"I'll meet you at our bench": adaptation, innovation and resilience among VCSE organisations who supported marginalised and minoritised communities during the Covid-19 pandemic in Northern England - a qualitative focus group study.

BACKGROUND: The Covid-19 pandemic has exacerbated pre-existing inequalities and increased adversity and challenges for vulnerable and marginalised communities worldwide. In the UK, the Voluntary Community and Social Enterprise (VCSE) sector play a vital role in supporting the health and wellbeing of people who are marginalised or experiencing multiple complex needs. However, only a small number of studies have focused on the impact that Covid-19 had on the VCSE sector. METHODS: As part of a Health Inequalities Impact Assessment (HIIA), we conducted qualitative focus groups with staff and volunteers from five organisations to examine short, medium and longer-term impacts of Covid-19 upon the VCSE sector in Northern England. Nine online focus groups were conducted between March and July 2021. FINDINGS: Focus group transcripts were analysed using Framework Analysis and yielded three central themes: (1) exacerbation of pre-existing inequalities, adversity and challenges for vulnerable and marginalised populations; (2) the 'price' of being flexible, innovative and agile for VCSE staff and volunteers; and (3) the voluntary sector as a 'lifeline' - organisational pride and resilience. CONCLUSIONS: While the voluntary sector 'adapted at pace' to provide support during Covid-19 and in its continued aftermath, this resilience has potentially come at the cost of workforce and volunteer wellbeing, compounded by political obstacles and chronic shortage in funding and support. The VCSE sector has a vital role to play in the post-lockdown 'levelling up' agenda. The expertise, capacity and resilience of VCSE organisations, and their ability to respond to Covid-19, should be celebrated, recognised and supported adequately to maintain its resilience. To not do so threatens the sector's sustainability and risks jeopardising attempts to involve the sector in addressing the social determinants of health.

SARS-CoV-2 Transmission Risk in the School Environment: a pilot case-ascertained prospective study to inform future school-based surveillance.

BACKGROUND: There is no current active or passive disease surveillance programme focused on schools in South Africa. As such the country is missing an opportunity to rapidly and effectively flag and address pathogen outbreaks, for example SARS-CoV-2, in a key closed setting. Furthermore, the role of school transmission in the spread of the SARS-CoV-2 virus within communities is uncertain.  Objective. This pilot study, conducted during March 2022 in Cape Town, aimed to indicate the feasibility of conducting intense active contact-tracing in a school environment prior to a large national study to compare school versus community SARS-CoV-2 transmission risk.  Methods. We conducted a pilot school-level case-ascertained prospective study with a component of enhanced surveillance. Following study initiation, the first learner at a participating school who tested SARS-CoV-2 positive (via Polymerase Chain Reaction (PCR) or a Rapid Antigen Test (RAT)) was invited to join the study as the index case and all their school-based close contacts were followed up telephonically, monitored for symptoms for 14 days, and tested using a PCR if any symptoms were reported.  Results. On 8th March 2022, a student with RAT laboratory-confirmed COVID-19 was identified and they and their guardian consented to participate as the index case. Of the 11 eligible close contacts, six provided consent/assent and completed symptom monitoring calls until the end of the 14-day study period. The Secondary Attack Rate (SAR) was 2/11 (18.18%) of all close contacts who were at risk of infection, 2/4 (50.0%) of all those close contacts who developed symptoms, and 2/4 (50.0%) of all those close contacts who developed symptoms and were tested for SARS-CoV-2. During the same period, the school reported that nine of the 926 learner body tested COVID-19 positive (0.97%). Total hours spent conducting monitoring for 6 learners was 27 hours, with each learner requiring approximately 4.5 hours of contact time during the study period.  Conclusion. This is the first South African school-based COVID-19 transmission study, the results of which can inform national discussions regarding the role of schools and school-based active and passive surveillance in pathogen prevention and control.

The impact of COVID-19 on the hot food takeaway planning regulatory environment: perspectives of local authority professionals in the North East of England.

