PeRsOnaliSed care Planning for oldER people with frailty (PROSPER): protocol for a randomised controlled trial.

BACKGROUND: Frailty is common in older age and is characterised by loss of biological reserves across multiple organ systems. These changes associated with frailty mean older people can be vulnerable to sudden, dramatic changes in health because of relatively small problems. Older people with frailty are at increased risk of adverse outcomes including disability, hospitalisation, and care home admission, with associated reduction in quality of life and increased NHS and social care costs. Personalised Care Planning offers an anticipatory, preventative approach to supporting older adults to live independently for longer, but it has not been robustly evaluated in a population of older adults with frailty. METHODS: Following an initial feasibility study, this multi-centre, individually randomised controlled trial aims to establish whether personalised care planning for older people improves health-related quality of life. It will recruit 1337 participants from general practices across Yorkshire and Humber and Mid-Mersey in the North of England. Eligible patients will be aged 65 and over with an electronic frailty index score of 0.21 or above, living in their own homes, without severe cognitive impairment and not in receipt of end-of-life care. Following confirmation of eligibility, informed consent and baseline data collection, participants will be individually randomised to the PeRsOnaliSed care Planning for oldER people with frailty (PROSPER) intervention or usual care in a 2.6:1 allocation ratio. Participants will not be blinded to allocation, but data collection and analysis will be blinded. The intervention will be delivered over 12 weeks by a Personal Independence Co-ordinator worker based within a voluntary sector organisation, Age UK. The primary outcomes are health-related quality of life, measured using both the physical and mental components of the Short-Form 12 Item Health Questionnaire at 12 months after randomisation. Secondary outcomes comprise activities of daily living, self-management capabilities and loneliness, admission to care homes, hospitalisations, and health and social care resource use at 12 months post randomisation. Parallel cost-effectiveness and process evaluations will be conducted alongside the trial. DISCUSSION: The PROSPER study will evaluate the effectiveness and cost-effectiveness of a personalised care planning approach for older people with frailty and inform the process of its implementation. TRIAL REGISTRATION: ISRCTN16123291 .  Registered on  28 August 2020.

The relationship between weight-related indicators and depressive symptoms during adolescence and adulthood: results from two twin studies.

BACKGROUND: The association between weight and depressive symptoms is well established, but the direction of effects remains unclear. Most studies rely on body mass index (BMI) as the sole weight indicator, with few examining the aetiology of the association between weight indicators and depressive symptoms. METHODS: We analysed data from the Twins Early Development Study (TEDS) and UK Adult Twin Registry (TwinsUK) (7658 and 2775 twin pairs, respectively). A phenotypic cross-lagged panel model assessed the directionality between BMI and depressive symptoms at ages 12, 16, and 21 years in TEDS. Bivariate correlations tested the phenotypic association between a range of weight indicators and depressive symptoms in TwinsUK. In both samples, structural equation modelling of twin data investigated genetic and environmental influences between weight indicators and depression. Sensitivity analyses included two-wave phenotypic cross-lagged panel models and the exclusion of those with a BMI <18.5. RESULTS: Within TEDS, the relationship between BMI and depression was bidirectional between ages 12 and 16 with a stronger influence of earlier BMI on later depression. The associations were unidirectional thereafter with depression at 16 influencing BMI at 21. Small genetic correlations were found between BMI and depression at ages 16 and 21, but not at 12. Within TwinsUK, depression was weakly correlated with weight indicators; therefore, it was not possible to generate precise estimates of genetic or environmental correlations. CONCLUSIONS: The directionality of the relationship between BMI and depression appears to be developmentally sensitive. Further research with larger genetically informative samples is needed to estimate the aetiological influence on these associations.

Characterization of patients receiving surgical versus non-surgical treatment for infective endocarditis in West Virginia.

