Trends in weight gain recorded in English primary care before and during the Coronavirus-19 pandemic: An observational cohort study using the OpenSAFELY platform.

BACKGROUND: Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic. METHODS AND FINDINGS: With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of weight gain between the prepandemic and pandemic periods. However, changes in healthcare activity during the pandemic may have introduced new bias to the data. CONCLUSIONS: We found female sex, younger age, deprivation, white British ethnicity, and mental health conditions were associated with rapid pandemic weight gain and extreme acceleration in rate of weight gain between the prepandemic and pandemic periods. Our findings highlight the need to incorporate sociodemographic, physical, and mental health characteristics when formulating research, policies, and interventions targeting BMI in the period of post pandemic service restoration and in future pandemic planning.

Factors associated with unmet need for support to maintain independence in later life: a systematic review of quantitative and qualitative evidence.

BACKGROUND: populations are considered to have an 'unmet need' when they could benefit from, but do not get, the necessary support. Policy efforts to achieve equitable access to long-term care require an understanding of patterns of unmet need. A systematic review was conducted to identify factors associated with unmet need for support to maintain independence in later life. METHODS: seven bibliographic databases and four non-bibliographic evidence sources were searched. Quantitative observational studies and qualitative systematic reviews were included if they reported factors associated with unmet need for support to maintain independence in populations aged 50+, in high-income countries. No limits to publication date were imposed. Studies were quality assessed and a narrative synthesis used, supported by forest plots to visualise data. FINDINGS: forty-three quantitative studies and 10 qualitative systematic reviews were included. Evidence across multiple studies suggests that being male, younger age, living alone, having lower levels of income, poor self-rated health, more functional limitations and greater severity of depression were linked to unmet need. Other factors that were reported in single studies were also identified. In the qualitative reviews, care eligibility criteria, the quality, adequacy and absence of care, and cultural and language barriers were implicated in unmet need. CONCLUSIONS: this review identifies which groups of older people may be most at risk of not accessing the support they need to maintain independence. Ongoing monitoring of unmet need is critical to support policy efforts to achieve equal ageing and equitable access to care.

The relationship between deprivation and frailty trajectories over 1 year and at the end of life: a case-control study.

BACKGROUND: We investigated the association between area-level, multi-domain deprivation and frailty trajectories in the last year of life and over 1 year in a matched non-end-of-life sample. METHODS: A 1-year longitudinal case-control study using primary care electronic health records from 20 460 people age ≥ 75. Cases (died 1 January 2015 to 1 January 2016) were 1:1 matched to controls by age, sex and practice location. Monthly interval frailty measured using a 36-item electronic frailty index (eFI: range 0-1, lower scores mean less frailty). Deprivation measured using Index of Multiple Deprivation (IMD) quintiles. We used latent growth curves to model the relationship between IMD and eFI trajectory. RESULTS: Living in a less deprived area was associated with faster increase in eFI for cases (0.005% per month, 95%confidence interval [CI]: 0.001, 0.010), but not controls, and was associated with lower eFI at study baseline in cases (-0.29% per IMD quintile, 95%CI -0.45, -0.13) and controls (-0.35% per quintile, 95%CI -0.51, -0.20). CONCLUSIONS: Overall, greater area-level deprivation is associated with higher levels of frailty, but people who survive to ≥75 have similar 1-year frailty trajectories, regardless of area-level deprivation. Interventions to reduce frailty should target younger age groups, especially those living in the most deprived areas.

Measuring frailty and its association with key outcomes in the ambulance setting: a cross sectional observational study.

