Primary care-based interventions for secondary prevention of opioid dependence in chronic non-cancer pain patients on pharmaceutical opioids: systematic review.

BACKGROUND: Globally almost one third of adults with chronic non-cancer pain (CNCP) are prescribed opioids. Prevention of opioid dependence among these patients is a public health priority. AIM: Synthesise the evidence on the effectiveness of primary care-based interventions for secondary prevention of opioid dependence in CNCP patients on pharmaceutical opioids. DESIGN & SETTING: Systematic review of randomised controlled trials (RCTs) and comparative non-randomised studies of interventions from high-income countries. METHOD: We searched five databases for studies on non-tapering secondary prevention interventions such as tools for predicting dependence, screening tools for early recognition of dependence, prescribing/medication monitoring, and specialist support. We examined multiple outcomes, including reduction in opioid dosage. Primary analyses were restricted to RCTs with data synthesised using an effect direction plot. Risk of bias was assessed using the Cochrane risk of bias (RoB2) tool. RESULTS: Of 7,102 identified reports, 18 studies were eligible (8 RCTs). Most used multiple interventions/components. Of the seven RCTs at low risk of bias or 'some concerns', five showed a positive intervention effect on at least one relevant outcome, four of which included a nurse care manager and/or other specialist support. The remaining two RCTs showed no positive effect of automated symptom monitoring and optimised analgesic management by a nurse care manager/physician pain specialist team, or of a mobile opioid management app. CONCLUSION: We identify a clear need for further adequately powered high quality studies. The conclusions that can be drawn on intervention effectiveness are limited by the sparsity and inconsistency of available data.

CAR-T Cell Therapy in Ovarian Cancer: Where Are We Now?

The success of chimeric antigen receptor T-cell (CAR-T) therapies in the treatment of hematologic malignancies has led to the investigation of their potential in the treatment of solid tumors, including ovarian cancer. While the immunosuppressive microenvironment of ovarian cancer has been a barrier in their implementation, several early phase clinical trials are currently evaluating CAR-T cell therapies targeting mesothelin, folate receptor a, HER2, MUC16, and B7H3. Ongoing challenges include cytokine-associated and "on-target, off-tumor" toxicities, while most common adverse events include cytokine release syndrome, hemophagocytic lymphohistiocytosis/macrophage activation-like syndrome (HLH/MAS), and neurotoxicity. In the present review, we summarize the current status of CAR-T therapy in ovarian cancer and discuss future directions.

The Agile Co-production and Evaluation framework for developing public health interventions, messaging and guidance.

A lesson identified from the COVID-19 pandemic is that we need to extend existing best practice for intervention development. In particular, we need to integrate (a) state-of-the-art methods of rapidly coproducing public health interventions and messaging to support all population groups to protect themselves and their communities with (b) methods of rapidly evaluating co-produced interventions to determine which are acceptable and effective. This paper describes the Agile Co-production and Evaluation (ACE) framework, which is intended to provide a focus for investigating new ways of rapidly developing effective interventions and messaging by combining co-production methods with large-scale testing and/or real-world evaluation. We briefly review some of the participatory, qualitative and quantitative methods that could potentially be combined and propose a research agenda to further develop, refine and validate packages of methods in a variety of public health contexts to determine which combinations are feasible, cost-effective and achieve the goal of improving health and reducing health inequalities.

A systematic review of communication interventions for countering vaccine misinformation.

