Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Factors associated with current substance use among a sample of homeless individuals in Cape Town, South Africa: a secondary data analysis.

Homelessness is a global issue that is often associated with substance use. Research on this relationship in low- to middle-income countries (LMIC) is limited. We aimed to explore which factors are associated with substance use through secondary data analysis of a sample of 472 adults who attended services for homeless individuals in Cape Town, South Africa. Logistic regression was utilized to investigate if length of homelessness was associated with current alcohol and drug use respectively, after accounting for other factors. Current drug use (44.9%) was higher than current alcohol use (22.7%) and the most prevalent lifetime drug was methamphetamine (32.6%). After adjusting for lifetime substance use, and source of income, length of homelessness was not significantly associated with current alcohol use (less than on year: OR = 2.60; 95% CI: 0.78-8.66; one or more years: OR = 0.90; 95% CI: 0.32-2.57) or current drug use (less than one year: OR = 0.78; 95% CI: 0.41-1.47; one year or more: OR = 1.04; 95% CI: 0.56-1.93). These results highlight the need to further investigate other factors that may influence current alcohol or drug use among populations at risk of being homeless, and to utilize validated measures of substance and other mental health conditions.

The association between silica exposure, silicosis and tuberculosis: a systematic review and meta-analysis.

BACKGROUND: While the association between occupational inhalation of silica dust and pulmonary tuberculosis has been known for over a century, there has never been a published systematic review, particularly of experience in the current era of less severe silicosis and treatable tuberculosis. We undertook a systematic review of the evidence for the association between (1) silicosis and pulmonary tuberculosis, and (2) silica exposure and pulmonary tuberculosis controlling for silicosis, and their respective exposure-response gradients. METHODS: We searched PUBMED and EMBASE, and selected studies according to a priori inclusion criteria. We extracted, summarised and pooled the results of published case-control and cohort studies of silica exposure and/or silicosis and incident active tuberculosis. Study quality was assessed on the Newcastle-Ottawa Scale. Where meta-analysis was possible, effect estimates were pooled using inverse-variance weighted random-effects models. Otherwise narrative and graphic synthesis was undertaken. Confidence regarding overall effect estimates was assessed using the GRADE schema. RESULTS: Nine studies met the inclusion criteria. Meta-analysis of eight studies of silicosis and tuberculosis yielded a pooled relative risk of 4.01 (95% confidence interval (CI) 2.88, 5.58). Exposure-response gradients were strong with a low silicosis severity threshold for increased risk. Our GRADE assessment was high confidence in a strong association. Meta-analysis of five studies of silica exposure controlling for or excluding silicosis yielded a pooled relative risk of 1.92 (95% CI 1.36, 2.73). Exposure-response gradients were observable in individual studies but not finely stratified enough to infer an exposure threshold. Our GRADE assessment was low confidence in the estimated effect owing to inconsistency and use of proxies for silica exposure. CONCLUSIONS: The evidence is robust for a strongly elevated risk of tuberculosis with radiological silicosis, with a low disease severity threshold. The effect estimate is more uncertain for silica exposure without radiological silicosis. Research is needed, particularly cohort studies measuring silica exposure in different settings, to characterise the effect more accurately as well as the silica exposure threshold that could be used to prevent excess tuberculosis risk.

Guidelines for Reporting Trial Protocols and Completed Trials Modified Due to the COVID-19 Pandemic and Other Extenuating Circumstances: The CONSERVE 2021 Statement.

Importance: Extenuating circumstances can trigger unplanned changes to randomized trials and introduce methodological, ethical, feasibility, and analytical challenges that can potentially compromise the validity of findings. Numerous randomized trials have required changes in response to the COVID-19 pandemic, but guidance for reporting such modifications is incomplete. Objective: As a joint extension for the CONSORT and SPIRIT reporting guidelines, CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstances) aims to improve reporting of trial protocols and completed trials that undergo important modifications in response to extenuating circumstances. Evidence: A panel of 37 international trial investigators, patient representatives, methodologists and statisticians, ethicists, funders, regulators, and journal editors convened to develop the guideline. The panel developed CONSERVE following an accelerated, iterative process between June 2020 and February 2021 involving (1) a rapid literature review of multiple databases (OVID Medline, OVID EMBASE, and EBSCO CINAHL) and gray literature sources from 2003 to March 2021; (2) consensus-based panelist meetings using a modified Delphi process and surveys; and (3) a global survey of trial stakeholders. Findings: The rapid review yielded 41 673 citations, of which 38 titles were relevant, including emerging guidance from regulatory and funding agencies for managing the effects of the COVID-19 pandemic on trials. However, no generalizable guidance for all circumstances in which trials and trial protocols might face unanticipated modifications were identified. The CONSERVE panel used these findings to develop a consensus reporting guidelines following 4 rounds of meetings and surveys. Responses were received from 198 professionals from 34 countries, of whom 90% (n = 178) indicated that they understood the concept definitions and 85.4% (n = 169) indicated that they understood and could use the implementation tool. Feedback from survey respondents was used to finalize the guideline and confirm that the guideline's core concepts were applicable and had utility for the trial community. CONSERVE incorporates an implementation tool and checklists tailored to trial reports and trial protocols for which extenuating circumstances have resulted in important modifications to the intended study procedures. The checklists include 4 sections capturing extenuating circumstances, important modifications, responsible parties, and interim data analyses. Conclusions and Relevance: CONSERVE offers an extension to CONSORT and SPIRIT that could improve the transparency, quality, and completeness of reporting important modifications to trials in extenuating circumstances such as COVID-19.

