The cascade of care for children and adolescents with HIV in the UK and Ireland, 2010 to 2016.

INTRODUCTION: The UNAIDS 90-90-90 targets for the cascade of care are widely used to monitor the success of HIV care programmes but there are few studies in children. We assessed the cascade for children and adolescents living with HIV in the national Collaborative HIV Paediatric Study (CHIPS) in the UK and Ireland. METHODS: Utilizing longitudinal data from CHIPS we compared the cascade of care for 2010, 2013 and 2016. Among children diagnosed with HIV and not known to be lost to follow-up at the start of each calendar year, we summarized the proportion in active paediatric care during that year (defined as having ≥1 clinic visit, CD4 or viral load measurement, or change to antiretroviral therapy (ART) regimen), and of these, the proportion on ART at last visit in that year. Among those on ART, the proportion with viral suppression (<200 copies/mL) and good immune status (WHO immunological stage none-/mild-for-age) at last visit in the year were summarized. Among those in care in 2016, outcomes were compared by current age, place of birth (born abroad vs. UK/Ireland) and sex. RESULTS: Of children in paediatric HIV care at the start of 2010, 2013 and 2016 (n = 1249, 1157, 905 respectively), the proportion in active care during that calendar year was high throughout at 97 to 99%. Of those in active care, the proportion on ART increased from 79% to 85% and 92% respectively (p < 0.001). Among those on ART, the proportion with viral suppression and good immune status was stable at 83% to 86% and 85% to 88%, respectively, across the years. Among children in care in 2016, those aged ≥15 years were less likely to be virally suppressed (79% vs. 91%, p < 0.001) or to have good immune status (78% vs. 94%, p < 0.001) compared to younger children; there were no differences by place of birth or sex. CONCLUSIONS: Children and adolescents in the UK and Ireland national cohort had high retention in care. The proportion on ART increased significantly over time although there was no change in viral suppression or good immune status. Poorer outcomes among adolescents highlight the need for targeted support for this population

Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study

Aims/hypothesis: The aim of this prospective nationwide study was to examine antenatal pregnancy care and pregnancy outcomes in women with type 1 and type 2 diabetes, and to describe changes since 2002/2003. Methods: This national population-based cohort included 3036 pregnant women with diabetes from 155 maternity clinics in England and Wales who delivered during 2015. The main outcome measures were maternal glycaemic control, preterm delivery (before 37 weeks), infant large for gestational age (LGA), and rates of congenital anomaly, stillbirth and neonatal death. Results: Of 3036 women, 1563 (51%) had type 1, 1386 (46%) had type 2 and 87 (3%) had other types of diabetes. The percentage of women achieving HbA1c < 6.5% (48 mmol/mol) in early pregnancy varied greatly between clinics (median [interquartile range] 14.3% [7.7–22.2] for type 1, 37.0% [27.3–46.2] for type 2). The number of infants born preterm (21.7% vs 39.7%) and LGA (23.9% vs 46.4%) were lower for women with type 2 compared with type 1 diabetes (both p < 0.001). The prevalence rates for congenital anomaly (46.2/1000 births for type 1, 34.6/1000 births for type 2) and neonatal death (8.1/1000 births for type 1, 11.4/1000 births for type 2) were unchanged since 2002/2003. Stillbirth rates are almost 2.5 times lower than in 2002/2003 (10.7 vs 25.8/1000 births for type 1, p = 0.0012; 10.5 vs 29.2/1000 births for type 2, p = 0.0091). Conclusions/interpretation: Stillbirth rates among women with type 1 and type 2 diabetes have decreased since 2002/2003. Rates of preterm delivery and LGA infants are lower in women with type 2 compared with type 1 diabetes. In women with type 1 diabetes, suboptimal glucose control and high rates of perinatal morbidity persist with substantial variations between clinics

Specialist group therapy for firesetting behaviour: evidence of a treatment effect from a non-randomised pilot trial with male prisoners

Despite huge societal costs associated with firesetting, no standardized therapy has been developed to address this hugely damaging behavior. This study reports the evaluation of the first standardized CBT group designed specifically to target deliberate firesetting in male prisoners (the Firesetting Intervention Programme for Prisoners; FIPP). Fifty-four male prisoners who had set a deliberate fire were referred for FIPP treatment by their prison establishment and psychologically assessed at baseline, immediately post treatment, and three-months post treatment. Prisoners who were treatment eligible yet resided at prison establishments not identified for FIPP treatment were recruited as Treatment as Usual controls and tested at equivalent time-points. Results showed that FIPP participants improved on one of three primary outcomes (i.e., problematic fire interest and associations with fire), and made some improvement on secondary outcomes (i.e., attitudes towards violence and antisocial attitudes) post treatment relative to controls. Most notable gains were made on the primary outcome of fire interest and associations with fire and individuals who gained in this area tended to self-report more serious firesetting behavior. FIPP participants maintained all key improvements at three-month follow up. These outcomes suggest that CBT should be targeted at those holding the most serious firesetting history

Is there an association between seeing incidents of alcohol or drug use in films and young Scottish adults' own alcohol or drug use? A cross sectional study

&lt;p&gt;Background: As the promotion of alcohol and tobacco to young people through direct advertising has become increasingly restricted, there has been greater interest in whether images of certain behaviours in films are associated with uptake of those behaviours in young people. Associations have been reported between exposure to smoking images in films and smoking initiation, and between exposure to film alcohol images and initiation of alcohol consumption, in younger adolescents in the USA and Germany. To date no studies have reported on film images of recreational drug use and young people's own drug use.&lt;/p&gt; &lt;p&gt;Methods: Cross sectional multivariable logistic regression analysis of data collected at age 19 (2002-4) from a cohort of young people (502 boys, 500 girls) previously surveyed at ages 11 (in 1994-5), 13 and 15 in schools in the West of Scotland. Outcome measures at age 19 were: exceeding the 'sensible drinking' guidelines ('heavy drinkers') and binge drinking (based on alcohol consumption reported in last week), and ever use of cannabis and of 'hard' drugs. The principle predictor variables were an estimate of exposure to images of alcohol, and of drug use, in films, controlling for factors related to the uptake of substance use in young people.&lt;/p&gt; &lt;p&gt;Results: A third of these young adults (33%) were classed as 'heavy drinkers' and half (47%) as 'binge drinkers' on the basis of their previous week's consumption. Over half (56%) reported ever use of cannabis and 13% ever use of one or more of the 'hard' drugs listed. There were linear trends in the percentage of heavy drinkers (p = .018) and binge drinkers (p = 0.012) by film alcohol exposure quartiles, and for ever use of cannabis by film drug exposure (p = .000), and for ever use of 'hard' drugs (p = .033). The odds ratios for heavy drinking (1.56, 95% CI 1.06-2.29 comparing highest with lowest quartile of film alcohol exposure) and binge drinking (1.59, 95% CI 1.10-2.30) were attenuated by adjustment for gender, social class, family background (parental structure, parental care and parental control), attitudes to risk-taking and rule-breaking, and qualifications (OR heavy drinking 1.42, 95% CI 0.95-2.13 and binge drinking 1.49, 95% CI 1.01-2.19), and further so when adjusting for friends' drinking status (when the odds ratios were no longer significant). A similar pattern was seen for ever use of cannabis and 'hard' drugs (unadjusted OR 1.80, 95% CI 1.24-2.62 and 1.57, 95% CI 0.91-2.69 respectively, 'fully' adjusted OR 1.41 (0.90-2.22 and 1.28 (0.66-2.47) respectively).&lt;/p&gt; &lt;p&gt;Conclusions: Despite some limitations, which are discussed, these cross-sectional results add to a body of work which suggests that it is important to design good longitudinal studies which can determine whether exposure to images of potentially health-damaging behaviours lead to uptake of these behaviours during adolescence and early adulthood, and to examine factors that might mediate this relationship.&lt;/p&gt

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

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Developing anti-icing and anti-frosting technology is vital for many different energy generation and consumption systems such as wind turbines, aircraft and heat exchangers, where ice and frost formation is a barrier for efficiency and can severely damage infrastructure and injure people. This work investigates anti-icing and anti-frosting properties of aluminium hierarchical structures with varying geometric parameters. These structures consisted of micro-milled microstructures with nanoscale roughness due to the milling. Fixed-pitch and gradient-pitch structures were tested, the latter of which have not been tested for ice adhesion previously. The structures are characterised for their geometric and surface wetting properties using a scanning electron microscope and a goniometer respectively, then tested for anti-icing properties using a force probe and anti-frosting properties using a wind tunnel with Peltier cooling. Both systems were custom built for this purpose. These aluminium surfaces rely only on topographic modifications - no lubricants, coatings or polymers, which tend to be prone to damage and impractical to reapply in many applications. It was found that these gradient-pitch microstructures had equivalent or better anti-icing/anti-frosting performance than the fixed-pitch structures for both ice adhesion and frosting delay