Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review.

Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing insulin actions. For several decades this drug has been used globally to successfully control hyperglycemia. Lactic acidosis has been shown to be a major adverse effect of metformin in some type-2 diabetic patients, but several studies suggest that it is a typically well-tolerated and safe drug in most patients. Further, recent studies also indicate its potential to reduce the symptoms associated with various inflammatory complications and infectious diseases including coronavirus disease 2019 (COVID-19). These studies suggest that besides diabetes, metformin could be used as an adjuvant drug to control inflammatory and infectious diseases. In this article, we discuss the current understanding of the role of the anti-diabetic drug metformin in the prevention of various inflammatory complications and infectious diseases in both diabetics and non-diabetics.

Modelling the impact of COVID-19 and routine MenACWY vaccination on meningococcal carriage and disease in the UK.

Country-wide social distancing and suspension of non-emergency medical care due to the COVID-19 pandemic will undoubtedly have affected public health in multiple ways. While non-pharmaceutical interventions are expected to reduce the transmission of several infectious diseases, severe disruptions to healthcare systems have hampered diagnosis, treatment, and routine vaccination. We examined the effect of this disruption on meningococcal disease and vaccination in the UK. By adapting an existing mathematical model for meningococcal carriage, we addressed the following questions: What is the predicted impact of the existing MenACWY adolescent vaccination programme? What effect might social distancing and reduced vaccine uptake both have on future epidemiology? Will catch-up vaccination campaigns be necessary? Our model indicated that the MenACWY vaccine programme was generating substantial indirect protection and suppressing transmission by 2020. COVID-19 social distancing is expected to have accelerated this decline, causing significant long-lasting reductions in both carriage prevalence of meningococcal A/C/W/Y strains and incidence of invasive meningococcal disease. In all scenarios modelled, pandemic social mixing effects outweighed potential reductions in vaccine uptake, causing an overall decline in carriage prevalence from 2020 for at least 5 years. Model outputs show strong consistency with recently published case data for England.

Estimating hepatitis B virus prevalence among key population groups for European Union and European Economic Area countries and the United Kingdom: a modelling study.

BACKGROUND: Hepatitis B virus (HBV) epidemiology in Europe differs by region and population risk group, and data are often incomplete. We estimated chronic HBV prevalence as measured by surface antigen (HBsAg) among general and key population groups for each country in the European Union, European Economic Area and the United Kingdom (EU/EEA/UK), including where data are currently unavailable. METHODS: We combined data from a 2018 systematic review (updated in 2021), data gathered directly by the European Centre for Disease Control (ECDC) from EU/EEA countries and the UK and further country-level data. We included data on adults from the general population, pregnant women, first time blood donors (FTBD), men who have sex with men (MSM), prisoners, people who inject drugs (PWID), and migrants from 2001 to 2021, with three exceptions made for pre-2001 estimates. Finite Mixture Models (FMM) and Beta regression were used to predict country and population group HBsAg prevalence. A separate multiplier method was used to estimate HBsAg prevalence among the migrant populations within each country, due to biases in the data available. RESULTS: There were 595 included studies from 31 countries (N = 41,955,969 people): 66 were among the general population (mean prevalence ([Formula: see text]) 1.3% [range: 0.0-7.6%]), 52 among pregnant women ([Formula: see text]1.1% [0.1-5.3%]), 315 among FTBD ([Formula: see text]0.3% [0.0-6.2%]), 20 among MSM ([Formula: see text]1.7% [0.0-11.2%]), 34 among PWID ([Formula: see text]3.9% [0.0-16.9%]), 24 among prisoners ([Formula: see text]2.9% [0.0-10.7%]), and 84 among migrants ([Formula: see text]7.0% [0.2-37.3%]). The FMM grouped countries into 3 classes. We estimated HBsAg prevalence among the general population to be < 1% in 24/31 countries, although it was higher in 7 Eastern/Southern European countries. HBsAg prevalence among each population group was higher in most Eastern/Southern European than Western/Northern European countries, whilst prevalence among PWID and prisoners was estimated at > 1% for most countries. Portugal had the highest estimated prevalence of HBsAg among migrants (5.0%), with the other highest prevalences mostly seen in Southern Europe. CONCLUSIONS: We estimated HBV prevalence for each population group within each EU/EAA country and the UK, with general population HBV prevalence to be < 1% in most countries. Further evidence is required on the HBsAg prevalence of high-risk populations for future evidence synthesis.

