The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study.

BACKGROUND: Antihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. METHODS AND FINDINGS: This was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. CONCLUSIONS: Antihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Educational inequality in multimorbidity: causality and causal pathways. A mendelian randomisation study in UK Biobank.

BACKGROUND: Multimorbidity, typically defined as having two or more long-term health conditions, is associated with reduced wellbeing and life expectancy. Understanding the determinants of multimorbidity, including whether they are causal, may help with the design and prioritisation of prevention interventions. This study seeks to assess the causality of education, BMI, smoking and alcohol as determinants of multimorbidity, and the degree to which BMI, smoking and alcohol mediate differences in multimorbidity by level of education. METHODS: Participants were 181,214 females and 155,677 males, mean ages 56.7 and 57.1 years respectively, from UK Biobank. We used a Mendelian randomization design; an approach that uses genetic variants as instrumental variables to interrogate causality. RESULTS: The prevalence of multimorbidity was 55.1%. Mendelian randomization suggests that lower education, higher BMI and higher levels of smoking causally increase the risk of multimorbidity. For example, one standard deviation (equivalent to 5.1 years) increase in genetically-predicted years of education decreases the risk of multimorbidity by 9.0% (95% CI: 6.5 to 11.4%). A 5 kg/m2 increase in genetically-predicted BMI increases the risk of multimorbidity by 9.2% (95% CI: 8.1 to 10.3%) and a one SD higher lifetime smoking index increases the risk of multimorbidity by 6.8% (95% CI: 3.3 to 10.4%). Evidence for a causal effect of genetically-predicted alcohol consumption on multimorbidity was less strong; an increase of 5 units of alcohol per week increases the risk of multimorbidity by 1.3% (95% CI: 0.2 to 2.5%). The proportions of the association between education and multimorbidity explained by BMI and smoking are 20.4% and 17.6% respectively. Collectively, BMI and smoking account for 31.8% of the educational inequality in multimorbidity. CONCLUSIONS: Education, BMI, smoking and alcohol consumption are intervenable causal risk factors for multimorbidity. Furthermore, BMI and lifetime smoking make a considerable contribution to the generation of educational inequalities in multimorbidity. Public health interventions that improve population-wide levels of these risk factors are likely to reduce multimorbidity and inequalities in its occurrence.

Association between hypertensive disorders of pregnancy and later risk of cardiovascular outcomes.

BACKGROUND: Hypertensive disorders of pregnancy are common pregnancy complications that are associated with greater cardiovascular disease risk for mothers. However, risk of cardiovascular disease subtypes associated with gestational hypertension or pre-eclampsia is unclear. The present study aims to compare the risk of cardiovascular disease outcomes for women with and without a history of gestational hypertension and pre-eclampsia using national hospital admissions data. METHODS: This was a retrospective cohort study of national medical records from all National Health Service hospitals in England. Women who had one or more singleton live births in England between 1997 and 2015 were included in the analysis. Risk of total cardiovascular disease and 19 pre-specified cardiovascular disease subtypes, including stroke, coronary heart disease, cardiomyopathy and peripheral arterial disease, was calculated separately for women with a history of gestational hypertension and pre-eclampsia compared to normotensive pregnancies. RESULTS: Amongst 2,359,386 first live births, there were 85,277 and 74,542 hospital admissions with a diagnosis of gestational hypertension and pre-eclampsia, respectively. During 18 years (16,309,386 person-years) of follow-up, the number and incidence of total CVD for normotensive women, women with prior gestational hypertension and women with prior pre-eclampsia were n = 8668, 57.1 (95% CI: 55.9-58.3) per 100,000 person-years; n = 521, 85.8 (78.6-93.5) per 100,000 person-years; and n = 518, 99.3 (90.9-108.2) per 100,000 person-years, respectively. Adjusted HRs (aHR) for total CVD were aHR (95% CI) = 1.45 (1.33-1.59) for women with prior gestational hypertension and aHR = 1.62 (1.48-1.78) for women with prior pre-eclampsia. Gestational hypertension was strongly associated with dilated cardiomyopathy, aHR = 2.85 (1.67-4.86), and unstable angina, aHR = 1.92 (1.33-2.77). Pre-eclampsia was strongly associated with hypertrophic cardiomyopathy, aHR = 3.27 (1.49-7.19), and acute myocardial infarction, aHR = 2.46 (1.72-3.53). Associations were broadly homogenous across cardiovascular disease subtypes and increased with a greater number of affected pregnancies. CONCLUSIONS: Women with either previous gestational hypertension or pre-eclampsia are at greater risk of a range of cardiovascular outcomes. These women may benefit from clinical risk assessment or early interventions to mitigate their greater risk of various cardiovascular outcomes.

