Liver fibrosis assessed via non-invasive tests is associated with incident heart failure in a general population cohort.

AIMS: To determine whether liver fibrosis is associated with heart failure in a general population cohort, and if genetic polymorphisms (PNPLA3 rs738409; TM6SF2 rs58542926), linked to increased risk of liver fibrosis and decreased risk of coronary artery disease, modify this association. METHODS: Using UK Biobank data, we prospectively examined the relationship between non-invasive fibrosis markers [NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) and AST to platelet ratio index (APRI)] and incident hospitalization/death from heart failure (n=413,860). Cox-regression estimated hazard ratios (HR) for incident heart failure. Effects of PNPLA3 and TM6SF2 on the association between liver fibrosis and heart failure were estimated by stratifying for genotype, and testing for an interaction between genotype and liver fibrosis using a likelihood ratio test. RESULTS: 12,527 incident cases of heart failure occurred over a median of 10.7 years. Liver fibrosis was associated with an increased risk of hospitalization or death from heart failure (multivariable adjusted high risk NFS score HR 1.59 [1.47-1.76], p<0.0001; FIB-4 HR 1.69 [1.55-1.84], p<0.0001; APRI HR 1.85 [1.56-2.19], p<0.0001; combined fibrosis scores HR 1.90 [1.44-2.49], p<0.0001). These associations persisted for people with metabolic dysfunction-associated steatotic liver disease (MASLD), MASLD with alcohol consumption (Met-ALD) and harmful alcohol consumption. PNPLA3 rs738409 GG and TM6SF2 rs58542926 TT did not attenuate the positive association between fibrosis markers and heart failure. For PNPLA3 a statistically significant interaction was found between PNPLA3 rs738409, FIB-4, APRI score and heart failure. CONCLUSION: In the general population, serum markers of liver fibrosis are associated with increased hospitalization/death from heart failure. Genetic polymorphisms associated with liver fibrosis were not positively associated with elevated heart failure risk.

Potentially modifiable factors associated with health-related quality of life among people with chronic kidney disease: baseline findings from the National Unified Renal Translational Research Enterprise CKD (NURTuRE-CKD) cohort.

Background: Many non-modifiable factors are associated with poorer health-related quality of life (HRQoL) experienced by people with chronic kidney disease (CKD). We hypothesize that potentially modifiable factors for poor HRQoL can be identified among CKD patients, providing potential targets for intervention. Method: The National Unified Renal Translational Research Enterprise Chronic Kidney Disease (NURTuRE-CKD) cohort study recruited 2996 participants from nephrology centres with all stages of non-dialysis-dependent CKD. Baseline data collection for sociodemographic, anthropometric, biochemical and clinical information, including Integrated Palliative care Outcome Scale renal, Hospital Anxiety and Depression score (HADS) and the 5-level EuroQol-5D (EQ-5D-5L) as HRQoL measure, took place between 2017 and 2019. EQ-5D-5L dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) were mapped to an EQ-5D-3L value set to derive index value. Multivariable mixed effects regression models, adjusted for known factors affecting HRQoL with recruitment region as a random effect, were fit to assess potentially modifiable factors associated with index value (linear) and within each dimension (logistic). Results: Among the 2958/2996 (98.7%) participants with complete EQ-5D data, 2201 (74.4%) reported problems in at least one EQ-5D-5L dimension. Multivariable linear regression identified independent associations between poorer HRQoL (EQ-5D-3L index value) and obesity (body mass index ≥30.0 kg/m2, ß -0.037, 95% CI -0.058 to -0.016, P = .001), HADS depression score ≥8 (ß -0.159, -0.182 to -0.137, P < .001), anxiety score ≥8 (ß -0.090, -0.110 to -0.069, P < .001), taking ≥10 medications (ß -0.065, -0.085 to -0.046, P < .001), sarcopenia (ß -0.062, -0.080 to -0.043, P < .001) haemoglobin <100 g/L (ß -0.047, -0.085 to -0.010, P = .012) and pain (ß -0.134, -0.152 to -0.117, P < .001). Smoking and prescription of prednisolone independently associated with problems in self-care and usual activities respectively. Renin-angiotensin system inhibitor (RASi) prescription associated with fewer problems with mobility and usual activities. Conclusion: Potentially modifiable factors including obesity, pain, depression, anxiety, anaemia, polypharmacy, smoking, steroid use and sarcopenia associated with poorer HRQoL in this cohort, whilst RASi use was associated with better HRQoL in two dimensions.