Reflections from the 'Hold the door open' project: Inviting older adults across the UK to shape dissemination of health research findings.

BACKGROUND: This project sought to expand patient and public involvement (PPI) practices to the development of research finding dissemination with people aged 55+ years. The project is innovative due to its UK-wide approach and use of PPI to plan better ways to share findings of health research with older adults, extending PPI beyond research project initiation to support dissemination activities. OBJECTIVE: The aim of this study is to understand how to develop effective public engagement activities with older adults to disseminate findings of health research. We hope to promote greater inclusivity and advance our understanding of this demographic. METHODS: This project combined three approaches: (i) an online questionnaire to ask what activities older adults enjoy; (ii) online planning workshops seeking public contributors' input in event planning and (iii) community events to share research findings and raise awareness of PPI. Activities were carried out in Cardiff, Belfast, Glasgow and Tewkesbury. RESULTS: The planning workshops clarified that in-person activities and offering options for activities were important. Based on feedback from our contributors, all our events focused around a talk and question and answer session. Other short activities included light exercise and a writing activity. DISCUSSION: Our multiphase approach helped us develop informative activities that reflected the questionnaire results and the feedback from the workshops, as we tailored our events to each location. A phased approach allowed both researchers and contributors to gradually deepen their understanding. CONCLUSION: Further awareness raising is needed to develop the role older adults currently hold in health research activities. Working closely with existing communities can help broaden diversity. PATIENT OR PUBLIC CONTRIBUTION: Thirty-three public contributors helped facilitate this project. Two of these also contributed to this article by writing a reflection of their experiences, one of whom also provided feedback for the article.

The potential public health impact of adolescent 4CMenB vaccination on Neisseria gonorrhoeae infection in England: a modelling study.

INTRODUCTION: Diagnoses of gonorrhoea in England rose by 26% between 2018 and 2019. Recent evidence that a vaccine against meningococcal B disease currently offered to infants in the UK (4CMenB) could additionally protect (with 31% efficacy) against gonorrhoea has led to renewed hope for a vaccine. A Phase 2 proof-of-concept trial of 4CMenB vaccination against gonorrhoea in adults is currently underway. OBJECTIVES: To investigate the potential public health impact of adolescent gonorrhoea vaccination in England, considering different implementation strategies. METHODS: We developed a deterministic transmission-dynamic model of gonorrhoea infection among heterosexual 13-64-year-olds stratified by age, sex and sexual activity. We explored the impact of a National Immunisation Programme (NIP) among 14-year-olds for a vaccine with 31% efficacy, 6 years' duration of protection, and 85% uptake. We also explored how impact might change for varying efficacy (20-50%) and uptake (75-95%), the addition of a catch-up programme, the use of boosters, and varying duration of protection. RESULTS: An NIP against gonorrhoea could lead to 50,000 (95% credible interval, CrI 31,000-80,000) and 849,000 (95%CrI 476,000-1,568,000) gonorrhoea infections being averted over 10 and 70 years, respectively, in England, for a vaccine with 31% efficacy and 85% uptake. This is equivalent to 25% (95%CrI 17-33%) of heterosexual infections being averted over 70 years. Vaccine impact is predicted to increase over time and be greatest among 13-18-year-olds (39% of infections 95%CrI 31-49% averted) over 70 years. Varying vaccine efficacy and duration of protection had a noticeable effect on impact. Catch-up and booster vaccination increased the short- and long-term impact, respectively. CONCLUSIONS: A partially-effective vaccine against gonorrhoea infection, delivered to 14-year-olds alongside the MenACWY vaccine, could have an important population impact on gonorrhoea. Catch-up and booster vaccination could be considered alongside cohort vaccination to increase impact.

Estimates of hepatitis B virus prevalence among general population and key risk groups in EU/EEA/UK countries: a systematic review.