Novel oral iron therapy for iron deficiency anaemia: How to value safety in a new drug?

AIMS: Novel oral iron supplements may be associated with a reduced incidence of adverse drug reactions compared to standard treatments of iron deficiency anaemia. The aim was to establish their value-based price under conditions of uncertainty surrounding their tolerability. METHODS: A discrete-time Markov model was developed to assess the value-based price of oral iron preparations based on their incremental cost per quality-adjusted life year (QALY) gained from the perspective of the NHS in the UK. Primary and secondary care resource use and health state occupancy probabilities were estimated from routine electronic health records; and unit costs and health state utilities were derived from published sources. Patients were pre-menopausal women with iron deficiency anaemia who were prescribed oral iron supplementation between 2000 and 2014. RESULTS: The model reflecting current use of iron salts yielded a mean total cost to the NHS of £779, and 0.84 QALYs over 12 months. If a new iron preparation were to reduce the risk of adverse drug reactions by 30-40%, then its value-based price, based on a threshold of £20 000 per QALY, would be in the region of £10-£13 per month, or about 7-9 times the average price of basic iron salts. CONCLUSIONS: There are no adequate, direct comparisons of new oral iron supplements to ferrous iron salts, and therefore other approaches are needed to assess their value. Our modelling shows that they are potentially cost-effective at prices that are an order of magnitude higher than existing iron salts.

Aspirin reduces cardiovascular events in patients with pneumonia: a prior event rate ratio analysis in a large primary care database.

BACKGROUND: Ischaemic stroke and myocardial infarction (MI) are common after pneumonia and are associated with long-term mortality. Aspirin may attenuate this risk and should be explored as a therapeutic option. METHODS: We extracted all patients with pneumonia (aged over 50 years) from the Clinical Practice Research Datalink (CPRD), a large UK primary care database, from inception until January 2019. We then performed a prior event rate ratio (PERR) analysis with propensity score matching (PSM), an approach that allows for control of measured and unmeasured confounding, with aspirin usage as the exposure and ischaemic events as the outcome. The primary outcome was the combined outcome of ischaemic stroke and MI. Secondary outcomes were ischaemic stroke and MI individually. Relevant confounders (smoking, comorbidities, age and gender) were included in the analysis. FINDINGS: 48 743 patients were eligible for matching. Of these, 9864 were aspirin users who were matched to 9864 non-users. Aspirin users had a reduced risk of the primary outcome (adjusted hazard ratio 0.64, 95% CI 0.52-0.79) in the PERR analysis. For both secondary outcomes, aspirin use was also associated with a reduced risk for MI (hazard ratio 0.46, 95% CI 0.30-0.72) and stroke (hazard ratio 0.70, 95% CI 0.55-0.91), respectively. INTERPRETATION: This study provides supporting evidence that aspirin use is associated with reduced ischaemic events after pneumonia in a primary care setting. This drug may have a future clinical role in preventing this important complication.

Epidemiology of pleural empyema in English hospitals and the impact of influenza.

