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Clinical decision making flow chart. This flow chart provides a simple outline of the method which will be employed to perform an intial assessment at follow-up of whether medication harm has occurred based on patient interview, hospital re-admission and General Practice records. This will be followed by a final assessment of potential medication harm events, classified by likelihood, cause, severity and preventability of the event. The binary outcome of this assessment to determine the occurrence (or not) of medication harm will inform the logistic regression and risk prediction model development. The model will be internally validated and its ability to predict medicaiton harm will be compared to the ability of discharging clinicians to predict medication harm at the point of hospital discharge
Source publication
Background
Medication related harm (MRH) is a common cause of morbidity and hospital admission in the elderly, and has significant cost implications for both primary and secondary healthcare resources. The development of risk prediction models has become an increasingly common phenomenon in medicine and can be useful to guide objective clinical dec...
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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....
Citations
... The baseline data to be collected and methodology will be similar to the original PRIME Study [43]. Baseline data to be collected from consenting participants (and participants consenting through their consultee) will include demographic (age, gender, ethnicity), clinical (discharge diagnosis, co-morbidities, renal function, electrolytes, hepatic function), and social indicators data (living arrangements and care package on discharge). ...
Background
Medication-related harm (MRH) is an escalating global challenge especially among older adults. The period following hospital discharge carries high-risk for MRH due to medication discrepancies, limited patient/carer education and support, and poor communication between hospital and community professionals. Discharge Medical Service (DMS), a newly introduced NHS scheme, aims to reduce post-discharge MRH through an electronic communication between hospital and community pharmacists. Our study team has previously developed a risk-prediction tool (RPT) for MRH in the 8-weeks period post discharge from a UK hospital cohort of 1280 patients. In this study, we aim to find out if a Medicines Management Plan (MMP) linked to the DMS is more effective than the DMS alone in reducing rates of MRH.
Method
Using a randomized control trial design, 682 older adults ≥ 65 years due to be discharged from hospital will be recruited from 4 sites. Participants will be randomized to an intervention arm (individualised medicine management plan (MMP) plus DMS) or a control arm (DMS only) using a 1:1 ratio stratification. Baseline data will include patients’ clinical and social demographics, and admission and discharge medications. At 8-weeks post-discharge, a telephone interview and review of GP records by the study pharmacist will verify MRH in both arms. An economic and process evaluation will assess the cost and acceptability of the study methods.
Data analysis
Univariate analysis will be done for baseline variables comparing the intervention and control arms. A multivariate logistic regression will be done incorporating these variables. Economic evaluation will compare the cost-of-service use among the study arms and modelled to provide national estimates. Qualitative data from focus-group interviews will explore practitioners’ understanding, and acceptance of the MMP, DMS and the RPT.
Conclusion
This study will inform the use of an objective, validated RPT for MRH among older adults after hospital discharge, and provide a clinical, economic, and service evaluation of a specific medicines management plan alongside the DMS in the National Health Service (UK).
... The baseline data to be collected and methodology will be similar to the original PRIME Study 43 . Baseline data to be collected from consenting participants (and participants consenting through their consultee) will include demographic (age, gender, ethnicity), clinical (discharge diagnosis, co-morbidities, renal function, electrolytes, hepatic function), and social indicators data (living arrangements and care package on discharge). ...
Background
Medication-related harm (MRH) is an escalating global challenge especially among older adults. The period following hospital discharge carries high-risk for MRH due to medication discrepancies, limited patient/carer education and support, and poor communication between hospital and community professionals. Discharge Medical Service (DMS), a newly introduced NHS scheme, aims to reduce post-discharge MRH through an electronic communication between hospital and community pharmacists. Our study team has previously developed a risk-prediction tool (RPT) for MRH in the 8-weeks period post discharge from a UK hospital cohort of 1280 patients.