BACKGROUND: Misinformation and disinformation around vaccines has grown in recent years, exacerbated during the Covid-19 pandemic. Effective strategies for countering vaccine misinformation and disinformation are crucial for tackling vaccine hesitancy. We conducted a systematic review to identify and describe communications-based strategies used to prevent and ameliorate the effect of mis- and dis-information on people's attitudes and behaviours surrounding vaccination (objective 1) and examined their effectiveness (objective 2). METHODS: We searched CINAHL, Web of Science, Scopus, MEDLINE, Embase, PsycInfo and MedRxiv in March 2021. The search strategy was built around three themes(1) communications and media; (2) misinformation; and (3) vaccines. For trials addressing objective 2, risk of bias was assessed using the Cochrane risk of bias in randomized trials tool (RoB2). RESULTS: Of 2000 identified records, 34 eligible studies addressed objective 1, 29 of which also addressed objective 2 (25 RCTs and 4 before-and-after studies). Nine 'intervention approaches' were identified; most focused on content of the intervention or message (debunking/correctional, informational, use of disease images or other 'scare tactics', use of humour, message intensity, inclusion of misinformation warnings, and communicating weight of evidence), while two focused on delivery of the intervention or message (timing and source). Some strategies, such as scare tactics, appear to be ineffective and may increase misinformation endorsement. Communicating with certainty, rather than acknowledging uncertainty around vaccine efficacy or risks, was also found to backfire. Promising approaches include communicating the weight-of-evidence and scientific consensus around vaccines and related myths, using humour and incorporating warnings about encountering misinformation. Trying to debunk misinformation, informational approaches, and communicating uncertainty had mixed results. CONCLUSION: This review identifies some promising communication strategies for addressing vaccine misinformation. Interventions should be further evaluated by measuring effects on vaccine uptake, rather than distal outcomes such as knowledge and attitudes, in quasi-experimental and real-life contexts.

Interventions to enhance testing and linkage to treatment for hepatitis C infection for people who inject drugs: A systematic review and meta-analysis.

BACKGROUND: With the advent of direct acting antiviral (DAA) therapies for the treatment of hepatitis C virus (HCV), the World Health Organization recommended a goal to eliminate HCV as a public health threat globally by 2030. With the majority of new and existing infections in high income countries occurring among people who inject drugs, achieving this goal will require the design and implementation of interventions which address the unique barriers to HCV care faced by this population. METHODS: In this systematic review and meta-analysis, we searched bibliographic databases and conference abstracts to July 21, 2020 for studies assessing interventions to improve the following study outcomes: HCV antibody testing, HCV RNA testing, linkage to care, and treatment initiation. We included both randomised and non-randomised studies which included a comparator arm. We excluded studies which enrolled only paediatric populations (<18 years old) and studies where the intervention was conducted in a different healthcare setting than the control or comparator. This analysis was restricted to studies conducted among people who inject drugs. Data were extracted from the identified records and meta-analysis was used to pool the effect of interventions on study outcomes. This study was registered in PROSPERO (CRD42020178035). FINDINGS: Of 15,342 unique records, 45 studies described the implementation of an intervention to improve HCV testing, linkage to care and treatment initiation among people who inject drugs. These included 27 randomised trials and 18 non-randomised studies with the risk of bias rated as "critical" for most non-randomised studies. Patient education and patient navigation to address patient-level barriers to HCV care were shown to improve antibody testing uptake and linkage to HCV care respectively although patient education did not improve antibody testing when restricted to randomised studies. Provider care coordination to address provider level barriers to HCV care was effective at improving antibody testing uptake. Three different interventions to address systems-level barriers to HCV care were effective across different stages of HCV care: point-of-care antibody testing (linkage to care); dried blood-spot testing (antibody testing uptake); and integrated care (linkage to care and treatment initiation). INTERPRETATION: Multiple interventions are available that can address the barriers to HCV care for people who inject drugs at the patient-, provider-, and systems-level. The design of models of care to improve HCV testing and treatment among people who inject drugs must consider the unique barriers to care that this population faces. Further research, including high-quality randomised controlled trials, are needed to robustly assess the impact these interventions can have in varied populations and settings.

Daily use of lateral flow devices by contacts of confirmed COVID-19 cases to enable exemption from isolation compared with standard self-isolation to reduce onward transmission of SARS-CoV-2 in England: a randomised, controlled, non-inferiority trial.