Pleural empyema represents a significant healthcare burden due to extended hospital admissions and potential requirement for surgical intervention. This study aimed to assess changes in incidence and management of pleural empyema in England over the past 10 years and the potential impact of influenza on rates.Hospital Episode Statistics data were used to identify patients admitted to English hospitals with pleural empyema between 2008 and 2018. Linear regression was used to analyse the relationship between empyema rates and influenza incidence recorded by Public Health England. The relationship between influenza and empyema was further explored using serological data from a prospective cohort study of patients presenting with pleural empyema.Between April 2008 and March 2018 there were 55 530 patients admitted with pleural empyema. There was male predominance (67% versus 33%), which increased with age. Cases have increased significantly from 4447 in 2008 to 7268 in 2017. Peaks of incidence correlated moderately with rates of laboratory-confirmed influenza in children and young adults (r=0.30). For nine of the 10 years studied, the highest annual point incidence of influenza coincided with the highest admission rate for empyema (with a 2-week lag). In a cohort study of patients presenting to a single UK hospital with pleural empyema/infection, 24% (17 out of 72) had serological evidence of recent influenza infection, compared to 7% in seasonally matched controls with simple parapneumonic or cardiogenic effusions (p<0.001).Rates of empyema admissions in England have increased steadily with a seasonal variation that is temporally related to influenza incidence. Patient-level serological data from a prospective study support the hypothesis that influenza may play a pathogenic role in empyema development.

International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European Quality study.

BACKGROUND: People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. RESULTS: Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021]. CONCLUSIONS: Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

The Use of Primary Care Big Data in Understanding the Pharmacoepidemiology of COVID-19: A Consensus Statement From the COVID-19 Primary Care Database Consortium.

The use of big data containing millions of primary care medical records provides an opportunity for rapid research to help inform patient care and policy decisions during the first and subsequent waves of the coronavirus disease 2019 (COVID-19) pandemic. Routinely collected primary care data have previously been used for national pandemic surveillance, quantifying associations between exposures and outcomes, identifying high risk populations, and examining the effects of interventions at scale, but there is no consensus on how to effectively conduct or report these data for COVID-19 research. A COVID-19 primary care database consortium was established in April 2020 and its researchers have ongoing COVID-19 projects in overlapping data sets with over 40 million primary care records in the United Kingdom that are variously linked to public health, secondary care, and vital status records. This consensus agreement is aimed at facilitating transparency and rigor in methodological approaches, and consistency in defining and reporting cases, exposures, confounders, stratification variables, and outcomes in relation to the pharmacoepidemiology of COVID-19. This will facilitate comparison, validation, and meta-analyses of research during and after the pandemic.

A multi-stakeholder approach to the co-production of the research agenda for medicines optimisation.

BACKGROUND: Up to 50% of medicines are not used as intended, resulting in poor health and economic outcomes. Medicines optimisation is 'a person-centred approach to safe and effective medicines use, to ensure people obtain the best possible outcomes from their medicines'. The purpose of this exercise was to co-produce a prioritised research agenda for medicines optimisation using a multi-stakeholder (patient, researcher, public and health professionals) approach. METHODS: A three-stage, multiple method process was used including: generation of preliminary research questions (Stage 1) using a modified Nominal Group Technique; electronic consultation and ranking with a wider multi-stakeholder group (Stage 2); a face-to-face, one-day consensus meeting involving representatives from all stakeholder groups (Stage 3). RESULTS: In total, 92 research questions were identified during Stages 1 and 2 and ranked in order of priority during stage 3. Questions were categorised into four areas: 'Patient Concerns' [e.g. is there a shared decision (with patients) about using each medicine?], 'Polypharmacy' [e.g. how to design health services to cope with the challenge of multiple medicines use?], 'Non-Medical Prescribing' [e.g. how can the contribution of non-medical prescribers be optimised in primary care?], and 'Deprescribing' [e.g. what support is needed by prescribers to deprescribe?]. A significant number of the 92 questions were generated by Patient and Public Involvement representatives, which demonstrates the importance of including this stakeholder group when identifying research priorities. CONCLUSIONS: A wide range of research questions was generated reflecting concerns which affect patients, practitioners, the health service, as well the ethical and philosophical aspects of the prescribing and deprescribing of medicines. These questions should be used to set future research agendas and funding commissions.