Method
Using a randomized control trial design, 682 older adults ≥ 65years due to be discharged from hospital will be recruited from 4 sites. Participants will be randomized to an intervention arm (individualised medicine management plan (MMP) plus DMS) or a control arm (DMS only) using a 1:1 ratio stratification. Baseline data will include patients’ clinical and social demographics, and admission and discharge medications. At 8-weeks post-discharge, a telephone interview and review of GP records by the study pharmacist will verify MRH in both arms. An economic and process evaluation will assess the cost and acceptability of the study methods.
Data Analysis
Univariate analysis will be done for baseline variables comparing the intervention and control arms. A multivariate logistic regression will be done incorporating these variables. Economic evaluation will compare the cost-of-service use among the study arms and modelled to provide national estimates. Qualitative data from focus-group interviews will explore practitioners’ understanding, and acceptance of the MMP, DMS and the RPT.
Conclusion
This study will inform the use of an objective, validated RPT for MRH among older adults after hospital discharge, and provide a clinical, economic, and service evaluation of a specific medicines management plan alongside the DMS in the National Health Service (UK).
... In the 'Prospective study to develop a model to stratify the risk of medication related harm in hospitalized elderly patients in the UK' (PRIME) patient cohort, BP-lowering drugs were the most prescribed medicines [9]. In this subanalysis of PRIME, we will quantify serious MRH events such as death, hospitalisation and readmission from BPlowering drugs [9,10]. We explore clinical and sociodemographic characteristics predicting MRH in older people taking BP-lowering drugs which is key to optimising treatment decisions and reducing harm. ...
... PRIME was a prospective cohort study that recruited patients aged ≥65, near the time of hospital discharge. The protocol and main results have been previously published [9,10]. Patients were recruited from five NHS hospitals in the UK between September 2013 and November 2015. ...
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.
... This study, therefore, aimed to determine whether frailty is independently associated with MRH requiring healthcare utilisation within a UK multi-centre prospective cohort study (The Predicting RIsk of Medication-related harm in Elderly (PRIME) study) [12]. The PRIME Study developed a risk-prediction model to identify older adults at risk of post-discharge MRH that was superior to routine clinical judgement [2,[12][13][14]. ...
... This study, therefore, aimed to determine whether frailty is independently associated with MRH requiring healthcare utilisation within a UK multi-centre prospective cohort study (The Predicting RIsk of Medication-related harm in Elderly (PRIME) study) [12]. The PRIME Study developed a risk-prediction model to identify older adults at risk of post-discharge MRH that was superior to routine clinical judgement [2,[12][13][14]. ...
... The data presented here relate to a sub-study of the PRIME study, the methods for which are described in detail in the published protocol [12]. The PRIME study was approved by the National Research Ethics Service, East of England (REC Reference 13/EE/0075), and was funded by NIHR Research for Patient Benefit and Guy's and St. Thomas' Charity. ...
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.
... The data presented here relate to a sub-study of the PRIME study, the methods for which are described in detail in the published protocol (10). The PRIME study was approved by the National Research Ethics Service, East of England (REC Reference 13/EE/0075), and was funded by NIHR Research for Patient Benefit and Guy's and St. Thomas' Charity. ...
Objectives
To determine the association between frailty and medication-related harm requiring healthcare utilisation.
Design
Prospective observational cohort study.
Setting
6 primary and 5 secondary care sites across South East England, September 2013 – November 2015.
Participants
1280 participants, 65 years old or over, 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 adverse drug reactions, non-adherence and medication error determined via triangulation of: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of re-admission 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 polypharmacy and frailty.
Results
Healthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06 to 49.26, p = 0.004), independent of age, gender, and polypharmacy. With increasing polypharmacy, the need for healthcare use as a result of MRH increases from a probability of around 0.2 to 0.4. This is also the case for frailty.
Conclusions
Frailty is as important as polypharmacy in its association with MRH. 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.
Trial registration
Approved by the National Research Ethics Service, East of England (REC Reference 13/EE/0075)
... When operationalizing CDM as clinical judgement (n = 21), the majority of studies [39,[43][44][45][46][47][48][49][50][51][52][53][54] investigating decision aids such as a tool, rule or standardized testing, found them to improve diagnostic accuracy and reduce uncertainty. However, an almost similarly large percentage found no difference [36,42,55,56] or a decline in performance [57][58][59][60]. ...
