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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.

Additional file 1: Appendix 1. Formula for calculating patient risk of experiencing MRH within 8 weeks post hospital discharge. Appendix 2. Visual analogue of risk prediction tool. Appendix 3. Study participants flow chart.

Objective: medication-related problems (MRP) are common for older adults and can lead to harm. The older person’s perspective on MRP has been seldom reported in published literature. This study explored the lived experience of MRP in older adults with varying functional levels, focussing on the hospital discharge period.\ud \ud Design, setting, participants: this qualitative study was conducted in Brighton and Hove, UK. A purposive sample of 20 older people with experience of MRP, involving carers, took part in focus groups and semi-structured interviews. Data were thematically analysed using a ‘framework’ approach.\ud \ud Results: four major themes associated with MRP were identified; (1) experience of the healthcare system, (2) practicalities of using medicines, (3) management of medication problems and (4) participant beliefs. Participants encountered problems in communication with healthcare professionals such as passive listening and paternalistic consultations. A conflict was acknowledged between participants’ implicit trust in the healthcare system and their negative experience of MRP. Participants felt vulnerable around hospital discharge, describing reduced capacity to comprehend information, pressured discharge circumstances and lack of integrated care in the community. Drug formulations, packaging and information leaflets were felt to be poorly tailored to the needs of older people.\ud \ud Conclusions: the lived experience of older people with MRP in this study was multifaceted and complex. Participants felt communication was poor around hospital discharge, and insufficient support with medicines was offered in the community when problems arose. Harm due to MRP might be reduced if the contributory factors described by patients inform clinical and policy-level intervention.

Introduction Multimorbidity, polypharmacy and susceptibility to adverse drug reactions (ADR) are common problems in old age. Understanding the age-related biological changes that occur at a cellular level, may assist in identifying novel therapeutic targets. The nuclear factor erythroid 2-like 2 (Nrf2) transcription factor regulates antioxidant and drug metabolising pathways in the cell. Data from rodent models showed that Nrf2 protein expression declines with age. If similar findings are observed in humans, it may help to explain why older people are vulnerable to multimorbidity and ADRs. This study investigates whether Nrf2 expression (both mRNA and protein) decreases with increasing age in humans.\ud \ud Methods Fifty-five adults were recruited to our study (age range: 18-75 years). Participants donated 6 mL of venous blood, from which peripheral blood mononuclear cells (PBMCs) were separated and analysed for Nrf2 mRNA and protein expression (real time quantitative polymerase chain reaction and enzyme-linked immunosorbant assay respectively). \ud \ud Results Our data showed that Nrf2 protein expression was approximately 50% lower in individuals aged >30 years (0.065 ±0.014 EU 30 years, p70 year age categories respectively; p

Introduction Multimorbidity and adverse drug reactions (ADR) are problems associated with ageing populations. Exploring underlying genetic predispositions might help to risk-stratify patients for early intervention. The nuclear factor erythroid 2-like 2 (Nrf2) protein regulates antioxidant and de-toxifying effectors in the cell. Nrf2 expression declines with age, potentially increasing vulnerability to multimorbidity and ADR. We hypothesise that single nucleotide polymorphisms (SNPs) at 3 loci in the Nrf2 gene are associated with multimorbidity and ADR in older adults. \ud Methods One-hundred and twenty-seven patients were recruited from a sub-population of the PRIME study (a multicentre prospective cohort study that followed older adults over 8-weeks post-discharge to determine ADR status). Donated genetic material was sequenced to determine genotype at 3 loci: rs6721961, rs35652124 and rs6706649 and then analysed for association with ADR (Naranjo Algorithm), multimorbidity (3 conditions defined by the Charlson Index (CI)).\ud Results One-hundred and twelve patients (mean age 76.6±7.3 years, 55.4% female) were successfully genotyped. In patients aged 65-79, those with the rs35652124 A allele showed increased odds of having 3 co-morbidities (OR 9.03 95%CI 1.16-70.2, p=0.0127). Individuals with the CGG haplotype in this age-group showed reduced odds of multimorbidity (OR 0.11, 95% CI 0.01-0.86, p=0.001). No association between Nrf2 geno/haplotype and ADR was identified.\ud Conclusions Polymorphisms in the Nrf2 gene are associated with multimorbidity, but not ADR, in older adults.

