Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland:Scottish Family Health Study (GS:SFHS)

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD

The impact of policing and homelessness on violence experienced by women who sell sex in London:a modelling study

Street-based sex workers experience considerable homelessness, drug use and police enforcement, making them vulnerable to violence from clients and other perpetrators. We used a deterministic compartmental model of street-based sex workers in London to estimate whether displacement by police and unstable housing/homelessness increases client violence. The model was parameterized and calibrated using data from a cohort study of sex workers, to the baseline percentage homeless (64%), experiencing recent client violence (72%), or recent displacement (78%), and the odds ratios of experiencing violence if homeless (1.97, 95% confidence interval 0.88–4.43) or displaced (4.79, 1.99–12.11), or of experiencing displacement if homeless (3.60, 1.59–8.17). Ending homelessness and police displacement reduces violence by 67% (95% credible interval 53–81%). The effects are non-linear; halving the rate of policing or becoming homeless reduces violence by 5.7% (3.5–10.3%) or 6.7% (3.7–10.2%), respectively. Modelled interventions have small impact with violence reducing by: 5.1% (2.1–11.4%) if the rate of becoming housed increases from 1.4 to 3.2 per person-year (Housing First initiative); 3.9% (2.4–6.9%) if the rate of policing reduces by 39% (level if recent increases had not occurred); and 10.2% (5.9–19.6%) in combination. Violence reduces by 26.5% (22.6–28.2%) if half of housed sex workers transition to indoor sex work. If homelessness decreased and policing increased as occurred during the COVID-19 pandemic in 2020, the impact on violence is negligible, decreasing by 0.7% (8.7% decrease-4.1% increase). Increasing housing and reducing policing among street-based sex workers could substantially reduce violence, but large changes are needed

Effect of police enforcement and extreme social inequalities on violence and mental health among women who sell sex: findings from a cohort study in London, UK

OBJECTIVES: To examine legal and social determinants of violence, anxiety/depression among sex workers. METHODS: A participatory prospective cohort study among women (inclusive of transgender) ≥18 years, selling sex in the last 3 months in London between 2018 and 2019. We used logistic generalised estimating equation models to measure associations between structural factors on recent (6 months) violence from clients or others (local residents, strangers), depression/anxiety (Patient Health Questionnaire-4). RESULTS: 197 sex workers were recruited (96% cisgender-women; 46% street-based; 54% off-street) and 60% completed a follow-up questionnaire. Street-based sex workers experienced greater inequalities compared with off-street in relation to recent violence from clients (73% vs 36%); police (42% vs 7%); intimate partner violence (IPV) (56% vs 18%) and others (67% vs 17%), as well as homelessness (65% vs 7%) and recent law enforcement (87% vs 9%). Prevalence of any STI was 17.5% (17/97). For street-based sex workers, recent arrest was associated with violence from others (adjusted OR (aOR) 2.77; 95% CI 1.11 to 6.94) and displacement by police was associated with client violence (aOR 4.35; 95% CI 1.36 to 13.90). Financial difficulties were also associated with client violence (aOR 4.66; 95% CI 1.64 to 13.24). Disability (aOR 3.85; 95% CI 1.49 to 9.95) and client violence (aOR 2.55; 95% CI 1.10 to 5.91) were associated with anxiety/depression. For off-street sex workers, financial difficulties (aOR 3.66; 95% CI 1.64 to 8.18), unstable residency (aOR 3.19; 95% CI 1.36 to 7.49), IPV (aOR 3.77; 95% CI 1.30 to 11.00) and alcohol/drug use were associated with client violence (aOR 3.16; 95% CI 1.26 to 7.92), while always screening and refusing clients was protective (aOR 0.36; 95% CI 0.15 to 0.87). Disability (aOR 5.83; 95% CI 2.34 to 14.51), unmet mental health needs (aOR 3.08; 95% CI 1.15 to 8.23) and past eviction (aOR 3.99; 95% CI 1.23 to 12.92) were associated with anxiety/depression. CONCLUSIONS: Violence, anxiety/depression are linked to poverty, unstable housing and police enforcement. We need to modify laws to allow sex workers to work safely and increase availability of housing and mental health services

