English Cohort Research Articles

Sex and education differences in trajectories of physiological ageing: longitudinal analysis of a prospective English cohort study.

Physiological age (PA) derived from clinical indicators including blood-based biomarkers and tests of physiological function can be compared with chronological age to examine disparities in health between older adults of the same age. Though education interacts with sex to lead to inequalities in healthy ageing, their combined influence on longitudinally-measured PA has not been explored. We derived PA based on longitudinally-measured clinical indicators and examined how sex and education interact to inform PA trajectories. Three waves of clinical indicators (2004/05-2012/13) drawn from the English Longitudinal Study of Ageing (ages 50-100 years) were used to estimate PA, which was internally validated by confirming associations with incident chronic conditions, functional limitations, and memory impairment after adjustment for chronological age and sex. Joint models were used to construct PA trajectories in 8,891 ELSA participants to examine sex and educational disparities in PA. Among the least educated participants, there were negligible sex differences in PA until age 60 (sex difference [men-women] age 50=-0.6 years [95% confidence interval=-2.2-0.6]; age 60=0.4 [-0.6-1.4]); at age 70, women were 1.5 years (0.7-2.2) older than men. Among the most educated participants, women were 3.8 years (1.6-6.0) younger than men at age 50, and 2.7 years (0.4-5.0) younger at age 60, with a non-significant sex difference at age 70. Higher education provides a larger midlife buffer to physiological ageing for women than men. Policies to promote gender equity in higher education may contribute to improving women's health across a range of ageing-related outcomes.

Primary Progressive Aphasia in Italian and English: A Cross-Linguistic Cohort Study.

Current formulations of primary progressive aphasia (PPA) derive largely from English-speaking patients. We hypothesized that language-specific characteristics influence PPA phenotypes in 2 contrasting languages: Italian and English. We undertook a retrospective, cross-sectional, observational comparison of 2 patient cohorts representing all major PPA syndromes, in London and Florence. Neuropsychological scores in a range of linguistic and general cognitive domains were normalized to native speaker controls and dichotomized as impaired/unimpaired. Proportions were compared using χ2 tests and adjusted for symptom duration and severity of cognitive impairment using logistic regression. The cohorts comprised 106 (48.1% female) Italian speakers (14 nonfluent/agrammatic [nfvPPA], 20 semantic [svPPA], 41 logopenic variant [lvPPA], 31 mixed PPA [mPPA]) and 166 (45.2% female) English speakers (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA). Comparing cohorts, the English cohort was younger (mean 62.7 [SD = 8.4] vs 65.9 [7.8] years; p = 0.003, Cohen d = 0.39), with longer symptom duration (4.6 [4.3] vs 3.1 [2.5] years; p = 0.048, d = 1.08), a higher proportion of nfvPPA cases (42% vs 13%, χ2 = 25.4, p < 0.001), and lower proportions of lvPPA (25% vs 38%, χ2 = 5.46, p = 0.019) and mPPA (5% vs 29%, χ2 = 29.3, p < 0.001). English-speaking nfvPPA patients had less frequent expressive agrammatism (46% vs 93%, p = 0.015, odds ratio [OR] 16.05, 95% CI 1.70-151.13) but more frequently impaired single-word comprehension (60% vs 8%, p = 0.013, OR 0.06, 95% CI 0.00-0.56). English svPPA patients had more frequent surface dyslexia (68% vs 30%, p = 0.046, OR 0.24, 95% CI 0.06-0.97) and dysgraphia (38% vs 10%, p = 0.021, OR 0.09, 95% CI 0.01-0.70) while English lvPPA patients had more frequently impaired single-word comprehension (89% vs 29%, p < 0.001, OR 0.05, 95% CI 0.01-0.28), word repetition (61% vs 26%, p = 0.020, OR 0.24, 95% CI 0.07-0.80), nonword repetition (78% vs 30%, p = 0.010, OR 0.18, 95% CI 0.05-0.06), nonverbal working memory (69% vs 36%, p = 0.005, OR 0.10, 95% CI 0.02-0.51), and visuomotor function (89% vs 25%, p < 0.001, OR 0.02, 95% CI 0.01-0.20). Language-specific characteristics influenced PPA phenotypes, with more frequent expressive agrammatism in Italian (reflecting its morphologic complexity), more frequently impaired word processing in English (reflecting its articulatory, acoustic, and orthographic complexity), and increased prevalence of mPPA in Italian. These findings have implications for PPA diagnosis and management. Limitations of test heterogeneity and cohort size should be addressed in future, prospective, multicenter initiatives using cross-linguistic tools.

