UK Cohort Research Articles

Physical Activity And All-cause Mortality In Type 2 Diabetes: A Cross-country Comparison

The main physical activity recommendation (i.e. 150-300 minutes of moderate intensity activity (MVPA) per week) for individuals with type 2 diabetes (T2D) is identical to the general adult recommendation despite substantially less evidence for the recommendation aimed at those living with chronic conditions. PURPOSE: To examine the dose-response associations between leisure-time physical activity (LTPA) and risk of death in individuals with prevalent T2D; and to compare the magnitude of this association between the UK and China. METHODS: Individuals with prevalent T2D in the UK Biobank (UKB) and China Kadoorie Biobank (CKB) prospective cohort studies. Deaths were obtained from registries. Self-reported leisure-time physical activity was categorized as ‘no activity’ (reference), and activity ‘below’ (1-149 min of MVPA/week), ’meeting’ (150-300 min MVPA/w), or ‘above’ (>300 min of MVPA/w) the physical activity recommendations. Individuals with prevalent diseases were excluded. Associations with all-cause mortality were determined using multivariable-adjusted cox proportional hazard regression models. The continuous dose-response pattern was modelled using restricted cubic splines. RESULTS: We included 14,876 (mean (SD) age: 59.5 (7.2) years) and 17,459 (57.7 (9.7) years) men and women with T2D from UKB and CKB, respectively. During a median of 11.3 and 9.7 years of follow-up, 1227 (UKB) and 2351 (CKB) deaths were recorded. In UKB, Hazard ratios were 0.95 (95%CI 0.78, 1.15), 0.88 (0.70, 1.09) and 0.81 (0.66, 1.00) ‘below’, ’meeting’, and ‘above’ physical activity recommendations, respectively. The same contrasts yielded similar magnitude of associations in CKB; 0.87 (0.68, 1.09), 0.88 (0.75, 1.04) and 0.77 (0.70, 0.85). The continuous dose-response analysis did not support an optimal threshold or point of no added benefit in UKB (p-values for non-linearity 0.78), but no further risk reduction was observed above 600 min of MVPA/w in CKB (p-value for non-linearity 0.03). CONCLUSION: LTPA is inversely associated with mortality risk in individuals with T2D. Meeting current physical activity recommendations were associated with a 12% lower risk in both the UK and China cohorts. Stronger associations were observed at higher activity levels with conflicting support for an upper limit of benefit.

17 COVID-19 vaccine hesitancy among a UK cohort of patients living with HIV

17 COVID-19 vaccine hesitancy among a UK cohort of patients living with HIV

Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

Understanding how parents’ cognitive and non-cognitive skills influence offspring education is essential for educational, family and economic policy. We use genetics (GWAS-by-subtraction) to assess a latent, broad non-cognitive skills dimension. To index parental effects controlling for genetic transmission, we estimate indirect parental genetic effects of polygenic scores on childhood and adulthood educational outcomes, using siblings (N = 47,459), adoptees (N = 6407), and parent-offspring trios (N = 2534) in three UK and Dutch cohorts. We find that parental cognitive and non-cognitive skills affect offspring education through their environment: on average across cohorts and designs, indirect genetic effects explain 36–40% of population polygenic score associations. However, indirect genetic effects are lower for achievement in the Dutch cohort, and for the adoption design. We identify potential causes of higher sibling- and trio-based estimates: prenatal indirect genetic effects, population stratification, and assortative mating. Our phenotype-agnostic, genetically sensitive approach has established overall environmental effects of parents’ skills, facilitating future mechanistic work.