Introduction\ud Frailty has been under investigated as a risk factor for medication-related harm (MRH) in older adults[1]. We sought to determine whether frailty is independently associated with MRH in a large multicentre prospective cohort, the PRIME study. \ud \ud Methods\ud The PRIME study recruited 1280 older adults at hospital discharge from 5 hospitals in England between 2013 to 2015[2]. MRH and associated healthcare use within 8-weeks post-discharge were identified by senior pharmacists using (1) hospital readmission data, (2) primary care records, (3) patient telephone interviews. Based on the Rockwood approach[3], we developed a frailty index including 55 deficits from multiple domains (morbidity, cognition, mood, strength and mobility, nutrition, daily function). Frailty was defined using the established cut-off of 20% deficits[4], and internally validated using Kaplan-Meier plots comparing survival in frail and non-frail patients. We then used logistic regression analysis to investigate the relationship between frailty and MRH requiring healthcare. \ud \ud Results\ud 1116 patients completed follow-up (median age 81.9 years, range 65-103 years, 58.4% female). 446 patients (40%) were frail in our cohort. 36% of frail patients experienced MRH compared with 25% in non-frail patients. There was a strong relationship between frailty and MRH (OR 1.67, 95% CI 1.29-2.17, p

Introduction\ud Strong evidence exists for a relationship between polypharmacy and mortality[1], independent of comorbidity. The mechanisms underlying this relationship are unclear. Medication-related harm (MRH) may occur due to non-adherence or adverse drug reactions. We sought to determine if MRH due to non-adherence or adverse drug reactions may explain the association between polypharmacy and mortality.\ud \ud Methods\ud The PRIME study recruited 1280 older adults at hospital discharge from 5 hospitals in England between 2013 to 2015[2]. Patients were followed up in the community for 8-weeks by senior pharmacists to identify MRH using data from hospital readmissions, GP records and patient interviews. Mortality data at 12 months post-discharge were obtained from hospital records. Non-adherence was determined using a modified version of a validated questionnaire[3]. Adverse drug reactions were assessed using the Naranjo algorithm[4]. Adjusted logistic regression models were used to investigate the relationship between (1) number of medicines and MRH, (2) MRH and mortality.\ud \ud Results\ud 1116 out of 1280 patients completed follow-up (median age 82 years, range 65-103 years, 58% female). Patients were discharged with a median of 9 medicines (range 0-27). A higher number of medicines was strongly associated with MRH due to non-adherence (p

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 this study was to investigate the incidence, severity, preventability and cost of medication-related harm (MRH) in older adults in England post-discharge.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 eight weeks by senior pharmacists, using 3 data sources (hospital readmission review, participant telephone interview and primary care records), to identify MRH and associated health service utilisation.RESULTS: Four hundred and thirteen participants (37%) experienced MRH (556 MRH events per 1000 discharges). Three hundred and thirty-six (81%) cases were serious, and 214 (52%) potentially preventable. Four participants experienced fatal MRH. The most common MRH events were gastrointestinal (n=158, 25%) and neurological (n=111, 18%). Medicine classes associated with the highest risk of MRH were opiates, antibiotics, and benzodiazepines. Three hundred and twenty-eight (79%) participants with MRH sought healthcare over the eight-week follow-up. The incidence of MRH associated hospital readmission was 78 per 1000 discharges. Post-discharge 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.

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.

Background Injury prevention has featured as a relatively low priority on Government health agendas in Europe and elsewhere, the result of which has been a lack of national policy development. Successful policy making criteria have not been used to systematically evaluate injury and violence prevention policies. Aim To provide a content analysis of national policies to address violence and injury prevention in the WHO European Region so as to inform where improvements can be made in developing policy. Methods A network of health ministry focal persons, an internet search of relevant Ministry web-sites, and a Google-search using key words were used to identify national policies for violence and injury prevention. A framework was used for policy content analysis. Results The majority of national policies had been developed after 2003. 80 English-language policies from 26 countries were analysed further and 43 non-English policies from 16 countries were excluded. The majority of policies fulfilled the criteria for successful health policy making: lead body, intersectoral collaboration, budgets, government approval, defined implementations, timeframe, evaluation. Some areas warranted attention such as quantitative objectives, target population and implementing interventions not based on evidence. Conclusions Encouraging progress is being made in the WHO European Region. Following the criteria for successful policy making more closely could increase the effectiveness of the preparation and implementation of policies for violence and injury prevention. Areas that warrant attention include setting targets for child maltreatment and domestic violence prevention, as do certain types of injury and violence prevention such as suicide prevention.