percentage score of MRH in adults over 65 in the 8 weeks following hospital discharge. This qualitative study aimed to explore the views of hospital pharmacists around enablers and barriers to clinical implementation of the PRIME-RPT. METHODS: Ten hospital pharmacists: (band 6, n = 3; band 7, n = 2; band 8, n = 5) participated in semistructured interviews at the Royal Sussex County Hospital (Brighton, UK). The pharmacists were presented with five case-vignettes each with a calculated PRIME-RPT score to help guide discussion. Case-vignettes were designed to be representative of common clinical encounters. Data were thematically analysed using a "framework" approach. RESULTS: Seven themes emerged in relation to the PRIME-RPT: (1) providing a medicine-prioritisation aide; (2) acting as a deprescribing alert; (3) facilitating a holistic review of patient medication management; (4) simplifying communication of MRH to patients and the multidisciplinary team; (5) streamlining community follow-up and integration of risk discussion into clinical practice; (6) identifying barriers for the RPTs integration in clinical practice; and (7) acknowledging its limitations. CONCLUSION: Hospital pharmacists found the PRIME-RPT beneficial in identifying older patients at high risk of MRH following hospital discharge, facilitating prioritising interventions to those at highest risk while still acknowledging its limitations.

Medication compliance aids unpackaged: A national survey.

AIMS: Sixty-four million pharmacy-filled multicompartment medication compliance aids (MCAs) are dispensed by pharmacies in England each year. Despite the widespread use of MCAs and evidence that their use may be associated with harm there is no national consensus regarding MCA provision by acute hospital Trusts in England. The aim was to determine current practice for initiation and supply of MCAs in acute hospital Trusts in England and the potential consequences for patients and hospitals. METHODS: A 26-item survey was distributed to all acute hospital Trusts in England. The questionnaire covered: policy, initiation, supply and review of MCAs; alternatives offered; and pharmacy staffing and capacity related to MCAs. RESULTS: Seventy-two out of 138 (52%) Trusts responded to the survey: 70 Trusts responded regarding policy for MCA provision, with 60 (86%) having a policy regarding this; 33/55 (60%) that supplied MCAs on discharge supplied a different prescription length for MCA vs. non-MCA prescriptions; 49/55 (89%) Trusts provided only 1 brand of MCA; 47/55 (85%) MCA-supplying Trusts identified frequent difficulties with MCAs and 13/55 (24%) reported employing staff specifically to complete MCAs; and 30/35 (86%) MCA-initiating Trusts had an assessment process for initiation, with care agency request reportedly the most common reason for initiation. CONCLUSION: There is a lack of a national approach to MCA provision and initiation by acute hospital Trusts in England. This leads to significant variation in care and has the potential to put MCA users at an increased risk of medication-related harm.

Characterising older adults' risk of harm from blood-pressure lowering medications: a sub-analysis from the PRIME study.

AIM: Cardiovascular disease (CVD) is common amongst frail older people. The evidence base for CVD commonly excludes older adults with multimorbidity or chronic conditions. Most cardiovascular drugs have the potential to lower blood pressure (BP) and therefore cause medication-related harm (MRH). We aimed to identify key clinical and sociodemographic characteristics associated with MRH in older people taking BP-lowering drugs for whatever indication they were prescribed. METHODS: The PRIME (prospective study to develop a model to stratify the risk of MRH in hospitalised elderly patients in the UK) study investigating the incidence and cost of MRH in older people across Southern England. Adults ≥65 years were recruited from five teaching hospitals at hospital discharge and followed up for 8 weeks. Telephone interviews with study participants, review of primary care records and hospital readmissions were undertaken to identify MRH. PRIME study participants taking BP-lowering drugs (as defined by National Institute for Health and Care Excellence hypertension guidelines) were included in this analysis. RESULTS: One hundred and four (12%) study patients experienced a total of 153 MRH events associated with BP-lowering drugs. Patients on four BP-lowering drugs were five times more likely to experience MRH compared to those taking one medication (OR 4.96; 95%CI 1.63-15.13; P = 0.01). Most MRH events were classified 'serious' (80%, n = 123), requiring dose change or treatment cessation. Almost half of MRH were potentially preventable (49%, n = 75). CONCLUSION: Polypharmacy from BP-lowering drugs in older people is associated with preventable harm. Decisions around cardiovascular risk reduction should be carefully considered in view of MRH arising from BP-lowering drugs.