P103 Analysis of cumulative life course impairment in tertiary psoriasis care: insights from the initial delivery of the DermCLCI-r questionnaire in an English cohort

Abstract Chronic diseases such as psoriasis place an ongoing and aggregate burden on patients throughout their life, leading to a negative life-changing impact on decisions and opportunities in patients’ lives. This phenomenon is known as Cumulative Life Course Impairment (CLCI), yet no tools which measure CLCI in a standardized way in patients exist. The DermCLCI-r questionnaire is a novel 25-item questionnaire assessing the impact of psoriasis over the whole course of a patients’ disease journey. This questionnaire is undergoing simultaneous validation in German and English language between centres in Germany and England in a 1-year longitudinal study against existing quality of life tools. This study explores CLCI measured in psoriasis patients from a large tertiary psoriasis clinic in England at the initial assessment with the DermCLCI-r questionnaire and correlates it with clinical and quality of life data. The English data (n = 98) showed 60.2% male; mean age, 51.37 years; mean, 27.98 years since psoriasis diagnosis; mean age of diagnosis, 23.0; mean psoriasis area and severity index (PASI), 3.3; 94% on systemic therapy; 44% PASI &amp;gt; 2; mean DLQI 5.1. 55.1% of patients reported experiencing at least one life-changing experience due to their disease, with a mean number of 4.35 life-changing experiences per patient. The most common life-changing experiences were ‘feeling stressed by the disease’ (31.6%), ‘nervousness, anxiety or tenseness’ (27.6%), ‘impairments regarding choice of clothing’ (26.5%), ‘effort with the treatment of the disease’ (26.5%) and ‘limitations in physical performance’ (25.5%). Ongoing cumulative life stress was experienced by 65.3% of patients, with a mean of 5.53 separate items contributing to their current disease burden. Relevant items in the DermCLCIr tool correlated significantly with total DLQI score, e.g. ‘impairments in quality of life’ (0.568), ‘feeling stressed by the disease’ (0.519), and ‘limitations in physical performance’ (0.492), P &amp;lt; 0.001 respectively. CLCI significantly impacts the majority of patients in tertiary psoriasis care and has contributed to multiple ongoing and life-changing experiences in this patient group; the DermCLCI-r questionnaire is able to identify these. The ability to detect CLCI could allow earlier conservative or therapeutic management of life-changing elements of the psoriasis disease experience, and could potentially reduce the negative personal and social impact of psoriasis. Completion of the longitudinal validation study will further assess the accuracy of the DermCLCI-r questionnaire in aiding clinical decision-making on the holistic management of psoriasis patients.

Primary progressive aphasia in Italian and English: a cross‐linguistic cohort study

AbstractBackgroundPrimary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language abilities, with clinical variants (nonfluent/agrammatic variant [nfvPPA], semantic variant [svPPA], logopenic variant [lvPPA], and mixed‐PPA [mPPA]) categorized based on linguistic features. This study aims to compare PPA cohorts of native speakers of two different languages: English (an analytic language with deep orthography) and Italian (a synthetic language with shallow orthography).MethodsWe considered 166 English participants (70 nfvPPA, 45 svPPA, 42 lvPPA, 9 mPPA) and 106 Italian participants (14 nfvPPA, 20 svPPA, 42 lvPPA, 31 mPPA). Starting from the neuropsychological battery used to assess patients, we extracted one test for each cognitive and linguistic function that can be compared between cohorts. Comparisons were adjusted for symptom duration and Mini‐mental State Examination scores.ResultsThe English cohort included a higher proportion of nfvPPA patients (42% vs. 13%, p&lt;0.001), while the Italian cohort showed higher proportions of lvPPA (25% vs. 38%, p = 0.019) and mPPA (5% vs. 29%, p&lt;0.001). English nfvPPA patients were more frequently impaired in single‐word comprehension (60% vs. 8%, p = 0.013), while Italian nfvPPA patients exhibited more agrammatism (46% vs. 93%, p = 0.015). English svPPA had a higher proportion of surface dyslexia (68% vs. 30%, p = 0.046) and spelling impairment (38% vs. 10%, p = 0.021). English lvPPA had broader impairments, including single‐word comprehension (89% vs. 29%, p&lt;0.001), repetition of words (61% vs. 26%, p = 0.03), nonverbal working memory (69% vs. 36%, p = 0.005), and visuospatial perception (89% vs. 25%, p&lt;0.001).ConclusionsThis study reveals linguistic and cognitive distinctions between English and Italian PPA cohorts, emphasizing the impact of language‐specific characteristics on symptomatology. Cultural and linguistic nuances should be considered in PPA diagnosis and management, calling for more tailored assessments and criteria.

