Healthcare in England was affected by the COVID-19 pandemic across the pancreatic cancer pathway: A cohort study using OpenSAFELY-TPP.

Background: Healthcare across all sectors, in the UK and globally, was negatively affected by the COVID-19 pandemic. We analysed healthcare services delivered to people with pancreatic cancer from January 2015 to March 2023 to investigate the effect of the COVID-19 pandemic. Methods: With the approval of NHS England, and drawing from a nationally representative OpenSAFELY-TPP dataset of 24 million patients (over 40% of the English population), we undertook a cohort study of people diagnosed with pancreatic cancer. We queried electronic healthcare records for information on the provision of healthcare services across the pancreatic cancer pathway. To estimate the effect of the COVID-19 pandemic, we predicted the rates of healthcare services if the pandemic had not happened. We used generalised linear models and the pre-pandemic data from January 2015 to February 2020 to predict rates in March 2020 to March 2023. The 95% confidence intervals of the predicted values were used to estimate the significance of the difference between the predicted and observed rates. Results: The rate of pancreatic cancer and diabetes diagnoses in the cohort was not affected by the pandemic. There were 26,840 people diagnosed with pancreatic cancer from January 2015 to March 2023. The mean age at diagnosis was 72 (±11 SD), 48% of people were female, 95% were of White ethnicity, and 40% were diagnosed with diabetes. We found a reduction in surgical resections by 25-28% during the pandemic. In addition, 20%, 10%, and 4% fewer people received body mass index, glycated haemoglobin, and liver function tests, respectively, before they were diagnosed with pancreatic cancer. There was no impact of the pandemic on the number of people making contact with primary care, but the number of contacts increased on average by 1-2 per person amongst those who made contact. Reporting of jaundice decreased by 28%, but recovered within 12 months into the pandemic. Emergency department visits, hospital admissions, and deaths were not affected. Conclusions: The pandemic affected healthcare in England across the pancreatic cancer pathway. Positive lessons could be learnt from the services that were resilient and those that recovered quickly. The reductions in healthcare experienced by people with cancer have the potential to lead to worse outcomes. Current efforts should focus on addressing the unmet needs of people with cancer. Funding: This work was jointly funded by the Wellcome Trust (222097/Z/20/Z); MRC (MR/V015757/1, MC_PC-20059, MR/W016729/1); NIHR (NIHR135559, COV-LT2-0073), and Health Data Research UK (HDRUK2021.000, 2021.0157). This work was funded by Medical Research Council (MRC) grant reference MR/W021390/1 as part of the postdoctoral fellowship awarded to AL and undertaken at the Bennett Institute, University of Oxford. The views expressed are those of the authors and not necessarily those of the NIHR, NHS England, UK Health Security Agency (UKHSA), or the Department of Health and Social Care. Funders had no role in the study design, collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study.