A multi-centre cohort study on healthcare use due to medication-related harm: the role of frailty and polypharmacy.

OBJECTIVES: To determine the association between frailty and medication-related harm requiring healthcare utilisation. DESIGN: Prospective observational cohort study. SETTING: Six primary and five secondary care sites across South East England, September 2013-November 2015. PARTICIPANTS: One thousand and two hundred and eighty participants, ≥65 years old, who were due for discharge from general medicine and older persons' wards following an acute episode of care. Exclusion criteria were limited life expectancy, transfer to another hospital and consent not gained. MAIN OUTCOME MEASURES: Medication-related harm requiring healthcare utilisation (including primary, secondary or tertiary care consultations related to MRH), including adverse drug reactions, non-adherence and medication error determined via the review of data from three sources: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of readmission to recruiting hospital. Frailty was measured using a Frailty Index, developed using a standardised approach. Marginal estimates were obtained from logistic regression models to examine how probabilities of healthcare service use due to medication-related harm were associated with increasing number of medicines and frailty. RESULTS: Healthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06-49.26, P = 0.004), independent of age, gender, and number of medicines. With increasing frailty, the need for healthcare use as a result of MRH increases from a probability of around 0.2-0.4. This is also the case for the number of medicines. CONCLUSIONS: Frailty is associated with MRH, independent of polypharmacy. Reducing the burden of frailty through an integrated health and social care approach, alongside strategies to reduce inappropriate polypharmacy, may reduce MRH related healthcare utilisation.

Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials.

BACKGROUND: Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. METHODS: A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. RESULTS: Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. CONCLUSION: So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

A systematic review of the evidence for deprescribing interventions among older people living with frailty.

BACKGROUND: Older people living with frailty are often exposed to polypharmacy and potential harm from medications. Targeted deprescribing in this population represents an important component of optimizing medication. This systematic review aims to summarise the current evidence for deprescribing among older people living with frailty. METHODS: The literature was searched using Medline, Embase, CINAHL, PsycInfo, Web of Science, and the Cochrane library up to May 2020. Interventional studies with any design or setting were included if they reported deprescribing interventions among people aged 65+ who live with frailty identified using reliable measures. The primary outcome was safety of deprescribing; whereas secondary outcomes included clinical outcomes, medication-related outcomes, feasibility, acceptability and cost-related outcomes. Narrative synthesis was used to summarise findings and study quality was assessed using Joanna Briggs Institute checklists. RESULTS: Two thousand three hundred twenty-two articles were identified and six (two randomised controlled trials) were included with 657 participants in total (mean age range 79-87 years). Studies were heterogeneous in their designs, settings and outcomes. Deprescribing interventions were pharmacist-led (n = 3) or multidisciplinary team-led (n = 3). Frailty was identified using several measures and deprescribing was implemented using either explicit or implicit tools or both. Three studies reported safety outcomes and showed no significant changes in adverse events, hospitalisation or mortality rates. Three studies reported positive impact on clinical outcomes including depression, mental health status, function and frailty; with mixed findings on falls and cognition; and no significant impact on quality of life. All studies described medication-related outcomes and reported a reduction in potentially inappropriate medications and total number of medications per-patient. Feasibility of deprescribing was reported in four studies which showed that 72-91% of recommendations made were implemented. Two studies evaluated and reported the acceptability of their interventions and further two described cost saving. CONCLUSION: There is a paucity of research about the impact of deprescribing in older people living with frailty. However, included studies suggest that deprescribing could be safe, feasible, well tolerated and can lead to important benefits. Research should now focus on understanding the impact of deprescribing on frailty status in high risk populations. TRIAL REGISTRATION: The review was registered on the international prospective register of systematic reviews (PROSPERO) ID number: CRD42019153367 .