10 year risk of death in adolescents with learning disability or autism in England: a national cohort study using linked health and education data from ECHILD

BackgroundTransition from adolescent to adult health and education services is a vulnerable period for young people with learning disability (LD) or autism spectrum disorders (ASD), yet there is a lack of information on their risk of death in that period. MethodsWe developed an English national cohort of 11-year-olds enrolled in state schools between 2009/10-20014/15, followed-up until their 22nd birthday, death or 31st August 2020 using linked health, mortality and education data from the ECHILD database. LD and ASD were indicated using diagnoses from hospital admissions or if LD or ASD were a reason for special educational needs provision in education records before age 11. We estimated crude mortality rates and compared with unaffected peers using rate ratios (RR). ResultsThe cohort comprised 3,080,516 young people (52% boys), of whom 4,589 (0.15%) died (crude mortality rate: 0.17/1000 person-years, 95% CI: 0.16-0.17/1000). 45,174 (1.5%) young people were autistic (85% boys; 15% with co-existing LD), of whom 113 died (mortality rate: 0.29/1000 person-years, 95%CI: 0.24-0.35/1000). Mortality was 1.7 times higher for autistic young people compared to their peers (RR: 1.7, 95% CI: 1.4-2.1). Among 40,264 (1.3% of all) young people with LD (63% boys; 17% with co-existing ASD) there were 812 deaths (mortality rate: 2.31/1000, 95%CI: 2.15-2.47/1000PY). They had 17 times higher risk of death (RR: 16.4, 95%CI: 15.2-17.7). ConclusionsYoung people with LD/ASD are more likely to die than their peers. Findings on disparities within these groups according to co-existing comorbidities, sex and socioeconomic factors will be reported.

Screening for psychological distress in childhood and mental health-related hospital attendance among young adults

ObjectivesThe prevalence of mental disorders is high and increasing among children and young people. Investigating the relationship between self-reported poor mental health and mental health service utilisation can provide evidence on the benefits of universal screening, but longitudinal data is rare. ApproachData from a nationally representative English cohort (Next Steps) were linked to NHS Hospital Episode Statistics. GHQ-12 assessed psychological distress in Next Steps at age 15; participants were followed until their first mental health-related hospital presentations or were censored at the end of the study (age 27). Cox proportionate hazard models with survey weights estimated associations. ResultsOut of 4058 young people included in the analyses, 19% reported high levels of distress at age 15. During the 12-year follow-up, 5.3%, 2.9% and 2.7% of the participants had at least one mental disorder, drug/alcohol misuse and self-harm presentation, respectively, and 4.2% had a mental health treatment. Higher GHQ-12 scores were associated with mental disorder presentations (HR=1.10, 95% CI:1.04-1.16), and mental health treatments (HR=1.14, 95% CI:1.08-1.20). Associations were weaker for young people living in deprived areas, or if their main parent had lower education. ConclusionsAdolescent psychological distress predicts subsequent hospital attendance in young adulthood, but there are treatment gaps in service utilisation among more disadvantaged individuals. Detecting youth with mental health difficulties through universal screening, may facilitate early intervention, improve life-course outcomes, and reduce secondary healthcare use. ImplicationsLinked cohort and administrative data can improve our understanding on long-term healthcare utilisation and treatment needs.

Estimating disease burden using national linked electronic health records: a study using an English population-based cohort.

Electronic health records (EHRs) have the potential to be used to produce detailed disease burden estimates. In this study we created disease estimates using national EHR for three high burden conditions, compared estimates between linked and unlinked datasets and produced stratified estimates by age, sex, ethnicity, socio-economic deprivation and geographical region. EHRs containing primary care (Clinical Practice Research Datalink), secondary care (Hospital Episode Statistics) and mortality records (Office for National Statistics) were used. We used existing disease phenotyping algorithms to identify cases of cancer (breast, lung, colorectal and prostate), type 1 and 2 diabetes, and lower back pain. We calculated age-standardised incidence of first cancer, point prevalence for diabetes, and primary care consultation prevalence for low back pain. 7.2 million people contributing 45.3 million person-years of active follow-up between 2000-2014 were included. CPRD-HES combined and CPRD-HES-ONS combined lung and bowel cancer incidence estimates by sex were similar to cancer registry estimates. Linked CPRD-HES estimates for combined Type 1 and Type 2 diabetes were consistently higher than those of CPRD alone, with the difference steadily increasing over time from 0.26% (2.99% for CPRD-HES vs. 2.73 for CPRD) in 2002 to 0.58% (6.17% vs. 5.59) in 2013. Low back pain prevalence was highest in the most deprived quintile and when compared to the least deprived quintile the difference in prevalence increased over time between 2000 and 2013, with the largest difference of 27% (558.70 per 10,000 people vs 438.20) in 2013. We use national EHRs to produce estimates of burden of disease to produce detailed estimates by deprivation, ethnicity and geographical region. National EHRs have the potential to improve disease burden estimates at a local and global level and may serve as more automated, timely and precise inputs for policy making and global burden of disease estimation.