Background:
Clinical decision-making (CDM) is an important competency for young doctors especially under complex and uncertain conditions in geriatric emergency medicine (GEM). However, research in this field is characterized by vague conceptualizations of CDM. To evolve and evaluate evidence-based knowledge of CDM, it is important to identify different definitions and their operationalizations in studies on GEM.
Objective:
A scoping review of empirical articles was conducted to provide an overview of the documented evidence of findings and conceptualizations of CDM in GEM.
Methods:
A detailed search for empirical studies focusing on CDM in a GEM setting was conducted in PubMed, ProQuest, Scopus, EMBASE and Web of Science. In total, 52 publications were included in the analysis, utilizing a data extraction sheet, following the PRISMA guidelines. Reported outcomes were summarized.
Results:
Four themes of operationalization of CDM emerged: CDM as dispositional decisions, CDM as cognition, CDM as a model, and CDM as clinical judgement. Study results and conclusions naturally differed according to how CDM was conceptualized. Thus, frailty-heuristics lead to biases in treatment of geriatric patients and the complexity of this patient group was seen as a challenge for young physicians engaging in CDM.
Conclusions:
This scoping review summarizes how different studies in GEM use the term CDM. It provides an analysis of findings in GEM and call for more stringent definitions of CDM in future research, so that it might lead to better clinical practice.
... When operationalizing CDM as clinical judgement (n = 21), the majority of studies (40,(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55) investigating decision aids (i.e. a tool, rule or standardized testing) found them to improve diagnostic accuracy and reduce uncertainty. However, an almost similarly large percentage found no difference (37,43,56,57) or a decline in performance (58)(59)(60)(61). ...
Background: Clinical decision-making (CDM) is an important competency for young doctors, especially under complex and uncertain conditions, which is present in geriatric emergency medicine (GEM). Research in this field is however characterized by an unclear conceptualization of CDM. To evolve and evaluate evidence-based knowledge of CDM, it is thus important to identify different definitions and their operationalisations in studies on GEM.
Objective: A scoping review of empirical articles was designed to provide an overview of the documented evidence of findings and conceptualizations of CDM in GEM.
Methods: A detailed search for empirical studies focusing on CDM in a GEM setting was conducted in PubMed, ProQuest, Scopus, EMBASE and Web of Science. In total, 52 publications were included in the analysis, utilizing a data extraction sheet, following the PRISMA guidelines. Reported outcomes were summarized.
Results: Four themes of operationalization of CDM emerged; CDM as dispositional decisions, CDM as cognition, CDM as a model, and CDM as clinical judgement. Study results and conclusions differed according to how CDM was conceptualized. It was evident how especially frailty- heuristics lead to biases in treatment of geriatric patients, and that the complexity of this patient group was seen as a challenge for CDM.
Conclusions: This scoping review summarizes how different studies in GEM use the term CDM. It provides a snapshot of findings in GEM. Potentially, findings from CDM research can guide implementation of adequate CDM strategies in clinical practice but this requires application of more stringent definitions of CDM in future research.
... The risk prediction tool reported in this paper was developed using data from a multicentre, prospective cohort study; Prospective study to develop a model to stratify the RIsk of Medication-related harm in hospitalised Elderly patients (PRIME). 15 26 Detailed methods are in the published protocol. 26 This study is reported in accordance with the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement. ...
... 15 26 Detailed methods are in the published protocol. 26 This study is reported in accordance with the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) statement. 27 Research nurses recruited inpatients (age ≥65 years) close to discharge from medical wards, between 2013 and 2015, in five NHS teaching hospitals in England. ...
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.
... Association of NFE2L2 Genotype/Haplotype With ADRs, Multimorbidity, and Frailty Participants and recruitment A subset of older patients who had recently participated in the PRIME study (4,21) was invited to send a cheek-swab of genetic material to establish their genotype at three NFE2L2 SNP loci (rs35652124, rs6706649, and rs6721961) and to provide consent for study coordinators to access participant data collected during the original PRIME study. The PRIME study was a large multicenter study investigating the incidence and cost implications for medication-related harm (including ADR) in older people 8 weeks post-hospital discharge. ...