BACKGROUND & AIMS: Planning regulations have been used to prevent the over-proliferation of hot food takeaways, minimising the impact of local obesogenic environments. To help mitigate the effects of lockdown, the UK government introduced temporary changes in March 2020 to Planning Regulations for England, allowing food retailers to open for takeaway services beyond 'ancillary' level without needing to apply for planning permission through permitted development rights (PDR). Businesses are required to notify their local authority (LA) when they implement PDRs. To better understand the impact of regulations on the policy and practice of key professional groups, Public Health England commissioned Teesside University to undertake scoping research in the North East of England. METHODS: A focus group and interviews were conducted with 15 professionals from 7 of 12 North East LAs. Professions included Planners, Public Health Leads, Environmental Health Officers and Town Centre Managers. Data were analysed using a codebook thematic analysis approach. An interpretation meeting with some participants was conducted. RESULTS: LAs were not aware of most businesses notifying them of new regulation adherence despite taking up PDRs, but were considered low-priority with many lacking formal recording procedures. There were concerns about health consequences of the changes, and consensus relating to ongoing issues with capacity across all professional groups, largely due to the continuing pandemic and absence of a strategy out of temporary measures. Concerns existed around ensuring cessation of restaurants trading as takeaways, and hygiene inspections backlog. Many (personally) saw new takeaways as a lifeline, offering broader menus and preserving local economies. CONCLUSION: Lack of information around the number of restaurants/pubs using PDR to trade as takeaway services, ongoing capacity issues of LAs and, at the time, the absence of a strategy post regulation changes, meant there were high levels of uncertainty regarding the impacts of these temporary measures.

HIV care coverage among HIV-positive adolescent girls and young women in South Africa: Results from the HERStory Study.

BACKGROUND: Health service coverage cascades measure the proportion of a population in need of a service that experienced a positive health outcome from the service, and enable tracking of progress in achieving universal health coverage and inequities in care coverage. OBJECTIVES: To investigate HIV care coverage among HIV-positive adolescent girls and young women (AGYW) living in six South African districts, compare coverage by age and socioeconomic status (SES), and investigate other associated factors including participation in a combination HIV prevention intervention. METHODS: The HERStory Study was an evaluation of the combination intervention, comprising a representative household survey of AGYW aged 15 - 24 years living in six intervention districts. From September 2017 to November 2018, biological, sociodemographic and behavioural data were collected. HIV-positive status, initiation of antiretroviral therapy (ART) and viral suppression were determined through laboratory tests (enzyme-linked immunosorbent assay for HIV antibodies, antiretroviral (ARV) metabolites and viral load (VL) testing). Viral suppression was defined as a VL <1 000 copies/mL. Knowledge of HIV-positive status was self-reported, and participants testing positive for ARV metabolites were assumed to have known their HIV-positive status. Unconditional HIV care cascades were created, stratified by age and SES. We used Pearson's χ2 tests corrected for survey-based analysis to describe factors associated with knowledge of HIV status, and being on ART. RESULTS: Of the 4 399 participants, 568 were HIV-positive (12.4%), of whom 60.8% (95% confidence interval (CI) 57.1 - 64.5) knew their status, 50.6% (95% CI 46.6 - 54.0) were on ART, and 62.1% (95% CI 58.4 - 65.9) were virally suppressed. Most participants (84.9%) were in the lower SES group, and they had better coverage than the higher SES group: 61.9% (95% CI 58.3 - 65.4) knew their status, 52.1% (95% CI 48.4 - 55.9) were on ART, and 64.9% (95% CI 61.3 - 68.4) were virally suppressed, compared with 55.0% (95% CI 42.1 - 68.0), 40.0% (95% CI 29.2 - 50.8), and 46.6% (95% CI 34.5 - 58.7), respectively. Participants aged 15 - 19 years had slightly inferior coverage to the 20 - 24-year-old group: 57.5% knew their status, 46.1% were on ART and 59.5% were virally suppressed, compared with 62.3%, 52.2% and 63.3%. CONCLUSIONS: These findings emphasise the need to close the gaps in HIV care coverage among AGYW, of whom only 61% knew their HIV-positive status and only 62% were virally suppressed. There is pro-poor inequality in HIV care coverage, with those in lower socioeconomic groups more likely to be virally suppressed.

Rapid review of the effects of cloth and medical masks for preventing transmission of SARS-CoV-2 in community and household settings.