Continuous glucose monitoring (CGM) for 308 older-age participants in an English birth cohort: variability and correlates

Introduction &amp; BackgroundEpochs of hyperglycaemia and hypoglycaemia may each increase risk of common chronic diseases and impair both cognitive and physical function even in people without diabetes. Older people may have greater frequency of adverse glycaemic excursions, partly due to disordered autonomic function and sleep quality. Data for older, non-diabetic people are however scant. Objectives &amp; Approach1) To describe blood glucose variability (completed) and 2) its socio-demographic and lifestyle correlates in a predominantly non-diabetic cohort of older adults (planned). Participants were recruited during 2021-2023 from an English birth cohort (the 1946 National Survey for Health and Development Study). They wore a continuous glucose monitor (Freestyle libre Abbott), which measured circulating glucose four times/hour, for seven days. Summary statistics and time outside range (4.4-7.8mmol/L) were calculated. Further information on glycaemic excursions and day-to-day variability will be gleaned using the R “iglu” package. For all CGM summary and excursion measures, future analyses will investigate: associations with HbA1c, socio-demographics, body composition, physical activity, diet and alcohol use. Results will be stratified by sleep/ wake time periods estimated from simultaneous actigraphy (Philips Actiwatch Spectrum Plus). Sensitivity analyses will exclude people taking hypo/ hyperglycaemic medications and those with diabetes. Relevance to Digital FootprintsDerived summary measures can be used by future studies to give insights into glycaemic variability as a population-level risk factor. This work will bring together multiple data sources, i.e. from CGM, actigraphy and baseline cohort data. ResultsParticipants were aged 75-76 years, 45% female and 10% had diagnosed diabetes; median (IQR) BMI was 26.8 (24.6-29.2) kg/m2. CGM data from 308 participants was collected, for a median (IQR) of 6.9 (6.7-7.6) days. Average glucose over the recording period was 5.7mmol/L (5.3-6.2mmol/L), standard deviation was 1.0mmol/L (0.8-1.3mmol/L), time outside range was 12.8% (6.2-24.7%) and 16% of participants spent ≥1 hour/day above and ≥1 hour/day below range. Conclusions &amp; ImplicationsCGM was feasible for this cohort of older adults, and demonstrated high levels of time outside range for a predominantly non-diabetic group. Future analysis will determine whether enhanced characterisation of glycaemic variability is a potentially more accurate tool for predicting future disease risk than isolated glucose measurements.

Disagreement concerning atopic dermatitis subtypes between an English prospective cohort (ALSPAC) and linked electronic health records.

Subtypes of atopic dermatitis (AD) have been derived from the Avon Longitudinal Study of Parents and Children (ALSPAC) based on the presence and severity of symptoms reported in questionnaires (severe-frequent, moderate-frequent, moderate-declining, mild-intermittent, unaffected-rare). Good agreement between ALSPAC and linked electronic health records (EHRs) would increase trust in the clinical validity of these subtypes and allow inference of subtypes from EHRs alone, which would enable their study in large primary care databases. Firstly, to explore whether the presence and number of AD records in EHRs agree with AD symptom and severity reports from ALSPAC. Secondly, to explore whether EHRs agree with ALSPAC-derived AD subtypes. Thirdly, to construct models to classify ALSPAC-derived AD subtypes using EHRs. We used data from the ALSPAC prospective cohort study from 11 timepoints until age 14 years (1991-2008), linked to local general practice EHRs. We assessed how far ALSPAC questionnaire responses and derived subtypes agreed with AD as established in EHRs using different AD definitions (e.g. diagnosis and/or prescription) and other AD-related records. We classified AD subtypes using EHRs, fitting multinomial logistic regression models, tuning hyperparameters and evaluating performance in the testing set [receiver operating characteristic (ROC) area under the curve (AUC), accuracy, sensitivity and specificity]. Overall, 8828 individuals out of a total 13 898 had been assigned an AD subtype and also had linked EHRs. The number of AD-related codes in EHRs generally increased with the severity of the AD subtype. However, not all patients with the severe-frequent subtype had AD in EHRs, and many with the unaffected-rare subtype did have AD in EHRs. When predicting the ALSPAC AD subtype using EHRs, the best tuned model had an ROC AUC of 0.65, a sensitivity of 0.29 and a specificity of 0.83 (both macro-averaged). When different sets of predictors were used, individuals with missing EHR coverage were excluded, and subtypes were combined, sensitivity was not considerably improved. ALSPAC and EHRs disagreed not only on AD subtypes, but also on whether children had AD or not. Researchers should be aware that individuals considered to have AD in one source may not be considered to have AD in another.

Primary and secondary care service use and costs associated with frailty in an ageing population: longitudinal analysis of an English primary care cohort of adults aged 50 and over, 2006-2017.