National PReCePT Programme: a before-and-after evaluation of the implementation of a national quality improvement programme to increase the uptake of magnesium sulfate in preterm deliveries

Objective To evaluate the effectiveness and cost-effectiveness of the National PReCePT Programme (NPP) in increasing use of magnesium sulfate (MgSO4) in preterm births.Design Before-and-after study.Setting Maternity units (N=137) within NHS England and the Academic Health Science Network (AHSN) in 2018.Participants Babies born ≤30 weeks’ gestation admitted to neonatal units in England.Interventions The NPP was a quality improvement (QI) intervention including the PReCePT (Preventing Cerebral Palsy in Pre Term labour) QI toolkit and materials (preterm labour proforma, staff training presentations, parent leaflet, posters for the unit and learning log), regional AHSN-level support, and up to 90 hours funded backfill for a midwife ‘champion’ to lead implementation.Main outcome measures MgSO4 uptake post implementation was compared with pre-NPP implementation uptake. Implementation and lifetime costs were estimated.Results Compared with pre-implementation estimates, the average MgSO4 uptake for babies born ≤30 weeks’ gestation, in 137 maternity units in England, increased by 6.3 percentage points (95% CI 2.6 to 10.0 percentage points) to 83.1% post implementation, accounting for unit size, maternal, baby and maternity unit factors, time trends, and AHSN. Further adjustment for early/late initiation of NPP activities increased the estimate to 9.5 percentage points (95% CI 4.3 to 14.7 percentage points). From a societal and lifetime perspective, the health gains and cost savings associated with the NPP effectiveness generated a net monetary benefit of £866 per preterm baby and the probability of the NPP being cost-effective was greater than 95%.Conclusion This national QI programme was effective and cost-effective. National programmes delivered via coordinated regional clinical networks can accelerate uptake of evidence-based therapies in perinatal care

Mental Health Through Movement

Children’s mental health: ‘has become an issue of real concern, in the media and to both politicians and NHS leaders, over the last five years in particular. It has prompted numerous inquiries, reports, recommendations and pledges by politicians and NHS leaders to improve the situation’: https://www.theguardian.com/society/2018/nov/22/what-is-happening-withchildrens-mental-health On July 1st 2019, the Local Government Association released statistics to show that: ‘There were 205,720 cases where a child was identified as having a mental health issue in 2017/18, compared with 133,600 in 2014/15- up 54%’: https://www.local.gov.uk/about/news/councils-seeing-more-560-child-mentalhealth-cases-every-day It is within this context that the All-Party Parliamentary Group on A Fit and Healthy Childhood presents its 14th Report: ‘Positive Mental Health Through Movement’. With 1 in 10 children now having a mental health diagnosis and 1 in 4 an undiagnosed mental health issue, this, our third Report on the issue of child mental health, addresses the link between positive mental health and physical activity and movement experiences at a time when, paradoxically, today’s children and young people are more inactive and play less than ever before. The growing recognition of a link between mental health and movement is fortuitous because from September 2019, health education in English schools will be statutory alongside the expectation that they will offer their pupils at least 30 ‘active minutes’ per day. The APPG on A Fit and Healthy Childhood welcomes the change whilst recognising that those responsible for implementing the new strategy (including practitioners and families) will need guidance as they help children to develop individual strategies to address future adverse events and foster the positive sense of self that will enable them to lead fulfilled, healthy lives. This Report is therefore presented as a practical contribution to an essential debate. It offers new strategies against the persistence of historical and traditional ways of thinking; examines and collates best practice in the devolved Home Countries as well as the wider world and discusses exactly what is required to ensure that future child mental health strategy is holistic. It is respectful of equalities and is aware that the successful outcome of policies is entirely dependent upon the expertise and confidence of those tasked with the responsibility of delivering them. As the 21st century advances, we consider the effects of the digital age and its impact on children and young people’s mental health and wellbeing and the crucial role of parents and carers who want the best for their children in a societal climate where, all too often, fears of ‘nanny state’ meddling serve to isolate families who suffer in silence – until a disaster that may have been all too predictable and preventable overtakes them, making a private grief a public concern. The trajectory of progress in mental health policy has been ‘stop start’ rather than linear, with legislative change in 1959 and 1983, an increase in spending from 1997- 2010 and radical changes to child and adolescent mental health services (CAMHS) in 2000. The Wessely Independent Review of the Mental Health Act is another such milestone: https://www.gov.uk/government/groups/independent-review-of-the-mentalhealth-act The APPG on A Fit and Healthy Childhood anticipates that the Government will fulfil its pledge to parents, children and practitioners by introducing much needed mental health legislation - and that our trio of Reports and the holistic theme of this one will help to inform a strategy that works for 21st century children