BACKGROUND: Infective endocarditis (IE) has increased in rural states such as West Virginia (WV) with high injection drug use. IE is medically managed with antimicrobial treatment alone or combined with surgical treatment. This study aimed to characterize the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients in WV's rural centers. METHODS: This retrospective review of electronic health records includes all adults hospitalized for IE at major rural tertiary cardiovascular centers in WV during 2014-2018. Descriptive statistics were presented on demographics, history of injection drug use, clinical characteristics, and hospital utilization by surgery status, and multivariable logistic regression examined the association of surgery with key predictor variables, generating odds ratios (OR). RESULTS: Of the 780 patients with IE, 38% had surgery, with a 26-fold increase in patients undergoing surgery between 2014-2018. Comparing surgery and non-surgery patients revealed significant differences. Surgery patients were significantly younger (median age 35.6 vs. 40.5 years; p<0.001); had higher rates of drug use history (80% vs. 65%; p<0.001), psychiatric disorders (57% vs. 31%; p<0.001), and readmissions (18% vs.12%; p = 0.015). Surgery patients had lower rates of discharge against medical advice (11% vs.17%; p = 0.028) and in-hospital mortality (5% vs.12%; p<0.001). In the multivariable logistic regression, surgery was associated with injection drug use (OR: 1.9; 95% CI:1.09-3. 3), indications for surgery (OR: 1.68; 95% CI:1.48-1.91), left-sided IE (OR: 2.14; 95%CI:1.43-3.19) and later years (OR:3.75; 95%CI:2.5-5.72). CONCLUSION: This study characterizes the predictors associated with surgical treatment and rates of inpatient mortality and readmission among IE patients across rural WV. The decision to perform cardiac surgery on IE patients is complex. Results with increased injection drug use-associated IE emphasize the importance of comprehensive care by a multidisciplinary team for optimal management of patients with IE.

Tropical mountain ice core δ18O: A Goldilocks indicator for global temperature change.

Very high tropical alpine ice cores provide a distinct paleoclimate record for climate changes in the middle and upper troposphere. However, the climatic interpretation of a key proxy, the stable water oxygen isotopic ratio in ice cores (δ18Oice), remains an outstanding problem. Here, combining proxy records with climate models, modern satellite measurements, and radiative-convective equilibrium theory, we show that the tropical δ18Oice is an indicator of the temperature of the middle and upper troposphere, with a glacial cooling of -7.35° ± 1.1°C (66% CI). Moreover, it severs as a "Goldilocks-type" indicator of global mean surface temperature change, providing the first estimate of glacial stage cooling that is independent of marine proxies as -5.9° ± 1.2°C. Combined with all estimations available gives the maximum likelihood estimate of glacial cooling as -5.85° ± 0.51°C.

Living alone and mental health: parallel analyses in UK longitudinal population surveys and electronic health records prior to and during the COVID-19 pandemic.

BACKGROUND: People who live alone experience greater levels of mental illness; however, it is unclear whether the COVID-19 pandemic had a disproportionately negative impact on this demographic. OBJECTIVE: To describe the mental health gap between those who live alone and with others in the UK prior to and during the COVID-19 pandemic. METHODS: Self-reported psychological distress and life satisfaction in 10 prospective longitudinal population surveys (LPSs) assessed in the nearest pre-pandemic sweep and three periods during the pandemic. Recorded diagnosis of common and severe mental illnesses between March 2018 and January 2022 in electronic healthcare records (EHRs) within the OpenSAFELY-TPP. FINDINGS: In 37 544 LPS participants, pooled models showed greater psychological distress (standardised mean difference (SMD): 0.09 (95% CI: 0.04; 0.14); relative risk: 1.25 (95% CI: 1.12; 1.39)) and lower life satisfaction (SMD: -0.22 (95% CI: -0.30; -0.15)) for those living alone pre-pandemic. This gap did not change during the pandemic. In the EHR analysis of c.16 million records, mental health conditions were more common in those who lived alone (eg, depression 26 (95% CI: 18 to 33) and severe mental illness 58 (95% CI: 54 to 62) more cases more per 100 000). For common mental health disorders, the gap in recorded cases in EHRs narrowed during the pandemic. CONCLUSIONS: People living alone have poorer mental health and lower life satisfaction. During the pandemic, this gap in self-reported distress remained; however, there was a narrowing of the gap in service use. CLINICAL IMPLICATIONS: Greater mental health need and potentially greater barriers to mental healthcare access for those who live alone need to be considered in healthcare planning.

A cross-lagged twin study of emotional symptoms, social isolation and peer victimisation from early adolescence to emerging adulthood.