Characteristics, service use and mortality of clusters of multimorbid patients in England: a population-based study.

BACKGROUND: Multimorbidity is associated with mortality and service use, with specific types of multimorbidity having differential effects. Additionally, multimorbidity is often negatively associated with participation in research cohorts. Therefore, we set out to identify clusters of multimorbidity patients and how they are differentially associated with mortality and service use across age groups in a population-representative sample. METHODS: Linked primary and secondary care electronic health records contributed by 382 general practices in England to the Clinical Practice Research Datalink (CPRD) were used. The study included a representative set of multimorbid adults (18 years old or more, N = 113,211) with two or more long-term conditions (a total of 38 conditions were included). A random set of 80% of the multimorbid patients (N = 90,571) were stratified by age groups and clustered using latent class analysis. Consistency between obtained multimorbidity phenotypes, classification quality and associations with demographic characteristics and primary outcomes (GP consultations, hospitalisations, regular medications and mortality) was validated in the remaining 20% of multimorbid patients (N = 22,640). RESULTS: We identified 20 patient clusters across four age strata. The clusters with the highest mortality comprised psychoactive substance and alcohol misuse (aged 18-64); coronary heart disease, depression and pain (aged 65-84); and coronary heart disease, heart failure and atrial fibrillation (aged 85+). The clusters with the highest service use coincided with those with the highest mortality for people aged over 65. For people aged 18-64, the cluster with the highest service use comprised depression, anxiety and pain. The majority of 85+-year-old multimorbid patients belonged to the cluster with the lowest service use and mortality for that age range. Pain featured in 13 clusters. CONCLUSIONS: This work has highlighted patterns of multimorbidity that have implications for health services. These include the importance of psychoactive substance and alcohol misuse in people under the age of 65, of co-morbid depression and coronary heart disease in people aged 65-84 and of cardiovascular disease in people aged 85+.

Development and validation of the Cambridge Multimorbidity Score.

BACKGROUND: Health services have failed to respond to the pressures of multimorbidity. Improved measures of multimorbidity are needed for conducting research, planning services and allocating resources. METHODS: We modelled the association between 37 morbidities and 3 key outcomes (primary care consultations, unplanned hospital admission, death) at 1 and 5 years. We extracted development (n = 300 000) and validation (n = 150 000) samples from the UK Clinical Practice Research Datalink. We constructed a general-outcome multimorbidity score by averaging the standardized weights of the separate outcome scores. We compared performance with the Charlson Comorbidity Index. RESULTS: Models that included all 37 conditions were acceptable predictors of general practitioner consultations (C-index 0.732, 95% confidence interval [CI] 0.731-0.734), unplanned hospital admission (C-index 0.742, 95% CI 0.737-0.747) and death at 1 year (C-index 0.912, 95% CI 0.905-0.918). Models reduced to the 20 conditions with the greatest combined prevalence/weight showed similar predictive ability (C-indices 0.727, 95% CI 0.725-0.728; 0.738, 95% CI 0.732-0.743; and 0.910, 95% CI 0.904-0.917, respectively). They also predicted 5-year outcomes similarly for consultations and death (C-indices 0.735, 95% CI 0.734-0.736, and 0.889, 95% CI 0.885-0.892, respectively) but performed less well for admissions (C-index 0.708, 95% CI 0.705-0.712). The performance of the general-outcome score was similar to that of the outcome-specific models. These models performed significantly better than those based on the Charlson Comorbidity Index for consultations (C-index 0.691, 95% CI 0.690-0.693) and admissions (C-index 0.703, 95% CI 0.697-0.709) and similarly for mortality (C-index 0.907, 95% CI 0.900-0.914). INTERPRETATION: The Cambridge Multimorbidity Score is robust and can be either tailored or not tailored to specific health outcomes. It will be valuable to those planning clinical services, policymakers allocating resources and researchers seeking to account for the effect of multimorbidity.