Medication-related harm: a geriatric syndrome.

The WHO Global Patient Safety Challenge: Medication Without Harm recognises medication-related harm (MRH) as a global public health issue. Increased life-expectancy coupled with multimorbidity and polypharmacy leads to an increased incidence of MRH, especially in older adults: at a cost of approximately £400 million to the National Health Service (NHS) in England. Harm from medicines has long been recognised by geriatricians, and strategies have been developed to mitigate harm. In general, these have focused on the challenges of polypharmacy and appropriateness of medicines, but impact on the quality of life, clinical and economic outcomes has been variable and often disappointing. The problem of MRH in older adults will continue to grow unless a new approach is adopted. Emerging evidence suggests that we need to take a broader approach as described in our conceptual model, where well-recognised physiological changes are incorporated, as well as other rarely considered psychosocial issues that influences MRH. Parallels may be drawn between this approach and the management of geriatric syndromes. We propose there must be a greater emphasis on MRH, and it, of itself, should be considered as a geriatric syndrome, to bring the spotlight onto the problem and to send a clear signal from geriatric experts that this is an important issue that needs to be addressed using a co-ordinated and tailored approach across health and social care boundaries. This requires a more proactive approach to monitor and review the medicines of older adults in response to their changing need.

Can doctors identify older patients at risk of medication harm following hospital discharge? A multicentre prospective study in the UK.

AIMS: Medication-related harm (MRH) is common in older adults following hospital discharge. In resource-limited health systems, interventions to reduce this risk can be targeted at high-risk patients. This study aims to determine whether (1) doctors can predict which older patients will experience MRH requiring healthcare following hospital discharge, (2) clinical experience and confidence in prediction influence the accuracy of the prediction. METHODS: This was a multicentre observational prospective study involving five teaching hospitals in England between September 2013 and November 2015. Doctors discharging patients (aged ≥65 years) from medical wards predicted the likelihood of their patient experiencing MRH requiring healthcare (hospital readmission or community healthcare) in the initial 8-week period post-discharge. Patients were followed up by senior pharmacists to determine MRH occurrence. RESULTS: Data of 1066 patients (83%) with completed predictions and follow-up, out of 1280 recruited patients, were analysed. Patients had a median age of 82 years (65-103 years), and 58% were female. Most predictions (85%) were made by junior doctors with less than 5 years' clinical experience. There was no relationship between doctors' predictions and patient MRH (OR 1.10, 95% CI 0.82-1.46, P = 0.53), irrespective of years of clinical experience. Doctors' predictions were more likely to be accurate when they reported higher confidence in their prediction, especially in predicting MRH-associated hospital readmissions (OR 1.58, 95% CI 1.42-1.76, P < 0.001). CONCLUSIONS: Clinical judgement of doctors is not a reliable tool to predict MRH in older adults post-discharge.

Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK.

AIMS: Polypharmacy is increasingly common in older adults, placing them at risk of medication-related harm (MRH). Patients are particularly vulnerable to problems with their medications in the period following hospital discharge due to medication changes and poor information transfer between hospital and primary care. The aim of the present study was to investigate the incidence, severity, preventability and cost of MRH in older adults in England postdischarge. METHODS: An observational, multicentre, prospective cohort study recruited 1280 older adults (median age 82 years) from five teaching hospitals in Southern England, UK. Participants were followed up for 8 weeks by senior pharmacists, using three data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilization. RESULTS: Overall, 413 participants (37%) experienced MRH (556 MRH events per 1000 discharges), of which 336 (81%) cases were serious and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n = 158, 25%) or neurological (n = 111, 18%). The medicine classes associated with the highest risk of MRH were opiates, antibiotics and benzodiazepines. A total of 328 (79%) participants with MRH sought healthcare over the 8-week follow-up. The incidence of MRH-associated hospital readmission was 78 per 1000 discharges. Postdischarge MRH in older adults is estimated to cost the National Health Service £396 million annually, of which £243 million is potentially preventable. CONCLUSIONS: MRH is common in older adults following hospital discharge, and results in substantial use of healthcare resources.