BACKGROUND: Emotional symptoms, such as anxiety and depressive symptoms, are common during adolescence, often persist over time, and can precede the emergence of severe anxiety and depressive disorders. Studies suggest that a vicious cycle of reciprocal influences between emotional symptoms and interpersonal difficulties may explain why some adolescents suffer from persisting emotional symptoms. However, the role of different types of interpersonal difficulties, such as social isolation and peer victimisation, in these reciprocal associations is still unclear. In addition, the lack of longitudinal twin studies conducted on emotional symptoms during adolescence means that the genetic and environmental contributions to these relationships during adolescence remain unknown. METHODS: Participants (N = 15,869) from the Twins Early Development Study completed self-reports of emotional symptoms, social isolation and peer victimisation at 12, 16 and 21 years old. A phenotypic cross-lagged model examined reciprocal associations between variables over time, and a genetic extension of this model examined the aetiology of the relationships between variables at each timepoint. RESULTS: First, emotional symptoms were reciprocally and independently associated with both social isolation and peer victimisation over time, indicating that different forms of interpersonal difficulties uniquely contributed to emotional symptoms during adolescence and vice versa. Second, early peer victimisation predicted later emotional symptoms via social isolation in mid-adolescence, indicating that social isolation may constitute an intermediate pathway through which peer victimisation predicts longer-term emotional symptoms. Finally, individual differences in emotional symptoms were mostly accounted for by non-shared environmental factors at each timepoint, and both gene-environment and individual-specific environmental mechanisms were involved in the relationships between emotional symptoms and interpersonal difficulties. CONCLUSIONS: Our study highlights the necessity to intervene early in adolescence to prevent the escalation of emotional symptoms over time and to consider social isolation and peer victimisation as important risk factors for the long-term persistence of emotional symptoms.

Prevalence of Substance Abuse Among Trauma Patients in Rural West Virginia.

BACKGROUND:  Substance abuse poses considerable clinical, economic, and social challenges. West Virginia is hailed as the epicenter of the substance abuse in the United States, the prevalence and pattern of different trauma mechanisms in a rural context or in patients with different forms of substance abuse remain unclear. OBJECTIVE:  We performed the following analysis to understand the prevalence of substance abuse in patients with different trauma mechanisms in the rural setting with high substance abuse in the West Virginia. METHODS:  We performed a cross-sectional retrospective analysis of adult trauma patients (motor vehicle, fall, assault, firearm suicide, brawl/rape and machinery) hospitalized in two tertiary care hospitals in West Virginia between 2006 and 2016. We identified all patients who had a urine drug screen (UDS) test and extracted the data related to the substance and trauma. RESULTS:  Among 8734 patients screened using UDS, 5940 (68.1%) patients were tested positive for the substance. Opiates, alcohol, benzodiazepines, and cannabis were the four most common substances identified in trauma victims. In all instances, the prescribed drug was less than 20%. Fatal outcome was observed in 366 patients in the sample, with 44% (n=162) testing positive for UDS, 12% (n=45) testing positive for only alcohol, and 15% (n=56) testing positive for both alcohol and UDS. Regarding the trauma mechanism, the motor vehicle accident (MVA) was the most prominent with a clear association of substance abuse with fatal outcome. CONCLUSION:  The most prevalent trauma mechanism was a MVA, with a strong link between drug usage and mortality. Due to the high incidence of positive substance abuse screens, UDS tests may need to be more widely implemented in trauma in the West Virginia region. The findings of this study might help in establishing regional or national policies to reduce acute substance abuse.

Thymidine Phosphorylase Deficiency or Inhibition Preserves Cardiac Function in Mice With Acute Myocardial Infarction.

Background Ischemic cardiovascular disease is the leading cause of death worldwide. Current pharmacologic therapy has multiple limitations, and patients remain symptomatic despite maximal medical therapies. Deficiency or inhibition of thymidine phosphorylase (TYMP) in mice reduces thrombosis, suggesting that TYMP could be a novel therapeutic target for patients with acute myocardial infarction (AMI). Methods and Results A mouse AMI model was established by ligation of the left anterior descending coronary artery in C57BL/6J wild-type and TYMP-deficient (Tymp-/-) mice. Cardiac function was monitored by echocardiography or Langendorff assay. TYMP-deficient hearts had lower baseline contractility. However, cardiac function, systolic left ventricle anterior wall thickness, and diastolic wall strain were significantly greater 4 weeks after AMI compared with wild-type hearts. TYMP deficiency reduced microthrombus formation after AMI. TYMP deficiency did not affect angiogenesis in either normal or infarcted myocardium but increased arteriogenesis post-AMI. TYMP deficiency enhanced the mobilization of bone marrow stem cells and promoted mesenchymal stem cell (MSC) proliferation, migration, and resistance to inflammation and hypoxia. TYMP deficiency increased the number of larger MSCs and decreased matrix metalloproteinase-2 expression, resulting in a high homing capability. TYMP deficiency induced constitutive AKT phosphorylation in MSCs but reduced expression of genes associated with retinoid-interferon-induced mortality-19, a molecule that enhances cell death. Inhibition of TYMP with its selective inhibitor, tipiracil, phenocopied TYMP deficiency, improved post-AMI cardiac function and systolic left ventricle anterior wall thickness, attenuated diastolic stiffness, and reduced infarct size. Conclusions This study demonstrated that TYMP plays an adverse role after AMI. Targeting TYMP may be a novel therapy for patients with AMI.

Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts. Methods: Samples were collected from 9361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N=4256; ALSPAC, N=4622), and in TwinsUK only in November 2021-January 2022 (N=3575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection, and SARS-CoV-2 vaccination variables. Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had threefold greater odds of SARS-CoV-2 infection over the next 6-9 months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (two- to fourfold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies. Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC ([MC_PC_20030] and [MC_PC_20059]). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant [COV-LT-0009]). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: [217065/Z/19/Z]) and the University of Bristol provide core support for ALSPAC.

Vaccination against the virus that causes COVID-19 triggers the body to produce antibodies that help fight future infections. But some people generate more antibodies after vaccination than others. People with lower levels of antibodies are more likely to get COVID-19 in the future. Identifying people with low antibody levels after COVID-19 vaccination is important. It could help decide who receives priority for future vaccination. Previous studies show that people with certain health conditions produce fewer antibodies after one or two doses of a COVID-19 vaccine. For example, people with weakened immune systems. Now that third booster doses are available, it is vital to determine if they increase antibody levels for those most at risk of severe COVID-19. Cheetham et al. show that a third booster dose of a COVID-19 vaccine boosts antibodies to high levels in 90% of individuals, including those at increased risk. In the experiments, Cheetham et al. measured antibodies against the virus that causes COVID-19 in 9,361 individuals participating in two large long-term health studies in the United Kingdom. The experiments found that UK individuals advised to shield from the virus because they were at increased risk of complications had lower levels of antibodies after one or two vaccine doses than individuals without such risk factors. This difference was also seen after a third booster dose, but overall antibody levels had large increases. People who received the Oxford/AstraZeneca vaccine as their first dose also had lower antibody levels after one or two doses than those who received the Pfizer/BioNTech vaccine first. Positively, this difference in antibody levels was no longer seen after a third booster dose. Individuals with lower antibody levels after their first dose were also more likely to have a case of COVID-19 in the following months. Antibody levels were high in most individuals after the third dose. The results may help governments and public health officials identify individuals who may need extra protection after the first two vaccine doses. They also support current policies promoting booster doses of the vaccine and may support prioritizing booster doses for those at the highest risk from COVID-19 in future vaccination campaigns.

Characterising patterns of COVID-19 and long COVID symptoms: evidence from nine UK longitudinal studies.

Multiple studies across global populations have established the primary symptoms characterising Coronavirus Disease 2019 (COVID-19) and long COVID. However, as symptoms may also occur in the absence of COVID-19, a lack of appropriate controls has often meant that specificity of symptoms to acute COVID-19 or long COVID, and the extent and length of time for which they are elevated after COVID-19, could not be examined. We analysed individual symptom prevalences and characterised patterns of COVID-19 and long COVID symptoms across nine UK longitudinal studies, totalling over 42,000 participants. Conducting latent class analyses separately in three groups ('no COVID-19', 'COVID-19 in last 12 weeks', 'COVID-19 > 12 weeks ago'), the data did not support the presence of more than two distinct symptom patterns, representing high and low symptom burden, in each group. Comparing the high symptom burden classes between the 'COVID-19 in last 12 weeks' and 'no COVID-19' groups we identified symptoms characteristic of acute COVID-19, including loss of taste and smell, fatigue, cough, shortness of breath and muscle pains or aches. Comparing the high symptom burden classes between the 'COVID-19 > 12 weeks ago' and 'no COVID-19' groups we identified symptoms characteristic of long COVID, including fatigue, shortness of breath, muscle pain or aches, difficulty concentrating and chest tightness. The identified symptom patterns among individuals with COVID-19 > 12 weeks ago were strongly associated with self-reported length of time unable to function as normal due to COVID-19 symptoms, suggesting that the symptom pattern identified corresponds to long COVID. Building the evidence base regarding typical long COVID symptoms will improve diagnosis of this condition and the ability to elicit underlying biological mechanisms, leading to better patient access to treatment and services.