Effect of Antihypertensive Medication Reduction vs Usual Care on Short-term Blood Pressure Control in Patients With Hypertension Aged 80 Years and Older: The OPTIMISE Randomized Clinical Trial.

Importance: Deprescribing of antihypertensive medications is recommended for some older patients with polypharmacy and multimorbidity when the benefits of continued treatment may not outweigh the harms. Objective: This study aimed to establish whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events during 12-week follow-up. Design, Setting, and Participants: The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE) study was a randomized, unblinded, noninferiority trial conducted in 69 primary care sites in England. Participants, whose primary care physician considered them appropriate for medication reduction, were aged 80 years and older, had systolic blood pressure lower than 150 mm Hg, and were receiving at least 2 antihypertensive medications were included. Participants enrolled between April 2017 and September 2018 and underwent follow-up until January 2019. Interventions: Participants were randomized (1:1 ratio) to a strategy of antihypertensive medication reduction (removal of 1 drug [intervention], n = 282) or usual care (control, n = 287), in which no medication changes were mandated. Main Outcomes and Measures: The primary outcome was systolic blood pressure lower than 150 mm Hg at 12-week follow-up. The prespecified noninferiority margin was a relative risk (RR) of 0.90. Secondary outcomes included the proportion of participants maintaining medication reduction and differences in blood pressure, frailty, quality of life, adverse effects, and serious adverse events. Results: Among 569 patients randomized (mean age, 84.8 years; 276 [48.5%] women; median of 2 antihypertensive medications prescribed at baseline), 534 (93.8%) completed the trial. Overall, 229 (86.4%) patients in the intervention group and 236 (87.7%) patients in the control group had a systolic blood pressure lower than 150 mm Hg at 12 weeks (adjusted RR, 0.98 [97.5% 1-sided CI, 0.92 to ∞]). Of 7 prespecified secondary end points, 5 showed no significant difference. Medication reduction was sustained in 187 (66.3%) participants at 12 weeks. Mean change in systolic blood pressure was 3.4 mm Hg (95% CI, 1.1 to 5.8 mm Hg) higher in the intervention group compared with the control group. Twelve (4.3%) participants in the intervention group and 7 (2.4%) in the control group reported at least 1 serious adverse event (adjusted RR, 1.72 [95% CI, 0.7 to 4.3]). Conclusions and Relevance: Among older patients treated with multiple antihypertensive medications, a strategy of medication reduction, compared with usual care, was noninferior with regard to systolic blood pressure control at 12 weeks. The findings suggest antihypertensive medication reduction in some older patients with hypertension is not associated with substantial change in blood pressure control, although further research is needed to understand long-term clinical outcomes. Trial Registration: EudraCT Identifier: 2016-004236-38; ISRCTN identifier: 97503221.

Developing a measure of polypharmacy appropriateness in primary care: systematic review and expert consensus study.

BACKGROUND: Polypharmacy is an increasing challenge for primary care. Although sometimes clinically justified, polypharmacy can be inappropriate, leading to undesirable outcomes. Optimising care for polypharmacy necessitates effective targeting and monitoring of interventions. This requires a valid, reliable measure of polypharmacy, relevant for all patients, that considers clinical appropriateness and generic prescribing issues applicable across all medications. Whilst there are several existing measures of potentially inappropriate prescribing, these are not specifically designed with polypharmacy in mind, can require extensive clinical input to complete, and often cover a limited number of drugs. The aim of this study was to identify what experts consider to be the key elements of a measure of prescribing appropriateness in the context of polypharmacy. METHODS: Firstly, we conducted a systematic review to identify generic (not drug specific) prescribing indicators relevant to polypharmacy appropriateness. Indicators were subject to content analysis to enable categorisation. Secondly, we convened a panel of 10 clinical experts to review the identified indicators and assess their relative clinical importance. For each indicator category, a brief evidence summary was developed, based on relevant clinical and indicator literature, clinical guidance, and opinions obtained from a separate patient discussion panel. A two-stage RAND/UCLA Appropriateness Method was used to reach consensus amongst the panel on a core set of indicators of polypharmacy appropriateness. RESULTS: We identified 20,879 papers for title/abstract screening, obtaining 273 full papers. We extracted 189 generic indicators, and presented 160 to the panel grouped into 18 classifications (e.g. adherence, dosage, clinical efficacy). After two stages, during which the panel introduced 18 additional indicators, there was consensus that 134 indicators were of clinical importance. Following the application of decision rules and further panel consultation, 12 indicators were placed into the final selection. Panel members particularly valued indicators concerned with adverse drug reactions, contraindications, drug-drug interactions, and the conduct of medication reviews. CONCLUSIONS: We have identified a set of 12 indicators of clinical importance considered relevant to polypharmacy appropriateness. Use of these indicators in clinical practice and informatics systems is dependent on their operationalisation and their utility (e.g. risk stratification, targeting and monitoring polypharmacy interventions) requires subsequent evaluation. TRIAL REGISTRATION: Registration number: PROSPERO ( CRD42016049176 ).

