Treatment interventions to maintain abstinence from alcohol in primary care: systematic review and network meta-analysis.

OBJECTIVE: To determine the most effective interventions in recently detoxified, alcohol dependent patients for implementation in primary care. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, PsycINFO, Cochrane CENTRAL, ClinicalTrials.gov, and the World Health Organization's International Clinical Trials Registry Platform. STUDY SELECTION: Randomised controlled trials comparing two or more interventions that could be used in primary care. The population was patients with alcohol dependency diagnosed by standardised clinical tools and who became detoxified within four weeks. DATA EXTRACTION: Outcomes of interest were continuous abstinence from alcohol (effectiveness) and all cause dropouts (as a proxy for acceptability) at least 12 weeks after start of intervention. RESULTS: 64 trials (43 interventions) were included. The median probability of abstinence across placebo arms was 25%. Compared with placebo, the only intervention associated with increased probability of abstinence and moderate certainty evidence was acamprosate (odds ratio 1.86, 95% confidence interval 1.49 to 2.33, corresponding to an absolute probability of 38%). Of the 62 included trials that reported all cause dropouts, interventions associated with a reduced number of dropouts compared with placebo (probability 50%) and moderate certainty of evidence were acamprosate (0.73, 0.62 to 0.86; 42%), naltrexone (0.70, 0.50 to 0.98; 41%), and acamprosate-naltrexone (0.30, 0.13 to 0.67; 17%). Acamprosate was the only intervention associated with moderate confidence in the evidence of effectiveness and acceptability up to 12 months. It is uncertain whether other interventions can help maintain abstinence and reduce dropouts because of low confidence in the evidence. CONCLUSIONS: Evidence is lacking for benefit from interventions that could be implemented in primary care settings for alcohol abstinence, other than for acamprosate. More evidence from high quality randomised controlled trials is needed, as are strategies using combined interventions (combinations of drug interventions or drug and psychosocial interventions) to improve treatment of alcohol dependency in primary care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.

Examining subgroup effects by socioeconomic status of public health interventions targeting multiple risk behaviour in adolescence.

BACKGROUND: Multiple risk behaviour (MRB) refers to two or more risk behaviours such as smoking, drinking alcohol, poor diet and unsafe sex. Such behaviours are known to co-occur in adolescence. It is unknown whether MRB interventions are equally effective for young people of low and high socioeconomic status (SES). There is a need to examine these effects to determine whether MRB interventions have the potential to narrow or widen inequalities. METHODS: Two Cochrane systematic reviews that examined interventions to reduce adolescent MRB were screened to identify universal interventions that reported SES. Study authors were contacted, and outcome data stratified by SES and intervention status were requested. Risk behaviour outcomes alcohol use, smoking, drug use, unsafe sex, overweight/obesity, sedentarism, peer violence and dating violence were examined in random effects meta-analyses and subgroup analyses conducted to explore differences between high SES and low SES adolescents. RESULTS: Of 49 studies reporting universal interventions, only 16 also reported having measured SES. Of these 16 studies, four study authors provided data sufficient for subgroup analysis. There was no evidence of subgroup differences for any of the outcomes. For alcohol use, the direction of effect was the same for both the high SES group (RR 1.26, 95% CI: 0.96, 1.65, p = 0.09) and low SES group (RR 1.14, 95% CI: 0.98, 1.32, p = 0.08). The direction of effect was different for smoking behaviour in favour of the low SES group (RR 0.83, 95% CI: 0.66, 1.03, p = 0.09) versus the high SES group (RR 1.16, 95% CI: 0.82, 1.63, p = 0.39). For drug use, the direction of effect was the same for both the high SES group (RR 1.29, 95% CI: 0.97, 1.73, p = 0.08) and the low SES group (RR 1.28, 95% CI: 0.84, 1.96, p = 0.25). CONCLUSIONS: The majority of studies identified did not report having measured SES. There was no evidence of subgroup difference for all outcomes analysed among the four included studies. There is a need for routine reporting of demographic information within studies so that stronger evidence of effect by SES can be demonstrated and that interventions can be evaluated for their impact on health inequalities.

The effect of parental drinking on alcohol use in young adults: the mediating role of parental monitoring and peer deviance.