BACKGROUND: Little is known about frailty in the ambulance setting, or its association with outcomes relevant to ambulance services. We sought to measure frailty in people aged ≥ 50 attended by an ambulance, and describe the relationship between frailty, odds of conveyance to hospital, and duration at scene. METHODS: An observational study between 01/01/2021-30/06/2021 in North East Ambulance Service, England. Participants were aged ≥ 50 attended by an ambulance, excluding patients requiring immediate treatment for a life-threatening condition or with Glasgow Coma Scale < 15. Paramedics (n = 112) measured patient frailty using the Clinical Frailty Scale (CFS). Additional information was extracted from ambulance care records. Weighted regression models examined associations between frailty, hospital conveyance, and duration at scene. RESULTS: Three thousand and fifty-six callouts were observed (mean patient age: 78.1 years, 57.2% female). Frailty prevalence (CFS ≥ 5) was 58.7%. Median duration at scene was 47.0 min (interquartile range 34.0-67.0 min). Ambulances spent a median of 8.2 (95%CI:5.4-11.0) minutes longer with frail patients than non-frail patients. Frail patients were less likely to be conveyed to hospital than non-frail patients (OR:0.75, 95%CI:0.60-0.94). CONCLUSION: Frailty is common among people aged ≥ 50 attended by an ambulance and an important influence on workload. Ambulance services need a good understanding of frailty to meet patient needs. As populations age, community support should be prioritised to deliver appropriate frailty care and reduce demands on ambulance services.

Deep learning-based automated speech detection as a marker of social functioning in late-life depression.

BACKGROUND: Late-life depression (LLD) is associated with poor social functioning. However, previous research uses bias-prone self-report scales to measure social functioning and a more objective measure is lacking. We tested a novel wearable device to measure speech that participants encounter as an indicator of social interaction. METHODS: Twenty nine participants with LLD and 29 age-matched controls wore a wrist-worn device continuously for seven days, which recorded their acoustic environment. Acoustic data were automatically analysed using deep learning models that had been developed and validated on an independent speech dataset. Total speech activity and the proportion of speech produced by the device wearer were both detected whilst maintaining participants' privacy. Participants underwent a neuropsychological test battery and clinical and self-report scales to measure severity of depression, general and social functioning. RESULTS: Compared to controls, participants with LLD showed poorer self-reported social and general functioning. Total speech activity was much lower for participants with LLD than controls, with no overlap between groups. The proportion of speech produced by the participants was smaller for LLD than controls. In LLD, both speech measures correlated with attention and psychomotor speed performance but not with depression severity or self-reported social functioning. CONCLUSIONS: Using this device, LLD was associated with lower levels of speech than controls and speech activity was related to psychomotor retardation. We have demonstrated that speech activity measured by wearable technology differentiated LLD from controls with high precision and, in this study, provided an objective measure of an aspect of real-world social functioning in LLD.

Metabolic risk factors and incident advanced liver disease in non-alcoholic fatty liver disease (NAFLD): A systematic review and meta-analysis of population-based observational studies.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. Many individuals have risk factors associated with NAFLD, but the majority do not develop advanced liver disease: cirrhosis, hepatic decompensation, or hepatocellular carcinoma. Identifying people at high risk of experiencing these complications is important in order to prevent disease progression. This review synthesises the evidence on metabolic risk factors and their potential to predict liver disease outcomes in the general population at risk of NAFLD or with diagnosed NAFLD. METHODS AND FINDINGS: We conducted a systematic review and meta-analysis of population-based cohort studies. Databases (including MEDLINE, EMBASE, the Cochrane Library, and ClinicalTrials.gov) were searched up to 9 January 2020. Studies were included that reported severe liver disease outcomes (defined as liver cirrhosis, complications of cirrhosis, or liver-related death) or advanced fibrosis/non-alcoholic steatohepatitis (NASH) in adult individuals with metabolic risk factors, compared with individuals with no metabolic risk factors. Cohorts selected on the basis of a clinically indicated liver biopsy were excluded to better reflect general population risk. Risk of bias was assessed using the QUIPS tool. The results of similar studies were pooled, and overall estimates of hazard ratio (HR) were obtained using random-effects meta-analyses. Of 7,300 unique citations, 22 studies met the inclusion criteria and were of sufficient quality, with 18 studies contributing data suitable for pooling in 2 random-effects meta-analyses. Type 2 diabetes mellitus (T2DM) was associated with an increased risk of incident severe liver disease events (adjusted HR 2.25, 95% CI 1.83-2.76, p < 0.001, I2 99%). T2DM data were from 12 studies, with 22.8 million individuals followed up for a median of 10 years (IQR 6.4 to 16.9) experiencing 72,792 liver events. Fourteen studies were included in the meta-analysis of obesity (BMI > 30 kg/m2) as a prognostic factor, providing data on 19.3 million individuals followed up for a median of 13.8 years (IQR 9.0 to 19.8) experiencing 49,541 liver events. Obesity was associated with a modest increase in risk of incident severe liver disease outcomes (adjusted HR 1.20, 95% CI 1.12-1.28, p < 0.001, I2 87%). There was also evidence to suggest that lipid abnormalities (low high-density lipoprotein and high triglycerides) and hypertension were both independently associated with incident severe liver disease. Significant study heterogeneity observed in the meta-analyses and possible under-publishing of smaller negative studies are acknowledged to be limitations, as well as the potential effect of competing risks on outcome. CONCLUSIONS: In this review, we observed that T2DM is associated with a greater than 2-fold increase in the risk of developing severe liver disease. As the incidence of diabetes and obesity continue to rise, using these findings to improve case finding for people at high risk of liver disease will allow for effective management to help address the increasing morbidity and mortality from liver disease. TRIAL REGISTRATION: PROSPERO CRD42018115459.