Frailty becomes more prevalent and healthcare needs increase with age. Information on the impact of frailty on population level use of health services and associated costs is needed to plan for ageing populations. To describe primary and secondary care service use and associated costs by electronic Frailty Index (eFI) category. Retrospective cohort using electronic health records. Participants aged ≥50 registered in primary care practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre, 2006-2017. Primary and secondary care use (totals and means) were stratified by eFI category and age group. Standardised 2017 costs were used to calculate primary, secondary and overall costs. Generalised linear models explored associations between frailty, sociodemographic characteristics. Adjusted mean costs and cost ratios were produced. Individual mean annual use of primary and secondary care services increased with increasing frailty severity. Overall cohort care costs for were highest in mild frailty in all 12years, followed by moderate and severe, although the proportion of the population with severe frailty can be expected to increase over time. After adjusting for sociodemographic factors, compared to the fit category, individual annual costs doubled in mild frailty, tripled in moderate and quadrupled in severe. Increasing levels of frailty are associated with an additional burden of individual service use. However, individuals with mild and moderate frailty contribute to higher overall costs. Earlier intervention may have the most potential to reduce service use and costs at population level.

Long-Term Exposure to Low Concentrations of Ambient Benzene and Mortality in a National English Cohort.

Background: Benzene affects human health through environmental exposure in addition to occupational contact. However, few studies have examined the associations between long-term exposure to low concentrations of ambient benzene and mortality risks in nonoccupational settings.Methods: This prospective cohort study consists of 393,042 participants without stroke, myocardial infarction, or cancer at baseline from the UK Biobank. Annual average concentrations of benzene for each year during follow-up were measured using air dispersion models. The main outcomes were all-cause mortality and mortality from specific causes. Cox proportional-hazards models with time-varying exposure measurements were used to estimate the hazard ratios and 95% confidence intervals (CIs) for mortality risks. Restricted cubic spline models were used to estimate exposure-response relationships.Measurements and Main Results: With each interquartile range increase in the average annual concentration of benzene, the adjusted hazard ratios of mortality risk from all causes, cardiovascular disease, cancer, and respiratory disease were 1.26 (95% CI, 1.24-1.27), 1.24 (95% CI, 1.21-1.28), 1.27 (95% CI, 1.25-1.29), and 1.25 (95% CI, 1.20-1.30), respectively. The monotonically increasing exposure-response curves showed no threshold and plateau within the observed concentration range. Furthermore, the effect of benzene exposure on mortality persisted across different subgroups and was somewhat stronger in younger and White people (P for interaction < 0.05).Conclusions: Long-term exposure to low concentrations of ambient benzene significantly increases mortality risk in the general population. Ambient benzene represents a potential threat to public health, and further investigations are needed to support timely pollution regulation and health protection.

Maternal depressive symptoms and young people's higher education participation and choice of university: Evidence from a longitudinal cohort study

BackgroundParticipation in higher education has significant and long-lasting consequences for people's socioeconomic trajectories. Maternal depression is linked to poorer educational achievement for children in school, but its impact on university attendance is unclear. MethodsIn an English longitudinal cohort study (N = 8952), we explore whether young people whose mothers experienced elevated depressive symptoms are less likely to attend university, and the role of potential mediators in the young person: educational achievement in school, depressive symptoms, and locus of control. We also examine whether maternal depressive symptoms influence young people's choice of university, and non-attendees' reasons for not participating in higher education. ResultsYoung people whose mothers experienced more recurrent depressive symptoms were less likely to attend university (OR = 0.88, CI = 0.82,0.94, p < 0.001) per occasion of elevated maternal depressive symptoms) after adjusting for confounders. Mediation analysis indicated this was largely explained by educational achievement in school (e.g., 82.7 % mediated by age 16 achievement) and locus of control at 16. There was mixed evidence for an impact on choice of university. For participants who did not study at university, maternal depressive symptoms were linked to stating as a reason having had other priorities to do with family or children (OR: 1.17, CI = 1.02,1.35). LimitationsLack of data on the other parent's depression, loss to follow-up, possibly selective non-response. ConclusionsYoung people whose mothers experience elevated depressive symptoms on multiple occasions are less likely to participate in higher education; educational achievement in secondary school, but not the young people's own depressive symptoms, substantially mediated the effect.

The Impact of Oral Antibiotics Prior to Cancer Diagnosis on Overall Patient Survival: Findings from an English Population-Based Cohort Study.