Primary and secondary care service use and costs associated with frailty in an ageing population: longitudinal analysis of an English primary care cohort of adults aged 50 and over, 2006-2017.

BACKGROUND: Frailty becomes more prevalent and healthcare needs increase with age. Information on the impact of frailty on population level use of health services and associated costs is needed to plan for ageing populations. AIM: To describe primary and secondary care service use and associated costs by electronic Frailty Index (eFI) category. DESIGN AND SETTING: Retrospective cohort using electronic health records. Participants aged ≥50 registered in primary care practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre, 2006-2017. METHODS: Primary and secondary care use (totals and means) were stratified by eFI category and age group. Standardised 2017 costs were used to calculate primary, secondary and overall costs. Generalised linear models explored associations between frailty, sociodemographic characteristics. Adjusted mean costs and cost ratios were produced. RESULTS: Individual mean annual use of primary and secondary care services increased with increasing frailty severity. Overall cohort care costs for were highest in mild frailty in all 12 years, followed by moderate and severe, although the proportion of the population with severe frailty can be expected to increase over time. After adjusting for sociodemographic factors, compared to the fit category, individual annual costs doubled in mild frailty, tripled in moderate and quadrupled in severe. CONCLUSIONS: Increasing levels of frailty are associated with an additional burden of individual service use. However, individuals with mild and moderate frailty contribute to higher overall costs. Earlier intervention may have the most potential to reduce service use and costs at population level.

Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis.

Background: Cascade testing the relatives of people with familial hypercholesterolaemia is an efficient approach to identifying familial hypercholesterolaemia. The cascade-testing protocol starts with identifying an index patient with familial hypercholesterolaemia, followed by one of three approaches to contact other relatives: indirect approach, whereby index patients contact their relatives; direct approach, whereby the specialist contacts the relatives; or a combination of both direct and indirect approaches. However, it is unclear which protocol may be most effective. Objectives: The objectives were to determine the yield of cases from different cascade-testing protocols, treatment patterns, and short- and long-term outcomes for people with familial hypercholesterolaemia; to evaluate the cost-effectiveness of alternative protocols for familial hypercholesterolaemia cascade testing; and to qualitatively assess the acceptability of different cascade-testing protocols to individuals and families with familial hypercholesterolaemia, and to health-care providers. Design and methods: This study comprised systematic reviews and analysis of three data sets: PASS (PASS Software, Rijswijk, the Netherlands) hospital familial hypercholesterolaemia databases, the Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked primary-secondary care data set, and a specialist familial hypercholesterolaemia register. Cost-effectiveness modelling, incorporating preceding analyses, was undertaken. Acceptability was examined in interviews with patients, relatives and health-care professionals. Result: Systematic review of protocols: based on data from 4 of the 24 studies, the combined approach led to a slightly higher yield of relatives tested [40%, 95% confidence interval (CI) 37% to 42%] than the direct (33%, 95% CI 28% to 39%) or indirect approaches alone (34%, 95% CI 30% to 37%). The PASS databases identified that those contacted directly were more likely to complete cascade testing (p < 0.01); the CPRD-HES data set indicated that 70% did not achieve target treatment levels, and demonstrated increased cardiovascular disease risk among these individuals, compared with controls (hazard ratio 9.14, 95% CI 8.55 to 9.76). The specialist familial hypercholesterolaemia register confirmed excessive cardiovascular morbidity (standardised morbidity ratio 7.17, 95% CI 6.79 to 7.56). Cost-effectiveness modelling found a net health gain from diagnosis of -0.27 to 2.51 quality-adjusted life-years at the willingness-to-pay threshold of £15,000 per quality-adjusted life-year gained. The cost-effective protocols cascaded from genetically confirmed index cases by contacting first- and second-degree relatives simultaneously and directly. Interviews found a service-led direct-contact approach was more reliable, but combining direct and indirect approaches, guided by index patients and family relationships, may be more acceptable. Limitations: Systematic reviews were not used in the economic analysis, as relevant studies were lacking or of poor quality. As only a proportion of those with primary care-coded familial hypercholesterolaemia are likely to actually have familial hypercholesterolaemia, CPRD analyses are likely to underestimate the true effect. The cost-effectiveness analysis required assumptions related to the long-term cardiovascular disease risk, the effect of treatment on cholesterol and the generalisability of estimates from the data sets. Interview recruitment was limited to white English-speaking participants. Conclusions: Based on limited evidence, most cost-effective cascade-testing protocols, diagnosing most relatives, select index cases by genetic testing, with services directly contacting relatives, and contacting second-degree relatives even if first-degree relatives have not been tested. Combined approaches to contact relatives may be more suitable for some families. Future work: Establish a long-term familial hypercholesterolaemia cohort, measuring cholesterol levels, treatment and cardiovascular outcomes. Conduct a randomised study comparing different approaches to contact relatives. Study registration: This study is registered as PROSPERO CRD42018117445 and CRD42019125775. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 16. See the NIHR Journals Library website for further project information.