What is the evidence that people with frailty have needs for palliative care at the end of life? A systematic review and narrative synthesis.

BACKGROUND: The number of older people living and dying with frailty is rising, but our understanding of their end-of-life care needs is limited. AIM: To synthesise evidence on the end-of-life care needs of people with frailty. DESIGN: Systematic review of literature and narrative synthesis. Protocol registered prospectively with PROSPERO (CRD42016049506). DATA SOURCES: Fourteen electronic databases (CINAHL, Cochrane, Embase, EThOS, Google, Medline, NDLTD, NHS Evidence, NICE, Open grey, Psychinfo, SCIE, SCOPUS and Web of Science) searched from inception to October 2017 and supplemented with bibliographic screening and reference chaining. Studies were included if they used an explicit definition or measure of frailty. Quality was assessed using the National Institute for Health tool for observational studies. RESULTS: A total of 4,998 articles were retrieved. Twenty met the inclusion criteria, providing evidence from 92,448 individuals (18,698 with frailty) across seven countries. Thirteen different measures or definitions of frailty were used. People with frailty experience pain and emotional distress at levels similar to people with cancer and also report a range of physical and psychosocial needs, including weakness and anxiety. Functional support needs were high and were highest where people with frailty were cognitively impaired. Individuals with frailty often expressed a preference for reduced intervention, but these preferences were not always observed at critical phases of care. CONCLUSION: People with frailty have varied physical and psychosocial needs at the end of life that may benefit from palliative care. Frailty services should be tailored to patient and family needs and preferences at the end of life.

Frailty trajectories to identify end of life: a longitudinal population-based study.