BACKGROUND: Evidence on mask use in the general population is needed to inform SARS-CoV-2 responses. OBJECTIVES: To assess the effectiveness of cloth and medical masks for preventing SARS-CoV-2 transmission in community settings. METHODS: Two rapid reviews were conducted searching three electronic databases (PubMed, Embase, Cochrane Library) and two clinical trials registries on 30 and 31 March 2020. RESULTS: We screened 821 records and assessed nine full-text articles for eligibility. One and seven RCTs were included for cloth and medical mask reviews, respectively. No SARS-CoV-2-specific RCTs and no cloth mask RCTs in community settings were identified. A single hospital-based RCT provided indirect evidence that, compared with medical masks, cloth masks probably increase clinical respiratory illnesses (relative risk (RR) 1.56; 95% confidence interval (CI) 0.98 - 2.49) and laboratory-confirmed respiratory virus infections (RR 1.54; 95% CI 0.88 - 2.70). Evidence for influenza-like illnesses (ILI) was uncertain (RR 13.00; 95% CI 1.69 - 100.03). Two RCTs provide low-certainty evidence that medical masks may make little to no difference to ILI infection risk versus no masks (RR 0.98; 95% CI 0.81 - 1.19) in the community setting. Five RCTs provide low-certainty evidence that medical masks may slightly reduce infection risk v. no masks (RR 0.81; 95% CI 0.55 - 1.20) in the household setting. CONCLUSIONS: Direct evidence for cloth and medical mask efficacy and effectiveness in the community is limited. Decision-making for mask use may consider other factors such as feasibility and SARS-CoV-2 transmission dynamics; however, well-designed comparative effectiveness studies are required.

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

BACKGROUND: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC). METHODS: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC. The recommended phase 2 dose (RP2D) was identified using a 3+3 design. The single-arm phase 2 assessed overall response (ORR) per RECIST 1.1 in patients previously treated with bevacizumab. Secondary objectives included progression free survival (PFS) and duration of response. RESULTS: The RP2D was established as 15 mg/m2 EP0057 Q2W plus 80 mg/m2 paclitaxel administered 3 weeks on/1 week off. Nine patients enrolled on phase 1b, with no DLTs; 21 additional patients enrolled on phase 2. All completed >1 cycle. Median age was 62 (44-76) years, 57% ≥3 prior therapies. For the primary analysis, 6/19 patients with prior bevacizumab had confirmed responses (ORR=31.6% (95% CI: 15.4% to 54.0%)) including one complete response (CR). Median PFS was 5.4 months. Most common grade 3/4 adverse events attributed to treatment were decreased neutrophil count (13, 43%) and anemia (3, 10%). CONCLUSIONS: Although the observed ORR was not statistically better than the historical control rate, EP0057 remains an interesting option for treatment of recurrent EOC. EP0057 exhibits high plasma drug retention, slow clearance, and controlled slow release of CPT from the polymer when administered alone and with paclitaxel. (NCT02389985) 242 words.

Adolescent girls and young women: Policy-to-implementation gaps for addressing sexual and reproductive health needs in South Africa.

Sexual and reproductive health (SRH) services for adolescent girls and young women (AGYW) remain inadequate - both globally and in South Africa (SA). We systematically scoped the available policies and guidelines for SRH-related policy for AGYW in SA. We found many available policies and guidelines to address issues of family planning, HIV prevention and care and antenatal and maternal care. Despite the wealth of guidance, SA's high rates of pregnancy and HIV transmission continue unabated. Our policy review and analysis identified issues for researchers and policymakers to consider when developing and implementing programmes to improve SRH services. We suggest that considering national policies alongside evidence of what is effective, as well as contextual barriers to and enablers of strategies to address AGYW needs for SRH, are among the key steps to addressing the policy-to-implementation gap.

Interventions for preventing unintended pregnancies among adolescents.

South Africa (SA) has an increasingly high rate of unintended pregnancies among adolescents, which are coupled with poor contraception knowledge. We highlight a systematic review that evaluated the effects of prevention interventions for unintended adolescent pregnancies, and provide implications for practice that are relevant to the SA context. The findings suggest the need for multifaceted interventions that are aligned with adolescent sexual and reproductive health best practices to address the unmet contraception knowledge gap, as well as unintended pregnancies among adolescents.

Moving towards universal health coverage: Strengthening the evidence ecosystem for the South African health system.