Multiple sclerosis and COVID-19: Assessing risk perception, patient behaviors and access to disease-modifying therapies

BackgroundFollowing the outbreak of COVID-19, global healthcare systems have had to rapidly adapt. People with multiple sclerosis (pwMS) were required to make decisions about their individual risk and consequent work and social behaviors. This study aimed to evaluate risk perception and patterns of shielding behavior amongst pwMS at the onset of the COVID-19 pandemic and the subsequent impact on patients’ employment and access to disease modifying therapies (DMTs). MethodsPostal surveys were sent to 1690 people within a UK population-based MS cohort during the first wave of the COVID-19 pandemic. Patients were surveyed on: (i) perceived vulnerability to COVID-19; (ii) isolation behavior; (iii) interruption to DMT; (iv) employment status; (v) level of satisfaction with their current working arrangement. ResultsResponses were received from 1000 pwMS. Two thirds of patients reported isolating at home during the first wave of the pandemic. This behavior was associated with increased age (p<0.0001), higher disability (p<0.0001) and use of high-efficacy DMTs (p = 0.02). The majority of patients reported feeling vulnerable (82%) with perceived vulnerability associated with higher EDSS (p<0.0001) and receiving a high-efficacy DMT (p = 0.04). Clinician-defined risk was associated with shielding behavior, with those at high-risk more likely to self-isolate/shield (p<0.0001). Patients on high-efficacy DMTs were more likely to have an interruption to their treatment (50%) during the first wave of the pandemic. Most pwMS experienced a change to their working environment, and most were satisfied with the adjustments. ConclusionThis study highlights the risk perception, social behavioral practices and changes to treatment experienced by pwMS during the first wave of the COVID-19 pandemic in a large, well-described UK cohort. The results may help inform management of pwMS during future pandemic waves.

Cardiovascular health in the menopause transition: a longitudinal study of up to 3892 women with up to four repeated measures of risk factors

BackgroundWomen experience adverse changes in cardiovascular health in mid-life; whether the menopausal transition influences these remains strongly debated. The aim of this study was to examine associations of reproductive age (time since final menstrual period (FMP)) with change in carotid intima media thickness (CIMT) and cardiovascular risk factors and determine the role of chronological and reproductive age.MethodsWe used data from 1702 women from a pregnancy-based UK cohort who had up to four repeat cardiovascular health measures between mean age 51 (SD = 4.0) and 56 (SD = 3.6) years and experienced a natural menopause. Multilevel models were used to assess the relationship between cardiovascular measures and time since FMP (reproductive age), whilst adjusting for the underlying effects of chronological age and confounders (socioeconomic factors, body mass index, smoking, alcohol, parity, age at menarche). In addition, we looked at the relationship between cardiovascular measures by chronological age according to menopausal stages (pre-menopause, peri-menopause and post-menopause) using information from women who had and had not experienced menopause (N = 3892).ResultsThere was no strong evidence that reproductive age was associated with CIMT (difference in mean 0.8 μm/year, 95% CI − 0.4, 2.1), whereas there was a strong positive association of chronological age (7.6 μm/year, 95% CI 6.3, 8.9). Consistent with this, we found weaker linear associations of reproductive compared with chronological age for atherosclerotic risk factors, such as with systolic blood pressure (− 0.1 mmHg/year, 95% CI − 0.3, 0.1, and 0.4 mmHg/year, 95% CI 0.2, 0.5, respectively) and non-HDL-cholesterol (0.02 mmol/l/year, 95% CI 0.005, 0.03, and 0.06, 95% CI 0.04, 0.07, respectively). In contrast, associations with fat mass (0.06 kg/m2/year, 95% CI 0.03, 0.10, and 0 kg/m2/year, 95% CI − 0.04, 0.04, respectively) and C-reactive protein (0.01, 95% CI 0.001, 0.02, and 0.01, 95% CI − 0.001, 0.02 natural logged mg/l/year, respectively) were stronger for reproductive compared with chronological age. Both reproductive and chronological age were (weakly) positively associated with glucose (0.002, 95% CI 0.0001, 0.003, and 0.002, 95% CI 0.0001, 0.003 natural logged mmol/l/year, respectively).ConclusionsOur results suggest that going through the menopausal transition does not further increase women’s risk of atherosclerosis (measured by CIMT) beyond effects of ageing. Menopausal transition may, in additional to ageing, modestly increase adiposity and glucose levels and therefore a possible associated diabetes risk.