BACKGROUND: Timely recognition of the end of life allows patients to discuss preferences and make advance plans, and clinicians to introduce appropriate care. We examined changes in frailty over 1 year, with the aim of identifying trajectories that could indicate where an individual is at increased risk of all-cause mortality and may require palliative care. METHODS: Electronic health records from 13,149 adults (cases) age 75 and over who died during a 1-year period (1 January 2015 to 1 January 2016) were age, sex and general practice matched to 13,149 individuals with no record of death over the same period (controls). Monthly frailty scores were obtained for 1 year prior to death for cases, and from 1 January 2015 to 1 January 2016 for controls using the electronic frailty index (eFI; a cumulative deficit measure of frailty, available in most English primary care electronic health records, and ranging in value from 0 to 1). Latent growth mixture models were used to investigate longitudinal patterns of change and associated impact on mortality. Cases were reweighted to the population level for tests of diagnostic accuracy. RESULTS: Three distinct frailty trajectories were identified. Rapidly rising frailty (initial increase of 0.022 eFI per month before slowing from a baseline eFI of 0.21) was associated with a 180% increase in mortality (OR 2.84, 95% CI 2.34-3.45) for 2.2% of the sample. Moderately increasing frailty (eFI increase of 0.007 per month, with baseline of 0.26) was associated with a 65% increase in mortality (OR 1.65, 95% CI 1.54-1.76) for 21.2% of the sample. The largest (76.6%) class was stable frailty (eFI increase of 0.001 from a baseline of 0.26). When cases were reweighted to population level, rapidly rising frailty had 99.1% specificity and 3.2% sensitivity (positive predictive value 19.8%, negative predictive value 93.3%) for predicting individual risk of mortality. CONCLUSIONS: People aged over 75 with frailty who are at highest risk of death have a distinctive frailty trajectory in the last 12 months of life, with a rapid initial rise from a low baseline, followed by a plateau. Routine measurement of frailty can be useful to support clinicians to identify people with frailty who are potential candidates for palliative care, and allow time for intervention.

Older Adults' Social Relationships and Health Care Utilization: A Systematic Review.

BACKGROUND: Deficiencies in older people's social relationships (including loneliness, social isolation, and low social support) have been implicated as a cause of premature mortality and increased morbidity. Whether they affect service use is unclear. OBJECTIVES: To determine whether social relationships are associated with older adults' use of health services, independently of health-related needs. SEARCH METHODS: We searched 8 electronic databases (MEDLINE, Embase, CINAHL, Web of Science, PsycINFO, Scopus, the Cochrane Library, and the Centre for Reviews and Dissemination) for data published between 1983 and 2016. We also identified relevant sources from scanning the reference lists of included studies and review articles, contacting authors to identify additional studies, and searching the tables of contents of key journals. SELECTION CRITERIA: Studies met inclusion criteria if more than 50% of participants were older than 60 years or mean age was older than 60 years; they included a measure of social networks, received social support, or perceived support; and they reported quantitative data on the association between social relationships and older adults' health service utilization. DATA COLLECTION AND ANALYSIS: Two researchers independently screened studies for inclusion. They extracted data and appraised study quality by using standardized forms. In a narrative synthesis, we grouped the studies according to the outcome of interest (physician visits, hospital admissions, hospital readmissions, emergency department use, hospital length of stay, utilization of home- and community-based services, contact with general health services, and mental health service use) and the domain of social relationships covered (social networks, received social support, or perceived support). For each service type and social relationship domain, we assessed the strength of the evidence across studies according to the quantity and quality of studies and consistency of findings. MAIN RESULTS: The literature search retrieved 26 077 citations, 126 of which met inclusion criteria. Data were reported across 226 678 participants from 19 countries. We identified strong evidence of an association between weaker social relationships and increased rates of readmission to hospital (75% of high-quality studies reported evidence of an association in the same direction). In evidence of moderate strength, according to 2 high-quality and 3 medium-quality studies, smaller social networks were associated with longer hospital stays. When we considered received and perceived social support separately, they were not linked to health care use. Overall, the evidence did not indicate that older patients with weaker social relationships place greater demands on ambulatory care (including physician visits and community- or home-based services) than warranted by their needs. AUTHORS' CONCLUSIONS: Current evidence does not support the view that, independently of health status, older patients with lower levels of social support place greater demands on ambulatory care. Future research on social relationships would benefit from a consensus on clinically relevant concepts to measure. Public Health Implications. Our findings are important for public health because they challenge the notion that lonely older adults are a burden on all health and social care services. In high-income countries, interventions aimed at reducing social isolation and loneliness are promoted as a means of preventing inappropriate service use. Our review cautions against assuming that reductions in care utilization can be achieved by intervening to strengthen social relationships.

Loneliness as a risk factor for care home admission in the English Longitudinal Study of Ageing.