Epidemiology and association with outcomes of polypharmacy in patients undergoing surgery: retrospective, population-based cohort study.

BACKGROUND: The aim of this study was to determine the prevalence of preoperative polypharmacy and the incidence of postoperative polypharmacy/hyper-polypharmacy in surgical patients and their association with adverse outcomes. METHODS: This was a retrospective, population-based cohort study among patients older than or equal to 18 years undergoing surgery at a university hospital between 2005 and 2018. Patients were categorized based on the number of medications: non-polypharmacy (fewer than 5); polypharmacy (5-9); and hyper-polypharmacy (greater than or equal to 10). The 30-day mortality, prolonged hospitalization (greater than or equal to 10 days), and incidence of readmission were compared between medication-use categories. RESULTS: Among 55 997 patients, the prevalence of preoperative polypharmacy was 32.3 per cent (95 per cent c.i. 33.5 to 34.3) and the prevalence of hyper-polypharmacy was 25.5 per cent (95 per cent c.i. 25.2 to 25.9). Thirty-day mortality was higher for patients exposed to preoperative hyper-polypharmacy (2.3 per cent) and preoperative polypharmacy (0.8 per cent) compared with those exposed to non-polypharmacy (0.6 per cent) (P < 0.001). The hazards ratio (HR) of long-term mortality was higher for patients exposed to hyper-polypharmacy (HR 1.32 (95 per cent c.i. 1.25 to 1.40)) and polypharmacy (HR 1.07 (95 per cent c.i. 1.01 to 1.14)) after adjustment for patient and procedural variables. The incidence of longer hospitalization (greater than or equal to 10 days) was higher for hyper-polypharmacy (11.3 per cent) and polypharmacy (6.3 per cent) compared with non-polypharmacy (4.1 per cent) (P < 0.001). The 30-day incidence of readmission was higher for patients exposed to hyper-polypharmacy (10.2 per cent) compared with polypharmacy (6.1 per cent) and non-polypharmacy (4.8 per cent) (P < 0.001). Among patients not exposed to polypharmacy, the incidence of new postoperative polypharmacy/hyper-polypharmacy was 33.4 per cent (95 per cent c.i. 32.8 to 34.1), and, for patients exposed to preoperative polypharmacy, the incidence of postoperative hyper-polypharmacy was 16.3 per cent (95 per cent c.i. 16.0 to 16.7). CONCLUSION: Preoperative polypharmacy and new postoperative polypharmacy/hyper-polypharmacy are common and associated with adverse outcomes. This highlights the need for increased emphasis on optimizing medication usage throughout the perioperative interval. REGISTRATION NUMBER: NCT04805151 (http://clinicaltrials.gov).

A Systematic Review of the Current Evidence from Randomised Controlled Trials on the Impact of Medication Optimisation or Pharmacological Interventions on Quantitative Measures of Cognitive Function in Geriatric Patients.

BACKGROUND: Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people's cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. METHODS: A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. RESULTS: Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). CONCLUSION: This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients.

Clinical Judgement Analysis: An innovative approach to explore the individual decision-making processes of pharmacists.