Genomic Stratification of Clozapine Prescription Patterns Using Schizophrenia Polygenic Scores

BackgroundTreatment-resistant schizophrenia affects approximately 30% of individuals with the disorder. Clozapine is the medication of choice in treatment-resistant schizophrenia, but optimizing administration and dose titration is complex. The identification of factors influencing clozapine prescription and response, including genetics, is of interest in a precision psychiatry framework. MethodsWe used linear regression models accounting for demographic, pharmacological, and clinical covariates to determine whether a polygenic risk score (PRS) for schizophrenia would be associated with the highest dose recorded during clozapine treatment. Analyses were performed across 2 independent multiancestry samples of individuals from a UK patient monitoring system, CLOZUK2 (n = 3133) and CLOZUK3 (n = 909), and a European sample from a Norwegian therapeutic drug monitoring service (n = 417). In a secondary analysis merging both UK cohorts, logistic regression models were used to estimate the relationship between schizophrenia PRSs and clozapine doses classified as low, standard, or high. ResultsAfter controlling for relevant covariates, the schizophrenia PRS was correlated with the highest clozapine dose on record for each individual across all samples: CLOZUK2 (β = 12.22, SE = 3.78, p = .001), CLOZUK3 (β = 12.73, SE = 5.99, p = .034), and the Norwegian cohort (β = 46.45, SE = 18.83, p = .014). In a secondary analysis, the schizophrenia PRS was associated with taking clozapine doses >600 mg/day (odds ratio = 1.279, p = .006). ConclusionsThe schizophrenia PRS was associated with the highest clozapine dose prescribed for an individual in records from 3 independent samples, suggesting that the genetic liability for schizophrenia might index factors associated with therapeutic decisions in cohorts of patients with treatment-resistant schizophrenia.

Prognostic model for atrial fibrillation after cardiac surgery: a UK cohort study

ObjectiveTo develop a validated clinical prognostic model to determine the risk of atrial fibrillation after cardiac surgery as part of the PARADISE project (NIHR131227).MethodsProspective cohort study with linked electronic health records from a cohort of 5.6 million people in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. For model development, we considered a priori candidate predictors including demographics, medical history, medications, and clinical biomarkers. We evaluated associations between covariates and the AF incidence at the end of follow-up using logistic regression with the least absolute shrinkage and selection operator. The model was validated internally with the bootstrap method; subsequent performance was examined by discrimination quantified with the c-statistic and calibration assessed by calibration plots. The study follows TRIPOD guidelines.ResultsBetween 1998 and 2016, 33,464 patients received cardiac surgery among the 5,601,803 eligible individuals. The final model included 13-predictors at baseline: age, year of index surgery, elevated CHA2DS2-VASc score, congestive heart failure, hypertension, acute coronary syndromes, mitral valve disease, ventricular tachycardia, valve surgery, receiving two combined procedures (e.g., valve replacement + coronary artery bypass grafting), or three combined procedures in the index procedure, statin use, and ethnicity other than white or black (statins and ethnicity were protective). This model had an optimism-corrected C-statistic of 0.68 both for the derivation and validation cohort. Calibration was good.ConclusionsWe developed a model to identify a group of individuals at high risk of AF and adverse outcomes who could benefit from long-term arrhythmia monitoring, risk factor management, rhythm control and/or thromboprophylaxis.Graphical abstract

Predictors of longer-term depression trajectories during the COVID-19 pandemic: a longitudinal study in four UK cohorts

BackgroundThe COVID-19 pandemic has caused an increase in mental ill health compared with prepandemic levels. Longer-term trajectories of depression in adults during the pandemic remain unclear.ObjectiveWe used latent growth curve...

Identifying patterns of religiosity in adults from a large UK cohort using latent class analysis

Background: Religiosity is a complex, multifaceted construct, comprising a variety of beliefs and behaviours. Much of the previous research that seeks to quantify religiosity has made use of variable-centred approaches, which place individuals on a continuum of religiosity. However, alternative approaches provide a way to examine different types of religiosity, represented by heterogeneous classes of religious (non)belief. The aim of this study was to apply a person-centred approach to understanding religious beliefs. Methods: The present study used latent class analysis to identify classes of belief and non-belief in mothers (n=12429) and their partners (n=9953) from the Avon Longitudinal Study of Parents and Children, a large cohort study based in the UK. For this, we used a range of religious belief indicators. We also examined a number of socioeconomic factors, to identify differences between classes, using logistic regression. Results: We identified four different classes of religiosity which we named Highly Religious, Moderately Religious, Agnostic, and Atheist, with similar configurations in both men and women. We also found that class membership was associated with several socioeconomic factors. Conclusions: The findings provide an insight into different patterns of religiosity in adults in the UK. These classes could be used as exposures in future studies of religiosity and how it relates to a variety of outcomes in both mothers, partners, and their offspring.