Changes in the adult consequences of adolescent mental ill-health: findings from the 1958 and 1970 British birth cohorts.

BACKGROUND: Adolescent mental health difficulties are increasing over time. However, it is not known whether their adulthood health and socio-economic sequelae are changing over time. METHODS: Participants (N = 31 349) are from two prospective national birth cohort studies: 1958 National Child Development Study (n = 16 091) and the 1970 British Cohort Study (n = 15 258). Adolescent mental health was operationalised both as traditional internalising and externalising factors and a hierarchical bi-factor. Associations between adolescent psychopathology and age 42 health and wellbeing (mental health, general health, life satisfaction), social (cohabitation, voting behaviour) and economic (education and employment) outcomes are estimated using linear and logistic multivariable regressions across cohorts, controlling for a wide range of early life potential confounding factors. RESULTS: The prevalence of adolescent mental health difficulties increased and their associations with midlife health, wellbeing, social and economic outcomes became more severe or remained similar between those born in 1958 and 1970. For instance, a stronger association with adolescent mental health difficulties was found for those born in 1970 for midlife psychological distress [odds ratio (OR) 1970 = 1.82 (1.65-1.99), OR 1958 = 1.60 (1.43-1.79)], cohabitation [OR 1970 = 0.64 (0.59-0.70), OR 1958 = 0.79 (0.72-0.87)], and professional occupations [OR 1970 = 0.75 (0.67-0.84), OR 1958 = 1.05 (0.88-1.24)]. The associations of externalising symptoms with later outcomes were mainly explained by their shared variance with internalising symptoms. CONCLUSION: The widening of mental health-based inequalities in midlife outcomes further supports the need to recognise that secular increases in adolescent mental health symptoms is a public health challenge with measurable negative consequences through the life-course. Increased public health efforts to minimise adverse outcomes are needed.

Use of δ18Oatm in dating a Tibetan ice core record of Holocene/Late Glacial climate.

Ice cores from the northwestern Tibetan Plateau (NWTP) contain long records of regional climate variability, but refrozen meltwater and dust in these cores has hampered development of robust timescales. Here, we introduce an approach to dating the ice via the isotopic composition of atmospheric O2 in air bubbles (δ18Oatm), along with annual layer counting and radiocarbon dating. We provide a robust chronology for water isotope records (δ18Oice and d-excess) from three ice cores from the Guliya ice cap in the NWTP. The measurement of δ18Oatm, although common in polar ice core timescales, has rarely been used on ice cores from low-latitude, high-altitude glaciers due to (1) low air pressure, (2) the common presence of refrozen melt that adds dissolved gases and reduces the amount of air available for analysis, and (3) the respiratory consumption of molecular oxygen (O2) by micro-organisms in the ice, which fractionates the δ18O of O2 from the atmospheric value. Here, we make corrections for melt and respiration to address these complications. The resulting records of water isotopes from the Guliya ice cores reveal climatic variations over the last 15,000 y, the timings of which correspond to those observed in independently dated lake and speleothem records and confirm that the Guliya ice cap existed before the Holocene. The millennial-scale drivers of δ18Oice are complex and temporally variable; however, Guliya δ18Oice values since the mid-20th century are the highest since the beginning of the Holocene and have increased with regional air temperature.

Inequalities in healthcare disruptions during the COVID-19 pandemic: evidence from 12 UK population-based longitudinal studies.

OBJECTIVES: We investigated associations between multiple sociodemographic characteristics (sex, age, occupational social class, education and ethnicity) and self-reported healthcare disruptions during the early stages of the COVID-19 pandemic. DESIGN: Coordinated analysis of prospective population surveys. SETTING: Community-dwelling participants in the UK between April 2020 and January 2021. PARTICIPANTS: Over 68 000 participants from 12 longitudinal studies. OUTCOMES: Self-reported healthcare disruption to medication access, procedures and appointments. RESULTS: Prevalence of healthcare disruption varied substantially across studies: between 6% and 32% reported any disruption, with 1%-10% experiencing disruptions in medication, 1%-17% experiencing disruption in procedures and 4%-28% experiencing disruption in clinical appointments. Females (OR 1.27; 95% CI 1.15 to 1.40; I2=54%), older persons (eg, OR 1.39; 95% CI 1.13 to 1.72; I2=77% for 65-75 years vs 45-54 years) and ethnic minorities (excluding white minorities) (OR 1.19; 95% CI 1.05 to 1.35; I2=0% vs white) were more likely to report healthcare disruptions. Those in a more disadvantaged social class were also more likely to report healthcare disruptions (eg, OR 1.17; 95% CI 1.08 to 1.27; I2=0% for manual/routine vs managerial/professional), but no clear differences were observed by education. We did not find evidence that these associations differed by shielding status. CONCLUSIONS: Healthcare disruptions during the COVID-19 pandemic could contribute to the maintenance or widening of existing health inequalities.