BACKGROUND: Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population. METHODS: In this population-based study, we examined multimorbidity and comorbidity patterns stratified by ethnicity or race, sex, and age for 308 health conditions using electronic health records from individuals included on the Clinical Practice Research Datalink linked with the Hospital Episode Statistics admitted patient care dataset in England. We included individuals who were older than 1 year and who had been registered for at least 1 year in a participating general practice during the study period (between April 1, 2010, and March 31, 2015). We identified the most common combinations of conditions and comorbidities for index conditions. We defined comorbidity as the accumulation of additional conditions to an index condition over an individual's lifetime. We used network analysis to identify conditions that co-occurred more often than expected by chance. We developed online interactive tools to explore multimorbidity and comorbidity patterns overall and by subgroup based on ethnicity, sex, and age. FINDINGS: We collected data for 3 872 451 eligible patients, of whom 1 955 700 (50·5%) were women and girls, 1 916 751 (49·5%) were men and boys, 2 666 234 (68·9%) were White, 155 435 (4·0%) were south Asian, and 98 815 (2·6%) were Black. We found that a higher proportion of boys aged 1-9 years (132 506 [47·8%] of 277 158) had two or more diagnosed conditions than did girls in the same age group (106 982 [40·3%] of 265 179), but more women and girls were diagnosed with multimorbidity than were boys aged 10 years and older and men (1 361 232 [80·5%] of 1 690 521 vs 1 161 308 [70·8%] of 1 639 593). White individuals (2 097 536 [78·7%] of 2 666 234) were more likely to be diagnosed with two or more conditions than were Black (59 339 [60·1%] of 98 815) or south Asian individuals (93 617 [60·2%] of 155 435). Depression commonly co-occurred with anxiety, migraine, obesity, atopic conditions, deafness, soft-tissue disorders, and gastrointestinal disorders across all subgroups. Heart failure often co-occurred with hypertension, atrial fibrillation, osteoarthritis, stable angina, myocardial infarction, chronic kidney disease, type 2 diabetes, and chronic obstructive pulmonary disease. Spinal fractures were most strongly non-randomly associated with malignancy in Black individuals, but with osteoporosis in White individuals. Hypertension was most strongly associated with kidney disorders in those aged 20-29 years, but with dyslipidaemia, obesity, and type 2 diabetes in individuals aged 40 years and older. Breast cancer was associated with different comorbidities in individuals from different ethnic groups. Asthma was associated with different comorbidities between males and females. Bipolar disorder was associated with different comorbidities in younger age groups compared with older age groups. INTERPRETATION: Our findings and interactive online tools are a resource for: patients and their clinicians, to prevent and detect comorbid conditions; research funders and policy makers, to redesign service provision, training priorities, and guideline development; and biomedical researchers and manufacturers of medicines, to provide leads for research into common or sequential pathways of disease and inform the design of clinical trials. FUNDING: UK Research and Innovation, Medical Research Council, National Institute for Health and Care Research, Department of Health and Social Care, Wellcome Trust, British Heart Foundation, and The Alan Turing Institute.

Ethnic and Sexual Identity-Related Inequalities in Adolescent Health and Well-Being in a National Population-Based Study.

Purpose: This study employed an intersectional framework to examine impact of inequalities related to sexual minority (SM) and ethnic minority (EM) identities in risk for health, well-being, and health-related behaviors in a nationally representative sample. Methods: Participants included 9789 (51% female) adolescents aged 17 years from the U.K.-wide Millennium Cohort Study, with data on self-identified sexual and ethnic identities. Adolescents were grouped into White heterosexual, White-SM, EM-heterosexual, and EM-SM categories. Questionnaires assessed mental health (e.g., self-reported psychological distress, doctor-diagnosed depression, attempted suicide), general health (self-rated health, chronic illness, body mass index), and health-related behaviors (e.g., smoking, substance use). Associations were analyzed using multivariable logistic regression. Results: SM individuals (White: 18% and EM: 3%) had increased odds for mental health difficulties and attempted suicide, with higher odds for White-SM individuals than for EM-SM individuals. Compared with White heterosexual individuals, White-SM and EM-SM individuals had higher risk for psychological distress (adjusted odds ratios [OR] 3.47/2.24 for White-SM/EM-SM, respectively) and emotional symptoms (OR 3.17/1.65). They had higher odds for attempted suicide (OR 2.78/2.02), self-harm (OR 3.06/1.52), and poor sleep quality (OR 1.88/1.67). In contrast, the White heterosexual and White-SM groups had similarly high proportions reporting risky behaviors except for drug use (OR 1.45) and risky sex (OR 1.40), which were more common in White-SM individuals. EM-heterosexual and EM-SM individuals had decreased odds for health-related behaviors. Conclusion: SM (White and EM) individuals had substantially worse mental health compared with heterosexual peers. Adverse health-related behaviors were more common in White-SM individuals. Investigation into the mechanisms leading to these differences is needed.

The UK Coronavirus Job Retention Scheme and smoking, alcohol consumption and vaping during the COVID-19 pandemic: evidence from eight longitudinal population surveys.

BACKGROUND: Employment disruptions can impact smoking and alcohol consumption. During the COVID-19 pandemic, many countries implemented furlough schemes to prevent job loss. We examine how furlough was associated with smoking, vaping and alcohol consumption in the UK. METHODS: Data from 27,841 participants in eight UK adult longitudinal surveys were analysed. Participants self-reported employment status and current smoking, current vaping and alcohol consumption (>4 days/week or 5+ drinks per typical occasion) both before and during the early stages of the pandemic (April-July 2020). Risk ratios were estimated within each study using modified Poisson regression, adjusting for a range of potential confounders, including pre-pandemic behaviour. Findings were synthesised using random effects meta-analysis. RESULTS: Compared to stable employment and after adjustment for pre-pandemic characteristics, furlough was not associated with smoking (ARR = 1.05; 95% CI: 0.95-1.16; I2: 10%), vaping (ARR = 0.89; 95% CI: 0.74-1.08; I2: 0%) or drinking (ARR = 1.03; 95% CI: 0.94-1.13; I2: 48%). There were similar findings for no longer being employed, and stable unemployment, though this varied by sex: stable unemployment was associated with smoking for women (ARR = 1.35; 95% CI: 1.00-1.82; I2: 47%) but not men (0.84; 95% CI: 0.67-1.05; I2: 0%). No longer being employed was associated with vaping among women (ARR = 2.74; 95% CI: 1.59-4.72; I2: 0%) but not men (ARR = 1.25; 95% CI: 0.83-1.87; I2: 0%). CONCLUSIONS: We found no clear evidence of furlough or unemployment having adverse impacts on smoking, vaping or drinking behaviours during the early stages of the COVID-19 pandemic in the UK. Differences in risk compared to those who remained employed were largely explained by pre-pandemic characteristics.

The UK Coronavirus Job Retention Scheme and diet, physical activity, and sleep during the COVID-19 pandemic: evidence from eight longitudinal population surveys.

BACKGROUND: In March 2020, the UK implemented the Coronavirus Job Retention Scheme (furlough) to minimise job losses. Our aim was to investigate associations between furlough and diet, physical activity, and sleep during the early stages of the COVID-19 pandemic. METHODS: We analysed data on 25,092 participants aged 16-66 years from eight UK longitudinal studies. Changes in employment, including being furloughed, were based on employment status before and during the first lockdown. Health behaviours included fruit and vegetable consumption, physical activity, and sleep. Study-specific estimates obtained using modified Poisson regression, adjusting for socio-demographic characteristics and pre-pandemic health and health behaviours, were statistically pooled using random effects meta-analysis. Associations were also stratified by sex, age, and education. RESULTS: Across studies, between 8 and 25% of participants were furloughed. Compared to those who remained working, furloughed workers were slightly less likely to be physically inactive (RR = 0.85; [95% CI 0.75-0.97]; I 2 = 59%) and did not differ overall with respect to low fruit and vegetable consumption or atypical sleep, although findings for sleep were heterogenous (I 2 = 85%). In stratified analyses, furlough was associated with lower fruit and vegetable consumption among males (RR = 1.11; [1.01-1.22]; I 2 = 0%) but not females (RR = 0.84; [0.68-1.04]; I 2 = 65%). Considering changes in quantity, furloughed workers were more likely than those who remained working to report increases in fruit and vegetable consumption, exercise, and hours of sleep. CONCLUSIONS: Those furloughed exhibited similar health behaviours to those who remained in employment during the initial stages of the pandemic. There was little evidence to suggest that adoption of such social protection policies in the post-pandemic recovery period and during future economic crises had adverse effects on population health behaviours.

Sex and dependence related neuroanatomical differences in regular cannabis users: findings from the ENIGMA Addiction Working Group.

Males and females show different patterns of cannabis use and related psychosocial outcomes. However, the neuroanatomical substrates underlying such differences are poorly understood. The aim of this study was to map sex differences in the neurobiology (as indexed by brain volumes) of dependent and recreational cannabis use. We compared the volume of a priori regions of interest (i.e., amygdala, hippocampus, nucleus accumbens, insula, orbitofrontal cortex (OFC), anterior cingulate cortex and cerebellum) between 129 regular cannabis users (of whom 70 were recreational users and 59 cannabis dependent) and 114 controls recruited from the ENIGMA Addiction Working Group, accounting for intracranial volume, age, IQ, and alcohol and tobacco use. Dependent cannabis users, particularly females, had (marginally significant) smaller volumes of the lateral OFC and cerebellar white matter than recreational users and controls. In dependent (but not recreational) cannabis users, there was a significant association between female sex and smaller volumes of the cerebellar white matter and OFC. Volume of the OFC was also predicted by monthly standard drinks. No significant effects emerged the other brain regions of interest. Our findings warrant future multimodal studies that examine if sex and cannabis dependence are specific key drivers of neurobiological alterations in cannabis users. This, in turn, could help to identify neural pathways specifically involved in vulnerable cannabis users (e.g., females with cannabis dependence) and inform individually tailored neurobiological targets for treatment.

Impact of lockdown on key workers: findings from the COVID-19 survey in four UK national longitudinal studies.

BACKGROUND: Key workers played a pivotal role during the national lockdown in the UK's response to the COVID-19 pandemic. Although protective measures have been taken, the impact of the pandemic on key workers is yet to be fully elucidated. METHODS: Participants were from four longitudinal age-homogeneous British cohorts (born in 2001, 1990, 1970 and 1958). A web-based survey provided outcome data during the first UK national lockdown (May 2020) on COVID-19 infection status, changes in financial situation, trust in government, conflict with people around, household composition, psychological distress, alcohol consumption, smoking and sleep duration. Generalised linear models with logit link assessed the association between being a key worker and the above outcomes. Adjustment was made for cohort design, non-response, sex, ethnicity, adult socioeconomic position (SEP), childhood SEP, the presence of a chronic illness and receipt of a shielding letter. Meta-analyses were performed across the cohorts. FINDINGS: 13 736 participants were included. During lockdown, being a key worker was associated with increased chances of being infected with COVID-19 (OR 1.43, 95% CI 1.22 to 1.68) and experiencing conflict with people around (OR 1.19, 95% CI 1.03 to 1.37). However, key workers were less likely to be worse off financially (OR 0.32, 95% CI 0.24 to 0.65), to consume more alcohol (OR 0.88, 95% CI 0.79 to 0.98) or to smoke more (OR 0.60, 95% CI 0.44 to 0.80) during lockdown. Interestingly, being a key worker was not associated with psychological distress (OR 0.95, 95% CI 0.85 to 1.05). INTERPRETATION: Being a key worker during the first UK COVID-19 lockdown was a double-edged sword, with both benefits and downsides. The UK government had the basic duty to protect its key workers from SARS-CoV-2 infection, but it may have failed to do so, and there is an urgent need to rectify this in light of the ongoing third wave.

Associations Between Adolescent Mental Health and Health-Related Behaviors in 2005 and 2015: A Population Cross-Cohort Study.

PURPOSE: Adolescent mental ill-health is a growing concern. There is little understanding of changes over time in the associations between mental health and health-related behaviors and outcomes (such as substance use, antisocial behavior, and obesity). We investigate whether the associations between different health and health-related outcomes in adolescence are changing over time in two recent cohorts of adolescents born 10 years apart. METHODS: Data from two UK birth cohort studies, the Avon Longitudinal Study of Parents and Children (ALSPAC, born 1991-92, N = 5,627, 50.7% female) and Millennium Cohort Study (MCS, born 2000-2, N = 11,318, 50.6% female) at age 14 are analyzed. The health outcomes of focus are depressive symptoms, substance use (alcohol, smoking, cannabis, and other drugs), antisocial behaviors (assault, graffiti, vandalism, shoplifting and rowdy behavior), weight (body mass index [BMI]), weight perception (perceive self as overweight), and sexual activity (had sexual intercourse). Regression analyses are conducted to examine associations between these variables with cohort as a moderator to examine cohort differences. RESULTS: The directions of associations between mental-health and health-related behaviors (e.g., smoking) are similar over time; however, their strength across the distribution has changed. While smoking and alcohol use behaviors are decreasing in adolescents, those that endorse these behaviors in 2015 are more likely to have co-occurring mental ill-health than those born in 2005. Similarly, higher BMI is more strongly associated with depressive symptoms in 2015 compared to 2005. CONCLUSIONS: Adverse health-related outcomes such as greater substance use, mental health difficulties, and higher BMI appear to be more likely to cluster together in the more recent cohort, with implications for public health planning, service provision, and lifelong disease burden.

Mental health, social adversity, and health-related outcomes in sexual minority adolescents: a contemporary national cohort study.

BACKGROUND: Sexual minority adolescents are more likely to have mental health problems, adverse social environments, and negative health outcomes compared with their heterosexual counterparts. There is a paucity of up-to-date population-level estimates of the extent of risk across these domains in the UK. We analysed outcomes across mental health, social environment, and health-related domains in sexual minority adolescents compared with their heterosexual counterparts in a large, contemporary national cohort. METHODS: The Millennium Cohort Study (MCS) is a birth cohort study in the UK following up children born between Sept 1, 2000, and Jan 11, 2002 across England, Wales, Scotland, and Northern Ireland. Children recruited from the MCS have been followed up over six recruitment sweeps to date at ages 9 months, 3 years, 5 years, 7 years, 11 years, and 14 years. We analysed mental health, social, and health-related outcomes in sexual minority versus heterosexual adolescents at age 14 years. Additionally, we estimated the accumulation of multiple adverse outcomes in both groups. The primary aim of the study was to assess whether sexual minority adolescents experienced more adverse outcomes than heterosexual adolescents. FINDINGS: Between January, 2015, and April, 2016, 9885 adolescents provided a response about their sexual attraction. 629 (6%) of 9885 adolescents (481 female participants and 148 male participants) were identified as sexual minorities. 9256 (94%) of 9885 participants (4431 female and 4825 male) were attracted to the opposite sex or not attracted to the same sex and identified as heterosexual. Sexual minority adolescents were more likely to experience high depressive symptoms (odds ratio [OR] 5·43, 95% CI 4·32-6·83; p<0·0001), self-harm (5·80, 4·55-7·41; p<0·0001), lower life satisfaction (3·66, 2·92-4·58; p<0·0001), lower self-esteem (ß 1·83, 95% CI 1·47-2·19; p<0·0001), and all forms of bullying and victimisation. Sexual minorities were more likely to have tried alcohol (OR 1·85, 95% CI 1·47-2·33; p<0·0001), smoking (2·41, 1·92 -3·03; p<0·0001), and cannabis (3·22, 2·24-4·61; p<0·0001), and also had increased odds of being less physically active (ß 0·36, 95% CI 0·25-0·46; p<0·0001), perceiving themselves as overweight (OR 1·73, 95% CI 1·40-2·14; p<0·0001), and dieting to lose weight (1·98, 1·58-2·48; p<0·0001). Sexual minority adolescents had more co-occurring mental health outcomes (mean 1·43 of 3 outcomes, 95% CI 1·34-1·52) compared with heterosexual adolescents (0·40 of 3 outcomes, 0·38-0·41), and more total cumulative difficulties (mean 9·43 of 28 outcomes, 95% CI 9·09-9·76 in sexual minority adolescents vs 6·16 of 28 outcomes, 6·08-6·23 in heterosexual adolescents). INTERPRETATION: Sexual minority adolescents in the UK experience disparities in mental health, social, and health-related outcomes despite living in a time of substantial progress in rights for sexual minorities. These adverse outcomes co-occur, with implications for lifelong health and social outcomes. Health and educational practitioners should be aware of the increased risk for adverse outcomes in sexual minority adolescents. FUNDING: None.

Changes in millennial adolescent mental health and health-related behaviours over 10 years: a population cohort comparison study.