Familial hypercholesterolaemia is an inherited condition that causes raised cholesterol levels from birth and increases risk of heart disease if left untreated. After someone in a family is found to have familial hypercholesterolaemia (called an index case), their close relatives need to be contacted and checked to see if they have familial hypercholesterolaemia, using genetic or cholesterol testing. This is called 'cascade testing'. We planned to find the most cost-effective and acceptable way to do this. The relatives could be contacted for testing by the index case (indirect approach), by a health-care professional (direct approach) or by a combination of both approaches. We found, based on looking at hospital records, that more relatives were tested if health-care professionals directly contacted relatives. In previous studies, slightly more relatives were tested for familial hypercholesterolaemia with a combination approach. Interviews with patients also suggested that the direct approach was the most effective, but the most acceptable and successful approach depends on family relationships: using one approach for some families and using both for other families. Furthermore, by looking at the health-care records of large numbers of patients, we confirmed that people with a recorded diagnosis of familial hypercholesterolaemia in general practice records have a much higher risk of heart disease than the general population, and this was especially so for those with previous heart disease and/or raised cholesterols levels when diagnosed. However, one-quarter of new patients with familial hypercholesterolaemia recorded in their records were not treated within 2 years, with less than one-third reaching recommended cholesterol levels. We used what we had learned to help us estimate the most cost-effective way to do cascade testing. This showed that if the health service directly contact all relatives simultaneously for further assessment, rather than the current approach whereby close (first-degree) relatives are contacted first, this was cost-effective and good value for money.

Mixed methods feasibility and usability testing of a childhood obesity risk estimation tool.

BACKGROUND: A Childhood Obesity Risk Estimation tool (SLOPE CORE) has been developed based on prediction models using routinely available maternity and early childhood data to estimate risk of childhood obesity at 4-5 years. This study aims to test the feasibility, acceptability and usability of SLOPE CORE within an enhanced health visiting (EHV) service in the UK, as one context in which this tool could be utilised. METHODS: A mixed methods approach was used to assess feasibility of implementing SLOPE CORE. Health Visitors (HVs) were trained to use the tool, and in the processes for recruiting parents into the study. HVs were recruited using purposive sampling and parents by convenience sampling. HVs and parents were invited to take part in interviews or focus groups to explore their experiences of the tool. HVs were asked to complete a system usability scale (SUS) questionnaire. RESULTS: Five HVs and seven parents took part in the study. HVs found SLOPE CORE easy to use with a mean SUS of 84.4, (n = 4, range 70-97.5) indicating excellent usability. Five HVs and three parents took part in qualitative work. The tool was acceptable and useful for both parents and HVs. Parents expressed a desire to know their child's risk of future obesity, provided this was accompanied by additional information, or support to modify risk. HVs appreciated the health promotion opportunity that the tool presented and felt that it facilitated difficult conversations around weight, by providing 'clinical evidence' for risk, and placing the focus of the conversation onto the tool result, rather than their professional judgement. The main potential barriers to use of the tool included the need for internet access, and concerns around time needed to have a sensitive discussion around a conceptually difficult topic (risk). CONCLUSIONS: SLOPE CORE could potentially be useful in clinical practice. It may support targeting limited resources towards families most at risk of childhood obesity. Further research is needed to explore how the tool might be efficiently incorporated into practice, and to evaluate the impact of the tool, and any subsequent interventions, on preventing childhood obesity.