Psychological distress, depression, anxiety, and life satisfaction following COVID-19 infection: evidence from 11 UK longitudinal population studies.

BACKGROUND: Evidence on associations between COVID-19 illness and mental health is mixed. We aimed to examine whether COVID-19 is associated with deterioration in mental health while considering pre-pandemic mental health, time since infection, subgroup differences, and confirmation of infection via self-reported test and serology data. METHODS: We obtained data from 11 UK longitudinal studies with repeated measures of mental health (psychological distress, depression, anxiety, and life satisfaction; mental health scales were standardised within each study across time) and COVID-19 status between April, 2020, and April, 2021. We included participants with information available on at least one mental health outcome measure and self-reported COVID-19 status (suspected or test-confirmed) during the pandemic, and a subset with serology-confirmed COVID-19. Furthermore, only participants who had available data on a minimum set of covariates, including age, sex, and pre-pandemic mental health were included. We investigated associations between having ever had COVID-19 and mental health outcomes using generalised estimating equations. We examined whether associations varied by age, sex, ethnicity, education, and pre-pandemic mental health, whether the strength of the association varied according to time since infection, and whether associations differed between self-reported versus confirmed (by test or serology) infection. FINDINGS: Between 21 Dec, 2021, and July 11, 2022, we analysed data from 54 442 participants (ranging from a minimum age of 16 years in one study to a maximum category of 90 years and older in another; including 33 200 [61·0%] women and 21 242 [39·0%] men) from 11 longitudinal UK studies. Of 40 819 participants with available ethnicity data, 36 802 (90·2%) were White. Pooled estimates of standardised differences in outcomes suggested associations between COVID-19 and subsequent psychological distress (0·10 [95% CI 0·06 to 0·13], I2=42·8%), depression (0·08 [0·05 to 0·10], I2=20·8%), anxiety (0·08 [0·05 to 0·10], I2=0·0%), and lower life satisfaction (-0·06 [-0·08 to -0·04], I2=29·2%). We found no evidence of interactions between COVID-19 and sex, education, ethnicity, or pre-pandemic mental health. Associations did not vary substantially between time since infection of less than 4 weeks, 4-12 weeks, and more than 12 weeks, and were present in all age groups, with some evidence of stronger effects in those aged 50 years and older. Participants who self-reported COVID-19 but had negative serology had worse mental health outcomes for all measures than those without COVID-19 based on serology and self-report. Participants who had positive serology but did not self-report COVID-19 did not show association with mental health outcomes. INTERPRETATION: Self-reporting COVID-19 was longitudinally associated with deterioration in mental health and life satisfaction. Our findings emphasise the need for greater post-infection mental health service provision, given the substantial prevalence of COVID-19 in the UK and worldwide. FUNDING: UK Medical Research Council and UK National Institute for Health and Care Research.

The mental health burden of racial and ethnic minorities during the COVID-19 pandemic.

Racial/ethnic minorities have been disproportionately impacted by COVID-19. The effects of COVID-19 on the long-term mental health of minorities remains unclear. To evaluate differences in odds of screening positive for depression and anxiety among various racial and ethnic groups during the latter phase of the COVID-19 pandemic, we performed a cross-sectional analysis of 691,473 participants nested within the prospective smartphone-based COVID Symptom Study in the United States (U.S.) and United Kingdom (U.K). from February 23, 2021 to June 9, 2021. In the U.S. (n=57,187), compared to White participants, the multivariable odds ratios (ORs) for screening positive for depression were 1·16 (95% CI: 1·02 to 1·31) for Black, 1·23 (1·11 to 1·36) for Hispanic, and 1·15 (1·02 to 1·30) for Asian participants, and 1·34 (1·13 to 1·59) for participants reporting more than one race/other even after accounting for personal factors such as prior history of a mental health disorder, COVID-19 infection status, and surrounding lockdown stringency. Rates of screening positive for anxiety were comparable. In the U.K. (n=643,286), racial/ethnic minorities had similarly elevated rates of positive screening for depression and anxiety. These disparities were not fully explained by changes in leisure time activities. Racial/ethnic minorities bore a disproportionate mental health burden during the COVID-19 pandemic. These differences will need to be considered as health care systems transition from prioritizing infection control to mitigating long-term consequences.

