Establishing and characterising large COVID-19 cohorts after mapping the Information System for Research in Primary Care in Catalonia to the OMOP Common Data Model

Background Few datasets have been established that capture the full breadth of COVID-19 patient interactions with a health system. Our first objective was to create a COVID-19 dataset that linked primary care data to COVID-19 testing, hospitalisation, and mortality data at a patient level. Our second objective was to provide a descriptive analysis of COVID-19 outcomes among the general population and describe the characteristics of the affected individuals. Methods We mapped patient-level data from Catalonia, Spain, to the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). More than 3,000 data quality checks were performed to assess the readiness of the database for research. Subsequently, to summarise the COVID-19 population captured, we established a general population cohort as of the 1st March 2020 and identified outpatient COVID-19 diagnoses or positive test results for SARS-CoV-2, hospitalisations with COVID-19, and COVID-19 deaths during follow-up, which went up until 30th June 2021. Findings Mapping data to the OMOP CDM was performed and high data quality was observed. The mapped database was used to identify a total of 5,870,274 individuals, who were included in the general population cohort as of 1st March 2020. Over follow up, 604,472 had either an outpatient COVID-19 diagnosis or positive test result, 58,991 had a hospitalisation with COVID-19, 5,642 had an ICU admission with COVID-19, and 11,233 had a COVID-19 death. People who were hospitalised or died were more commonly older, male, and with more comorbidities. Those admitted to ICU with COVID-19 were generally younger and more often male than those hospitalised in general and those who died. Interpretation We have established a comprehensive dataset that captures COVID-19 diagnoses, test results, hospitalisations, and deaths in Catalonia, Spain. Extensive data checks have shown the data to be fit for use. From this dataset, a general population cohort of 5.9 million individuals was identified and their COVID-19 outcomes over time were described. Funding Generalitat de Catalunya and European Health Data and Evidence Network (EHDEN).

Stress and spirituality in relation to HPA axis gene methylation among US Black women: results from the Black Women's Health Study and the Study on Stress, Spirituality and Health

Background: Few epigenetics studies have been conducted within the Black community to examine the impact of diverse psychosocial stressors and resources for resiliency on the stress pathway (hypothalamus-pituitary-adrenal axis). Methods: Among 1000 participants from the Black Women's Health Study, associations between ten psychosocial stressors and DNA methylation (DNAm) of four stress-related genes ( NR3C1, HSDB1, HSD11B2 and FKBP5) were tested. Whether religiosity or spirituality (R/S) significantly modified these stress-DNAm associations was also assessed. Results: Associations were found for several stressors with DNAm of individual CpG loci and average DNAm levels across each gene, but no associations remained significant after false discovery rate (FDR) correction. Several R/S variables appeared to modify the relationship between two stressors and DNAm, but no identified interaction remained significant after FDR correction. Conclusion: There is limited evidence for a strong signal between stress and DNAm of hypothalamus-pituitary-adrenal axis genes in this general population cohort of US Black women.

Standardized Comparison of Cardiovascular Risk Factors Prevalence in Spanish Women and Men Living with HIV and in the General Population

People living with HIV (PLWH) have an increased risk of cardiovascular (CV) disease, likely due to a higher prevalence of CV risk factors. We compared the age-standardized prevalence and management of CV risk factors in PLWH to that of the general population in Spain. Blood pressure, lipid, glucose, and anthropometric profiles were cross-sectionally compared along with the treatment of hypertension, dyslipidemia, and diabetes in a general population cohort and a PLWH cohort. Prevalence rates were standardized by the direct method by 10-year age groups in European standard populations and stratified by gender. We included 47,593 individuals aged 35 to 74 years, 28,360 from the general population cohort and 19,233 from the PLWH cohort. Compared to the general population, PLWH had a higher concentration of triglycerides (>35 mg/dL in women and >26 mg/dL in men) and a higher prevalence of smoking (>23% and >17%) and diabetes (>9.9% and >8.5%). The prevalence of treated diabetes, hypertension, and dyslipidemia were up to three-fold lower in both women and men living with HIV. There was a significant difference in PLWH compared to the general population in the lipid, glucose, and anthropometric profile. In addition, PLWH were less often treated for diagnosed diabetes, hypertension, and dyslipidemia.

Incidence of malignancy in multiple sclerosis: A cohort study in the Danish Multiple Sclerosis Registry

Background The association between multiple sclerosis and malignancy is controversial and a current appraisal is needed. Objective To determine the incidence of malignancy in patients with multiple sclerosis compared with the general population and in relation to disease-modifying therapy. Methods Patients with multiple sclerosis (1995 – 2015) were matched by birth year and sex to individuals without multiple sclerosis in the general population. Patients with multiple sclerosis initiating disease-modifying therapy were evaluated using landmark period analysis. Malignancy risk was assessed by incidence rates, incidence rate ratios, and standardised incidence ratios. Results The standardised incidence ratio of any malignancy (excluding non-melanoma skin cancer) in patients with multiple sclerosis ( n = 10,557) was 0.96 (95% CI 0.88 – 1.06), and there was no increased incidence of specific malignancy types compared with the general population cohort ( n = 103,761). At the 48-month landmark period, the age-adjusted incidence per 100,000 person-years of any malignancy (excluding non-melanoma skin cancer) was 436.7 (95% CI 361.0 – 512.4) in patients newly treated with immunomodulator-only and 675.1 (95% CI 130.4 – 1219.9) in patients newly treated with immunosuppressant-only. Conclusions There was no increased incidence of malignancy overall or by type in patients with multiple sclerosis compared neither with the general population nor in relation to disease-modifying therapy.