Health policy and systems research (HPSR) guides health system reforms and is essential for South Africa (SA)'s progress towards universal coverage of high-quality healthcare. For HPSR evidence to inform and strengthen health systems, it needs to flow efficiently between evidence producers, evidence synthesisers, evidence processers and disseminators and evidence implementors in an evidence ecosystem. A substantial body of evidence for health systems strengthening is generated in SA, and this informs national and international health system guidelines and guidance. In this manuscript, in celebration of the 50th anniversary of the SA Medical Research Council, we apply an evidence ecosystem lens to the SA health system, and discuss its current functioning in support of the achievement of a high-quality health system that is able to achieve universal health coverage. We use three case studies to describe successes, challenges and gaps in the functioning of the evidence ecosystem. The first case study focuses on using evidence to strengthen health-system governance and support for community health worker programmes. The second case focuses on managing the growing epidemic of drug-resistant tuberculosis, while the third case focuses on social protection, the child support grant and its impact on health. SA scientists are part of global initiatives to strengthen the health-systems evidence ecosystem, specifically through pioneering methods to synthesise evidence and produce evidence-informed guidelines to facilitate evidence use in health-system decision-making. SA institutes of health policy analysis facilitate involvement of evidence producers and synthesisers in the national health system policy-making process. A future priority is to further strengthen national initiatives to translate evidence into policy and practice and to sustain capacity for continuous technical support to health-systems policy development and implementation.

First social impact bond for the SAMRC: A novel financing strategy to address the health and social challenges facing adolescent girls and young women in South Africa.

A social impact bond (SIB) is an innovative financing mechanism to attract investors to social programmes traditionally funded by governments. In this article, in celebration of the 50th anniversary of the South African Medical Research Council (SAMRC), the authors describe the SAMRC's first foray into this new world of financing through a SIB to improve the health and quality of life of adolescent girls and young women (AGYW). The AGYW SIB is in its preparatory phase and is scheduled for implementation in 2020. The authors describe the mechanism, including financial flows and the process of customising the SIB to meet the needs of AGYW, focusing on HIV prevention and treatment and the prevention and management of unintended pregnancies in schoolgoing AGYW. The authors outline an approach to designing the package of interventions, the metrics associated with such a programme and the business model. It is hypothesised that the proposed approach will lead to an improvement in programmatic outcomes, monitoring and evaluation tools and cost-effectiveness, and will develop key learning data for the future use of SIBs in health service delivery.

Weak correlation of bleeding scores to platelet electron microscopy: A retrospective chart review of pediatric patients with delta-storage pool disorder.

BACKGROUND: Delta granule storage pool deficiency (δ-SPD) is a rare platelet disorder in which a deficiency of platelet granules leads to poor aggregation, resulting in varying clinical bleeding phenotypes. Children with δ-SPD have variable laboratory results, making the proper diagnosis and evaluation controversial. OBJECTIVES: To describe the demographic and laboratory trends of this population and to assess the value of electron microscopy in diagnostic evaluation and its correlation to bleeding symptoms. METHODS: We performed a retrospective review of 109 pediatric patients diagnosed with δ-SPD. We collected demographic information and bleeding scores using a validated bleeding assessment tool. A descriptive and exploratory analysis was performed. RESULTS: The majority of patients were female, with an average age at diagnosis of 11.61 years. Females were diagnosed at a significantly older age presenting most often with menorrhagia, while males presented most commonly with epistaxis. The majority showed normal lumiaggregometry, the mean platelet electron microscopy (PEM) value was 2.37, and the mean bleeding score was 6. Bleeding assessment tool and PEM had a significantly weak correlation. CONCLUSIONS: Patients with more dense granules per platelet had higher bleeding scores than those with fewer dense granules per platelet. The current body of evidence does not favor the use of PEM in routine clinical practice, and results are difficult to interpret. In patients with severe mucocutaneous bleeding symptoms and normal platelet aggregation studies, consideration should be given to an alternative diagnosis and further evaluation is warranted.

Genetic and phenotypic overlap of specific obsessive-compulsive and attention-deficit/hyperactive subtypes with Tourette syndrome.