Determinants of asthma control and exacerbations in moderate to severe asthma

Determinants of asthma control and exacerbations in moderate to severe asthma

Comparison and predictors of chronic migraine vs. new daily persistent headache presenting with a chronic migraine phenotype.

ObjectiveTo compare the clinical phenotype of patients with chronic migraine (CM) to patients with new daily persistent headache of the chronic migraine subtype (NDPH‐CM).MethodsA study was conducted of CM (n = 257) and NDPH‐CM (n = 76) from a tertiary headache center in the UK, and in the US of patients with daily CM (n = 60) and NDPH‐CM (n = 22).ResultsFrom the UK cohort, the age of first headache onset was lower in CM (mean ± SD: 16 ± 12 years) than in NDPH‐CM (mean ± SD: 23 ± 14 years; p < 0.001). There was a greater number of associated migrainous symptoms in CM compared to NDPH‐CM (median and interquartile range: 6, 5–8 vs. 5, 4–7; p < 0.001). A family history of headache was more common in CM compared to NDPH‐CM (82%, 202/248, vs. 53%, 31/59; p < 0.001). In the US cohort there were no differences. Osmophobia (B = −1.08; p = 0.002) and older age at presentation to the clinic (B = −0.06; p = 0.001) were negative predictors of NDPH‐CM.ConclusionNDPH‐CM is relatively less migrainous than CM in the UK cohort. Family history of headache is less common in NDPH‐CM, with negative predictors for NDPH‐CM including osmophobia and older age of presentation to the clinic. More work is required to understand the chronic migraine phenotype of new daily persistent headache.

Adversity, social support and risk of self-harm during the COVID-19 pandemic.

Little is known about the degree to which social factors interact with COVID-19-related adversity to increase the risk of self-harm thoughts and behaviours. Using data derived from a UK cohort study, Paul & Fancourt found that loneliness was associated with an increase in the odds of self-harm thoughts and behaviours, whereas high-quality social support protected against self-harm thoughts and behaviours. The authors concluded that it is the quality of social support and interactions, rather than the act of engaging in social interaction per se, that protects against self-harm in the context of adversity. The COVID-19 pandemic may exert longer-lasting effects on population mental health, and continued surveillance of mental health, including self-harm status, will be essential. If accompanied by appropriate measures of the availability and quality of social support, such monitoring could also inform the development of more effective adaptive interventions for those at risk of engaging in self-harm.

O-211 Families created through identity-release egg donation: parents’ understanding of, and feelings about, donor identification in early childhood