Background: loneliness has an adverse effect on health and well-being, and is common at older ages. Evidence that it is a risk factor for care home admission is sparse. Objective: to investigate the association between loneliness and care home admission. Setting: English Longitudinal Study of Ageing (ELSA). Participants: two-hundred fifty-four individuals across seven waves (2002-15) of ELSA who moved into care homes were age, sex matched to four randomly selected individuals who remained in the community. Methods: logistic regression models examined associations between loneliness, socio-demographic factors, functional status and health on moving into care homes. Results: loneliness (measured by the University of California, Los Angeles (UCLA) Loneliness Scale and a single-item question from the Center for Epidemiological Studies Depression Scale (CES-D)) was associated with moving into a care home (CES-D OR 2.13, 95% CI 1.43-3.17, P = 0.0002, UCLA OR 1.81, 95% CI 1.01-3.27, P = 0.05). The association persisted after adjusting for established predictors (age, sex, social isolation, depression, memory problems including diagnosis of Alzheimer's disease, disability, long-term physical health and wealth). The impact of loneliness (measured by CES-D) on admission accounted for a population attributable fraction of 19.9% (95% CI 7.8-30.4%). Conclusions: loneliness conveys an independent risk of care home admission that, unlike other risk factors, may be amenable to modification. Tackling loneliness amongst older adults may be a way of enhancing wellbeing and delaying or reducing the demand for institutional care.

Evaluating frailty scores to predict mortality in older adults using data from population based electronic health records: case control study.

BACKGROUND: recognising that a patient is nearing the end of life is essential, to enable professional carers to discuss prognosis and preferences for end of life care. OBJECTIVE: investigate whether an electronic frailty index (eFI) generated from routinely collected data, can be used to predict mortality at an individual level. DESIGN: historical prospective case control study. SETTING: UK primary care electronic health records. SUBJECTS: 13,149 individuals age 75 and over who died between 01/01/2015 and 01/01/2016, 1:1 matched by age and sex to individuals with no record of death in the same time period. METHODS: two subsamples were randomly selected to enable development and validation of the association between eFI 3 months prior to death and mortality. Receiver operator characteristic (ROC) analyses were used to examine diagnostic accuracy of eFI at 3 months prior to death. RESULTS: an eFI > 0.19 predicted mortality in the development sample at 75% sensitivity and 69% area under received operating curve (AUC). In the validation dataset this cut point gave 76% sensitivity, 53% specificity. CONCLUSIONS: the eFI measured at a single time point has low predictive value for individual risk of death, even 3 months prior to death. Although the eFI is a strong predictor or mortality at a population level, its use for individuals is far less clear.

The impact and measurement of social dysfunction in late-life depression: an evaluation of current methods with a focus on wearable technology.

OBJECTIVE: Depression is known to negatively impact social functioning, with patients commonly reporting difficulties maintaining social relationships. Moreover, a large body of evidence suggests poor social functioning is not only present in depression but that social functioning is an important factor in illness course and outcome. In addition, good social relationships can play a protective role against the onset of depressive symptoms, particularly in late-life depression. However, the majority of research in this area has employed self-report measures of social function. This approach is problematic, as due to their reliance on memory, such measures are prone to error from the neurocognitive impairments of depression, as well as mood-congruent biases. METHOD: Narrative review based on searches of the Web of Science and PubMed database(s) from the start of the databases, until the end of 2015. RESULTS: The present review provides an overview of the literature on social functioning in (late-life) depression and discusses the potential for new technologies to improve the measurement of social function in depressed older adults. In particular, the use of wearable technology to collect direct, objective measures of social activity, such as physical activity and speech, is considered. CONCLUSION: In order to develop a greater understanding of social functioning in late-life depression, future research should include the development and validation of more direct, objective measures in conjunction with subjective self-report measures. Copyright © 2016 John Wiley & Sons, Ltd.