BACKGROUND: The unique phenotypic and genetic aspects of obsessive-compulsive (OCD) and attention-deficit/hyperactivity disorder (ADHD) among individuals with Tourette syndrome (TS) are not well characterized. Here, we examine symptom patterns and heritability of OCD and ADHD in TS families. METHOD: OCD and ADHD symptom patterns were examined in TS patients and their family members (N = 3494) using exploratory factor analyses (EFA) for OCD and ADHD symptoms separately, followed by latent class analyses (LCA) of the resulting OCD and ADHD factor sum scores jointly; heritability and clinical relevance of the resulting factors and classes were assessed. RESULTS: EFA yielded a 2-factor model for ADHD and an 8-factor model for OCD. Both ADHD factors (inattentive and hyperactive/impulsive symptoms) were genetically related to TS, ADHD, and OCD. The doubts, contamination, need for sameness, and superstitions factors were genetically related to OCD, but not ADHD or TS; symmetry/exactness and fear-of-harm were associated with TS and OCD while hoarding was associated with ADHD and OCD. In contrast, aggressive urges were genetically associated with TS, OCD, and ADHD. LCA revealed a three-class solution: few OCD/ADHD symptoms (LC1), OCD & ADHD symptoms (LC2), and symmetry/exactness, hoarding, and ADHD symptoms (LC3). LC2 had the highest psychiatric comorbidity rates (⩾50% for all disorders). CONCLUSIONS: Symmetry/exactness, aggressive urges, fear-of-harm, and hoarding show complex genetic relationships with TS, OCD, and ADHD, and, rather than being specific subtypes of OCD, transcend traditional diagnostic boundaries, perhaps representing an underlying vulnerability (e.g. failure of top-down cognitive control) common to all three disorders.

Measuring adolescent mental health around the globe: psychometric properties of the self-report Strengths and Difficulties Questionnaire in South Africa, and comparison with UK, Australian and Chinese data.

AIMS: This study evaluated the psychometric properties of the Strengths and Difficulties Questionnaire Self-Report (SDQ-S) in South African adolescents, and compared findings with data from the UK, Australia and China. METHODS: A sample of 3451 South African adolescents in grade 8, the first year of secondary school (Mage = 13.7 years), completed the SDQ-S in Afrikaans, English or isiXhosa. Means, group differences and internal consistency were analysed using SPSS V22, and confirmatory factor analyses were conducted using MPlus V7. RESULTS: In the South African sample, significant gender differences were found for four of the five sub-scale means and for total difficulties, but gender differences of alpha scores were negligible. The internal consistency for the total difficulties, prosocial behaviour and emotional symptoms sub-scales were fair. UK cut-off values for caseness (set to identify the top 10% of scores in a UK sample) led to a higher proportion of South African adolescents classified in the 'abnormal' range on emotional and peer difficulties and a lower proportion classified in the 'abnormal' range for hyperactivity. South African cut-offs were therefore generated. The cross-country comparison with UK, Australian and Chinese data showed that South African adolescent boys and girls had the highest mean scores on total difficulties as well as on the subscales of emotional symptoms and conduct problems. In contrast, South African boys and girls had the lowest mean scores for hyperactivity/inattention. The UK boys and girls had the highest mean scores for hyperactivity/inattention, while the Australian sample had the highest scores for prosocial behaviours. The Chinese boys had the highest peer problem mean scores and Chinese boys and girls had the lowest means on prosocial behaviours. Confirmatory factor analyses showed significant item loadings with loadings higher than 0.40 for the emotional and prosocial behaviour sub-scales on the five-factor model, but not for all relevant items on the other three domains. CONCLUSIONS: Findings support the potential usefulness of the SDQ-S in a South African setting, but suggest that the SDQ-S should not be used with UK cut-off values, and indicate the need for further validation and standardisation work in South African adolescents. We recommend that in-country cut-offs for 'caseness' should be used for clinical purposes in South Africa, that cross-country comparisons should be made with caution, and that further examination of naturalistic clusters and factors of the SDQ should be performed in culturally and contextually diverse settings.

Heritability of tic disorders: a twin-family study.