Breaking bread: examining the impact of policy changes in access to state-funded provisions of gluten-free foods in England.

BACKGROUND: Coeliac disease affects approximately 1% of the population and is increasingly diagnosed in the United Kingdom. A nationwide consultation in England has recommend that state-funded provisions for gluten-free (GF) food should be restricted to bread and mixes but not banned, yet financial strain has prompted regions of England to begin partially or fully ceasing access to these provisions. The impact of these policy changes on different stakeholders remains unclear. METHODS: Prescription data were collected for general practice services across England (n = 7176) to explore changes in National Health Service (NHS) expenditure on GF foods over time (2012-2017). The effects of sex, age, deprivation and rurality on GF product expenditure were estimated using a multi-level gamma regression model. Spending rate within NHS regions that had introduced a 'complete ban' or a 'complete ban with age-related exceptions' was compared to spending in the same time periods amongst NHS regions which continued to fund prescriptions for GF products. RESULTS: Annual expenditure on GF products in 2012 (before bans were introduced in any area) was £25.1 million. Higher levels of GF product expenditure were found in general practices in areas with lower levels of deprivation, higher levels of rurality and higher proportions of patients aged under 18 and over 75. Expenditure on GF food within localities that introduced a 'complete ban' or a 'complete ban with age-related exceptions' were reduced by approximately 80% within the 3 months following policy changes. If all regions had introduced a 'complete ban' policy in 2014, the NHS in England would have made an annual cost-saving of £21.1 million (equivalent to 0.24% of the total primary care medicines expenditure), assuming no negative sequelae. CONCLUSIONS: The introduction of more restrictive GF prescribing policies has been associated with 'quick wins' for NHS regions under extreme financial pressure. However, these initial savings will be largely negated if GF product policies revert to recently published national recommendations. Better evidence of the long-term impact of restricting GF prescribing on patient health, expenses and use of NHS services is needed to inform policy.

Current and future cardiovascular disease risk assessment in the European Union: an international comparative study.

Background: Risk assessment is central to primary prevention of cardiovascular disease (CVD), but there remains a need to better understand the use of evidence-based interventions in practice. This study examines: (i) the policies and guidelines for risk assessment in Europe, (ii) the use of risk assessment tools in clinical practice and (iii) the barriers to, and facilitators of, risk assessment. Methods: Data were collected from academics, clinicians and policymakers in an online questionnaire targeted at experts from all European Union member states, and in 8 in-depth country case studies that were developed from a targeted literature review and 36 interviews. Results: The European Society of Cardiology (ESC) produces European guidelines for CVD risk assessment and recommends the Systematic COronary Risk Evaluation tool, which is the most widely used risk assessment tool in Europe. The use of risk assessment tools is variable. Lack of time and resources are important barriers. Integrating risk assessment tools into clinical systems and providing financial incentives to carry out risk assessments could increase implementation. Novel biomarkers would need to be supported by evidence of their clinical effectiveness and cost-effectiveness to be introduced in clinical practice. These findings were consistent across Europe. Conclusions: Efforts to improve the assessment of CVD risk in clinical practice should be carried out by or in collaboration with, the ESC. Increasing the use of existing risk assessment tools is likely to offer greater gains in primary prevention than the development of novel biomarkers.