Abstract Study question How well do parents understand identity-release donation, and how do they feel about potential donor-child contact? Summary answer Almost one-third of mothers (28%) and fathers (31%) did not understand the identifiable nature of their egg donation. Mothers expressed considerable ambivalence about donor-child contact. What is known already Egg donation is an increasingly common method of conception for women who are unable to use their own eggs. Identity-release egg donation has been the only treatment option available to patients wishing to pursue this route to parenthood in the UK since 2005. Despite this, little is known about how well parents understand this legislation, and how they feel about potential donor-child contact. At 18 years, donor-conceived offspring can request identifying information about their donor. The first UK cohort of identity-release offspring will turn 18 in 2023; understanding parents’ comprehension of, and feelings about, identity-release is therefore particularly timely. Study design, size, duration Data are reported from phase two of a longitudinal study of families created using open-identity egg donation, when children were aged five. At phase one, 85 families were recruited through 12 UK fertility clinics. An 85% response rate was subsequently achieved at phase two. A sub-sample of sixty-one mothers and 51 fathers were included in the present analyses. This qualitative investigation explored parents’ level of understanding of, and egg donation mothers’ feelings about, identity-release donation. Participants/materials, setting, methods In-depth, semi-structured interviews were conducted with mothers and fathers. The interviews contained a section on what parents understood about the identifiable nature of the donor. These data were analysed using qualitative content analysis. Mothers who understood the identifiable nature of their egg donation (n = 44) were then asked about their thoughts and feelings regarding the prospect of future donor-child contact. Mothers’ narratives were analysed using thematic analysis. Main results and the role of chance Almost one third of parents (27.9% of mothers, n = 17; 31.4% of fathers, n = 16) did not understand the identifiable nature of their egg donation. Qualitative content analysis revealed two main types of misunderstanding: i) parents whose understanding of identity-release was incorrect or incomplete (n = 26, 10 mothers, 13 fathers) and ii) parents who believed their donor was anonymous (n = 10, 7 mothers, 3 fathers). Thematic analysis revealed that egg donation mothers’ feelings about identity-release donation could be understood in relation to three main themes: 1) Identity-release as a threat, 2) Acceptance: it is what it is, and 3) Embracing identity-release. Mothers had complex and sometimes contradictory feelings about the prospect of future donor-child contact, and used a number of strategies to manage those feelings in day-to-day life. Donor-child contact was commonly perceived as a threat to the mother-child relationship, to the child, and to the donor. Conversely, the possibility of future donor-child contact was viewed by some mothers as an opportunity to be embraced; access to the donor’s identifying information was seen as essential to the child’s identity, and as a gateway to a broader family network. Limitations, reasons for caution Participants were predominantly from White, middle-class backgrounds. Further research with a more diverse sample is needed to improve generalisability. However, no other research has yet examined egg donation parents’ understanding of, and feelings about, identity-release donation in the UK. This research is therefore an important addition to the limited literature. Wider implications of the findings These findings indicate that parents would benefit from more comprehensive provision of information, both at time of treatment and following conception, to ensure they have fully understood the nature of the donation. Parents may also benefit from follow-up care to help manage any complex or difficult feelings about donor-child contact. Trial registration number N/A

Environmental variables and genome-environment interactions predicting IBD diagnosis in large UK cohort

A combination of genetic susceptibility and environmental exposure is thought to cause inflammatory bowel disease (IBD), but the non-genetic component remains poorly characterized. We therefore undertook a search for environmental variables and gene-environment interactions associated with future IBD diagnosis in a large UK cohort. Using self-report and electronic health records, we identified 1946 Crohn’s disease (CD) and 3715 ulcerative colitis (UC) patients after quality control in the UK Biobank. Based on prior literature and biological plausibility, we tested 38 candidate environmental variables for association with CD, UC, and overall IBD using Cox proportional hazard regressions. We also tested whether these variables interacted with polygenic risk in predicting disease, following up significant (FDR < 0.05) results with tests for SNP-environment associations. We performed robustness analyses on all significant results. As in previous reports, appendectomy protected against UC, smoking (both current and previous) elevated risk for CD, current smoking protected against UC, and previous smoking imparted a risk for UC. Childhood antibiotic use associated with IBD, as did sun exposure during the winter. Socioeconomic deprivation was conferred a risk for IBD, CD, and UC. We uncovered negative interactions between polygenic risk and previous oral contraceptive use for IBD and UC. Polygenic risk also interacted negatively with previous smoking in predicting UC. There were no individually significant SNP-environment interactions. Thus, for a limited set of environmental variables, there was strong evidence of association with IBD diagnosis in the UK Biobank, and interaction with polygenic risk was minimal.

IgG N-glycome changes during the course of severe COVID-19: An observational study