Clustering by multiple long-term conditions and social care needs: a cross-sectional study among 10 026 older adults in England.

BACKGROUND   : People with multiple long-term conditions (MLTC) face health and social care challenges. This study aimed to classify people by MLTC and social care needs (SCN) into distinct clusters and quantify the association between derived clusters and care outcomes. METHODS : A cross-sectional study was conducted using the English Longitudinal Study of Ageing, including people with up to 10 MLTC. Self-reported SCN was assessed through 13 measures of difficulty with activities of daily living, 10 measures of mobility difficulties and whether health status was limiting earning capability. Latent class analysis was performed to identify clusters. Multivariable logistic regression quantified associations between derived MLTC/SCN clusters, all-cause mortality and nursing home admission. RESULTS: Our study included 9171 people at baseline with a mean age of 66.3 years; 44.5% were men. Nearly 70.8% had two or more MLTC, the most frequent being hypertension, arthritis and cardiovascular disease. We identified five distinct clusters classified as high SCN/MLTC through to low SCN/MLTC clusters. The high SCN/MLTC included mainly women aged 70-79 years who were white and educated to the upper secondary level. This cluster was significantly associated with higher nursing home admission (OR=8.71; 95% CI: 4.22 to 18). We found no association between clusters and all-cause mortality. CONCLUSIONS: We have highlighted those at risk of worse care outcomes, including nursing home admission. Distinct clusters of individuals with shared sociodemographic characteristics can help identify at-risk individuals with MLTC and SCN at primary care level.

Prediction of childhood overweight and obesity at age 10-11: findings from the Studying Lifecourse Obesity PrEdictors and the Born in Bradford cohorts.

BACKGROUND: In England, 41% of children aged 10-11 years live with overweight or obesity. Identifying children at risk of developing overweight or obesity may help target early prevention interventions. We aimed to develop and externally validate prediction models of childhood overweight and obesity at age 10-11 years using routinely collected weight and height measurements at age 4-5 years and maternal and early-life health data. METHODS: We used an anonymised linked cohort of maternal pregnancy and birth health records in Hampshire, UK between 2003 and 2008 and child health records. Childhood body mass index (BMI), adjusted for age and sex, at 10-11 years was used to define the outcome of overweight and obesity (BMI ≥ 91st centile) in the models. Logistic regression models and multivariable fractional polynomials were used to select model predictors and to identify transformations of continuous predictors that best predict the outcome. Models were externally validated using data from the Born in Bradford birth cohort. Model performance was assessed using discrimination and calibration. RESULTS: Childhood BMI was available for 6566 children at 4-5 (14.6% overweight) and 10-11 years (26.1% overweight) with 10.8% overweight at both timepoints. The area under the curve (AUC) was 0.82 at development and 0.83 on external validation for the model only incorporating two predictors: BMI at 4-5 years and child sex. AUC increased to 0.84 on development and 0.85 on external validation on additionally incorporating maternal predictors in early pregnancy (BMI, smoking, age, educational attainment, ethnicity, parity, employment status). Models were well calibrated. CONCLUSIONS: This prediction modelling can be applied at 4-5 years to identify the risk for childhood overweight at 10-11 years, with slightly improved prediction with the inclusion of maternal data. These prediction models demonstrate that routinely collected data can be used to target early preventive interventions to reduce the prevalence of childhood obesity.

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

BACKGROUND: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD. METHODS: A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m2 or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality. RESULTS: 56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38-1.60]), all-cause mortality (HR 1.22 [1.14-1.31]) and ESRD (HR 1.26 [1.02-1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11-1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09-2.80] and 1.64 [1.30-2.08]) and all-cause mortality (HR 2.82 [2.48-3.21] and 1.82 [1.47-2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52-7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01-1.40]) and all-cause mortality (HR 1.31 [1.13-1.52]). CONCLUSIONS: In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD).

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated glomerular filtration rate (eGFR). RESULTS: A total of 2996 participants was enrolled. Median (interquartile range) age was 66 (54-74) years, eGFR 33.8 (24.0-46.6) mL/min/1.73 m2 and urine albumin to creatinine ratio 209 (33-926) mg/g; 58.5% were male. Of these participants, 1883 (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and to investigate underlying mechanisms to inform new treatment development.