Factors Associated With Engagement With a Web-Based Lifestyle Intervention Following Provision of Coronary Heart Disease Risk: Mixed Methods Study.

BACKGROUND: Web-based interventions provide the opportunity to combine the tailored approach of face-to-face interventions with the scalability and cost-effectiveness of public health interventions. This potential is often limited by low engagement. A number of studies have described the characteristics of individuals who engage more in Web-based interventions but few have explored the reasons for these variations. OBJECTIVE: We aimed to explore individual-level factors associated with different degrees of engagement with a Web-based behavior change intervention following provision of coronary heart disease (CHD) risk information, and the barriers and facilitators to engagement. METHODS: This study involved the secondary analysis of data from the Information and Risk Modification Trial, a randomized controlled trial of a Web-based lifestyle intervention alone, or alongside information on estimated CHD risk. The intervention consisted of three interactive sessions, each lasting up to 60 minutes, delivered at monthly intervals. Participants were characterized as high engagers if they completed all three sessions. Thematic analysis of qualitative data from interviews with 37 participants was combined with quantitative data on usage of the Web-based intervention using a mixed-methods matrix, and data on the views of the intervention itself were analyzed across all participants. RESULTS: Thirteen participants were characterized as low engagers and 24 as high engagers. There was no difference in age (P=.75), gender (P=.95), or level of risk (P=.65) between the groups. Low engagement was more often associated with: (1) reporting a negative emotional reaction in response to the risk score (P=.029), (2) perceiving that the intervention did not provide any new lifestyle information (P=.011), and (3) being less likely to have reported feeling an obligation to complete the intervention as part of the study (P=.019). The mixed-methods matrix suggested that there was also an association between low engagement and less success with previous behavior change attempts, but the statistical evidence for this association was weak (P=.16). No associations were seen between engagement and barriers or facilitators to health behavior change, or comments about the design of the intervention itself. The most commonly cited barriers related to issues with access to the intervention itself: either difficulties remembering the link to the site or passwords, a perceived lack of flexibility within the website, or lack of time. Facilitators included the nonjudgmental presentation of lifestyle information, the use of simple language, and the personalized nature of the intervention. CONCLUSIONS: This study shows that the level of engagement with a Web-based intervention following provision of CHD risk information is not influenced by the level of risk but by the individual's response to the risk information, their past experiences of behavior change, the extent to which they consider the lifestyle information helpful, and whether they felt obliged to complete the intervention as part of a research study. A number of facilitators and barriers to Web-based interventions were also identified, which should inform future interventions.

Information and Risk Modification Trial (INFORM): design of a randomised controlled trial of communicating different types of information about coronary heart disease risk, alongside lifestyle advice, to achieve change in health-related behaviour.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of death globally. Primary prevention of CVD requires cost-effective strategies to identify individuals at high risk in order to help target preventive interventions. An integral part of this approach is the use of CVD risk scores. Limitations in previous studies have prevented reliable inference about the potential advantages and the potential harms of using CVD risk scores as part of preventive strategies. We aim to evaluate short-term effects of providing different types of information about coronary heart disease (CHD) risk, alongside lifestyle advice, on health-related behaviours. METHODS/DESIGN: In a parallel-group, open randomised trial, we are allocating 932 male and female blood donors with no previous history of CVD aged 40-84 years in England to either no intervention (control group) or to one of three active intervention groups: i) lifestyle advice only; ii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic characteristics; and iii) lifestyle advice plus information on estimated 10-year CHD risk based on phenotypic and genetic characteristics. The primary outcome is change in objectively measured physical activity. Secondary outcomes include: objectively measured dietary behaviours; cardiovascular risk factors; current medication and healthcare usage; perceived risk; cognitive evaluation of provision of CHD risk scores; and psychological outcomes. The follow-up assessment takes place 12 weeks after randomisation. The experiences, attitudes and concerns of a subset of participants will be also studied using individual interviews and focus groups. DISCUSSION: The INFORM study has been designed to provide robust findings about the short-term effects of providing different types of information on estimated 10-year CHD risk and lifestyle advice on health-related behaviours. TRIAL REGISTRATION: Current Controlled Trials ISRCTN17721237 . Registered 12 January 2015.