SummaryBackgroundThe severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a respiratory illness named coronavirus disease 2019 (COVID-19), which is one of the main global health problems since 2019. Glycans attached to the Fc portion of immunoglobulin G (IgG) are important modulators of IgG effector functions. Fc region binds to different receptors on the surface of various immune cells, dictating the type of immune response. Here, we performed a large longitudinal study to determine whether the severity and duration of COVID-19 are associated with altered IgG glycosylation.MethodsUsing ultra-high-performance liquid chromatography analysis of released glycans, we analysed the composition of the total IgG N-glycome longitudinally during COVID-19 from four independent cohorts. We analysed 77 severe COVID-19 cases from the HR1 cohort (74% males, median age 72, age IQR 25-80); 31 severe cases in the HR2 cohort (77% males, median age 64, age IQR 41-86), 18 mild COVID-19 cases from the UK cohort (17% males, median age 50, age IQR 26-71) and 28 mild cases from the BiH cohort (71% males, median age 60, age IQR 12-78).FindingsMultiple statistically significant changes in IgG glycome composition were observed during severe COVID-19. The most statistically significant changes included increased agalactosylation of IgG (meta-analysis 95% CI [0.03, 0.07], adjusted meta-analysis P= <0.0001), which regulates proinflammatory actions of IgG via complement system activation and indirectly as a lack of sialylation and decreased presence of bisecting N-acetylglucosamine on IgG (meta-analysis 95% CI [-0.11, -0.08], adjusted meta-analysis P= <0.0001), which indirectly affects antibody-dependent cell-mediated cytotoxicity. On the contrary, no statistically significant changes in IgG glycome composition were observed in patients with mild COVID-19.InterpretationThe IgG glycome in severe COVID-19 patients is statistically significantly altered in a way that it indicates decreased immunosuppressive action of circulating immunoglobulins. The magnitude of observed changes is associated with the severity of the disease, indicating that aberrant IgG glycome composition or changes in IgG glycosylation may be an important molecular mechanism in COVID-19.FundingThis work has been supported in part by Croatian Science Foundation under the project IP-CORONA-2020-04-2052 and Croatian National Centre of Competence in Molecular Diagnostics (The European Structural and Investment Funds grant #KK.01.2.2.03.0006), by the UKRI/MRC (Cov-0331 - MR/V027883/1) and by the National Institutes for Health Research Nottingham Biomedical Research Centre and by Ministry Of Science, Higher Education and Youth Of Canton Sarajevo, grant number 27-02-11-4375-10/21.

Donor characteristics and their impact on kidney transplantation outcomes: Results from two nationwide instrumental variable analyses based on outcomes of donor kidney pairs accepted for transplantation.

SummaryBackgroundDonor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals.MethodsThis analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors.FindingsIncidences of congruent EGL (Netherlands: 1·2%, UK: 0·7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10-years Hazard Ratio for graft loss: 1·18 [1·03-1·35] p<0·018); and 5 years eGFR (48·6 [48·3–49·0] vs. 46·0 [44·5–47·6] ml/min in the symmetrical outcome group, p<0·001).InterpretationOur results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes.FundingNone.

Assessing Ethnic Inequalities in Diagnostic Interval of Common Cancers: A Population-Based UK Cohort Study.

Simple SummaryUK ethnic minorities have poorer outcomes of some cancers and are less likely to report positive health care experiences. We wanted to determine whether these differences are related to inequalities in time to diagnosis once patients sought medical help with cancer symptoms. We found that in five of the seven cancers studied, the minority groups experienced a longer time to diagnosis when compared with the White group. However, the differences were small and unlikely to be the sole explanation for the ethnic variation in cancer outcomes. Nonetheless, addressing such differences will help to improve trust and care experiences among ethnic minority groups.Background: This study investigated ethnic differences in diagnostic interval (DI)—the period between initial primary care presentation and diagnosis. Methods: We analysed the primary care-linked data of patients who reported features of seven cancers (breast, lung, prostate, colorectal, oesophagogastric, myeloma, and ovarian) one year before diagnosis. Accelerated failure time (AFT) models investigated the association between DI and ethnicity, adjusting for age, sex, deprivation, and morbidity. Results: Of 126,627 eligible participants, 92.1% were White, 1.99% Black, 1.71% Asian, 1.83% Mixed, and 2.36% were of Other ethnic backgrounds. Considering all cancer sites combined, the median (interquartile range) DI was 55 (20–175) days, longest in lung [127, (42–265) days], and shortest in breast cancer [13 (13, 8–18) days]. DI for the Black and Asian groups was 10% (AFT ratio, 95%CI 1.10, 1.05–1.14) and 16% (1.16, 1.10–1.22), respectively, longer than for the White group. Site-specific analyses revealed evidence of longer DI in Asian and Black patients with prostate, colorectal, and oesophagogastric cancer, plus Black patients with breast cancer and myeloma, and the Mixed group with lung cancer compared with White patients. DI was shorter for the Other group with lung, prostate, myeloma, and oesophagogastric cancer than the White group. Conclusion: We found limited and inconsistent evidence of ethnic differences in DI among patients who reported cancer features in primary care before diagnosis. Our findings suggest that inequalities in diagnostic intervals, where present, are unlikely to be the sole explanation for ethnic variations in cancer outcomes.