BACKGROUND: Genetic-epidemiological studies that estimate the contributions of genetic factors to variation in tic symptoms are scarce. We estimated the extent to which genetic and environmental influences contribute to tics, employing various phenotypic definitions ranging between mild and severe symptomatology, in a large population-based adult twin-family sample. METHOD: In an extended twin-family design, we analysed lifetime tic data reported by adult mono- and dizygotic twins (n = 8323) and their family members (n = 7164; parents and siblings) from 7311 families in the Netherlands Twin Register. We measured tics by the abbreviated version of the Schedule for Tourette and Other Behavioral Syndromes. Heritability was estimated by genetic structural equation modeling for four tic disorder definitions: three dichotomous and one trichotomous phenotype, characterized by increasingly strictly defined criteria. RESULTS: Prevalence rates of the different tic disorders in our sample varied between 0.3 and 4.5% depending on tic disorder definition. Tic frequencies decreased with increasing age. Heritability estimates varied between 0.25 and 0.37, depending on phenotypic definitions. None of the phenotypes showed evidence of assortative mating, effects of shared environment or non-additive genetic effects. CONCLUSIONS: Heritabilities of mild and severe tic phenotypes were estimated to be moderate. Overlapping confidence intervals of the heritability estimates suggest overlapping genetic liabilities between the various tic phenotypes. The most lenient phenotype (defined only by tic characteristics, excluding criteria B, C and D of DSM-IV) rendered sufficiently reliable heritability estimates. These findings have implications in phenotypic definitions for future genetic studies.

Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study.

OBJECTIVES: Famine exposure in utero can 'programme' an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure. DESIGN: A historical cohort study was performed as part of a wider cross-sectional survey. Exposure to famine was defined through birth date and historical records and participants were selected according to: (A) exposure to famine in postnatal life, (B) exposure to famine during gestation and (C) unexposed. SETTING: Matlab, a rural area in the Chittagong division of Bangladesh. PARTICIPANTS: Young adult men and women (n=190) recruited to a historical cohort study with a randomised subsample included in an epigenetic study (n=143). OUTCOME MEASURES: Primary outcome measures of weight, body mass index and oral glucose tolerance tests (0 and 120 min glucose). Secondary outcome measures included DNA methylation using genome-wide and targeted analysis of metastable epialleles sensitive to maternal nutrition. RESULTS: More young adults exposed to famine in gestation were underweight than those postnatally exposed or unexposed. In contrast, more young adults exposed to famine postnatally were overweight compared to those gestationally exposed or unexposed. Underweight adults exposed to famine in gestation in utero were hyperglycaemic following a glucose tolerance test, and those exposed postnatally had elevated fasting glucose, compared to those unexposed. Significant differences in DNA methylation at seven metastable epialleles (VTRNA2-1, PAX8, PRDM-9, near ZFP57, near BOLA, EXD3) known to vary with gestational famine exposure were identified. CONCLUSIONS: Famine exposure in developmental life programmed Bangladeshi offspring towards diabetes and obesity in adulthood but gestational and postnatal windows of exposure had variable effects on phenotype. DNA methylation differences were replicated at previously identified metastable epialleles sensitive to periconceptual famine exposure.

Prostate-specific antigen testing rates and referral patterns from general practice data in England.

BACKGROUND: There is currently no national screening programme for prostate cancer in England, but eligible men can request a prostate-specific antigen (PSA) test from their general practitioner (GP). There are no routinely available data to monitor the extent of PSA testing and referral. AIM: The aim of this study was to investigate the rate of PSA testing in general practice and subsequent patterns of referral. DESIGN AND SETTING: Data obtained from the Clinical Practice Research Datalink (CPRD) for men aged 45-84 years who had a PSA test during 2010-2011, registered in practices in England with linked Hospital Episode Statistics (HES) data. METHOD: Patient data were linked to previous tests and consultations. Rates of PSA testing and proportions of men retested and referred to secondary care were calculated. RESULTS: Overall, 8.74 (95% CI 8.67-8.82) of men per 100 person-years were tested at least once in 2010, and 9.45 (95% CI 9.37-9.53) in 2011. Rates increased with age and decreased with increasing level of deprivation. Of the 53,069 men tested in 2010, 11,289 (21.3%) had a previous PSA test within the past 12 months. Of men with raised PSA according to age specific guidelines, 22.4% (2113/9425) were referred to secondary care within 14 days, with 36% of the remainder retested within 6 months. CONCLUSIONS: Rates of PSA testing have increased compared with earlier studies; the data suggest that many GPs are retesting men with raised PSA rather than referring immediately. More routine data on PSA testing, including reasons for testing, and subsequent management and outcomes, are required.

Mobilization without immune depletion fails to restore immunological tolerance or preserve beta cell function in recent onset type 1 diabetes.