BackgroundThe burden of chronic hepatitis B virus (HBV) varies across the European Union (EU) and European Economic Area (EEA).AimWe aimed to update the 2017 HBV prevalence estimates in EU/EEA countries and the United Kingdom for 2018 to 2021.MethodsWe undertook a systematic review, adding to HBV prevalence estimates from an existing (2005-2017) database. Databases were searched for original English-language research articles including HBV surface antigen prevalence estimates among the general population, pregnant women, first-time blood donors (FTB), men who have sex with men (MSM), migrants and people in prison. Country experts contributed grey literature data. Risk of bias was assessed using a quality assessment framework.FindingsThe update provided 147 new prevalence estimates across the region (updated total n = 579). Median HBV prevalence in the general population was 0.5% and the highest was 3.8% (Greece). Among FTB, the highest prevalence was 0.8% (Lithuania). Estimates among pregnant women were highest in Romania and Italy (5.1%). Among migrants, the highest estimate was 31.7% (Spain). Relative to 2017 estimates, median prevalence among pregnant women decreased by 0.5% (to 0.3%) and increased by 0.9% (to 5.8%) among migrants. Among MSM, the highest estimate was 3.4% (Croatia). Prevalence among people in prison was highest in Greece (8.3%) and the median prevalence increased by 0.6% (to 2.1%).ConclusionsThe HBV prevalence is low in the general population and confined to risk populations in most European countries with some exceptions. Screening and treatment should be targeted to people in prison and migrants.

Opportunities and challenges for machine learning in weather and climate modelling: hard, medium and soft AI.

In September 2019, a workshop was held to highlight the growing area of applying machine learning techniques to improve weather and climate prediction. In this introductory piece, we outline the motivations, opportunities and challenges ahead in this exciting avenue of research. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

COVID-19 in older people: a rapid clinical review.

INTRODUCTION: the COVID-19 pandemic poses a high risk to older people. The aim of this article is to provide a rapid overview of the COVID-19 literature, with a specific focus on older adults. We frame our findings within an overview of the disease and have also evaluated the inclusion of older people within forthcoming clinical trials. METHODS: we searched PubMed and bioRxiv/medRxiv to identify English language papers describing the testing, treatment and prognosis of COVID-19. PubMed and bioRxiv/medRxiv searches took place on 20 and 24 March 2020, respectively. RESULTS: screening of over 1,100 peer-reviewed and pre-print papers yielded n = 22 on COVID-19 testing, n = 15 on treatment and n = 13 on prognosis. Viral polymerase chain reaction (PCR) and serology are the mainstays of testing, but a positive diagnosis may be increasingly supported by radiological findings. The current evidence for the effectiveness of antiviral, corticosteroid and immunotherapies is inconclusive, although trial data are largely based on younger people. In addition to age, male gender and comorbidities, specific laboratory and radiology findings are important prognostic factors. Evidence suggests that social distancing policies could have important negative consequences, particularly if in place for an extended period. CONCLUSION: given the established association between increasing age and poor prognosis in COVID-19, we anticipate that this rapid review of the current and emergent evidence might form a basis on which future work can be established. Exclusion of older people, particularly those with comorbidities, from clinical trials is well recognised and is potentially being perpetuated in the field of current COVID-19 research.

Influence of commissioned provider type and deprivation score on uptake of the childhood flu immunization.

BACKGROUND: Since 2015/16 the UK seasonal influenza immunization programme has included children aged 5 and 6 years. In the South West of England school-based providers, GPs or community pharmacies were commissioned to deliver the vaccine depending on the locality. We aimed to assess variation in vaccine uptake in relation to the type of commissioned provider, and levels of socioeconomic deprivation. METHODS: Data from the South West of England (2015-16 season) were analysed using multilevel logistic regression to assess variation in vaccine uptake by type of commissioned provider, allowing for clustering of children within delivery sites. RESULTS: Overall uptake in 5 and 6 year olds was 34.3% (37 555/109 404). Vaccine uptake was highest when commissioned through school-based programmes 50.2% (9983/19 867) and lowest when commissioned through pharmacies, 23.1% (4269/18 479). Delivery through schools resulted in less variation by site and equal uptake across age groups, in contrast to GP and pharmacy delivery for which uptake was lower among 6 year olds. Vaccine uptake decreased with increasing levels of deprivation across all types of commissioned provider. CONCLUSION: School-based programmes achieve the highest and most consistent rates of childhood influenza vaccination. Interventions are still needed to promote more equitable uptake of the childhood influenza vaccine.