Is polypharmacy always hazardous? A retrospective cohort analysis using linked electronic health records from primary and secondary care.

AIMS: Prescribing multiple medications is associated with various adverse outcomes, and polypharmacy is commonly considered suggestive of poor prescribing. Polypharmacy might thus be associated with unplanned hospitalization. We sought to test this assumption. METHODS: Scottish primary care data for 180 815 adults with long-term clinical conditions and numbers of regular medications were linked to national hospital admissions data for the following year. Using logistic regression (age, gender and deprivation adjusted), we modelled the association of prescribing with unplanned admission for patients with different numbers of long-term conditions. RESULTS: Admissions were more common in patients on multiple medications, but admission risk varied with the number of conditions. For patients with one condition, the odds ratio for unplanned admission for four to six medications was 1.25 (95% confidence interval 1.11-1.42) vs. one to three medications, and 3.42 (95% confidence interval 2.72-4.28) for ≥10 medications vs. one to three medications. However, this effect was greatly reduced for patients with multiple conditions; amongst patients with six or more conditions, those on four to six medications were no more likely to have unplanned admissions than those taking one to three medications (odds ratio 1.00; 95% confidence interval 0.88-1.14), and those taking ≥10 medications had a modestly increased risk of admission (odds ratio 1.50; 95% confidence interval 1.31-1.71). CONCLUSIONS: Unplanned hospitalization is strongly associated with the number of regular medications. However, the effect is reduced in patients with multiple conditions, in whom only the most extreme levels of polypharmacy are associated with increased admissions. Assumptions that polypharmacy is always hazardous and represents poor care should be tempered by clinical assessment of the conditions for which those drugs are being prescribed.

Cardiovascular polypharmacy is not associated with unplanned hospitalisation: evidence from a retrospective cohort study.

BACKGROUND: Polypharmacy is often considered suggestive of suboptimal prescribing, and is associated with adverse outcomes. It is particularly common in the context of cardiovascular disease, but it is unclear whether prescribing of multiple cardiovascular medicines, which may be entirely appropriate and consistent with clinical guidance, is associated with adverse outcome. The aim of this study was to assess the relationship between number of prescribed cardiovascular medicines and unplanned non-cardiovascular hospital admissions. METHODS: A retrospective cohort analysis of 180,815 adult patients was conducted using Scottish primary care data linked to hospital discharge data. Patients were followed up for one year for the outcome of unplanned non-cardiovascular hospital admission. The association between number of prescribed cardiovascular medicines and hospitalisation was modelled using logistic regression, adjusting for key confounding factors including cardiovascular and non-cardiovascular morbidity and non-cardiovascular prescribing. RESULTS: 25.4% patients were prescribed ≥1 cardiovascular medicine, and 5.7% were prescribed ≥5. At least one unplanned non-cardiovascular admission was experienced by 4.2% of patients. Admissions were more common in patients receiving multiple cardiovascular medicines (6.4% of patients prescribed 5 or 6 cardiovascular medicines) compared with those prescribed none (3.5%). However, after adjusting for key confounders, cardiovascular prescribing was associated with fewer non-cardiovascular admissions (OR 0.66 for 5 or 6 vs. no cardiovascular medicines, 95% CI 0.57-0.75). CONCLUSIONS: We found no evidence that increasing numbers of cardiovascular medicines were associated with an increased risk of unplanned non-cardiovascular hospitalisation, following adjustment for confounding. Assumptions that polypharmacy is hazardous and represents poor care should be moderated in the context of cardiovascular disease.