Context v. algorithm: evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis

Background A transdiagnostic and contextual framework of ‘clinical characterization’, combining clinical, psychopathological, sociodemographic, etiological, and other personal contextual data, may add clinical value over and above categorical algorithm-based diagnosis. Methods Prediction of need for care and health care outcomes was examined prospectively as a function of the contextual clinical characterization diagnostic framework in a prospective general population cohort (n = 6646 at baseline), interviewed four times between 2007 and 2018 (NEMESIS-2). Measures of need, service use, and use of medication were predicted as a function of any of 13 DSM-IV diagnoses, both separately and in combination with clinical characterization across multiple domains: social circumstances/demographics, symptom dimensions, physical health, clinical/etiological factors, staging, and polygenic risk scores (PRS). Effect sizes were expressed as population attributable fractions. Results Any prediction of DSM-diagnosis in relation to need and outcome in separate models was entirely reducible to components of contextual clinical characterization in joint models, particularly the component of transdiagnostic symptom dimensions (a simple score of the number of anxiety, depression, mania, and psychosis symptoms) and staging (subthreshold, incidence, persistence), and to a lesser degree clinical factors (early adversity, family history, suicidality, slowness at interview, neuroticism, and extraversion), and sociodemographic factors. Clinical characterization components in combination predicted more than any component in isolation. PRS did not meaningfully contribute to any clinical characterization model. Conclusion A transdiagnostic framework of contextual clinical characterization is of more value to patients than a categorical system of algorithmic ordering of psychopathology.

Cannabis and tobacco use prior to pregnancy and subsequent offspring birth outcomes: a 20-year intergenerational prospective cohort study

There is increasing evidence that the life-course origins of health and development begin before conception. We examined associations between timing and frequency of preconception cannabis and tobacco use and next generation preterm birth (PTB), low birth weight (LBW) and small for gestational age. 665 participants in a general population cohort were repeatedly assessed on tobacco and cannabis use between ages 14–29 years, before pregnancy. Associations were estimated using logistic regression. Preconception parent (either maternal or paternal) daily cannabis use age 15–17 was associated with sixfold increases in the odds of offspring PTB (aOR 6.65, 95% CI 1.92, 23.09), and offspring LBW (aOR 5.84, 95% CI 1.70–20.08), after adjusting for baseline sociodemographic factors, parent sex, offspring sex, family socioeconomic status, parent mental health at baseline, and concurrent tobacco use. There was little evidence of associations with preconception parental cannabis use at other ages or preconception parental tobacco use. Findings support the hypothesis that the early life origins of growth begin before conception and provide a compelling rationale for prevention of frequent use during adolescence. This is pertinent given liberalisation of cannabis policy.

Childhood neurodevelopmental markers and risk of premature mortality: Follow-up to age 60–65 years in the Aberdeen Children of the 1950s study

Background Individual neurodevelopmental disorders are associated with premature mortality. Little is known about the association between multiple neurodevelopmental markers and premature mortality at a population level. The ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) approach considers multiple neurodevelopmental parameters, assessing several markers in parallel that cluster, rather than considering individual diagnostic categories in isolation. Objectives To determine whether childhood neurodevelopmental markers, including reduced intellectual functioning, are associated with all-cause premature mortality. Methods and procedures In a general population cohort study (n = 12,150) with longitudinal follow up from childhood to middle age, Cox proportional hazard models were used to study the associations between childhood neurodevelopmental markers (Rutter B scale and IQ) and premature all-cause mortality. Outcomes and results The cognitive measures and 21 of the 26 Rutter B items were significantly associated with premature mortality in bivariate analyses with hazard ratios from 1.24 (95% CI 1.05–1.47) to 2.25 (95% CI 1.78–2.90). In the final adjusted model, neurodevelopmental markers suggestive of several domains including hyperactivity, conduct problems and intellectual impairment were positively associated with premature mortality and improved prediction of premature mortality. Conclusions A wide range of neurodevelopmental markers, including childhood IQ, were found to predict premature mortality in a large general population cohort with longitudinal follow up to 60–65 years of age. Implications These findings highlight the importance of a holistic assessment of children with neurodevelopmental markers that addresses a range of neurodevelopmental conditions. Our findings could open the door to a shift in child public mental health focus, where multiple and/or cumulative markers of neurodevelopmental conditions alert clinicians to the need for early intervention. This could lead to a reduction in the risk of broad health outcomes at a population level.

Childhood Trajectories of Hyperactivity/Inattention Symptoms and Diurnal Cortisol in Middle Adolescence: Results from a UK Birth Cohort

Objective Children with attention-deficit/hyperactivity disorder (ADHD) show hypoactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Whether the association between hyperactivity/inattention symptoms with HPA axis dysfunction holds in the general child population too is not clear. Method We assessed associations between longitudinal trajectories of hyperactivity/inattention symptoms during ages 4 to 13 years and basal cortisol profiles at age 15 in a British general population cohort. Results Adolescents with persistently high levels of hyperactivity/inattention symptoms since childhood showed lower total morning cortisol and a smaller diurnal decline, even after adjusting for confounders. No associations were found between any of the symptom trajectories and cortisol awakening response, diurnal slope or daily output of cortisol. Conclusion This study provides evidence for hypocortisolism among adolescents with chronic hyperactivity/inattention symptoms in the general population.