A DELPHI study on aspects of study design to overcome knowledge gaps on the burden of disease caused by serogroup B invasive meningococcal disease.

BACKGROUND: Value assessment of vaccination programs against serogroup B invasive meningococcal disease (IMD) is on the agenda of public health authorities. Current evidence on the burden due to IMD is unfit for pinning down the nature and magnitude of the full social and economic costs of IMD for two reasons. First, the concepts and components that need to be studied are not agreed, and second, measures of the concepts that have been studied are weak and inconsistent. Thus, the economic evaluation of the available serogroup B meningococcal (MenB) vaccines is difficult. The aims of this DELPHI study are to: (1) agree on the concepts and components determining the burden of MenB diseases that need to be studied; and (2) seek consensus on appropriate methods and study designs to measure quality of life (QoL) associated with MenB induced long-term sequelae in future studies. METHODS: We designed a DELPHI questionnaire based on the findings of a recent systematic review on the QoL associated with IMD-induced long-term sequelae, and iteratively interviewed a panel of international experts, including physicians, health economists, and patient representatives. Experts were provided with a controlled feedback based on the results of the previous round. RESULTS: Experts reached consensus on all questions after two DELPHI rounds. Major gaps in the literature relate (i) to the classification of sequelae, which allows differentiation of severity levels, (ii) to the choice of QoL measures, and (iii) to appropriate data sources to examine long-term changes and deficits in patients' QoL. CONCLUSIONS: Better conceptualisation of the structure of IMD-specific sequelae and of how their diverse forms of severity might impact the QoL of survivors of IMD as well as their family network and care-providers is needed to generate relevant, reliable and generalisable data on QoL in the future. The results of this DELPHI panel provide useful guidance on how to choose the study design, target population and appropriate QoL measures for future research and hence, help promote the appropriateness and consistency in study methodology and sample characteristics.

Estimating the effect of the 2005 change in BCG policy in England: a retrospective cohort study, 2000 to 2015.

BackgroundIn 2005 in England, universal Bacillus Calmette-Guérin (BCG) vaccination of school-age children was replaced by targeted BCG vaccination of high-risk neonates.AimEstimate the impact of the 2005 change in BCG policy on tuberculosis (TB) incidence rates in England.MethodsWe conducted an observational study by combining notifications from the Enhanced Tuberculosis Surveillance system, with demographic data from the Labour Force Survey to construct retrospective cohorts relevant to both the universal and targeted vaccination between 1 January 2000 and 31 December 2010. We then estimated incidence rates over a 5-year follow-up period and used regression modelling to estimate the impact of the change in policy on TB.ResultsIn the non-United Kingdom (UK) born, we found evidence for an association between a reduction in incidence rates and the change in BCG policy (school-age incidence rate ratio (IRR): 0.74; 95% credible interval (CrI): 0.61 to 0.88 and neonatal IRR: 0.62; 95%CrI: 0.44 to 0.88). We found some evidence that the change in policy was associated with an increase in incidence rates in the UK born school-age population (IRR: 1.08; 95%CrI: 0.97 to 1.19) and weaker evidence of an association with a reduction in incidence rates in UK born neonates (IRR: 0.96; 95%CrI: 0.82 to 1.14). Overall, we found that the change in policy was associated with directly preventing 385 (95%CrI: -105 to 881) cases.ConclusionsWithdrawing universal vaccination at school age and targeting vaccination towards high-risk neonates was associated with reduced incidence of TB. This was largely driven by reductions in the non-UK born with cases increasing in the UK born.

Agent-based modelling study of antimicrobial-resistant Neisseria gonorrhoeae transmission in men who have sex with men: towards individualised diagnosis and treatment.