Life course trajectories of affective symptoms and their early life predictors.

Background: Life course trajectories of affective symptoms (depression and anxiety) are heterogenous. However, few studies have investigated the role of early life risk factors in the development of these trajectories. The present study aimed to: (1) derive latent trajectories of affective symptoms over a period of more than 50 years (ages 13-69), and (2) examine early life risk factors for associations with specific life course trajectories of affective symptoms. Method: Participants are from the MRC National Survey of Health and Development (NSHD) (n = 5,362). Affective symptoms were measured prospectively at ages 13, 15, 36, 43, 53, 60-64 and 69. A latent variable modelling framework was implemented to model longitudinal profiles of affective symptoms. Twenty-four prospectively measured early life predictors were tested for associations with different symptom profiles using multinomial logistic regression. Results: Four life course profiles of affective symptoms were identified: (1) absence of symptoms (66.6% of the sample); (2) adolescent symptoms with good adult outcome (15.2%); (3) adult symptoms only (with no symptoms in adolescence and late life) (12.9%); (4) symptoms in adolescence and mid adulthood (5.2%). Of the 24 early life predictors observed, only four were associated with life course trajectories, with small effect sizes observed. Conclusions: People differ in their life course trajectories of anxiety and depression symptoms and that these differences are not largely influenced by early life factors tested in this study.

Mental and social wellbeing and the UK coronavirus job retention scheme: Evidence from nine longitudinal studies.

BACKGROUND: The COVID-19 pandemic has led to major economic disruptions. In March 2020, the UK implemented the Coronavirus Job Retention Scheme - known as furlough - to minimize the impact of job losses. We investigate associations between change in employment status and mental and social wellbeing during the early stages of the pandemic. METHODS: Data were from 25,670 respondents, aged 17-66, across nine UK longitudinal studies. Furlough and other employment changes were defined using employment status pre-pandemic and during the first lockdown (April-June 2020). Mental and social wellbeing outcomes included psychological distress, life satisfaction, self-rated health, social contact, and loneliness. Study-specific modified Poisson regression estimates, adjusting for socio-demographic characteristics and pre-pandemic mental and social wellbeing, were pooled using meta-analysis. Associations were also stratified by sex, age, education, and household composition. RESULTS: Compared to those who remained working, furloughed workers were at greater risk of psychological distress (adjusted risk ratio, ARR = 1.12; 95%CI: 0.97, 1.29), low life satisfaction (ARR = 1.14; 95%CI: 1.07, 1.22), loneliness (ARR = 1.12; 95%CI: 1.01, 1.23), and poor self-rated health (ARR = 1.26; 95%CI: 1.05, 1.50). Nevertheless, compared to furloughed workers, those who became unemployed had greater risk of psychological distress (ARR = 1.30; 95%CI: 1.12, 1.52), low life satisfaction (ARR = 1.16; 95%CI: 0.98, 1.38), and loneliness (ARR = 1.67; 95%CI: 1.08, 2.59). Effects were not uniform across all sub-groups. CONCLUSIONS: During the early stages of the pandemic, those furloughed had increased risk of poor mental and social wellbeing, but furloughed workers fared better than those who became unemployed, suggesting that furlough may have partly mitigated poorer outcomes.

Biomarker panel for early screening of trastuzumab -induced cardiotoxicity among breast cancer patients in west virginia.