BACKGROUND AND AIMS: Evidence demonstrating an association between parental alcohol use and offspring alcohol use from robust prospective studies is lacking. We tested the direct and indirect associations between parental and young adult alcohol use via early alcohol initiation, parental monitoring and associating with deviant peers. DESIGN: Prospective birth cohort study. Path analysis was used to assess the possible association between parental alcohol use (assessed at 12 years) and alcohol use in young adults (assessed at 18 years) via potential mediators (assessed at 14 and 15.5 years, respectively). SETTING: South West England. PARTICIPANTS: Data were available on 3785 adolescents and their parents from the Avon Longitudinal Study of Parents and Children. MEASUREMENTS: The continuous Alcohol Use Disorders Identification Test (AUDIT) score was used as the primary outcome measure. Maternal alcohol use was defined as light (< 4 units on any day), moderate (≥ 4 units on 1-3 days) and high-risk (≥ 4 units on ≥ 4 days in 1 week). Partner alcohol use was also defined as light, moderate and high risk. Socio-economic variables were included as covariates. FINDINGS: There was strong evidence of a total effect from maternal alcohol use to young adult alcohol use [moderate: b = 1.07, 95% confidence interval (CI) = 0.64, 1.49, P < 0.001; high risk: b = 1.71, 95% CI = 1.07, 2.35, P < 0.001]. The majority of this association was explained through early alcohol initiation (moderate: b = 0.14, 95% CI = 0.04, 0.25, P = 0.01; high risk: b = 0.24, 95% CI = 0.07, 0.40, P < 0.01) and early alcohol initiation/associating with deviant peers (moderate: b = 0.06, 95% CI = 0.02, 0.10, P < 0.01; high risk: b = 0.10, 95% CI = 0.03, 0.16, P < 0.01). There was strong evidence of a remaining direct effect (moderate: b = 0.81, 95% CI = 0.39, 1.22, P < 0.001; high risk: b = 1.28, 95% CI = 0.65, 1.91, P < 0.001). A similar pattern of results was evident for partner alcohol use. CONCLUSIONS: Young adults whose parents have moderate or high-risk alcohol consumption are more likely to consume alcohol than those with parents with lower alcohol consumption. This association appears to be partly accounted for by earlier alcohol use initiation and higher prevalence of association with deviant peers.

Therapeutic interventions for alcohol dependence in non-inpatient settings: a systematic review and network meta-analysis (protocol).

BACKGROUND: Alcohol dependence is common and serious cause of social and physical harm. However, the optimal management of those with moderate and severe alcohol dependence in primary and community care after detoxification remains unclear. The aim of this review is to evaluate the effectiveness of interventions for maintaining abstinence in people with alcohol dependence following detoxification. METHODS: We will systematically search electronic databases and clinical trial registries for randomized controlled trials (RCTs) examining the effectiveness of pharmacological and/or psychosocial interventions for maintaining abstinence in recently detoxified, alcohol-dependent adults. The searches will be complemented by checking references and citations from included studies and other relevant systematic reviews. No limitation on language, year, or publication status will be applied. RCTs will be selected using prespecified criteria. Descriptive information, study characteristics, and results of eligible RCTs will be extracted. A revised version of the Cochrane Risk of Bias tool (RoB 2.0) will be used to assess the risk of bias in eligible RCTs. Results will be synthesized and analyzed using network meta-analysis (NMA). Overall strength of the evidence and publication bias will be evaluated. Subgroup and sensitivity analysis will also be performed. DISCUSSION: This network meta-analysis aims to appraise and summarize the total evidence of therapeutic interventions for alcohol-dependent patients that require support for detoxification and can be treated in the community. The evidence will determine which combination of interventions are most promising for current practice and further investigation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016049779.

Effectiveness of hand hygiene interventions in reducing illness absence among children in educational settings: a systematic review and meta-analysis.

OBJECTIVE: To undertake a systematic review and meta-analysis to establish the effectiveness of handwashing in reducing absence and/or the spread of respiratory tract (RT) and/or gastrointestinal (GI) infection among school-aged children and/or staff in educational settings. DESIGN: Randomised-controlled trials (RCTs). SETTING: Schools and other settings with a formal educational component in any country. PATIENTS: Children aged 3-11 years, and/or staff working with them. INTERVENTION: Interventions with a hand hygiene component. MAIN OUTCOME MEASURES: Incidence of RT or GI infections or symptoms related to such infections; absenteeism; laboratory results of RT and/or GI infections. RESULTS: Eighteen cluster RCTs were identified; 13 school-based, 5 in child day care facilities or preschools. Studies were heterogeneous and had significant quality issues including small numbers of clusters and participants and inadequate randomisation. Individual study results suggest interventions may reduce children's absence, RT infection incidence and symptoms, and laboratory confirmed influenza-like illness. Evidence of impact on GI infection or symptoms was equivocal. CONCLUSIONS: Studies are generally not well executed or reported. Despite updating existing systematic reviews and identifying new studies, evidence of the effect of hand hygiene interventions on infection incidence in educational settings is mostly equivocal but they may decrease RT infection among children. These results update and add to knowledge about this crucial public health issue in key settings with a vulnerable population. More robust, well reported cluster RCTs which learn from existing studies, are required.

Interventions to prevent HIV and Hepatitis C in people who inject drugs: a review of reviews to assess evidence of effectiveness.