BACKGROUND: Pharmacy stands increasingly on the frontline of patient care, yet current studies of clinical decision-making by pharmacists only capture deliberative processes that can be stated explicitly. Decision-making incorporates both deliberative and intuitive processes. Clinical Judgement Analysis (CJA) is a method novel to pharmacy that uncovers intuitive decision-making and may provide a more comprehensive understanding of the decision-making processes of pharmacists. OBJECTIVES: This paper describes how CJA potentially uncovers the intuitive clinical decision-making processes of pharmacists. Using an illustrative decision-making example, the application of CJA will be described, including: METHOD: An illustrative study was used, applying an established method for CJA. The decision to initiate anticoagulation, alongside appropriate risk judgements, was chosen as the context. Expert anticoagulation pharmacists were interviewed to define and then refine variables (cues) involved in this decision. Decision tasks with sixty scenarios were developed to explore the effect of these cues on pharmacists' decision-making processes and distributed to participants for completion. Descriptive statistical and regression analyses were conducted for each participant. RESULTS: The method produced individual judgement models for each participant, for example, demonstrating that when judging stroke risk each participant's judgements could be accurately predicted using only 3 or 4 out of the possible 11 cues given. The method also demonstrated that participants appeared to consider multiple cues when making risk judgements but used an algorithmic approach based on one or two cues when making the clinical decision. CONCLUSION: CJA generates insights into the clinical decision-making processes of pharmacists not uncovered by the current literature. This provides a springboard for more in-depth explorations; explorations that are vital to the understanding and ongoing development of the role of pharmacists.

Medication-related harm in older adults following hospital discharge: development and validation of a prediction tool.

OBJECTIVES: To develop and validate a tool to predict the risk of an older adult experiencing medication-related harm (MRH) requiring healthcare use following hospital discharge. DESIGN, SETTING, PARTICIPANTS: Multicentre, prospective cohort study recruiting older adults (≥65 years) discharged from five UK teaching hospitals between 2013 and 2015. PRIMARY OUTCOME MEASURE: Participants were followed up for 8 weeks in the community by senior pharmacists to identify MRH (adverse drug reactions, harm from non-adherence, harm from medication error). Three data sources provided MRH and healthcare use information: hospital readmissions, primary care use, participant telephone interview. Candidate variables for prognostic modelling were selected using two systematic reviews, the views of patients with MRH and an expert panel of clinicians. Multivariable logistic regression with backward elimination, based on the Akaike Information Criterion, was used to develop the PRIME tool. The tool was internally validated. RESULTS: 1116 out of 1280 recruited participants completed follow-up (87%). Uncertain MRH cases ('possible' and 'probable') were excluded, leaving a tool derivation cohort of 818. 119 (15%) participants experienced 'definite' MRH requiring healthcare use and 699 participants did not. Modelling resulted in a prediction tool with eight variables measured at hospital discharge: age, gender, antiplatelet drug, sodium level, antidiabetic drug, past adverse drug reaction, number of medicines, living alone. The tool's discrimination C-statistic was 0.69 (0.66 after validation) and showed good calibration. Decision curve analysis demonstrated the potential value of the tool to guide clinical decision making compared with alternative approaches. CONCLUSIONS: The PRIME tool could be used to identify older patients at high risk of MRH requiring healthcare use following hospital discharge. Prior to clinical use we recommend the tool's evaluation in other settings.

Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models.

Adverse drug reaction (ADR) risk-prediction models for use in older adults have been developed, but it is not clear if they are suitable for use in clinical practice. This systematic review aimed to identify and investigate the quality of validated ADR risk-prediction models for use in older adults. Standard computerized databases, the gray literature, bibliographies, and citations were searched (2012) to identify relevant peer-reviewed studies. Studies that developed and validated an ADR prediction model for use in patients over 65 years old, using a multivariable approach in the design and analysis, were included. Data were extracted and their quality assessed by independent reviewers using a standard approach. Of the 13,423 titles identified, only 549 were associated with adverse outcomes of medicines use. Four met the inclusion criteria. All were conducted in inpatient cohorts in Western Europe. None of the models satisfied the four key stages in the creation of a quality risk prediction model; development and validation were completed, but impact and implementation were not assessed. Model performance was modest; area under the receiver operator curve ranged from 0.623 to 0.73. Study quality was difficult to assess due to poor reporting, but inappropriate methods were apparent. Further work needs to be conducted concerning the existing models to enable the development of a robust ADR risk-prediction model that is externally validated, with practical design and good performance. Only then can implementation and impact be assessed with the aim of generating a model of high enough quality to be considered for use in clinical care to prioritize older people at high risk of suffering an ADR.