Mental health, welfare and state support: Findings from a novel data linkage

Objectives To describe the process and outcomes of establishing a unique data linkage between mental healthcare records from the South London and Maudsley (SLaM) NHS Foundation Trust with benefits records from the Department for Work and Pensions. Methods 448,404 IDs of patients who accessed secondary mental healthcare services at SLaM were sent to the DWP, including personal identifiers. Data from SLaM covered years 2007-2019, whereas data from DWP covered years 2005-2020. A deterministic data linkage approach was used. Results A linkage rate of 93% was achieved. Patient groups who were less likely to be linked were women, those from a racial and ethnic minority background and younger patients. Benefit receipt was high among patients, with 83% of patients having received benefits during the 15-year follow-up period. Benefits most frequently received included unemployment related or income replacing disability benefits. Conclusion This data linkage is the first of its kind in the UK to demonstrate the use of routinely collected mental health and benefits data. It provides opportunities to generate much needed high-quality evidence that can be used to achieve change, investment in services and translation into policy and practice

Universal credit receipt among users of secondary mental health services: Findings from a novel data linkage

Objectives People with mental disorders are likely to be overrepresented among Universal Credit (UC) recipients. Despite this, individual level data is lacking on mental disorder diagnosis by UC status, and the intersectionality of different socio-demographic characteristics. Associations were explored between UC receipt, socio-demographic and diagnostic characteristics among mental health service users. Methods A novel data source consisting of linked electronic mental healthcare records and Department for Work and Pensions administrative benefits records of patients accessing a large mental healthcare service provider in South London was used. Benefits records were restricted to those that covered years 2013-2019. Only working-age patients were included (n=120,000). Results Preliminary results indicated that of the 120,000 working-age patients with linked data, 38,000 had received UC at some point between 2013-2019. Most UC recipients were allocated to a conditionality regime that required them to look for work, followed by those who did not have to meet any work-related requirements. Adjusted analyses indicated that UC recipients were more likely to be male, younger, lived in more deprived areas, and were from a non-White ethnic background. Interestingly, having a recorded psychiatric diagnosis meant that patients were less likely to have received UC. Conclusion Possible explanations for the findings will be discussed. In the longer term, our findings have the potential to impact welfare and public health policies, as well as patient care

Cohort profile: Working age adults accessing secondary mental healthcare services in South London (UK) and benefits – A data linkage of electronic mental healthcare records and benefits data

Objectives To present an overview of a cohort of working age adults accessing secondary mental healthcare services and benefits related to unemployment, sickness, disability, or income support and describe the different benefit types received across diagnostic and sociodemographic groups. Methods Using a novel data linkage containing electronic secondary mental health care records from the South London and Maudsley (SLaM) NHS Foundation Trust and benefits data from the Department for Work and Pensions (DWP), we present descriptive statistics on a cohort of working age adults. The data window covers the period January 2007-June 2020. Results We identified n=150,348 patients of working age (18-65 years), who had attended SLaM secondary mental health care services, 78.3% of which had received a benefit relating to unemployment, sickness, disability, or income support. Of this group, 68% had a recorded primary psychiatric diagnosis. We found that a much higher percentage of those with a primary psychiatric diagnosis received more than one benefit (69.4%) compared to those who had not received a primary psychiatric diagnosis (30.6%). Conclusions We showed types of benefits received among working age adults accessing secondary mental health care services. This cohort will be further examined to explore trajectories of mental health care and benefit receipt and provide evidence that will help to inform both DWP policies and mental health care delivery

Five years after Treat All implementation: Botswana's HIV response and future directions in the era of COVID-19.

BACKGROUND: As the relentless coronavirus disease-2019 (COVID-19) pandemic continues to spread across Africa, Botswana could face challenges maintaining the pathway towards control of its HIV epidemic. OBJECTIVE: Utilising the Spectrum GOALS module (GOALS-2021), the 5-year outcomes from the implementation of the Treat All strategy were analysed and compared with the original 2016 Investment Case (2016-IC) projections. Future impact of adopting the new Joint United Nations Programme on HIV/AIDS (UNAIDS) Global AIDS Strategy (2021-2026) targets and macroeconomic analysis estimating how the financial constraints from the COVID-19 pandemic could impact the available resources for Botswana's National HIV Response through 2030 were also considered. METHOD: Programmatic costs, population demographics, prevention and treatment outputs were determined. Previous 2016-IC data were uploaded for comparison, and inputs for the GOALS, AIM, DemProj, Resource Needs and Family Planning modules were derived from published reports, strategic plans, programmatic data and expert opinion. The economic projections were recalibrated with consideration of the impact of the COVID-19 pandemic. RESULTS: Decreases in HIV infections, incidence and mortality rates were achieved. Increases in laboratory costs were offset by estimated decreases in the population of people living with HIV (PLWH). Moving forward, young women and others at high risk must be targeted in HIV prevention efforts, as Botswana transitions from a generalised to a more concentrated epidemic. CONCLUSION: The Treat All strategy contributed positively to decreases in new HIV infections, mortality and costs. If significant improvements in differentiated service delivery, increases in human resources and HIV prevention can be realised, Botswana could become one of the first countries with a previously high-burdened generalised HIV epidemic to gain epidemic control, despite the demands of the COVID-19 pandemic

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

Purpose We assessed the associations between population-based polygenic risk scores (PRS) for breast (BC) or epithelial ovarian cancer (EOC) with cancer risks forBRCA1andBRCA2pathogenic variant carriers. Methods Retrospective cohort data on 18,935BRCA1and 12,339BRCA2female pathogenic variant carriers of European ancestry were available. Three versions of a 313 single-nucleotide polymorphism (SNP) BC PRS were evaluated based on whether they predict overall, estrogen receptor (ER)-negative, or ER-positive BC, and two PRS for overall or high-grade serous EOC. Associations were validated in a prospective cohort. Results The ER-negative PRS showed the strongest association with BC risk forBRCA1carriers (hazard ratio [HR] per standard deviation = 1.29 [95% CI 1.25-1.33],P = 3x10(-72)). ForBRCA2, the strongest association was with overall BC PRS (HR = 1.31 [95% CI 1.27-1.36],P = 7x10(-50)). HR estimates decreased significantly with age and there was evidence for differences in associations by predicted variant effects on protein expression. The HR estimates were smaller than general population estimates. The high-grade serous PRS yielded the strongest associations with EOC risk forBRCA1(HR = 1.32 [95% CI 1.25-1.40],P = 3x10(-22)) andBRCA2(HR = 1.44 [95% CI 1.30-1.60],P = 4x10(-12)) carriers. The associations in the prospective cohort were similar. Conclusion Population-based PRS are strongly associated with BC and EOC risks forBRCA1/2carriers and predict substantial absolute risk differences for women at PRS distribution extremes.Peer reviewe

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

The predictive ability of the 313 variant–based polygenic risk score for contralateral breast cancer risk prediction in women of European ancestry with a heterozygous BRCA1 or BRCA2 pathogenic variant

Abstract: Purpose: To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods: We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results: For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC < age 40 years, the cumulative PRS313 5th and 95th percentile 10-year CBC risks were 22% and 32% for BRCA1 and 13% and 23% for BRCA2 heterozygotes, respectively. Conclusion: The PRS313 can be used to refine individual CBC risks for BRCA1/2 heterozygotes of European ancestry, however the PRS313 needs to be considered in the context of a multifactorial risk model to evaluate whether it might influence clinical decision-making