Frailty transitions and prevalence in an ageing population: longitudinal analysis of primary care data from an open cohort of adults aged 50 and over in England, 2006-2017.

INTRODUCTION: frailty is common in older adults and is associated with increased health and social care use. Longitudinal information is needed on population-level incidence, prevalence and frailty progression to plan services to meet future population needs. METHODS: retrospective open cohort study using electronic health records of adults aged ≥50 from primary care in England, 2006-2017. Frailty was calculated annually using the electronic Frailty Index (eFI). Multistate models estimated transition rates between each frailty category, adjusting for sociodemographic characteristics. Prevalence overall for each eFI category (fit, mild, moderate and severe) was calculated. RESULTS: the cohort included 2,171,497 patients and 15,514,734 person-years. Frailty prevalence increased from 26.5 (2006) to 38.9% (2017). The average age of frailty onset was 69; however, 10.8% of people aged 50-64 were already frail in 2006. Estimated transitions from fit to any level of frailty were 48/1,000 person-years aged 50-64, 130/1,000 person-years aged 65-74, 214/1,000 person-years aged 75-84 and 380/1,000 person-years aged ≥ 85. Transitions were independently associated with older age, higher deprivation, female sex, Asian ethnicity and urban dwelling. Mean time spent in each frailty category decreased with age, with the longest period spent in severe frailty at all ages. CONCLUSIONS: frailty is prevalent in adults aged ≥50 and time spent in successive frailty states is longer as frailty progresses, resulting in extended healthcare burden. Larger population numbers and fewer transitions in adults aged 50-64 present an opportunity for earlier identification and intervention. A large increase in frailty over 12 years highlights the urgency of informed service planning in ageing populations.

Role of foetal kidney size on kidney function in childhood: the born in bradford cohort renal study.

BACKGROUND: Foetal and early childhood development contributes to the risk of adult non-communicable diseases such as hypertension and cardiovascular disease. We aimed to investigate whether kidney size at birth is associated with markers of kidney function at 7-11 years. METHODS: Foetal kidney dimensions were measured using ultrasound scans at 34 weeks gestation and used to derive kidney volume (cm3) in 1802 participants in the Born in Bradford (BiB) birth cohort. Blood and urine samples were taken from those who participated in the BiB follow-up at 7-11 years (n = 630) and analysed for serum creatinine, cystatin C, urea, and urinary albumin to creatinine ratio (ACR), protein to creatinine ratio (PCR) and retinol binding protein (RBP). Estimated glomerular filtration rate (eGFR) was calculated using Schwartz creatinine only and combined with cystatin C, and cystatin C only Zappitelli and Filler equations. Linear regression was used to examine the association between foetal kidney volume and eGFR, ACR, PCR and blood pressure, unadjusted and adjusted for confounders. RESULTS: Kidney volume was positively associated in adjusted models with eGFR calculated using Schwartz combined (0.64 ml/min diff per unit increase in volume, 95% CI 0.25 to 1.02), Zappitelli (0.79, 95% CI 0.38 to 1.20) and Filler (2.84, 95% CI 1.40 to 4.28). There was an association with the presence of albuminuria but not with its level, or with other urinary markers or with blood pressure. CONCLUSION: Foetal kidney volume was associated with small increases in eGFR in mid-childhood. Longitudinal follow-up to investigate the relationship between kidney volume and markers of kidney function as children go through puberty is required.

Household food insecurity risk indices for English neighbourhoods: Measures to support local policy decisions.

BACKGROUND: In England, the responsibility to address food insecurity lies with local government, yet the prevalence of this social inequality is unknown in small subnational areas. In 2018 an index of small-area household food insecurity risk was developed and utilised by public and third sector organisations to target interventions; this measure needed updating to better support decisions in different settings, such as urban and rural areas where pressures on food security differ. METHODS: We held interviews with stakeholders (n = 14) and completed a scoping review to identify appropriate variables to create an updated risk measure. We then sourced a range of open access secondary data to develop an indices of food insecurity risk in English neighbourhoods. Following a process of data transformation and normalisation, we tested combinations of variables and identified the most appropriate data to reflect household food insecurity risk in urban and rural areas. RESULTS: Eight variables, reflecting both household circumstances and local service availability, were separated into two domains with equal weighting for a new index, the Complex Index, and a subset of these to make up the Simple Index. Within the Complex Index, the Compositional Domain includes population characteristics while the Structural Domain reflects small area access to resources such as grocery stores. The Compositional Domain correlated well with free school meal eligibility (rs = 0.705) and prevalence of childhood obesity (rs = 0.641). This domain was the preferred measure for use in most areas when shared with stakeholders, and when assessed alongside other configurations of the variables. Areas of highest risk were most often located in the North of England. CONCLUSION: We recommend the use of the Compositional Domain for all areas, with inclusion of the Structural Domain in rural areas where locational disadvantage makes it more difficult to access resources. These measures can aid local policy makers and planners when allocating resources and interventions to support households who may experience food insecurity.