Background Antimicrobial-resistant (AMR) gonorrhoea is a global public health threat. Discriminatory point-of-care tests (POCT) to detect drug sensitivity are under development, enabling individualised resistance-guided therapy. METHODS: An individual-based dynamic transmission model of gonorrhoea infection in MSM living in London has been developed, incorporating ciprofloxacin-sensitive and resistant strains. The time-dependent sexual contact network is captured by periodically restructuring active connections to reflect the transience of contacts. Different strategies to improve treatment selection were explored, including discriminatory POCT and selecting partner treatment based on either the index case or partner susceptibility. Outcomes included population prevalence of gonorrhoea and drug dose counts. RESULTS: It is shown that using POCT to detect ciprofloxacin-sensitive infections could result in a large decrease in ceftriaxone doses (by 70% compared with the reference case in the simulations of this study). It also suggests that ceftriaxone use can be reduced with existing technologies, albeit to a lesser degree; either using index case sensitivity profiles to direct treatment of partners, or testing notified partners with strain discriminatory laboratory tests before treatment, reduced ceftriaxone use in our model (by 27% and 47% respectively). CONCLUSIONS: POCT to detect ciprofloxacin-sensitive gonorrhoea are likely to dramatically reduce reliance on ceftriaxone, but requires the implementation of new technology. In the meantime, the proportion of unnecessary ceftriaxone treatment by testing partners before treatment could be reduced significantly. Alternatively, index case sensitivity profiles could be used to select effective treatments for partners.

Post-consultation illness trajectories in children with acute cough and respiratory tract infection: prospective cohort study.

Background: Little is known about respiratory tract infection (RTI) severity in children following consultation. Objectives: To investigate post-consultation symptom trajectories in children with acute cough and RTI and whether baseline characteristics predict trajectory group. Methods: Prospective cohort study of 2296 children (3 months-16 years) whose parents were invited to report cough severity and duration using a 7-point Likert scale. Longitudinal latent class analysis (LLCA) was used to identify post-consultation symptom trajectories in the first 15 days, and multinomial models to predict class membership. Results: Complete data were available for 1408 children (61%). The best LLCA model identified five post-consultation symptom trajectory groups: 'very rapid recovery' (28.5%), 'rapid recovery' (37.7%), 'intermediate recovery' (18.2%), 'persistent symptoms' (9.5%) and 'initial deterioration with persistent symptoms' (6.0%). Compared with very rapid recovery, parent-reported severe cough in the 24 hours prior to consultation increased the likelihood of rapid recovery (OR 1.79 [95% CI 1.23, 2.60]), intermediate recovery (OR 2.13 [1.38, 3.30] and initial deterioration with persistent symptoms (OR 2.29 [1.26, 4.16]). Initial deterioration was also associated with 'severe barking cough' (OR 3.64 [1.50, 8.82]), 'severely reduced energy in the 24 hours prior to consultation' (OR 3.80 [1.62, 8.87] and higher parent-assessed illness severity at consultation (OR 2.21 [1.17, 4.18]). Conclusion: We identified five distinct symptom trajectory groups showing the majority of children improved post-consultation, with only one group experiencing illness deterioration. The few characteristics associated with group membership did not fall into a pattern that seemed clinically useful.

What gives rise to clinician gut feeling, its influence on management decisions and its prognostic value for children with RTI in primary care: a prospective cohort study.

BACKGROUND: The objectives were to identify 1) the clinician and child characteristics associated with; 2) clinical management decisions following from, and; 3) the prognostic value of; a clinician's 'gut feeling something is wrong' for children presenting to primary care with acute cough and respiratory tract infection (RTI). METHODS: Multicentre prospective cohort study where 518 primary care clinicians across 244 general practices in England assessed 8394 children aged ≥3 months and < 16 years for acute cough and RTI. The main outcome measures were: Self-reported clinician 'gut feeling'; clinician management decisions (antibiotic prescribing, referral for acute admission); and child's prognosis (reconsultation with evidence of illness deterioration, hospital admission in the 30 days following recruitment). RESULTS: Clinician years since qualification, parent reported symptoms (illness severity score ≥ 7/10, severe fever < 24 h, low energy, shortness of breath) and clinical examination findings (crackles/ crepitations on chest auscultation, recession, pallor, bronchial breathing, wheeze, temperature ≥ 37.8 °C, tachypnoea and inflamed pharynx) independently contributed towards a clinician 'gut feeling that something was wrong'. 'Gut feeling' was independently associated with increased antibiotic prescribing and referral for secondary care assessment. After adjustment for other associated factors, gut feeling was not associated with reconsultations or hospital admissions. CONCLUSIONS: Clinicians were more likely to report a gut feeling something is wrong, when they were more experienced or when children were more unwell. Gut feeling is independently and strongly associated with antibiotic prescribing and referral to secondary care, but not with two indicators of poor child health.