BACKGROUND: In the UK, during the study period (April to July, 2021), all contacts of people with COVID-19 were required to self-isolate for 10 days, which had adverse impacts on individuals and society. Avoiding the need to self-isolate for those who remain uninfected would be beneficial. We investigated whether daily use of lateral flow devices (LFDs) to test for SARS-CoV-2, with removal of self-isolation for 24 h if negative, could be a safe alternative to self-isolation as a means to minimise onward transmission of the virus. METHODS: We conducted a randomised, controlled, non-inferiority trial in adult contacts identified by COVID-19 contact tracing in England. Consenting participants were randomly assigned to self-isolation (single PCR test, 10-day isolation) or daily contact testing (DCT; seven LFD tests, two PCR tests, no isolation if negative on LFD); participants from a single household were assigned to the same group. Participants were prospectively followed up, with the effect of each intervention on onward transmission established from routinely collected NHS Test and Trace contact tracing data for participants who tested PCR-positive for SARS-CoV-2 during the study period and tertiary cases arising from their contacts (ie, secondary contacts). The primary outcome of the study was the attack rate, the percentage of secondary contacts (close contacts of SARS-CoV-2-positive study participants) who became COVID-19 cases (tertiary cases) in each group. Attack rates were derived from Bernoulli regression models using Huber-White (robust) sandwich estimator clustered standard errors. Attack rates were adjusted for household exposure, vaccination status, and ability to work from home. The non-inferiority margin was 1·9%. The primary analysis was a modified intention-to-treat analysis excluding those who actively withdrew from the study as data from these participants were no longer held. This study is registered with the Research Registry (number 6809). Data collection is complete; analysis is ongoing. FINDINGS: Between April 29 and July 28, 2021, 54 923 eligible individuals were enrolled in the study, with final group allocations (following withdrawals) of 26 123 (52·6%) participants in the DCT group and 23 500 (47·4%) in the self-isolation group. Overall, 4694 participants tested positive for SARS-CoV-2 by PCR (secondary cases), 2364 (10·1%) in the self-isolation group and 2330 (8·9%) in the DCT group. Adjusted attack rates (among secondary contacts) were 7·5% in the self-isolation group and 6·3% in the DCT group (difference of -1·2% [95% CI -2·3 to -0·2]; significantly lower than the non-inferiority margin of 1·9%). INTERPRETATION: DCT with 24 h exemption from self-isolation for essential activities appears to be non-inferior to self-isolation. This study, which provided evidence for the UK Government's daily lateral flow testing policy for vaccinated contacts of COVID-19 cases, indicated that daily testing with LFDs could allow individuals to reduce the risk of onward transmission while minimising the adverse effects of self-isolation. Although contacts in England are no longer required to isolate, the findings will be relevant for future policy decisions around COVID-19 or other communicable infections. FUNDING: UK Government Department of Health and Social Care.

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies1.

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.

Interventions to enhance testing, linkage to care, and treatment initiation for hepatitis C virus infection: a systematic review and meta-analysis.

BACKGROUND: Despite the goal set by WHO to eliminate hepatitis C virus (HCV) as a public health threat, uptake of HCV testing and treatment remains low. To achieve this target, evidence-based interventions are needed to address the barriers to care for people with, or at risk of, HCV infection. We aimed to assess the efficacy of interventions to improve HCV antibody testing, HCV RNA testing, linkage to HCV care, and treatment initiation. METHODS: In this systematic review and meta-analysis, we searched MEDLINE (PubMed), Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, and PsycINFO without language restrictions for reports published between database inception and July 21, 2020, assessing the following primary outcomes: HCV antibody testing; HCV RNA testing; linkage to HCV care; and direct-acting antiviral treatment initiation. We also searched key conference abstracts. We included randomised and non-randomised studies assessing non-pharmaceutical interventions that included a comparator or control group. Studies were excluded if they enrolled only paediatric populations (aged <18 years) or if they conducted the intervention in a different health-care setting to that of the control or comparator. Authors were contacted to clarify study details and to obtain additional population-level data. Data were extracted from the records identified into a pre-piloted and standardised data extraction form and a random-effects meta-analysis was used to pool the effects of the interventions on study outcomes. This study is registered in PROSPERO, CRD42020178035. FINDINGS: Of 15 342 unique records identified, 142 were included, which reported on 148 unique studies (47 randomised controlled trials and 101 non-randomised studies). Medical chart reminders, provider education, and point-of-care antibody testing significantly improved at least three study outcomes compared with a comparator or control. Interventions that simplified HCV testing, including dried blood spot testing, point-of-care antibody testing, reflex RNA testing, and opt-out screening, significantly improved testing outcomes compared with a comparator or control. Enhanced patient and provider support through patient education, provider care coordination, and provider education also significantly improved testing outcomes compared with a comparator or control. Integrated care and patient navigation or care coordination significantly improved linkage to care and the uptake of direct-acting antiviral treatment compared with a comparator or control. INTERPRETATION: Several interventions to improve HCV care that address several key barriers to HCV care were identified. New models of HCV care must be designed and implemented to address the barriers faced by the population of interest. Further high-quality research, including rigorously designed randomised studies, is still needed in key populations. FUNDING: None.