BACKGROUND: Injecting drug use is a major risk factor for the acquisition and transmission of HIV and Hepatitis C virus (HCV). Prevention of these infections among people who inject drugs (PWID) is critical to reduce ongoing transmission, morbidity and mortality. METHODS: A review of reviews was undertaken involving systematic literature searches of Medline, Embase, CINAHL, PsychINFO, IBSS and the Cochrane Library (2000-2011) to identify English language reviews regarding the effectiveness of harm reduction interventions in relation to HIV transmission, HCV transmission and injecting risk behaviour (IRB). Interventions included needle and syringe programmes (NSP); the provision of injection paraphernalia; opiate substitution treatment (OST); information, education and counselling (IEC); and supervised injecting facilities (SIFs). Reviews were classified into 'core' or 'supplementary' using critical appraisal criteria, and the strength of review-level evidence was assessed. RESULTS: Twelve core and thirteen supplementary reviews were included. From these reviews we identified: (i) for NSP: tentative review-level evidence to support effectiveness in reducing HIV transmission, insufficient review-level evidence relating to HCV transmission, but sufficient review-level evidence in relation to IRB; (ii) for OST: sufficient review-level evidence of effectiveness in relation to HIV transmission and IRB, but tentative review-level evidence in relation to HCV transmission; (iii) for IEC, the provision of injection paraphernalia and SIFs: tentative review-level evidence of effectiveness in reducing IRB; and either insufficient or no review-level evidence for these interventions in relation to HIV or HCV transmission. CONCLUSION: Review-level evidence indicates that harm reduction interventions can reduce IRB, with evidence strongest for OST and NSP. However, there is comparatively little review-level evidence regarding the effectiveness of these interventions in preventing HCV transmission among PWID. Further studies are needed to assess the effectiveness and impact of scaling up comprehensive packages of harm reduction interventions to minimise HIV and HCV transmission among PWID.

Impact of media reporting of cervical cancer in a UK celebrity on a population-based cervical screening programme.

OBJECTIVES: To determine the impact of media reporting of cervical cancer in a UK celebrity on cervical screening uptake, response time and colposcopy referral and attendance. SETTING: Population-based national cervical screening programme for women in Wales, UK. METHODS: A time series regression analysis of the Welsh national cervical screening and colposcopy databases was used to examine the number of smear tests carried out between 2000 and 2010, stratified by age group and deprivation indicators. Logistic regression was used to analyse colposcopy attendance. RESULTS: Over 33,000 more cervical screening tests than expected were carried out in the year of media reporting (2008/9), 11,539 (35%) of which were in the month of Jade Goody's death. The largest increase was evident in women aged 35-39 years (475 additional tests per month, 95% CI 331-619). Impacts were similar across deprivation quintiles. Colposcopy referrals increased by 18% during the year of media reporting. Increases were observed for all smear test results in 2008/9, particularly among younger women, and further rises were evident in 2009/10 for smear tests showing borderline changes and mild dyskaryosis. The proportion of women attending colposcopy appointments rose in the year of media reporting (χ(2) = 45.8, P < 0.001). CONCLUSIONS: Mass media reporting of cervical cancer in a UK celebrity was associated with a significant, but transient, increase in screening uptake and colposcopy referral and attendance. Mass media reporting can play a role in enhanced detection of abnormalities, but public health messages must be communicated effectively to minimize anxiety whilst maximizing case-finding and uptake among non-responders.

Primary CD4+ T-cell responses provide both helper and cytotoxic functions during Epstein-Barr virus infection and transformation of fetal cord blood B cells.

Most humans carry Epstein-Barr virus (EBV) in circulating memory B cells as a latent infection that is controlled by an immune response. When infected by EBV, B lymphocytes in fetal cord blood are readily transformed to lymphoblastoid cell lines (LCL). It is frequently assumed that this high efficiency of transformation is due to the absence of a primary immune response. However, cord blood lymphocytes stimulated with autologous LCL yield CD4+ T cells that can completely inhibit the growth of LCL by a major histocompatibility complex-restricted cytotoxic mechanism mediated by granulysin and granzyme B. Because EBV-transformed B cells maintain the phenotype of antigen-activated B-cell blasts, they can potentially receive inhibitory or helper functions from CD4+ T cells. To assess these functions, the effect of EBV-specific CD4+ T cells on the efficiency of virus transformation of autologous B cells was assayed. Paradoxically, although the cytotoxic CD4+ T-cell lines reduced EBV B-cell transformation at a high effector/target ratio of 10:1, they caused a twofold increase in B-cell transformation at the lower effector/target ratio of 1:1. Th1-polarized CD4+ T cells were more effective at inhibiting B-cell transformation, but Th2-polarized cell lines had reduced cytotoxic activity, were unable to inhibit LCL growth, and caused a 10-fold increase in transformation efficiency. Tonsil lymphoid follicles lacked NK cells and CD8+ T cells but contained CD4+ T cells. We propose that CD4+ T cells provide helper or cytotoxic functions to EBV-transformed B cells and that the balance of these functions within tonsil compartments is critical in establishing asymptomatic primary EBV infection and maintaining a stable lifelong latent infection.