Throat swabs in children with respiratory tract infection: associations with clinical presentation and potential targets for point-of-care testing.

Background and objectives: Diagnostic uncertainty over respiratory tract infections (RTIs) in primary care contributes to over-prescribing of antibiotics and drives antibiotic resistance. If symptoms and signs predict respiratory tract microbiology, they could help clinicians target antibiotics to bacterial infection. This study aimed to determine relationships between symptoms and signs in children presenting to primary care and microbes from throat swabs. Methods: Cross-sectional study of children ≥3 months to <16 years presenting with acute cough and RTI, with subset follow-up. Associations and area under receiver operating curve (AUROC) statistics sought between clinical presentation and baseline microbe detection. Microbe prevalence compared between baseline (symptomatic) and follow-up (asymptomatic) visits. Results: At baseline, ≥1 bacteria was detected in 1257/2113 (59.5%) children and ≥1 virus in 894/2127 (42%) children. Clinical presentation was not associated with detection of ≥1 bacteria [AUROC 0.54 (95% CI 0.52-0.56)] or ≥1 virus [0.64 (95% CI 0.61-0.66)]. Individually, only respiratory syncytial virus (RSV) was associated with clinical presentation [AUROC 0.80 (0.77-0.84)]. Prevalence fell between baseline and follow-up; more so in viruses (68% versus 26%, P < 0.001) than bacteria (56% versus 40%, P = 0.01); greatest reductions seen in RSV, influenza B and Haemophilus influenzae. Conclusion: Findings demonstrate that clinical presentation cannot distinguish the presence of bacteria or viruses in the upper respiratory tract. However, individual and overall microbe prevalence was greater when children were unwell than when well, providing some evidence that upper respiratory tract microbes may be the cause or consequence of the illness. If causal, selective microbial point-of-care testing could be beneficial.

The Effects of Live Attenuated Influenza Vaccine on Nasopharyngeal Bacteria in Healthy 2 to 4 Year Olds. A Randomized Controlled Trial.

RATIONALE: Viral infections of the upper respiratory tract may influence the commensal nasopharyngeal bacteria. Changes in the bacterial niche could affect transmission dynamics. Attenuated vaccine viruses can be used to investigate this empirically in humans. OBJECTIVES: To study the effects of mild viral upper respiratory infections on nasopharyngeal bacterial colonization using live attenuated influenza vaccine (LAIV) as a surrogate. METHODS: We used trivalent LAIV to evaluate the effects of viral infection on bacterial carriage and density of Streptococcus pneumoniae, Moraxella catarrhalis, Haemophilus influenzae, and Staphylococcus aureus. A total of 151 healthy children were randomized 1:1 to receive the vaccine starting either at recruitment (n = 74) or 28 days later (n = 77) in a stepped wedge fashion, allowing comparisons between recipients and nonrecipients as well as whole-group comparisons pre- and postvaccination. Bacterial carriage and density were determined using quantitative polymerase chain reaction assays. MEASUREMENTS AND MAIN RESULTS: A total of 151 children were recruited, 77 in the LAIV group and 74 in the control group. LAIV recipients (n = 63 analyzed) showed an apparent transient increase in H. influenzae carriage but no further significant differences in carriage prevalence of the four bacterial species compared with controls (n = 72 analyzed). S. pneumoniae density was substantially higher in vaccine recipients (16,687 vs. 1935 gene copies per milliliter) 28 days after the first dose (P < 0.001). Whole-group multivariable analysis (prevaccine, after one dose, and after two doses) also showed increases in density of other species and H. influenzae carriage prevalence. CONCLUSIONS: In the absence of any safety signals despite widespread use of the vaccine, these findings suggest that bacterial density, and thus transmission rates among children and to people in other age groups, may rise following attenuated influenza infections without associated clinical disease. LAIV could therefore be used as an experimental tool to elucidate the dynamics of transmission of nasopharyngeal bacteria.