Maternal Stressful Life Events During the Periconceptional Period and Orofacial Clefts: A Systematic Review and Meta-Analysis.

OBJECTIVE: To assess whether women who experience stressful life events during the periconceptional period are at higher risk of giving birth to a baby with an orofacial cleft (OFC). DESIGN: Systematic review and meta-analysis of studies reporting the proportion of babies born with OFC to mothers exposed and unexposed to population-level or personal-level stressful life events during the periconceptional period. Six electronic databases were searched from inception to August 2020. Risk of bias was assessed using the Newcastle-Ottawa scale. Odds ratios (ORs) for the odds of OFC in babies of exposed mothers relative to unexposed controls were extracted and/or calculated. Random effects meta-analysis was undertaken, stratified by cleft subtype. RESULTS: Of 12 eligible studies, 8 examined experience of personal events and 4 examined population-level events. Studies demonstrated low-moderate risk of bias and there was indication of publication bias. There was some evidence that personal stressful life events were associated with greater odds of cleft lip and/or palate (six studies, OR 1.63, 95% confidence interval (CI) 1.16, 2.30, P = 0.001) and cleft palate only (six studies, OR 1.45, 95% CI 1.02, 2.06, P = 0.04). Population-level events were associated with higher odds of OFC in studies that did not specify subtype (three studies, OR 1.64, 95% CI 1.19, 2.25, P = 0.002), but subtype stratified analyses were underpowered. Heterogeneity was high. CONCLUSIONS: Limited evidence indicated a weak positive association between maternal stressful life events during the periconceptional period and risk of OFC in the offspring, but further studies with greater consistency in research design are needed.

Settings for non-household transmission of SARS-CoV-2 during the second lockdown in England and Wales - analysis of the Virus Watch household community cohort study.

Background: "Lockdowns" to control serious respiratory virus pandemics were widely used during the coronavirus disease 2019 (COVID-19) pandemic.  However, there is limited information to understand the settings in which most transmission occurs during lockdowns, to support refinement of similar policies for future pandemics.  Methods: Among Virus Watch household cohort participants we identified those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outside the household.  Using survey activity data, we undertook multivariable logistic regressions assessing the contribution of activities on non-household infection risk.  We calculated adjusted population attributable fractions (APAF) to estimate which activity accounted for the greatest proportion of non-household infections during the pandemic's second wave. Results: Among 10,858 adults, 18% of cases were likely due to household transmission.  Among 10,475 participants (household-acquired cases excluded), including 874 non-household-acquired infections, infection was associated with: leaving home for work or education (AOR 1.20 (1.02 - 1.42), APAF 6.9%); public transport (more than once per week AOR 1.82 (1.49 - 2.23), public transport APAF 12.42%); and shopping (more than once per week AOR 1.69 (1.29 - 2.21), shopping APAF 34.56%).  Other non-household activities were rare and not significantly associated with infection. Conclusions: During lockdown, going to work and using public or shared transport independently increased infection risk, however only a minority did these activities.  Most participants visited shops, accounting for one-third of non-household transmission.  Transmission in restricted hospitality and leisure settings was minimal suggesting these restrictions were effective.   If future respiratory infection pandemics emerge these findings highlight the value of working from home, using forms of transport that minimise exposure to others, minimising exposure to shops and restricting non-essential activities.

Tobacco smoking and meningococcal disease in adolescents and young adults: a systematic review and meta-analysis.

OBJECTIVES: Systematically review the evidence on the association between active and passive tobacco smoking and invasive meningococcal disease (IMD) in adolescents and young adults aged 15-to-24-years. METHODS: Electronic searches were conducted in Ovid MEDLINE, EMBASE, and Web of Science to June 2020. Reference lists were hand-searched. Two independent reviewers screened articles for eligibility. Risk of bias was assessed using an adapted Risk of Bias in Non-Randomised Studies - of Interventions tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 312 records identified, 13 studies were included. Five studies provided data on the association between active smoking and IMD in the target age group; pooled odds ratio (OR): 1.45 (95% CI: 0.93-2.26). The overall OR, including eight studies with a wider participant age range, was 1.45 (95% CI: 1.12-1.88). For passive smoking, the equivalent ORs were 1.56 (95% CI: 1.09-2.25) and 1.30 (95% CI: 1.06-1.59) respectively. All studies were at high risk of bias. CONCLUSIONS: Active and passive smoking may be associated with IMD in adolescents and young adults. Since active smoking has also been linked to meningococcal carriage, and passive smoking to IMD in young children, smoking cessation should be encouraged to reduce transmission and IMD risk in all ages.