Mortality Among Adults With Cancer Undergoing Chemotherapy or Immunotherapy and Infected With COVID-19

Importance: Large cohorts of patients with active cancers and COVID-19 infection are needed to provide evidence of the association of recent cancer treatment and cancer type with COVID-19 mortality. // Objective: To evaluate whether systemic anticancer treatments (SACTs), tumor subtypes, patient demographic characteristics (age and sex), and comorbidities are associated with COVID-19 mortality. // Design, Setting, and Participants: The UK Coronavirus Cancer Monitoring Project (UKCCMP) is a prospective cohort study conducted at 69 UK cancer hospitals among adult patients (≥18 years) with an active cancer and a clinical diagnosis of COVID-19. Patients registered from March 18 to August 1, 2020, were included in this analysis. // Exposures: SACT, tumor subtype, patient demographic characteristics (eg, age, sex, body mass index, race and ethnicity, smoking history), and comorbidities were investigated. // Main Outcomes and Measures: The primary end point was all-cause mortality within the primary hospitalization. // Results: Overall, 2515 of 2786 patients registered during the study period were included; 1464 (58%) were men; and the median (IQR) age was 72 (62-80) years. The mortality rate was 38% (966 patients). The data suggest an association between higher mortality in patients with hematological malignant neoplasms irrespective of recent SACT, particularly in those with acute leukemias or myelodysplastic syndrome (OR, 2.16; 95% CI, 1.30-3.60) and myeloma or plasmacytoma (OR, 1.53; 95% CI, 1.04-2.26). Lung cancer was also significantly associated with higher COVID-19–related mortality (OR, 1.58; 95% CI, 1.11-2.25). No association between higher mortality and receiving chemotherapy in the 4 weeks before COVID-19 diagnosis was observed after correcting for the crucial confounders of age, sex, and comorbidities. An association between lower mortality and receiving immunotherapy in the 4 weeks before COVID-19 diagnosis was observed (immunotherapy vs no cancer therapy: OR, 0.52; 95% CI, 0.31-0.86). // Conclusions and Relevance: The findings of this study of patients with active cancer suggest that recent SACT is not associated with inferior outcomes from COVID-19 infection. This has relevance for the care of patients with cancer requiring treatment, particularly in countries experiencing an increase in COVID-19 case numbers. Important differences in outcomes among patients with hematological and lung cancers were observed

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT Randomised Controlled Trial according to treatment received

BACKGROUND:The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. OBJECTIVE:To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. DESIGN, SETTING, AND PARTICIPANTS:This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. INTERVENTION:Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. RESULTS AND LIMITATIONS:According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p=0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p=0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6mo) and urinary incontinence (55% at 6mo) after surgery, and of sexual dysfunction (88% at 6mo) and bowel dysfunction (5% at 6mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa. CONCLUSIONS:Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. PATIENT SUMMARY:More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes