Liver Fibrosis Assessed Via Noninvasive Tests Is Associated With Incident Heart Failure in a General Population Cohort.

BACKGROUND & AIMS: The aim of this study was 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 noninvasive fibrosis markers (nonalcoholic fatty liver disease [NAFLD] fibrosis score [NFS], Fibrosis-4 [FIB-4] and aspartate transaminase [AST] to platelet ratio index [APRI]) and incident hospitalization/death from heart failure (n = 413,860). Cox-regression estimated hazard ratios (HRs) 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: A total of 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; 95% confidence interval [CI],1.47-1.76; P < .0001; FIB-4 HR, 1.69; 95% CI, 1.55-1.84; P < .0001; APRI HR, 1.85; 95% CI, 1.56-2.19; P < .0001; combined fibrosis scores HR, 1.90; 95% CI, 1.44-2.49; P < .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.

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.

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.

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.

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.

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.

Interpregnancy weight gain and childhood obesity: analysis of a UK population-based cohort.

BACKGROUND: Maternal obesity increases the risk of adverse long-term health outcomes in mother and child including childhood obesity. We aimed to investigate the association between interpregnancy weight gain between first and second pregnancies and risk of overweight and obesity in the second child. METHODS: We analysed the healthcare records of 4789 women in Hampshire, UK with their first two singleton live births within a population-based anonymised linked cohort of routine antenatal records (August 2004 and August 2014) with birth/early life data for their children. Measured maternal weight and reported height were recorded at the first antenatal appointment of each pregnancy. Measured child height and weight at 4-5 years were converted to age- and sex-adjusted body mass index (BMI z-score). Log-binomial regression was used to examine the association between maternal interpregnancy weight gain and risk of childhood overweight and obesity in the second child. This was analysed first in the whole sample and then stratified by baseline maternal BMI category. RESULTS: The prevalence of overweight/obesity in the second child was 19.1% in women who remained weight stable, compared with 28.3% in women with ≥3 kg/m2 weight gain. Interpregnancy gain of ≥3 kg/m2 was associated with increased risk of childhood overweight/obesity (adjusted relative risk (95% CI) 1.17 (1.02-1.34)), with attenuation on adjusting for birthweight of the second child (1.08 (0.94-1.24)). In women within the normal weight range at first pregnancy, the risks of childhood obesity (≥95th centile) were increased with gains of 1-3 kg/m2 (1.74 (1.07-2.83)) and ≥3 kg/m2 (1.87 (1.18-3.01)). CONCLUSION: Children of mothers within the normal weight range in their first pregnancy who started their second pregnancy with a considerably higher weight were more likely to have obesity at 4-5 years. Supporting return to pre-pregnancy weight and limiting weight gain between pregnancies may achieve better long-term maternal and offspring outcomes.

Converting from face-to-face to postal follow-up and its effects on participant retention, response rates and errors: lessons from the EQUAL study in the UK.

BACKGROUND: Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3-6 months, known as "traditional follow-up" (TFU). In 2018, all living patients were invited to switch to "efficient follow-up" (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU. RESULTS: Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up. CONCLUSIONS: Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic.

Primary care consultations for respiratory tract symptoms during the COVID-19 pandemic: a cohort study including 70,000 people in South West England.

BACKGROUND: Primary care consultations for respiratory tract symptoms including identifying and managing COVID-19 during the pandemic have not been characterized. METHODS: A retrospective cohort analysis using routinely collected records from 70,431 adults aged 18+ in South England within the Electronic Care and Health Information Analytics (CHIA) database. Total volume and type of consultations (face-to-face, home visits, telephone, email/video, or out of hours) for respiratory tract symptoms between 1 January and 31 July 2020 (during the first wave of the pandemic) were compared with the equivalent period in 2019 for the same cohort. Descriptive statistics were used to summarize consultations by sociodemographic and clinical characteristics, and by COVID-19 diagnosis and outcomes (death, hospitalization, and pneumonia). RESULTS: Overall consultations for respiratory tract symptoms increased by 229% during the pandemic compared with the preceding year. This included significant increases in telephone consultations by 250%, a 1,574% increase in video/email consultations, 105% increase in home visits, and 92% increase in face-to-face consultations. Nearly 60% of people who presented with respiratory symptoms were tested for COVID-19 and 16% confirmed or clinically suspected to have the virus. Those with complications including pneumonia, requiring hospitalization, and who died were more likely to be seen in-person. CONCLUSION: During the pandemic, primary care substantially increased consultations for respiratory tract symptoms to identify and manage people with COVID-19. These findings should be balanced against national reports of reduced GP workload for non-COVID care.

The dynamics of frailty development and progression in older adults in primary care in England (2006-2017): a retrospective cohort profile.

BACKGROUND: Frailty is a common condition in older adults and has a major impact on patient outcomes and service use. Information on the prevalence in middle-aged adults and the patterns of progression of frailty at an individual and population level is scarce. To address this, a cohort was defined from a large primary care database in England to describe the epidemiology of frailty and understand the dynamics of frailty within individuals and across the population. This article describes the structure of the dataset, cohort characteristics and planned analyses. METHODS: Retrospective cohort study using electronic health records. Participants were aged ≥50 years registered in practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre between 2006 to 2017. Data include GP practice details, patient sociodemographic and clinical characteristics, twice-yearly electronic Frailty Index (eFI), deaths, medication use and primary and secondary care health service use. Participants in each cohort year by age group, GP and patient characteristics at cohort entry are described. RESULTS: The cohort includes 2,177,656 patients, contributing 15,552,946 person-years, registered at 419 primary care practices in England. The mean age was 61 years, 52.1% of the cohort was female, and 77.6% lived in urban environments. Frailty increased with age, affecting 10% of adults aged 50-64 and 43.7% of adults aged ≥65. The prevalence of long-term conditions and specific frailty deficits increased with age, as did the eFI and the severity of frailty categories. CONCLUSION: A comprehensive understanding of frailty dynamics will inform predictions of current and future care needs to facilitate timely planning of appropriate interventions, service configurations and workforce requirements. Analysis of this large, nationally representative cohort including participants aged ≥50 will capture earlier transitions to frailty and enable a detailed understanding of progression and impact. These results will inform novel simulation models which predict future health and service needs of older people living with frailty. STUDY REGISTRATION: Registered on www.clinicaltrials.gov October 25th 2019, NCT04139278 .

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.

Patient-Reported Measures and Lifestyle Are Associated With Deterioration in Nutritional Status in CKD Stage 4-5: The EQUAL Cohort Study.

OBJECTIVE: The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease. DESIGN AND METHODS: The European Quality Study on treatment in advanced chronic kidney disease (EQUAL) is a prospective, observational cohort study involving six European countries. We included 1,103 adults >65 years with incident estimated glomerular filtration rate <20 mL/min/1.73 m2 not on dialysis, attending nephrology care. Nutritional status was assessed with the 7-point Subjective Global Assessment tool (7-p SGA), patient-reported outcomes with RAND-36 and the Dialysis Symptom Index. Logistic regression was used to estimate the associations between potential risk factors and SGA decline. RESULTS: The majority of the patients had a normal nutritional status at baseline, 28% were moderately malnourished (SGA ≤5). Overall, mean SGA decreased by -0.18 points/year, (95% confidence interval -0.21; -0.14). More than one-third of the study participants (34.9%) deteriorated in nutritional status (1 point decline in SGA) and 10.9% had a severe decline in SGA (≥2 points). The proportion of patients with low SGA (≤5) increased every 6 months. Those who dropped in SGA also declined in estimated glomerular filtration rate and mental health score. Every 10 points decrease in physical function score increased the odds of decline in SGA by 23%. Lower physical function score at baseline, gastrointestinal symptoms, and smoking were risk factors for impaired nutritional status. There was an interaction between diabetes and physical function on SGA decline. CONCLUSIONS: Nutritional status deteriorated in more than one-third of the study participants during the first year of follow-up. Lower patient-reported physical function, more gastrointestinal symptoms, and current smoking were associated with decline in nutritional status.

A propensity score-matched analysis indicates screening for asymptomatic coronary artery disease does not predict cardiac events in kidney transplant recipients.

Screening for asymptomatic coronary artery disease prior to kidney transplantation aims to reduce peri- and post-operative cardiac events. It is uncertain if this is achieved. Here, we investigated whether pre-transplant screening with a stress test or coronary angiogram associated with any difference in major adverse cardiac events (MACE) up to five years post-transplantation. We examined a national prospective cohort recruited to the Access to Transplant and Transplant Outcome Measures study who received a kidney transplant between 2011-2017, and linked patient demographics and details of cardiac screening investigations to outcome data extracted from the Hospital Episode Statistics dataset and United Kingdom Renal Registry. Propensity score matched groups were analyzed using Kaplan-Meier and Cox survival analyses. Overall, 2572 individuals were transplanted in 18 centers; 51% underwent screening and the proportion undergoing screening by center ranged from 5-100%. The incidence of MACE at 90 days, one and five years was 0.9%, 2.1% and 9.4% respectively. After propensity score matching based on the presence or absence of screening, 1760 individuals were examined (880 each in screened and unscreened groups). There was no statistically significant association between screening and MACE at 90 days (hazard ratio 0.80, 95% Confidence Interval 0.31-2.05), one year (1.12, 0.51-2.47) or five years (1.31, 0.86-1.99). Age, male sex and history of ischemic heart disease were associated with MACE. Thus, there is no association between screening for asymptomatic coronary artery disease and MACE up to five years post-transplant. Practices involving unselected screening of transplant recipients should be reviewed.

Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggests aspirin did not improve outcomes in older adults with chronic kidney disease.