Cardiotoxicity is a well-known pathophysiological consequence in breast cancer patients receiving trastuzumab. Trastuzumab related cardiotoxicity typically results in an overall decline in cardiac function, primarily characterized by reduction in left ventricular ejection fraction (LVEF) and development of symptoms associated with heart failure. Current strategies for the monitoring of cardiac function, during trastuzumab therapy, includes serial echocardiography, which is cost ineffective as well as offers limited specificity, while offering limited potential in monitoring early onset of cardiotoxicity. However, biomarkers have been shown to be aberrant prior to any detectable functional or clinical deficit in cardiac function. Hence, this study aims to develop a panel of novel biomarkers and circulating miRNAs for the early screening of trastuzumab induced cardiotoxicity. Patients with clinical diagnosis of invasive ductal carcinoma were enrolled in the study, with blood specimen collected and echocardiography performed prior to trastuzumab therapy initiation at baseline, 3- and 6-months post trastuzumab therapy. Following 6-months of trastuzumab therapy, about 18% of the subjects developed cardiotoxicity, as defined by reduction in LVEF. Our results showed significant upregulation of biomarkers and circulating miRNAs, specific to cardiac injury and remodeling, at 3- and 6-months post trastuzumab therapy. These biomarkers and circulating miRNAs significantly correlated with the cardiac injury specific markers, troponin I and T. The findings in the present study demonstrates the translational applicability of the proposed biomarker panel in early preclinical diagnosis of trastuzumab induced cardiotoxicity, further allowing management of cardiac function decline and improved health outcomes for breast cancer patients.

Steep rise in drug use-associated infective endocarditis in West Virginia: Characteristics and healthcare utilization.

INTRODUCTION: Life-threatening infections such as infective endocarditis (IE) are increasing simultaneously with the injection drug use epidemic in West Virginia (WV). We utilized a newly developed, statewide database to describe epidemiologic characteristics and healthcare utilization among patients with (DU-IE) and without (non-DU-IE) drug use-associated IE in WV over five years. MATERIALS AND METHODS: This retrospective, observational study, incorporating manual review of electronic medical records, included all patients aged 18-90 years who had their first admission for IE in any of the four university-affiliated referral hospitals in WV during 2014-2018. IE was identified using ICD-10-CM codes and confirmed by chart review. Demographics, clinical characteristics, and healthcare utilization were compared between patients with DU-IE and non-DU-IE using Chi-square/Fisher's exact test or Wilcoxon rank sum test. Multivariable logistic regression analysis was conducted with discharge against medical advice/in-hospital mortality vs. discharge alive as the outcome variable and drug use as the predictor variable. RESULTS: Overall 780 unique patients had confirmed first IE admission, with a six-fold increase during study period (p = .004). Most patients (70.9%) had used drugs before hospital admission, primarily by injection. Compared to patients with non-DU-IE, patients with DU-IE were significantly younger (median age: 33.9 vs. 64.1 years; p < .001); were hospitalized longer (median: 25.5 vs. 15 days; p < .001); had a higher proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates (42.7% vs. 29.9%; p < .001), psychiatric disorders (51.2% vs. 17.3%; p < .001), cardiac surgeries (42.9% vs. 26.6%; p < .001), and discharges against medical advice (19.9% vs. 1.4%; p < .001). Multivariable regression analysis showed drug use was an independent predictor of the combined outcome of discharge against medical advice/in-hospital mortality (OR: 2.99; 95% CI: 1.67-5.64). DISCUSSION AND CONCLUSION: This multisite study reveals a 681% increase in IE admissions in WV over five years primarily attributable to injection drug use, underscoring the urgent need for both prevention efforts and specialized strategies to improve outcomes.

Sex Differences in Characteristics of Patients with Infective Endocarditis: A Multicenter Study.

Infectious diseases like infective endocarditis (IE) may manifest or progress differently between sexes. This study sought to identify the differences in demographic and clinical characteristics among male and female patients with IE. Data were obtained from a newly developed registry comprising all adult patients with first IE admission at the four major tertiary cardiovascular centers in West Virginia, USA during 2014−2018. Patient characteristics were compared between males and females using Chi-square test, Fisher's exact test, and Wilcoxon rank-sum test. A secondary analysis was restricted to IE patients with drug use only. Among 780 unique patients (390 males, 390 females), significantly more women (a) were younger than males (median age 34.9 vs. 41.4, p < 0.001); (b) reported drug use (77.7% vs. 64.1%, p < 0.001); (c) had tricuspid valve endocarditis (46.4% vs. 30.8%, p < 0.001); and (d) were discharged against medical advice (20% vs. 9.5%, p < 0.001). These differences persisted even within the subgroup of patients with drug use-associated IE. In a state with one of the highest incidences of drug use and overdose deaths, the significantly higher incident IE cases in younger women and higher proportion of women leaving treatment against medical advice are striking. Differential characteristics between male and female patients are important to inform strategies for specialized treatment and care.