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.

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.

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.

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.

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.

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.

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.

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.

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.

Measuring older people's socioeconomic position: a scoping review of studies of self-rated health, health service and social care use.

BACKGROUND: The challenges of measuring socioeconomic position in older populations were first set out two decades ago. However, the question of how best to measure older people's socioeconomic position remains pertinent as populations age and health inequalities widen. METHODS: A scoping review aimed to identify and appraise measures of socioeconomic position used in studies of health inequalities in older populations in high-income countries. Medline, Scopus, EMBASE, HMIC and references lists of systematic reviews were searched for observational studies of socioeconomic health inequalities in adults aged 60 years and over, published between 2000 and 2020. A narrative synthesis was conducted. FINDINGS: One-hundred and thirty-eight studies were included; 20 approaches to measuring socioeconomic position were identified. Few studies considered which pathways the chosen measures of socioeconomic position intended to capture. The validity of subjective socioeconomic position measures, and measures that assume shared income and educational capital, should be verified in older populations. Incomplete financial data risk under-representation of some older groups when missing data are socially patterned. Older study samples were largely homogeneous on measures of housing tenure, and to a lesser extent, measures of educational attainment. Measures that use only two response categories risk missing subtle differences in older people's socioeconomic circumstances. CONCLUSION: Poor choice of measures of socioeconomic position risk underestimating the size of health inequalities in older populations. Choice of measures should be shaped by considerations of theory, context and response categories that detect subtle, yet important, inequalities. Further evidence is required to ascertain the validity of some measures identified in this review.