Multisite Study of Evoked Potentials in Rett Syndrome.

OBJECTIVE: The aim of the current study was to evaluate the utility of evoked potentials as a biomarker of cortical function in Rett syndrome (RTT). As a number of disease-modifying therapeutics are currently under development, there is a pressing need for biomarkers to objectively and precisely assess the effectiveness of these treatments. METHOD: Yearly visual evoked potentials (VEPs) and auditory evoked potentials (AEPs) were acquired from individuals with RTT, aged 2 to 37 years, and control participants across 5 sites as part of the Rett Syndrome and Related Disorders Natural History Study. Baseline and year 1 data, when available, were analyzed and the repeatability of the results was tested. Two syndrome-specific measures from the Natural History Study were used for evaluating the clinical relevance of the VEP and AEP parameters. RESULTS: At the baseline study, group level comparisons revealed reduced VEP and AEP amplitude in RTT compared to control participants. Further analyses within the RTT group indicated that this reduction was associated with RTT-related symptoms, with greater severity associated with lower VEP and AEP amplitude. In participants with RTT, VEP and AEP amplitude was also negatively associated with age. Year 1 follow-up data analyses yielded similar findings and evidence of repeatability of EPs at the individual level. INTERPRETATION: The present findings indicate the promise of evoked potentials (EPs) as an objective measure of disease severity in individuals with RTT. Our multisite approach demonstrates potential research and clinical applications to provide unbiased assessment of disease staging, prognosis, and response to therapy. ANN NEUROL 2021;89:790-802.

Association Between Opioid Agonist Therapy and Testing, Treatment Uptake, and Treatment Outcomes for Hepatitis C Infection Among People Who Inject Drugs: A Systematic Review and Meta-analysis.

BACKGROUND: People who inject drugs (PWID) experience barriers to accessing testing and treatment for hepatitis C virus (HCV) infection. Opioid agonist therapy (OAT) may provide an opportunity to improve access to HCV care. This systematic review assessed the association of OAT and HCV testing, treatment, and treatment outcomes among PWID. METHODS: Bibliographic databases and conference presentations were searched for studies that assessed the association between OAT and HCV testing, treatment, and treatment outcomes (direct-acting antiviral [DAA] therapy only) among PWID (in the past year). Meta-analysis was used to pool estimates. RESULTS: Of 9877 articles identified, 22 studies conducted in Australia, Europe, North America, and Thailand were eligible and included. Risk of bias was serious in 21 studies and moderate in 1 study. Current/recent OAT was associated with an increased odds of recent HCV antibody testing (4 studies; odds ratio (OR), 1.80; 95% confidence interval [CI], 1.36-2.39), HCV RNA testing among those who were HCV antibody-positive (2 studies; OR, 1.83; 95% CI, 1.27-2.62), and DAA treatment uptake among those who were HCV RNA-positive (7 studies; OR, 1.53; 95% CI, 1.07-2.20). There was insufficient evidence of an association between OAT and treatment completion (9 studies) or sustained virologic response following DAA therapy (9 studies). CONCLUSIONS: OAT can increase linkage to HCV care, including uptake of HCV testing and treatment among PWID. This supports the scale-up of OAT as part of strategies to enhance HCV treatment to further HCV elimination efforts.

Association between opioid agonist therapy use and HIV testing uptake among people who have recently injected drugs: a systematic review and meta-analysis.