Impact of Opioid Substitution Therapy on Antiretroviral Therapy Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected people who inject drugs (PWID) frequently encounter barriers accessing and remaining on antiretroviral therapy (ART). Some studies have suggested that opioid substitution therapy (OST) could facilitate PWID's engagement with HIV services. We conducted a systematic review and meta-analysis to evaluate the impact of concurrent OST use on ART-related outcomes among HIV-infected PWID. METHODS: We searched Medline, PsycInfo, Embase, Global Health, Cochrane, Web of Science, and Social Policy and Practice databases for studies between 1996 to November 2014 documenting the impact of OST, compared to no OST, on ART outcomes. Outcomes considered were coverage and recruitment onto ART, adherence, viral suppression, attrition from ART, and mortality. Meta-analyses were conducted using random-effects modeling, and heterogeneity assessed using Cochran Q test and I(2) statistic. RESULTS: We identified 4685 articles, and 32 studies conducted in North America, Europe, Indonesia, and China were included. OST was associated with a 69% increase in recruitment onto ART (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.32-2.15), a 54% increase in ART coverage (odds ratio [OR], 1.54; 95% CI, 1.17-2.03), a 2-fold increase in adherence (OR, 2.14; 95% CI, 1.41-3.26), and a 23% decrease in the odds of attrition (OR, 0.77; 95% CI, .63-.95). OST was associated with a 45% increase in odds of viral suppression (OR, 1.45; 95% CI, 1.21-1.73), but there was limited evidence from 6 studies for OST decreasing mortality for PWID on ART (HR, 0.91; 95% CI, .65-1.25). CONCLUSIONS: These findings support the use of OST, and its integration with HIV services, to improve the HIV treatment and care continuum among HIV-infected PWID.

Acute and long-term outcomes of SARS-CoV-2 infection in school-aged children in England: Study protocol for the joint analysis of the COVID-19 schools infection survey (SIS) and the COVID-19 mapping and mitigation in schools (CoMMinS) study.

BACKGROUND: The symptom profiles of acute SARS-CoV-2 infection and long-COVID in children and young people (CYP), risk factors, and associated healthcare needs, are poorly defined. The Schools Infection Survey 1 (SIS-1) was a nationwide study of SARS-CoV-2 infection in primary and secondary schools in England during the 2020/21 school year. The Covid-19 Mapping and Mitigation in Schools (CoMMinS) study was conducted in schools in the Bristol area over a similar period. Both studies conducted testing to identify current and previous SARS-CoV-2 infection, and recorded symptoms and school attendance. These research data have been linked to routine electronic health record (EHR) data. AIMS: To better understand the short- and long-term consequences of SARS-CoV-2 infection, and their risk factors, in CYP. METHODS: Retrospective cohort and nested case-control analyses will be conducted for SIS-1 and CoMMinS data linked to EHR data for the association between (1) acute symptomatic SARS-CoV-2 infection and risk factors; (2) SARS-CoV-2 infection and long-term effects on health: (a) persistent symptoms; (b) any new diagnosis; (c) a new prescription in primary care; (d) health service attendance; (e) a high rate of school absence. RESULTS: Our study will improve understanding of long-COVID in CYP by characterising the trajectory of long-COVID in CYP in terms of things like symptoms and diagnoses of conditions. The research will inform which groups of CYP are more likely to get acute- and long-term outcomes of SARS-CoV-2 infection, and patterns of related healthcare-seeking behaviour, relevant for healthcare service planning. Digested information will be produced for affected families, doctors, schools, and the public, as appropriate. CONCLUSION: Linked SIS-1 and CoMMinS data represent a unique and rich resource for understanding the impact of SARS-CoV-2 infection on children's health, benefiting from enhanced SARS-CoV-2 testing and ability to assess a wide range of outcomes.