Changes over time in the health and functioning of older people moving into care homes: analysis of data from the English Longitudinal Study of Ageing.

Background: the number of people requiring care home support is projected to rise in future years, but little information is available on the needs of new care home residents. Objective: to measure the health and functioning of people moving into care homes and how they have changed between 2002 and 2015. Setting: English Longitudinal Study of Ageing. Participants: two hundred fifty-four of the 313 (1.99%) individuals who moved from the community into a care home, and were interviewed in the survey wave prior to entry. Main outcome measures: changes over time for number of health conditions and functional deficits (deficits in activities of daily living (ADL), and instrumental ADLs (IADLs)), assessed in the survey wave prior to admission. Results: over time there were significant increases in the total number of health conditions and functional deficits amongst soon to be care home entrants (P = 0.0011), the proportion with high blood pressure (OR 1.37, 95% CI: 1.17-1.62, P < 0.0001), memory problems (OR 1.33, 95% CI: 1.11-1.61, P = 0.0021) or total number of IADL deficits (P = 0.008). Non-significant increases were observed in the proportion of care home entrants with cancer (OR 1.23, 95% CI: 0.93-1.65, P = 0.15), lung disease (OR 1.21, 95% CI: 0.85-1.75), heart disease (OR 1.12, 95% CI: 0.95-1.30) and arthritis (OR 1.11, 95% CI: 0.95-1.30). Stroke and ADL deficits did not increase. No differential ageing effect was observed. Conclusions: the support needs of care home entrants in England appear to be increasing over time. This has important implications for the provision and funding of care home places and community services.

Immunometabolic Blood Biomarkers of Developmental Trajectories of Depressive Symptoms: Findings From the ALSPAC Birth Cohort.

Studies of longitudinal trends of depressive symptoms in young people could provide insight into aetiologic mechanism, heterogeneity and origin of common cardiometabolic comorbidities for depression. Depression is associated with immunological and metabolic alterations, but immunometabolic characteristics of developmental trajectories of depressive symptoms remain unclear. Using depressive symptoms scores measured on 10 occasions between ages 10 and 25 years in the Avon Longitudinal Study of Parents and Children (n=7302), we identified four distinct trajectories: low-stable (70% of the sample), adolescent-limited (13%), adulthood-onset (10%) and adolescent-persistent (7%). We examined associations of these trajectories with: i) anthropometric, cardiometabolic and psychiatric phenotypes using multivariable regression (n=1709-3410); ii) 67 blood immunological proteins and 57 metabolomic features using empirical Bayes moderated linear models (n=2059 and n=2240 respectively); and iii) 28 blood cell counts and biochemical measures using multivariable regression (n=2256). Relative to the low-stable group, risk of depression and anxiety in adulthood was higher for all other groups, especially in the adolescent-persistent (ORdepression=22.80, 95% CI 15.25-34.37; ORGAD=19.32, 95% CI 12.86-29.22) and adulthood-onset (ORdepression=7.68, 95% CI 5.31-11.17; ORGAD=5.39, 95% CI 3.65-7.94) groups. The three depression-related trajectories vary in their immunometabolic profile, with evidence of little or no alterations in the adolescent-limited group. The adulthood-onset group shows widespread classical immunometabolic changes (e.g., increased immune cell counts and insulin resistance), while the adolescent-persistent group is characterised by higher BMI both in childhood and adulthood with few other immunometabolic changes. These findings point to distinct mechanisms and intervention opportunities for adverse cardiometabolic profile in different groups of young people with depression.

Genetic architecture of routinely acquired blood tests in a British South Asian cohort.

Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.

Weight trends among adults with diabetes or hypertension during the COVID-19 pandemic: an observational study using OpenSAFELY.