Granulocyte colony-stimulating factor (G-CSF) has been used to restore immune competence following chemoablative cancer therapy and to promote immunological tolerance in certain settings of autoimmunity. Therefore, we tested the potential of G-CSF to impact type 1 diabetes (T1D) progression in patients with recent-onset disease [n = 14; n = 7 (placebo)] and assessed safety, efficacy and mechanistic effects on the immune system. We hypothesized that pegylated G-CSF (6 mg administered subcutaneously every 2 weeks for 12 weeks) would promote regulatory T cell (Treg) mobilization to a degree capable of restoring immunological tolerance, thus preventing further decline in C-peptide production. Although treatment was well tolerated, G-CSF monotherapy did not affect C-peptide production, glycated haemoglobin (HbA1c) or insulin dose. Mechanistically, G-CSF treatment increased circulating neutrophils during the 12-week course of therapy (P < 0·01) but did not alter Treg frequencies. No effects were observed for CD4(+) : CD8(+) T cell ratio or the ratio of naive : memory (CD45RA(+)/CD45RO(+)) CD4(+) T cells. As expected, manageable bone pain was common in subjects receiving G-CSF, but notably, no severe adverse events such as splenomegaly occurred. This study supports the continued exploration of G-CSF and other mobilizing agents in subjects with T1D, but only when combined with immunodepleting agents where synergistic mechanisms of action have previously demonstrated efficacy towards the preservation of C-peptide.

Error-related brain activity dissociates hoarding disorder from obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with an abnormally large error-related negativity (ERN), an electrophysiological measure of error monitoring in response to performance errors, but it is unclear if hoarding disorder (HD) also shows this abnormality. This study aimed to determine whether the neurophysiological mechanisms underlying error monitoring are similarly compromised in HD and OCD. METHOD: We used a visual flanker task to assess ERN in response to performance errors in 14 individuals with HD, 27 with OCD, 10 with HD+OCD, and 45 healthy controls (HC). Age-corrected performance and ERN amplitudes were examined using analyses of variance and planned pairwise group comparisons. RESULTS: A main effect of hoarding on ERN (p = 0.031) was observed, indicating ERN amplitudes were attenuated in HD relative to non-HD subjects. A group × age interaction effect on ERN was also evident. In HD-positive subjects, ERN amplitude deficits were significantly greater in younger individuals (r = -0.479, p = 0.018), whereas there were no significant ERN changes with increasing age in OCD and HC participants. CONCLUSIONS: The reduced ERN in HD relative to OCD and HC provides evidence that HD is neurobiologically distinct from OCD, and suggests that deficient error monitoring may be a core pathophysiological feature of HD. This effect was particularly prominent in younger HD participants, further suggesting that deficient error monitoring manifests most strongly early in the illness course and/or in individuals with a relatively early illness onset.

Parental mood during pregnancy and post-natally is associated with offspring risk of Tourette syndrome or chronic tics: prospective data from the Avon Longitudinal Study of Parents and Children (ALSPAC).

Little is known about risk factors for Tourette syndrome (TS) and chronic tic disorders (CT) but maternal psychological morbidity in pregnancy may be associated with TS/CT. We examined whether pre- and post-natal parental anxiety and/or depression are associated with risk of TS/CT in the Avon Longitudinal Study of Parents and Children. We compared self-reported anxiety and depression measures collected prospectively at four time points (18 and 32 weeks prenatally, and 8 weeks and 8 months post-natally) among parents of children who subsequently met criteria for TS/CT at 13 years of age as compared to other children from the cohort. We adjusted for various socioeconomic measures and tested both for time period-specific exposure and chronic exposure using multivariable logistic regression models. 122 children had TS/CT (50 TS, 72 CT) and 5968 children had no tics. In crude analyses, both pre- and post-natal maternal anxiety and depression, but only post-natal paternal depression at 8 months, showed associations with TS/CT. In the final, adjusted multivariable models, chronic maternal anxiety (odds ratio 2.17, 95% CI 1.23, 3.84, p = 0.007) and pre-natal maternal depression (odds ratio 1.86, 95% CI 1.02, 3.39, p = 0.04) showed associations with TS/CT though the latter was consistent with chance (p = 0.07) after adjustment for past maternal depression. We find associations between maternal psychological morbidity pre- and post-natally and risk of future TS/CT in offspring. These associations may reflect either shared genetic susceptibility or a pre-natal exposure. Further work is required to see if these findings can be replicated in larger datasets.