Disease activity, burden and suffering in patients with ulcerative colitis in the UK cohort recruited into the global ICONIC study

ObjectiveThe Understanding the Impact of Ulcerative Colitis and Its Associated Disease Burden on Patients (ICONIC) was a 2-year, global, prospective, observational study assessing disease burden in adults recently diagnosed (≤36...

Ethnic inequalities in routes to diagnosis of cancer: a population-based UK cohort study

BackgroundUK Asian and Black ethnic groups have poorer outcomes for some cancers and are less likely to report a positive care experience than their White counterparts. This study investigated ethnic differences in the route to diagnosis (RTD) to identify areas in patients' cancer journeys where inequalities lie, and targeted intervention might have optimum impact.MethodsWe analysed data of 243,825 patients with 10 cancers (2006–2016) from the RTD project linked to primary care data. Crude and adjusted proportions of patients diagnosed via six routes (emergency, elective GP referral, two-week wait (2WW), screen-detected, hospital, and Other routes) were calculated by ethnicity. Adjusted odds ratios (including two-way interactions between cancer and age, sex, IMD, and ethnicity) determined cancer-specific differences in RTD by ethnicity.ResultsAcross the 10 cancers studied, most patients were diagnosed via 2WW (36.4%), elective GP referral (23.2%), emergency (18.2%), hospital routes (10.3%), and screening (8.61%). Patients of Other ethnic group had the highest proportion of diagnosis via the emergency route, followed by White patients. Asian and Black group were more likely to be GP-referred, with the Black and Mixed groups also more likely to follow the 2WW route. However, there were notable cancer-specific differences in the RTD by ethnicity.ConclusionOur findings suggest that, where inequalities exist, the adverse cancer outcomes among Asian and Black patients are unlikely to be arising solely from a poorer diagnostic process.

COVID-19 infection, hospitalisation and mortality rates in people with severe mental illness: findings from two UK cohort studies

IntroductionRecent systematic reviews have highlighted that people with Severe Mental Illness (SMI) have higher risks of infection, hospitalisation and death from COVID-19, although the full extent of these disparities are not yet established.ObjectivesUtilising electronic health records, we investigated COVID-19 related infection, hospitalisation and mortality among people with schizophrenia/psychosis, bipolar disorder (BD) and/or major depressive disorder (MDD) in two large UK samples: the UK Biobank (UKB) cohort study and GP-registered patients in Greater Manchester (GM).MethodsWe sampled 447,296 adults with and without SMI from UKB (inc. schizophrenia/psychosis=1,925, BD=1,483 and MDD=41,448, non-SMI=402,440) and 1,152,831 adults from GM (inc. schizophrenia/psychosis =46,859, BD=3,461, recurrent MDD=134,661, non-SMI = 922,264). Primary care, hospital and death records were linked to identify COVID-19 related outcomes. Logistic regression models were used to estimate unadjusted and adjusted Odds Ratios (ORs) to compare differences in COVID-19 outcomes by diagnosis, controlling for sociodemographic factors and comorbidities.ResultsWe will report the findings of unadjusted and adjusted analyses, comparing ORs for people with and without SMI, by diagnosis. Findings will be compared between the two datasets, with attention to the demographic and clinical profiles of each sample. We will consider the role of demographic characteristics and comorbidities in attenuating outcomes.ConclusionsEmerging evidence suggests that people with SMI have higher risks of COVID-19 infection, hospitalisation and mortality. Based on two large datasets utilising EHRs, we present findings from the UK on COVID-19 outcomes among people with SMI, a country that has been severely affected by COVID-19.DisclosureNo significant relationships.