BACKGROUND: COVID-19 pandemic restrictions may have influenced behaviours related to weight. AIM: To describe patterns of weight change among adults living in England with type 2 diabetes (T2D) and/or hypertension during the pandemic. DESIGN AND SETTING: An observational cohort study using the routinely collected health data of approximately 40% of adults living in England, accessed through the OpenSAFELY service inside TPP. METHOD: Clinical and sociodemographic characteristics associated with rapid weight gain (>0.5 kg/m2/year) were investigated using multivariable logistic regression. RESULTS: Data were extracted on adults with T2D (n = 1 231 455, 43.9% female, and 76.0% White British) or hypertension (n = 3 558 405, 49.7% female, and 84.3% White British). Adults with T2D lost weight overall (median δ = -0.1 kg/m2/year [interquartile range {IQR} -0.7-0.4]). However, rapid weight gain was common (20.7%) and associated with the following: sex (male versus female: adjusted odds ratio [aOR] 0.78 [95% confidence interval {CI} = 0.77 to 0.79]); age (older age reduced odds, for example, aged 60-69 years versus 18-29 years: aOR 0.66 [95% CI = 0.61 to 0.71]); deprivation (least deprived Index of Multiple Deprivation [IMD] quintile versus most deprived IMD quintile: aOR 0.87 [95% CI = 0.85 to 0.89]); White ethnicity (Black versus White: aOR 0.95 [95% CI = 0.92 to 0.98]); mental health conditions (for example, depression: aOR 1.13 [95% CI = 1.12 to 1.15]); and diabetes treatment (non-insulin treatment versus no pharmacological treatment: aOR 0.68 [95% CI = 0.67 to 0.69]). Adults with hypertension maintained stable weight overall (median δ = 0.0 kg/m2/year [IQR -0.6-0.5]); however, rapid weight gain was common (24.7%) and associated with similar characteristics as in T2D. CONCLUSION: Among adults living in England with T2D and/or hypertension, rapid pandemic weight gain was more common among females, younger adults, those living in more deprived areas, and those with mental health conditions.

Care Home Residency and Its Association with Ambulance Service Workload.

OBJECTIVES: Care home residents comprise a significant minority of ambulance patients, but little is known about how care homes impact ambulance service workload. This study aims to quantify differences in the workload of ambulance paramedics associated with patient residence (care home vs private). DESIGN: This was an observational study using routine ambulance service data and Clinical Frailty Scale scores from patients attended by 112 study paramedics between January 1, 2021, and June 30, 2021. SETTING AND PARTICIPANTS: 3056 patients (459 in care homes) aged ≥50 attended by the North East Ambulance Service NHS Foundation Trust, England. METHODS: This study used 2 outcome measures of treatment: time spent at scene and conveyance to hospital. Anonymized patient data and incident time logs were collected from ambulance electronic patient care records. The relationships between care home residency, conveyance to hospital, and time spent at scene were investigated using ordinal logistic regression and quantile regression. Models were weighted to address potential sampling imbalance using anonymised call logs containing all eligible ambulance callouts. RESULTS: Care home residents were less likely to be conveyed to hospital [odds ratio: 0.75 (0.59-0.96)] and received shorter treatment time than community residents [median -7.0 (-12.0, -1.9) minutes for patients conveyed to hospital, -2.8 (-5.4, -0.3) minutes for patients discharged at scene]. CONCLUSIONS AND IMPLICATIONS: Our results suggest that care homes provide support that reduces demand on the ambulance service and other "downstream" services in secondary care. This study also points to a need to enhance care for older people in private households to contain the demands on ambulance services. These findings have implications for countries like England, where ambulance services struggle to meet target response times, which may affect patient outcomes.

Which interventions are effective at decreasing or increasing emergency department attendances or hospital admissions from long-term care facilities? A systematic review.