BACKGROUND AND AIM: Globally, nearly one in five people who inject drugs (PWID) are living with HIV, and the rate of new HIV infections in PWID is increasing in some settings. Early diagnosis is crucial for effective HIV control. We reviewed the evidence on the association between opioid agonist therapy (OAT) and HIV testing uptake among PWID. METHODS: We conducted a systematic review searching MEDLINE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials and PsycINFO for studies published from January 2000 to March 2019. Reference lists and conference proceedings were hand-searched. Observational and intervention studies were eligible for inclusion. Risk of bias was assessed using the Risk of Bias in Non-Randomised Studies of Interventions (ROBINS-I) tool. Meta-analyses were conducted using random-effects models. RESULTS: Of 13 373 records identified, 11 studies from Australia, Europe, Malaysia and the United States were included. All studies had at least a serious risk of bias, largely due to confounding and selection bias, making it difficult to draw causal conclusions from the evidence. Ten studies provided data on the association between current OAT use and recent HIV testing. Six showed a positive association, while four provided little evidence of an association: pooled odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.28-2.27. Looking at having ever been on OAT and having ever been HIV tested, seven studies showed a positive association and three showed either weak or no evidence of an association: pooled OR = 3.82, 95% CI = 2.96-4.95. CONCLUSIONS: Opioid agonist therapy may increase uptake of HIV testing among people who inject drugs, providing further evidence that opioid agonist therapy improves the HIV treatment care cascade.

Comparison of Core Features in Four Developmental Encephalopathies in the Rett Natural History Study.

OBJECTIVE: Rett syndrome, CDKL5-deficiency disorder, FOXG1 disorder, and MECP2 duplication disorder are developmental encephalopathies with shared and distinct features. Although they are historically linked, no direct comparison has been performed. The first head-to-head comparison of clinical features in these conditions is presented. METHODS: Comprehensive clinical information was collected from 793 individuals enrolled in the Rett and Rett-Related Disorders Natural History Study. Clinical features including clinical severity, regression, and seizures were cross-sectionally compared between diagnoses to test the hypothesis that these are 4 distinct disorders. RESULTS: Distinct patterns of clinical severity, seizure onset age, and regression were present. Individuals with CDKL5-deficency disorder were the most severely affected and had the youngest age at seizure onset (2 months), whereas children with MECP2 duplication syndrome had the oldest median age at seizure onset (64 months) and lowest severity scores. Rett syndrome and FOGX1 were intermediate in both features. Smaller head circumference correlates with increased severity in all disorders and earlier age at seizure onset in MECP2 duplication syndrome. Developmental regression occurred in all Rett syndrome participants (median = 18 months) but only 23 to 34% of the other disorders. Seizure incidence prior to the baseline visit was highest for CDKL5 deficiency disorder (96.2%) and lowest for Rett syndrome (47.5%). Other clinical features including seizure types and frequency differed among groups. INTERPRETATION: Although these developmental encephalopathies share many clinical features, clear differences in severity, regression, and seizures warrant considering them as unique disorders. These results will aid in the development of disease-specific severity scales, precise therapeutics, and future clinical trials. ANN NEUROL 2020;88:396-406.

Prevalence and burden of HBV co-infection among people living with HIV: A global systematic review and meta-analysis.

Globally, in 2017 35 million people were living with HIV (PLHIV) and 257 million had chronic HBV infection (HBsAg positive). The extent of HIV-HBsAg co-infection is unknown. We undertook a systematic review to estimate the global burden of HBsAg co-infection in PLHIV. We searched MEDLINE, Embase and other databases for published studies (2002-2018) measuring prevalence of HBsAg among PLHIV. The review was registered with PROSPERO (#CRD42019123388). Populations were categorized by HIV-exposure category. The global burden of co-infection was estimated by applying regional co-infection prevalence estimates to UNAIDS estimates of PLHIV. We conducted a meta-analysis to estimate the odds of HBsAg among PLHIV compared to HIV-negative individuals. We identified 506 estimates (475 studies) of HIV-HBsAg co-infection prevalence from 80/195 (41.0%) countries. Globally, the prevalence of HIV-HBsAg co-infection is 7.6% (IQR 5.6%-12.1%) in PLHIV, or 2.7 million HIV-HBsAg co-infections (IQR 2.0-4.2). The greatest burden (69% of cases; 1.9 million) is in sub-Saharan Africa. Globally, there was little difference in prevalence of HIV-HBsAg co-infection by population group (approximately 6%-7%), but it was slightly higher among people who inject drugs (11.8% IQR 6.0%-16.9%). Odds of HBsAg infection were 1.4 times higher among PLHIV compared to HIV-negative individuals. There is therefore, a high global burden of HIV-HBsAg co-infection, especially in sub-Saharan Africa. Key prevention strategies include infant HBV vaccination, including a timely birth-dose. Findings also highlight the importance of targeting PLHIV, especially high-risk groups for testing, catch-up HBV vaccination and other preventative interventions. The global scale-up of antiretroviral therapy (ART) for PLHIV using a tenofovir-based ART regimen provides an opportunity to simultaneously treat those with HBV co-infection, and in pregnant women to also reduce mother-to-child transmission of HBV alongside HIV.