There is limited evidence in humans as to whether antibiotics impact the effectiveness of cancer treatments. Rodent studies have shown that disruption in gut microbiota due to antibiotics decreases cancer therapy effectiveness. We evaluated the associations between the antibiotic treatment of different time periods before cancer diagnoses and long-term mortality. Using the Clinical Practice Research Datalink GOLD, linked to the Cancer Registry's and the Office for National Statistics' mortality records, we delineated a study cohort that involved cancer patients who were prescribed antibiotics 0-3 months; 3-24 months; or more than 24 months before cancer diagnosis. Patients' exposure to antibiotics was compared according to the recency of prescriptions and time-to-event (all-cause mortality) by applying Cox models. 111,260 cancer patients from England were included in the analysis. Compared with antibiotic prescriptions that were issued in the past, patients who had been prescribed antibiotics shortly before cancer diagnosis presented an increased hazard ratio (HR) for mortality. For leukaemia, the HR in the Cancer Registry was 1.32 (95% CI 1.16-1.51), for lymphoma it was 1.22 (1.08-1.36), for melanoma it was 1.28 (1.10-1.49), and for myeloma it was 1.19 (1.04-1.36). Increased HRs were observed for cancer of the uterus, bladder, and breast and ovarian and colorectal cancer. Antibiotics that had been issued within the three months prior to cancer diagnosis may reduce the effectiveness of chemotherapy and immunotherapy. Judicious antibiotic prescribing is needed among cancer patients.

The relationship of perceived discrimination in healthcare and future falls among community-dwelling older persons from an English longitudinal cohort.

The objective of this study is to examine the relation between the perceived discrimination suffered by older adults aged 60 and over during a healthcare encounter and its effects on the likelihood of falling 4 and 8 years later. To identify discrimination, we used the English Longitudinal Study of Ageing (ELSA) data collected in 2010-2011 (wave 5) that asked respondents about feeling discriminated against by doctors or at hospitals in the past year. Falls were assessed by the question: "Have you fallen down in the last two years?" in subsequent waves. We performed longitudinal analyses using the 2014-2015 (wave 7) and 2018-2019 (wave 9) follow-ups. Multivariable logistic regression was used to estimate the odds ratios of falling. At baseline, 707 (15.1%) of all respondents experienced healthcare discrimination. Those suffering from discrimination in health care had 64% higher chances of falling 4 years later (odds ratio: 1.637, 95% confidence interval: 1.131-2.368) compared to those who did not, adjusting for age, sex, marital status, wealth, ethnicity, education levels, self-perceived health, depressive symptoms, and difficulties with basic and/or instrumental activities of daily living (ADL/IADL) and difficulties with walking. After 8 years, the effect was not statistically significant. Older age was the only significant detrimental factor at both 4 and 8 years. Understanding discrimination in health care is important to enable safe and welcoming environments for the timely future use of services. These results remind us of the physical risk and the complex panorama of bio-psychosocial determinants involved in tackling discrimination over time.

The risk of acute kidney injury in colorectal cancer survivors: an english population-based matched cohort study

BackgroundColorectal cancer survival has improved in recent decades but there are concerns that survivors may develop kidney problems due to adverse effects of cancer treatment or complications of the cancer itself. We quantified the risk of acute kidney injury (AKI) in colorectal cancer survivors compared to people with no prior cancer.MethodsRetrospective matched cohort study using electronic health record primary care data from the Clinical Practice Research Datalink GOLD linked to hospital data in England (HES-APC). Individuals with colorectal cancer between 1997–2018 were individually matched on age, sex, and GP practice to people with no prior cancer. We used Cox models to estimate hazard ratios for an incident hospital diagnosis of AKI in colorectal cancer survivors compared to individuals without cancer, overall and stratified by time since diagnosis adjusted for other individual-level factors (adj-HR).ResultsTwenty thousand three hundred forty colorectal cancer survivors were matched to 100,058 cancer-free individuals. Colorectal cancer survivors were at increased risk of developing AKI compared to people without cancer (adj-HR = 2.16; 95%CI 2.05–2.27). The HR was highest in the year after diagnosis (adj-HR 7.47, 6.66–8.37), and attenuated over time, but there was still increased AKI risk > 5 years after diagnosis (adj-HR = 1.26, 1.17–1.37). The association between colorectal cancer and AKI was greater for younger people, men, and those with pre-existing chronic kidney disease.ConclusionsColorectal cancer survivors were at increased risk of AKI for several years after cancer diagnosis, suggesting a need to prioritise monitoring, prevention, and management of kidney problems in this group of cancer survivors.

Modifiable risk factors for multiple sclerosis have consistent directions of effect across diverse ethnic backgrounds: a nested case–control study in an English population-based cohort