... The PRIME study recruited 1,280 older adults at hospital discharge from five hospitals in England between 2013 and 2015 (21). Patients were assessed for the presence of an ADR over an 8-week period by a senior pharmacist using the Narajo algorithm (22). ...
... When testing for age-related changes to NFE2L2 gene expression, participants were stratified in age categories (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)30-39, 40-49, 50-59, 60-69, >70). Log abundance and log-fold change of NFE2L2 as a function of age category were then analyzed using the Markov chain Monte Carlo (MCMC) analytical method described by Matz and colleagues (MCMC.qpcr ...
Susceptibility to adverse drug reactions (ADRs), multimorbidity, and frailty are associated with human ageing, yet there is wide variation in the severity and age at which individuals are afflicted. Identifying genetic markers of increased risk of this phenotype would help stratify individuals to specialist interventions. Nuclear factor erythroid derived-2 like 2 (Nrf2) regulates a cell’s response to stressors, including the expression of enzymes involved in drug-metabolism. Its expression has been shown to decline in animal ageing models. In this study we tested the hypothesis that Nrf2 gene transcription/translation decline in human ageing, and that single nucleotide polymorphisms (SNPs) in the Nrf2 gene are associated with increased ADR risk, multi-morbidity, and frailty in older people. Gene expression and protein levels were measured in peripheral blood mononuclear cells (PBMCs) donated from healthy patients aged 18-80 years old. Nrf2 genotypes were determined at three loci in a sub-population of patients recruited to the PRIME study (a multicentre prospective cohort study that followed older adults for 8-weeks post-discharge to determine ADR). Both Nrf2 gene and protein expression declined significantly with age in human PBMCs. In the PRIME sub-study population, the rs35652124 Nrf2 SNP was associated with increased ADR risk, and decreased frailty and multi-morbidity scores.
... It is possible that this tool may have overcategorized or undercategorized harm in some instances. However, similar risk classification tools have been used in other studies, (33,34) and the clinician panel considered final categorization appropriate in all instances. ...
People with decompensated cirrhosis are often prescribed a complex regimen of therapeutic and prophylactic medications. In other chronic diseases, polypharmacy increases the risk of medication misadventure and medication‐related problems (MRPs), with associated increased morbidity, mortality, and health care costs. This study examined MRPs in a cohort of ambulatory patients with a history of decompensated cirrhosis who were enrolled in a randomized controlled trial of a pharmacist‐led, patient‐oriented medication education intervention and assessed the association between MRPs and patient outcomes. A total of 375 MRPs were identified among 57 intervention patients (median, 6.0; interquartile range, 3.5‐8.0 per patient; maximum 17). Nonadherence (31.5%) and indication issues (29.1%) were the most prevalent MRP types. The risk of potential harm associated with MRPs was low in 18.9% of instances, medium in 33.1%, and high in 48.0%, as categorized by a clinician panel using a risk matrix tool. Patients had a greater incidence rate of high‐risk MRPs if they had a higher Child‐Pugh score (incidence rate ratio [IRR], 1.31; 95% confidence interval [CI], 1.09‐1.56); greater comorbidity burden (IRR, 1.15; 95% CI, 1.02‐1.29); and were taking more medications (IRR, 1.12; 95% CI, 1.04‐1.22). A total of 221 MRPs (58.9%) were resolved following pharmacist intervention. A greater proportion of high‐risk MRPs were resolved compared to those of low and medium risk (68.9% versus 49.7%; P < 0.001). During the 12‐month follow‐up period, intervention patients had a lower incidence rate of unplanned admissions compared to usual care (IRR, 0.52; 95% CI, 0.30‐0.92). Conclusion : High‐risk MRPs are prevalent among adults with decompensated cirrhosis. Pharmacist intervention facilitated identification and resolution of high‐risk MRPs and was associated with reduced incidence rate of unplanned hospital admissions in this group.