School-based interventions to prevent anxiety and depression in children and young people: a systematic review and network meta-analysis.

BACKGROUND: Rates of anxiety and depression are increasing among children and young people. Recent policies have focused on primary prevention of mental disorders in children and young people, with schools at the forefront of implementation. There is limited information for the comparative effectiveness of the multiple interventions available. METHODS: We did a systematic review and network meta-analysis, searching MEDLINE, Embase, PsycINFO, and Cochrane Central Register of Controlled trials for published and unpublished, passive and active-controlled randomised and quasi-randomised trials. We included educational setting-based, universal, or targeted interventions in which the primary aim was the prevention of anxiety and depression in children and young people aged 4-18 years. Primary outcomes were post-intervention self-report anxiety and depression, wellbeing, suicidal ideation, or self-harm. We assessed risk of bias following the Cochrane Handbook for Systematic Reviews of Interventions. We estimated standardised mean differences (SMD) using random effects network meta-analysis in a Bayesian framework. The study is registered with PROPSERO, number CRD42016048184. FINDINGS: 1512 full-text articles were independently screened for inclusion by two reviewers, from which 137 studies of 56 620 participants were included. 20 studies were assessed as being at low risk of bias for both random sequence generation and allocation concealment. There was weak evidence to suggest that cognitive behavioural interventions might reduce anxiety in primary and secondary settings. In universal secondary settings, mindfulness and relaxation-based interventions showed a reduction in anxiety symptoms relative to usual curriculum (SMD -0·65, 95% credible interval -1·14 to -0·19). There was a lack of evidence to support any one type of intervention being effective to prevent depression in universal or targeted primary or secondary settings. Comparison-adjusted funnel plots suggest the presence of small-study effects for the universal secondary anxiety analysis. Network meta-analysis was not feasible for wellbeing or suicidal ideation or self-harm outcomes, and results are reported narratively. INTERPRETATION: Considering unclear risk of bias and probable small study effects for anxiety, we conclude there is little evidence that educational setting-based interventions focused solely on the prevention of depression or anxiety are effective. Future research could consider multilevel, systems-based interventions as an alternative to the downstream interventions considered here. FUNDING: UK National Institute for Health Research.

Impact of repeat flooding on mental health and health-related quality of life: a cross-sectional analysis of the English National Study of Flooding and Health.

OBJECTIVE: To assess the association between flooding/repeat flooding and: (1) psychological morbidity (anxiety, depression, post-traumatic stress disorder (PTSD)) and (2) health-related quality of life (HRQoL) at 6 months post-flooding. DESIGN: Cross-sectional analysis of data from the English National Study of Flooding and Health. SETTING: Cumbria, England. PARTICIPANTS: Questionnaires were sent to 2500 residential addresses at 6 months post-flooding; 590 people responded. OUTCOMES: Probable depression was assessed using the Patient Health Questionnaire, probable anxiety using the Generalised Anxiety Disorder scale and probable PTSD using the short-form PTSD checklist (PCL-6). HRQoL was assessed using the EQ-5D-5L. Mental health outcomes were analysed using logistic regression; HRQoL dimensions using ordinal regression; and summary index/Visual Analogue Scale scores using linear regression. RESULTS: One hundred and nineteen participants had been flooded, over half of whom were experiencing a repeat flooding event (54%; n=64). Mental health outcomes were elevated among flooded compared with unaffected participants (adjusted OR for probable depression: 7.77, 95% CI: 1.51 to 40.13; anxiety: 4.16, 95% CI: 1.18 to 14.70; PTSD: 14.41, 95% CI: 3.91 to 53.13). The prevalence of depression was higher among repeat compared with single flooded participants, but this was not significant after adjustment. There was no difference in levels of anxiety or PTSD. Compared with unaffected participants, those flooded had lower EQ-5D-5L index scores (adjusted coefficient: -0.06, 95% CI: -0.12 to -0.01) and lower self-rated health scores (adjusted coefficient: -6.99, 95% CI: -11.96 to -2.02). There was, however, little difference in HRQoL overall between repeat and single flooded participants. CONCLUSIONS: Interventions are needed to help minimise the impact of flooding on people's mental health and HRQoL.