BackgroundMultiple sclerosis is a leading cause of non-traumatic neurological disability among young adults worldwide. Prior studies have identified modifiable risk factors for multiple sclerosis in cohorts of White ethnicity, such as infectious mononucleosis, smoking, and obesity during adolescence/early adulthood. It is unknown whether modifiable exposures for multiple sclerosis have a consistent impact on risk across ethnic groups.AimTo determine whether modifiable risk factors for multiple sclerosis have similar effects across diverse ethnic backgrounds.MethodsWe conducted a nested case–control study using data from the UK Clinical Practice Research Datalink. Multiple sclerosis cases diagnosed from 2001 until 2022 were identified from electronic healthcare records and matched to unaffected controls based on year of birth. We used stratified logistic regression models and formal statistical interaction tests to determine whether the effect of modifiable risk factors for multiple sclerosis differed by ethnicity.ResultsWe included 9662 multiple sclerosis cases and 118,914 age-matched controls. The cohort was ethnically diverse (MS: 277 South Asian [2.9%], 251 Black [2.6%]; Controls: 5043 South Asian [5.7%], 4019 Black [4.5%]). The age at MS diagnosis was earlier in the Black (40.5 [SD 10.9]) and Asian (37.2 [SD 10.0]) groups compared with White cohort (46.1 [SD 12.2]). There was a female predominance in all ethnic groups; however, the relative proportion of males was higher in the South Asian population (proportion of women 60.3% vs 71% [White] and 75.7% [Black]). Established modifiable risk factors for multiple sclerosis—smoking, obesity, infectious mononucleosis, low vitamin D, and head injury—were consistently associated with multiple sclerosis in the Black and South Asian cohorts. The magnitude and direction of these effects were broadly similar across all ethnic groups examined. There was no evidence of statistical interaction between ethnicity and any tested exposure, and no evidence to suggest that differences in area-level deprivation modifies these risk factor-disease associations. These findings were robust to a range of sensitivity analyses.Conclusions and relevanceEstablished modifiable risk factors for multiple sclerosis are applicable across diverse ethnic backgrounds. Efforts to reduce the population incidence of multiple sclerosis by tackling these risk factors need to be inclusive of people from diverse ethnicities.

Thrombocytopenic, thromboembolic and haemorrhagic events following second dose with BNT162b2 and ChAdOx1: self-controlled case series analysis of the English national sentinel cohort.

Thrombosis associated with thrombocytopenia was a matter of concern post first and second doses of BNT162b2 and ChAdOx1 COVID-19 vaccines. Therefore, it is important to investigate the risk of thrombocytopenic, thromboembolic and haemorrhagic events following a second dose of BNT162b2 and ChAdOx1 COVID-19 vaccines. We conducted a large-scale self-controlled case series analysis, using routine primary care data linked to hospital data, among 12.3 million individuals (16 years old and above) in England. We used the nationally representative Oxford-Royal College of General Practitioners (RCGP) sentinel network database with baseline and risk periods between 8th December 2020 and 11th June 2022. We included individuals who received two vaccine (primary) doses of the BNT162b2 mRNA (Pfizer-BioNTech) and two vaccine doses of ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our analyses. We carried out a self-controlled case series (SCCS) analysis for each outcome using a conditional Poisson regression model with an offset for the length of risk period. We reported the incidence rate ratios (IRRs) and 95% confidence intervals (CI) of thrombocytopenic, thromboembolic (including arterial and venous events) and haemorrhagic events, in the period of 0-27 days after receiving a second dose of BNT162b2 or ChAdOx1 vaccines compared to the baseline period (14 or more days prior to first dose, 28 or more days after the second dose and the time between 28 or more days after the first and 14 or more days prior to the second dose). We adjusted for a range of potential confounders, including age, sex, comorbidities and deprivation. Between December 8, 2020 and February 11, 2022, 6,306,306 individuals were vaccinated with two doses of BNT162b2 and 6,046,785 individuals were vaccinated with two doses of ChAdOx1. Compared to the baseline, our analysis show no increased risk of venous thromboembolic events (VTE) for both BNT162b2 (IRR 0.71, 95% CI: 0.65-0.770) and ChAdOx1 (IRR 0.91, 95% CI: 0.84-0.98); and similarly there was no increased risk for cerebral venous sinus thrombosis (CVST) for both BNT162b2 (IRR 0.87, 95% CI: 0.41-1.85) and ChAdOx1 (IRR 1.73, 95% CI: 0.82-3.68). We additionally report no difference in IRR for pulmonary embolus, and deep vein thrombosis, thrombocytopenia, including idiopathic thrombocytopenic purpura (ITP), and haemorrhagic events post second dose for both BNT162b2. Reassuringly, we found no associations between increased risk of thrombocytopenic, thromboembolic and haemorrhagic events post vaccination with second dose for either of these vaccines. Data and Connectivity: COVID-19 Vaccines Pharmacovigilance study.

Survival and critical care use among people with dementia in a large English cohort.