Change in treatment burden among people with multimorbidity: a follow-up survey.

BACKGROUND: Treatment burden is the effort required of patients to look after their health and the impact this has on their functioning and wellbeing. Little is known about change in treatment burden over time for people with multimorbidity. AIM: To quantify change in treatment burden, determine factors associated with this change, and evaluate a revised single-item measure for high treatment burden in older adults with multimorbidity. DESIGN AND SETTING: A 2.5-year follow-up of a cross-sectional postal survey via six general practices in Dorset, England. METHOD: GP practices identified participants of the baseline survey. Data on treatment burden (measured using the Multimorbidity Treatment Burden Questionnaire; MTBQ), sociodemographics, clinical variables, health literacy, and financial resource were collected. Change in treatment burden was described, and associations assessed using regression models. Diagnostic test performance metrics evaluated the revised single-item measure relative to the MTBQ. RESULTS: In total, 300 participants were recruited (77.3% response rate). Overall, there was a mean increase of 2.6 (standard deviation 11.2) points in treatment burden global score. Ninety-eight (32.7%) and 53 (17.7%) participants experienced an increase and decrease, respectively, in treatment burden category. An increase in treatment burden was associated with having >5 long-term conditions (adjusted ß 8.26, 95% confidence interval [CI] = 4.20 to 12.32) and living >10 minutes (versus ≤10 minutes) from the GP (adjusted ß 3.88, 95% CI = 1.32 to 6.43), particularly for participants with limited health literacy (mean difference: adjusted ß 9.59, 95% CI = 2.17 to 17.00). The single-item measure performed moderately (sensitivity 55.7%; specificity 92.4%. CONCLUSION: Treatment burden changes over time. Improving access to primary care, particularly for those living further away from services, and enhancing health literacy may mitigate increases in burden.

Understanding social care need through primary care big data: a rapid scoping review.

BACKGROUND: A more comprehensive understanding and measurement of adult social care need could contribute to efforts to develop more effective, holistic personalised care, particularly for those with multiple long-term conditions (MLTC). Progress in this area faces the challenge of a lack of clarity in the literature relating to how social care need is assessed and coded within variables included in primary care databases. AIM: To explore how social care need is assessed and coded within variables included in primary care databases. DESIGN & SETTING: An exploratory rapid scoping review of peer-reviewed articles and grey literature. METHOD: Articles were screened and extracted onto a charting sheet and findings were summarised descriptively. Articles were included if published in English and related to primary and social care using data from national primary care databases. RESULTS: The search yielded 4010 articles. Twenty-seven were included. Six articles used the term 'social care need', although related terminology was identified including 'need factors', 'social support', and 'social care support'. Articles mainly focused on specific components of social care need, including levels of social care usage or service utilisation and costs incurred to social care, primary care, and other providers in addressing needs. A limited range of database variables were found measuring social care need. CONCLUSION: Further research is needed on how social care need has been defined in a UK context and captured in primary care big databases. There is potential scope to broaden the definition of social care need, which captures social service needs and wider social needs.

Development and Validation of Population Clusters for Integrating Health and Social Care: Protocol for a Mixed Methods Study in Multiple Long-Term Conditions (Cluster-Artificial Intelligence for Multiple Long-Term Conditions).