Cannabis use and the risk of tuberculosis: a systematic review.

BACKGROUND: Cannabis has been identified as a possible risk factor in some tuberculosis (TB) outbreaks. As the most widely used (largely) illegal substance in Western countries this may be an important public health concern. We aim to systematically review the evidence on the association between cannabis use and TB (latent infection and active disease) to inform ongoing and future TB prevention and control strategies. METHODS: We conducted a systematic review. We searched Ovid Medline, Embase and PsycInfo, together with the World Health Organization website and Google Scholar, for all years to January 2018. Reference lists and conference abstracts were hand-searched, a forward citation search was conducted on the Web of Science, and experts were contacted. Two authors independently screened studies for inclusion, extracted data and assessed risk of bias using an adapted version of ROBINS-I ("Risk of Bias in Non-randomised Studies - of Interventions"). Data were narratively synthesised. RESULTS: Of 377 records identified, 11 studies were eligible. Study designs were heterogeneous. Six studies utilised a relevant comparator group. Four of these investigated the association between cannabis use and latent TB infection; all provided some evidence of an association, although only two of these had adjusted for confounders. The remaining two comparator studies investigated the association between cannabis use and active TB disease; neither found evidence of an association after adjusting for confounding. All six studies were at "Serious" risk of bias. The five studies which did not utilise a relevant comparator group were all indicative of TB outbreaks occurring among cannabis users, but the quality of the evidence was very weak. CONCLUSIONS: Evidence for an association between cannabis use and TB acquisition is weak. The topic warrants further robust primary research including the collection of consistent and accurate exposure information, including cannabis use practices, dose and frequency, and adjustment for confounders.

Needle and syringe programmes and opioid substitution therapy for preventing HCV transmission among people who inject drugs: findings from a Cochrane Review and meta-analysis.

AIMS: To estimate the effects of needle and syringe programmes (NSP) and opioid substitution therapy (OST), alone or in combination, for preventing acquisition of hepatitis C virus (HCV) in people who inject drugs (PWID). METHODS: Systematic review and meta-analysis. Bibliographic databases were searched for studies measuring concurrent exposure to current OST (within the last 6 months) and/or NSP and HCV incidence among PWID. High NSP coverage was defined as regular NSP attendance or ≥ 100% coverage (receiving sufficient or greater number of needles and syringes per reported injecting frequency). Studies were assessed using the Cochrane risk of bias in non-randomized studies tool. Random-effects models were used in meta-analysis. RESULTS: We identified 28 studies (n = 6279) in North America (13), United Kingdom (five), Europe (four), Australia (five) and China (one). Studies were at moderate (two), serious (17) critical (seven) and non-assessable risk of bias (two). Current OST is associated with 50% [risk ratio (RR) =0.50, 95% confidence interval (CI) = 0.40-0.63] reduction in HCV acquisition risk, consistent across region and with low heterogeneity (I2  = 0, P = 0.889). Weaker evidence was found for high NSP coverage (RR = 0.79, 95% CI = 0.39-1.61) with high heterogeneity (I2  = 77%, P = 0.002). After stratifying by region, high NSP coverage in Europe was associated with a 56% reduction in HCV acquisition risk (RR = 0.44, 95% CI = 0.24-0.80) with low heterogeneity (I2  = 12.3%, P = 0.337), but not in North America (RR = 1.58, I2  = 89.5%, P = < 0.001). Combined OST/NSP is associated with a 74% reduction in HCV acquisition risk (RR = 0.26, 95% CI = 0.07-0.89, I2  = 80% P = 0.007). According to Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria, the evidence on OST and combined OST/NSP is low quality, while NSP is very low. CONCLUSIONS: Opioid substitution therapy reduces risk of hepatitis C acquisition and is strengthened in combination with needle and syringe programmes (NSP). There is weaker evidence for the impact of needle syringe programmes alone, although stronger evidence that high coverage is associated with reduced risk in Europe.