BACKGROUND: There is evidence that mental health problems are increasing and substance use behaviours are decreasing. This paper aimed to investigate recent trends in mental ill health and health-related behaviours in two cohorts of UK adolescents in 2005 and 2015. METHODS: Prevalences in mental health (depressive symptoms, self-harm, anti-social behaviours, parent-reported difficulties) and health-related behaviours (substance use, weight, weight perception, sleep, sexual intercourse) were examined at age 14 in two UK birth cohorts; Avon Longitudinal Study of Parents and Children (ALSPAC, N = 5627, born 1991-92) and Millennium Cohort Study (MCS, N = 11 318, born 2000-02). Prevalences and trend estimates are presented unadjusted and using propensity score matching and entropy balancing to account for differences between samples. RESULTS: Depressive symptoms (9% to 14.8%) and self-harm (11.8% to 14.4%) were higher in 2015 compared with 2005. Parent-reported emotional difficulties, conduct problems, hyperactivity and peer problems were higher in 2015 compared with 2005 (5.7-8.9% to 9.7-17.7%). Conversely, substance use (tried smoking, 9.2% to 2.9%; tried alcohol, 52.1% to 43.5%, cannabis, 4.6% to 3.9%), sexual activity (2% to 0.9%) and anti-social behaviours (6.2-40.1% to 1.6-27.7%) were less common or no different. Adolescents in 2015 were spending less time sleeping (<8 h 5.7% to 11.5%), had higher body mass index (BMI) (obese, 3.8% to 7.3%) and a greater proportion perceived themselves as overweight (26.5% to 32.9%). The findings should be interpreted bearing in mind limitations in ability to adequately harmonize certain variables and account for differences in attrition rates and generalizability of the two cohorts. CONCLUSIONS: Given health-related behaviours are often cited as risk factors for poor mental health, our findings suggest relationships between these factors might be more complex and dynamic in nature than currently understood. Substantial increases in mental health difficulties, BMI and poor sleep-related behaviours highlight an increasing public health challenge.

BMI Development and Early Adolescent Psychosocial Well-Being: UK Millennium Cohort Study.

BACKGROUND AND OBJECTIVES: The underlying influences on different patterns of BMI development are not well understood, and psychosocial outcomes linked to BMI development have been little investigated. Objectives were to identify BMI developmental trajectories across the first decade of life, examine early life predictors of trajectory membership, and investigate whether being on a particular BMI trajectory is associated with markers of psychosocial well-being. METHODS: We used latent class analysis to derive BMI trajectories by using data collected at ages 3, 5, 7, and 11 years on 16 936 participants from the Millennium Cohort Study. Regression models were used to estimate predictors of BMI trajectory membership and their psychosocial correlates. RESULTS: Four trajectories were identified: 83.8% had an average "stable" nonoverweight BMI, 0.6% were in a "decreasing" group, 13.1% had "moderate increasing" BMIs, and 2.5% had "high increasing" BMIs. Predictors of "moderate" and "high" increasing group membership were smoking in pregnancy (odds ratios [ORs] = 1.17 and 1.97, respectively), maternal BMI (ORs = 1.10 and 1.14), skipping breakfast (ORs = 1.66 and 1.76), nonregular bedtimes (ORs = 1.22 and 1.55). Children in the "moderate" and "high" increasing groups had worse scores for emotional symptoms, peer problems, happiness, body satisfaction, and self-esteem, and those in the "high increasing" group were more likely to have tried alcohol and cigarettes. CONCLUSIONS: Several potentially modifiable early life factors including smoking in pregnancy, skipping breakfast, and bedtime routines were important predictors of BMI development in the overweight and obese range, and high BMI growth was linked to worse psychosocial well-being.

School-level variation in health outcomes in adolescence: analysis of three longitudinal studies in England.

School factors are associated with many health outcomes in adolescence. However, previous studies report inconsistent findings regarding the degree of school-level variation for health outcomes, particularly for risk behaviours. This study uses data from three large longitudinal studies in England to investigate school-level variation in a range of health indicators. Participants were drawn from the Longitudinal Study of Young People in England, the Me and My School Study and the Research with East London Adolescent Community Health Survey. Outcome variables included risk behaviours (smoking, alcohol/cannabis use, sexual behaviour), behavioural difficulties and victimisation, obesity and physical activity, mental and emotional health, and educational attainment. Multi-level models were used to calculate the proportion of variance in outcomes explained at school level, expressed as intraclass correlations (ICCs) adjusted for gender, ethnicity and socio-economic status of the participants. ICCs for health outcomes ranged from nearly nil to .28 and were almost uniformly lower than for attainment (.17-.23). Most adjusted ICCs were smaller than unadjusted values, suggesting that school-level variation partly reflects differences in pupil demographics. School-level variation was highest for risk behaviours. ICCs were largely comparable across datasets, as well as across years within datasets, suggesting that school-level variation in health remains fairly constant across adolescence. School-level variation in health outcomes remains significant after adjustment for individual demographic differences between schools, confirming likely effects for school environment. Variance is highest for risk behaviours, supporting the utility of school environment interventions for these outcomes.