BACKGROUND: Multiple long-term health conditions (multimorbidity) (MLTC-M) are increasingly prevalent and associated with high rates of morbidity, mortality, and health care expenditure. Strategies to address this have primarily focused on the biological aspects of disease, but MLTC-M also result from and are associated with additional psychosocial, economic, and environmental barriers. A shift toward more personalized, holistic, and integrated care could be effective. This could be made more efficient by identifying groups of populations based on their health and social needs. In turn, these will contribute to evidence-based solutions supporting delivery of interventions tailored to address the needs pertinent to each cluster. Evidence is needed on how to generate clusters based on health and social needs and quantify the impact of clusters on long-term health and costs. OBJECTIVE: We intend to develop and validate population clusters that consider determinants of health and social care needs for people with MLTC-M using data-driven machine learning (ML) methods compared to expert-driven approaches within primary care national databases, followed by evaluation of cluster trajectories and their association with health outcomes and costs. METHODS: The mixed methods program of work with parallel work streams include the following: (1) qualitative semistructured interview studies exploring patient, caregiver, and professional views on clinical and socioeconomic factors influencing experiences of living with or seeking care in MLTC-M; (2) modified Delphi with relevant stakeholders to generate variables on health and social (wider) determinants and to examine the feasibility of including these variables within existing primary care databases; and (3) cohort study with expert-driven segmentation, alongside data-driven algorithms. Outputs will be compared, clusters characterized, and trajectories over time examined to quantify associations with mortality, additional long-term conditions, worsening frailty, disease severity, and 10-year health and social care costs. RESULTS: The study will commence in October 2021 and is expected to be completed by October 2023. CONCLUSIONS: By studying MLTC-M clusters, we will assess how more personalized care can be developed, how accurate costs can be provided, and how to better understand the personal and medical profiles and environment of individuals within each cluster. Integrated care that considers "whole persons" and their environment is essential in addressing the complex, diverse, and individual needs of people living with MLTC-M. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/34405.

Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a very common long-term condition and powerful risk factor for cardiovascular disease (CVD). Low-dose aspirin is of proven benefit in the secondary prevention of myocardial infarction (MI) and stroke in people with pre-existing CVD. However, in people without CVD, the rates of MI and stroke are much lower, and the benefits of aspirin in the primary prevention of CVD are largely balanced by an increased risk of bleeding. People with CKD are at greatly increased risk of CVD and so the absolute benefits of aspirin are likely to be greater than in lower-risk groups, even if the relative benefits are the same. Post hoc evidence suggests the relative benefits may be greater in the CKD population but the risk of bleeding may also be higher. A definitive study of aspirin for primary prevention in this high-risk group, recommended by the National Institute for Health and Care Excellence (NICE) in 2014, has never been conducted. The question has global significance given the rising burden of CKD worldwide and the low cost of aspirin. METHODS: ATTACK is a pragmatic multicentre, prospective, randomised, open-label, blinded endpoint adjudication superiority trial of aspirin 75 mg daily vs. standard care for the primary prevention of CVD in 25,210 people aged 18 years and over with CKD recruited from UK Primary Care. Participants aged 18 years and over with CKD (GFR category G1-G4) will be identified in Primary Care and followed up using routinely collected data and annual questionnaires for an average of 5 years. The primary outcome is the time to first major vascular event (composite of non-fatal MI, non-fatal stroke and cardiovascular death [excluding confirmed intracranial haemorrhage and other fatal cardiovascular haemorrhage]). Deaths from other causes (including fatal bleeding) will be treated as competing events. The study will continue until 1827 major vascular events have occurred. The principal safety outcome is major intracranial and extracranial bleeding; this is hypothesised to be increased in those randomised to take aspirin. The key consideration is then whether and to what extent the benefits of aspirin from the expected reduction in CVD events exceed the risks of major bleeding. DISCUSSION: This will be the first definitive trial of aspirin for primary CVD prevention in CKD patients. The research will be of great interest to clinicians, guideline groups and policy-makers, in the UK and globally, particularly given the high and rising prevalence of CKD that is driven by population ageing and epidemics of obesity and diabetes. The low cost of aspirin means that a positive result would be of relevance to low- and middle-income countries and the impact in the developed world less diluted by any inequalities in health care access. TRIAL REGISTRATION: ISRCTN: ISRCTN40920200 . EudraCT: 2018-000644-26 . CLINICALTRIALS: gov: NCT03796156.

Chronic high-altitude exposure and the epidemiology of ischaemic stroke: a systematic review.