The role of aspirin for primary prevention in older adults with chronic kidney disease (CKD) is unclear. Therefore, post hoc analysis of the randomized controlled trial ASPirin in Reducing Events in the Elderly (ASPREE) was undertaken comparing 100 mg of enteric-coated aspirin daily against matching placebo. Participants were community dwelling adults aged 70 years and older in Australia, 65 years and older in the United States, all free of a history of dementia or cardiovascular disease and of any disease expected to lead to death within five years. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m2 or urine albumin to creatinine ratio 3 mg/mmol or more. In 4758 participants with and 13004 without CKD, the rates of a composite endpoint (dementia, persistent physical disability or death), major adverse cardiovascular events and clinically significant bleeding in the CKD participants were almost double those without CKD. Aspirin's effects as estimated by hazard ratios were generally similar between CKD and non-CKD groups for dementia, persistent physical disability or death, major adverse cardiovascular events and clinically significant bleeding. Thus, in our analysis aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.

The combined effect of alcohol and body mass index on risk of chronic liver disease: A systematic review and meta-analysis of cohort studies.

BACKGROUND & AIMS: Increasingly populations are both overweight/obese and consume alcohol. The risk of liver disease from the combination of these factors is unclear. We performed a systematic review and meta-analysis to address this important gap in evidence. Protocol registered with PROSPERO(CRD42016046508). METHODS: We performed electronic searches of Ovid Medline, Embase Classic + Embase, until 17th June 2020 for cohort studies of adults without pre-existing liver disease. Primary outcome was morbidity/mortality from chronic liver disease. Exposures were alcohol consumption categorised as within or above UK recommended limits (14 units/112 g per week) and BMI categorised as normal, overweight or obese. Non-drinkers were excluded. A Poisson regression log-linear model was used to test for statistical interaction between alcohol and BMI and to conduct a one-stage meta-analysis. RESULTS: Searches identified 3129 studies-16 were eligible. Of these, nine cohorts (1,121,514 participants) had data available and were included in the analysis. The Poisson model showed no significant statistical interaction between alcohol consumption and BMI on the risk of chronic liver disease. Compared to normal weight participants drinking alcohol within UK recommended limits, relative risk of chronic liver disease in overweight participants drinking above limits was 3.32 (95% CI 2.88 to 3.83) and relative risk in obese participants drinking above limits was 5.39 (95% CI 4.62 to 6.29). CONCLUSIONS: This meta-analysis demonstrated a significantly increased risk of chronic liver disease in participants who were both overweight/obese and consumed alcohol above UK recommended limits. This evidence should inform advice given to patients and risk stratification by healthcare professionals.

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.

Risk of UTI in kidney stone formers: a matched-cohort study over a median follow-up of 19 years.

PURPOSE: To describe risk of UTI in Stone formers comparing to non-stone formers. METHODS: Retrospective cohort study using electronic records for patients across southern England. Stone formers referred to a tertiary referral centre in Southern England, comparator patients were age and sex matched with 3:1 ratio from same database. Those with no documentation were excluded. UTI defined using ICD-10 codes. Risk of UTI presented as hazard ratio with 95% confidence interval, generated using cox regression. Sample size calculated using 80% power and significance set at 0.05. RESULTS: Eight hundred and nineteen stone formers were included after 1000 records were screened for inclusion, with 2477 age and sex matched non-stone formers extracted from the same database. Sample size was calculated at 287 per group. Stone formers were at significantly increased risk of developing a UTI (HR 5.67; 95% CI 4.52-7.18, p < 0.001). Median follow-up was 19 years (IQR: 15-22). CONCLUSIONS: Kidney stone formers are at increased risk of developing urinary tract infections.

Integrated primary care and social services for older adults with multimorbidity in England: a scoping review.

BACKGROUND: As the prevalence of older adults with multimorbidity increases, greater integration of services is necessary to manage the physical and psycho-social needs of this cohort. This study describes and summarises current evidence, clinical provision and progress towards integrated primary care and social services for older adults with multimorbidity in England. METHODS: A scoping review was conducted involving systematic searches of a range of electronic academic and policy databases. Articles were screened and extracted in duplicate by two independent reviewers. Data were extracted onto a charting sheet and thematic synthesis was used to summarise findings. Articles were included if published in English and related to primary care, social care and multimorbidity in older adults in England. Conceptually, the review was framed using the Rainbow Model of Integrated Care. RESULTS: The search yielded 7656 articles of which 84 were included. Three themes were identified: (1) a focus on individual level services rather than multi-level or multi-sector integration, with an increasing emphasis on the need to consider broader determinants of population health as critical to integrated care for older adults with multimorbidity; (2) the need for policymakers to allow time for integration to embed, to enable new structures and relationships to develop and mature; and (3) the inherent tension between top-down and bottom-up driven approaches to integrated care requires a whole-systems structure, while allowing for local flexibilities. CONCLUSIONS: There is limited evidence of multi-level and multi-sector integration of services for older adults with multimorbidity in England. The literature increasingly acknowledges wider determinants of population health that are likely to require integration beyond primary care and social services. Improving clinical care in one or two sectors may not be as effective as simultaneously improving the organisation or design across services as one single system of provision. This may take time to establish and will require local input.