Admitting people with dementia to critical care units may not always lead to a clear survival benefit. Critical care admissions of people with dementia vary across countries. Little is known about the use and trends of critical care admissions of people with dementia in England. To investigate critical care use and survival among people with dementia in a large London catchment area. A retrospective cohort study using data from dementia assessment services in south London, UK (2007-20) linked with national hospitalisation data to ascertain critical care admissions. Outcomes included age-sex-standardised critical care use and 1-year post-critical care admission survival by dementia severity (binary: mild versus moderate/severe). We used logistic regression and Kaplan-Meier survival plots for investigating 1-year survival following a critical care admission and linear regressions for time trends. Of 19,787 people diagnosed with dementia, 726 (3.7%) had ≥1 critical care admission at any time after receiving their dementia diagnosis. The overall 1-year survival of people with dementia, who had a CCA, was 47.5% (n = 345). Dementia severity was not associated with 1-year survival following a critical care admission (mild dementia versus moderate-severe dementia odds of 1-year mortality OR: 0.90, 95% CI [0.66-1.22]). Over the 12-year period from 2008 to 2019, overall critical care use decreased (β = -0.05; 95% CI = -0.01, -0.0003; P = 0.03), while critical care admissions occurring during the last year of life increased (β = 0.11, 95% CI = 0.01, 0.20, P = 0.03). In this cohort, while critical care use among people with dementia declined overall, its use increased among those in their last year of life. Survival remains comparable to that observed in general older populations.

Personalised decision making to predict absolute metastatic risk in cutaneous squamous cell carcinoma: development and validation of a clinico-pathological model

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, affecting more than 2 million people worldwide yearly and metastasising in 2-5% of patients. However, current clinical staging systems do not provide estimates of absolute metastatic risk, hence missing the opportunity for more personalised treatment advice. We aimed to develop a clinico-pathological model that predicts the probability of metastasis in patients with cSCC. Nationwide cohorts from (1) all patients with a first primary cSCC in The Netherlands in 2007-2008 and (2) all patients with a cSCC in 2013-2015 in England were used to derive nested case-control cohorts. Pathology records of primary cSCCs that originated a loco-regional or distant metastasis were identified, and these cSCCs were matched to primary cSCCs of controls without metastasis (1:1 ratio). The model was developed on the Dutch cohort (n=390) using a weighted Cox regression model with backward selection and validated on the English cohort (n=696). Model performance was assessed using weighted versions of the C-index, calibration metrics, and decision curve analysis; and compared to the Brigham and Women's Hospital (BWH) and the American Joint Committee on Cancer (AJCC) staging systems. Members of the multidisciplinary Skin Cancer Outcomes (SCOUT) consortium were surveyed to interpret metastatic risk cutoffs in a clinical context. Eight out of eleven clinico-pathological variables were selected. The model showed good discriminative ability, with an optimism-corrected C-index of 0.80 (95% Confidence interval (CI) 0.75-0.85) in the development cohort and a C-index of 0.84 (95% CI 0.81-0.87) in the validation cohort. Model predictions were well-calibrated: the calibration slope was 0.96 (95% CI 0.76-1.16) in the validation cohort. Decision curve analysis showed improved net benefit compared to current staging systems, particularly for thresholds relevant for decisions on follow-up and adjuvant treatment. The model is available as an online web-based calculator (https://emc-dermatology.shinyapps.io/cscc-abs-met-risk/). This validated model assigns personalised metastatic risk predictions to patients with cSCC, using routinely reported histological and patient-specific risk factors. The model can empower clinicians and healthcare systems in identifying patients with high-risk cSCC and offering personalised care/treatment and follow-up. Use of the model for clinical decision-making in different patient populations must be further investigated. PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships.

COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study

COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited. We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N>18 million). Data were linked to the National Immunisation Management Service database, Second Generation Surveillance System for virology test data, Hospital Episode Statistics, and death registry data. We estimated adjusted vaccine effectiveness (aVE) against COVID-19 infection followed by hospitalisation and death among individuals in specific clinical risk groups using a cohort design during the delta-dominant period. We also report mortality statistics and results from our antibody surveillance in this population. aVE against severe endpoints was high, 14-69d following a third dose aVE was 96.4% (95.1%-97.4%) and 97.9% (97.2%-98.4%) for clinically vulnerable people given a Vaxzevria and Comirnaty primary course respectively. Lower aVE was observed in the immunosuppressed group: 88.6% (79.1%-93.8%) and 91.9% (85.9%-95.4%) for Vaxzevria and Comirnaty respectively. Antibody levels were significantly lower among the immunosuppressed group than those not in this risk group across all vaccination types and doses. The standardised case fatality rate within 28 days of a positive test was 3.9/1000 in people not in risk groups, compared to 12.8/1000 in clinical risk groups. Waning aVE with time since 2nd dose was also demonstrated, for example, Comirnaty aVE against hospitalisation reduced from 96.0% (95.1-96.7%) 14-69days post-dose 2-82.9% (81.4-84.2%) 182days+ post-dose 2. In all clinical risk groups high levels of vaccine effectiveness against severe endpoints were seen. Reduced vaccine effectiveness was noted among the immunosuppressed group.