INTRODUCTION: About 5.7% of the world population resides above 1500 m. It has been hypothesised that acute exposure to high-altitude locations can increase stroke risk, while chronic hypoxia can reduce stroke-related mortality. OBJECTIVE: This review aims to provide an overview of the available evidence on the association between long-term high-altitude exposure and ischaemic stroke. DESIGN: A systematic review was performed from 1 January 1960 to 1 December 2021 to assess the possible link between high-altitude exposure and ischaemic stroke. The AMED, EMBASE, Cochrane Library, PubMed, MEDLINE, the Europe PubMed Central and the Latin-American bibliographic database Scielo were accessed using the University of Southampton library tool Delphis. In this review, we included population and individual-based observational studies, including cross-sectional and longitudinal studies except for those merely descriptive individual-based case reports. Studies were limited to humans living or visiting high-altitude locations for at least 28 days as a cut-off point for chronic exposure. RESULTS: We reviewed a total of 1890 abstracts retrieved during the first step of the literature review process. The authors acquired in full text as potentially relevant 204 studies. Only 17 documents met the inclusion criteria and were finally included. Ten studies clearly suggest that living at high altitudes may be associated with an increased risk of stroke; however, five studies suggest that altitude may act as a protective factor for the development of stroke, while two studies report ambiguous results. CONCLUSIONS: This review suggests that the most robust studies are more likely to find that prolonged living at higher altitudes reduces the risk of developing stroke or dying from it. Increased irrigation due to angiogenesis and increased vascular perfusion might be the reason behind improved survival profiles among those living within this altitude range. In contrast, residing above 3500 m seems to be associated with an apparent increased risk of developing stroke, probably linked to the presence of polycythaemia and other associated factors such as increased blood viscosity.

Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for IBD: a retrospective cohort study.

BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored.

Characteristics and impact of Long Covid: Findings from an online survey.

BACKGROUND: Long Covid is a public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life. METHODS: We collected self-reported data through an online survey using convenience non-probability sampling. The survey enrolled adults who reported lab-confirmed (PCR or antibody) or suspected COVID-19 who were not hospitalised in the first two weeks of illness. This analysis was restricted to those with self-reported Long Covid. Univariate comparisons between those with and without confirmed COVID-19 infection were carried out and agglomerative hierarchical clustering was used to identify specific symptom clusters, and their demographic and functional correlates. RESULTS: We analysed data from 2550 participants with a median duration of illness of 7.6 months (interquartile range (IQR) 7.1-7.9). 26.5% reported lab-confirmation of infection. The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cognitive dysfunction and palpitations became more prevalent later in the illness. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress, and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n = 2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n = 305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n = 2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n = 283, 11.2%) exhibiting more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup. CONCLUSION: This is an exploratory survey of Long Covid characteristics. Whilst this is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions.

How do we engage people in testing for COVID-19? A rapid qualitative evaluation of a testing programme in schools, GP surgeries and a university.

BACKGROUND: The UK Scientific Advisory Group for Emergencies (SAGE) emphasises the need for high levels of engagement with communities and individuals to ensure the effectiveness of any COVID-19 testing programme. A novel pilot health surveillance programme to assess the feasibility of weekly community RT-LAMP (Reverse transcription loop-mediated isothermal amplification) testing for the SARS-CoV-2 virus using saliva samples collected at home was developed and piloted by the University of Southampton and Southampton City Council. METHODS: Rapid qualitative evaluation was conducted to explore experiences of those who took part in the programme, of those who declined and of those in the educational and healthcare organisations involved in the pilot testing who were responsible for roll-out. This included 77 interviews and 20 focus groups with 223 staff, students, pupils and household members from four schools, one university, and one community healthcare NHS trust. The insights generated and informed the design and modification of the Southampton COVID-19 Saliva Testing Programme and the next phase of community-testing. RESULTS: Discussions revealed that high levels of communication, trust and convenience were necessary to ensure people's engagement with the programme. Participants felt reassured by and pride in taking part in this novel programme. They suggested modifications to reduce the programme's environmental impact and overcome cultural barriers to participation. CONCLUSIONS: Participants' and stakeholders' motivations, challenges and concerns need to be understood and these insights used to modify the programme in a continuous, real-time process to ensure and sustain engagement with testing over the extended period necessary. Community leaders and stakeholder organisations should be involved throughout programme development and implementation to optimise engagement.