OBJECTIVE: UK long-term care facility residents account for 185 000 emergency hospital admissions each year. Avoidance of unnecessary hospital transfers benefits residents, reduces demand on the healthcare systems but is difficult to implement. We synthesised evidence on interventions that influence unplanned hospital admissions or attendances by long-term care facility residents. METHODS: This is a systematic review of randomised controlled trials. PubMed, MEDLINE, EMBASE, ISI Web of Science, CINAHL and the Cochrane Library were searched from 2012 to 2022, building on a review published in 2013. We included randomised controlled trials that evaluated interventions that influence (decrease or increase) acute hospital admissions or attendances of long-term care facility residents. Risk of bias and evidence quality were assessed using Cochrane Risk Of Bias-2 and Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Forty-three randomised studies were included in this review. A narrative synthesis was conducted and the weight of evidence described with vote counting. Advance care planning and goals of care setting appear to be effective at reducing hospitalisations from long-term care facilities. Other effective interventions, in order of increasing risk of bias, were: nurse practitioner/specialist input, palliative care intervention, influenza vaccination and enhancing access to intravenous therapies in long-term care facilities. CONCLUSIONS: Factors that affect hospitalisation and emergency department attendances of long-term care facility residents are complex. This review supports the already established use of advance care planning and influenza vaccination to reduce unscheduled hospital attendances. It is likely that more than one intervention will be needed to impact on healthcare usage across the long-term care facility population. The findings of this review are useful to identify effective interventions that can be combined, as well as highlighting interventions that either need evaluation or are not effective at decreasing healthcare usage. PROSPERO REGISTRATION NUMBER: CRD42020169604.

Genome-wide association study of thyroid-stimulating hormone highlights new genes, pathways and associations with thyroid disease.

Thyroid hormones play a critical role in regulation of multiple physiological functions and thyroid dysfunction is associated with substantial morbidity. Here, we use electronic health records to undertake a genome-wide association study of thyroid-stimulating hormone (TSH) levels, with a total sample size of 247,107. We identify 158 novel genetic associations, more than doubling the number of known associations with TSH, and implicate 112 putative causal genes, of which 76 are not previously implicated. A polygenic score for TSH is associated with TSH levels in African, South Asian, East Asian, Middle Eastern and admixed American ancestries, and associated with hypothyroidism and other thyroid disease in South Asians. In Europeans, the TSH polygenic score is associated with thyroid disease, including thyroid cancer and age-of-onset of hypothyroidism and hyperthyroidism. We develop pathway-specific genetic risk scores for TSH levels and use these in phenome-wide association studies to identify potential consequences of pathway perturbation. Together, these findings demonstrate the potential utility of genetic associations to inform future therapeutics and risk prediction for thyroid diseases.

Clinical frailty and performance scale translation in palliative care: scoping review.

BACKGROUND: Frailty is associated with advancing age and increases the risk of adverse outcomes and death. Routine assessment of frailty is becoming more common in a number of healthcare settings, but not in palliative care, where performance scales (eg, the Australia-modified Karnofsky Performance Status Scale (AKPS)) are more commonly employed. A shared understanding of performance and frailty measures could aid interspecialty collaboration in both end-of-life care research and clinical practice. AIMS: To identify and synthesise evidence comparing measures of performance routinely collected in palliative care with the Clinical Frailty Scale (CFS), and create a conversion chart to support interspecialty communication. METHODS: A scoping literature review with comprehensive searches of PubMed, Web of Science, Ovid SP, the Cochrane Library and reference lists. Eligible articles compared the CFS with the AKPS, Palliative Performance Scale (PPS), Karnofsky Performance Scale or Eastern Cooperative Oncology Group Performance Status or compared these performance scales, in patients aged >18 in any setting. RESULTS: Searches retrieved 3124 articles. Two articles directly compared CFS to the PPS. Thirteen studies translated between different performance scores, facilitating subsequent conversion to CFS, specifically: AKPS/PPS 10/20=very severe frailty, AKPS/PPS 30=severe frailty, AKPS/PPS 40/50=moderate frailty, AKPS/PPS60=mild frailty. CONCLUSION: We present a tool for converting between the CFS and performance measures commonly used in palliative care. A small number of studies provided evidence for the direct translation between CFS and the PPS. Therefore, more primary evidence is needed from a wider range of population settings, and performance measures to support this conversion.