Comparing the effects of HIV self-testing to standard HIV testing for key populations: a systematic review and meta-analysis.

BACKGROUND: We update a previous systematic review to inform new World Health Organization HIV self-testing (HIVST) recommendations. We compared the effects of HIVST to standard HIV testing services to understand which service delivery models are effective for key populations. METHODS: We did a systematic review of randomised controlled trials (RCTs) which compared HIVST to standard HIV testing in key populations, published from 1 January 2006 to 4 June 2019 in PubMed, Embase, Global Index Medicus, Social Policy and Practice, PsycINFO, Health Management Information Consortium, EBSCO CINAHL Plus, Cochrane Library and Web of Science. We extracted study characteristic and outcome data and conducted risk of bias assessments using the Cochrane ROB tool version 1. Random effects meta-analyses were conducted, and pooled effect estimates were assessed along with other evidence characteristics to determine the overall strength of the evidence using GRADE methodology. RESULTS: After screening 5909 titles and abstracts, we identified 10 RCTs which reported on testing outcomes. These included 9679 participants, of whom 5486 were men who have sex with men (MSM), 72 were trans people and 4121 were female sex workers. Service delivery models included facility-based, online/mail and peer distribution. Support components were highly diverse and ranged from helplines to training and supervision. HIVST increased testing uptake by 1.45 times (RR=1.45 95% CI 1.20, 1.75). For MSM and small numbers of trans people, HIVST increased the mean number of HIV tests by 2.56 over follow-up (mean difference = 2.56; 95% CI 1.24, 3.88). There was no difference between HIVST and SoC in regard to positivity among tested overall (RR = 0.91; 95% CI 0.73, 1.15); in sensitivity analysis of positivity among randomised HIVST identified significantly more HIV infections among MSM and trans people (RR = 2.21; 95% CI 1.20, 4.08) and in online/mail distribution systems (RR = 2.21; 95% CI 1.14, 4.32). Yield of positive results in FSW was not significantly different between HIVST and SoC. HIVST reduced linkage to care by 17% compared to SoC overall (RR = 0.83; 95% CI 0.74, 0.92). Impacts on STI testing were mixed; two RCTs showed no decreases in STI testing while one showed significantly lower STI testing in the intervention arm. There were no negative impacts on condom use (RR = 0.95; 95% CI 0.83, 1.08), and social harm was very rare. CONCLUSIONS: HIVST is safe and increases testing uptake and frequency as well as yield of positive results for MSM and trans people without negative effects on linkage to HIV care, STI testing, condom use or social harm. Testing uptake was increased for FSW, yield of positive results were not and linkage to HIV care was worse. Strategies to improve linkage to care outcomes for both groups are crucial for effective roll-out.

Dihydrocodeine for detoxification and maintenance treatment in individuals with opiate use disorders.

BACKGROUND: Medical treatment and detoxification from opiate disorders includes oral administration of opioid agonists. Dihydrocodeine (DHC) substitution treatment is typically low threshold and therefore has the capacity to reach wider groups of opiate users. Decisions to prescribe DHC to patients with less severe opiate disorders centre on its perceived safety, reduced toxicity, shorter half-life and more rapid onset of action, and potential retention of patients. This review set out to investigate the effects of DHC in comparison to other pharmaceutical opioids and placebos in the detoxification and substitution of individuals with opiate use disorders. OBJECTIVES: To investigate the effectiveness of DHC in reducing illicit opiate use and other health-related outcomes among adults compared to other drugs or placebos used for detoxification or substitution therapy. SEARCH METHODS: In February 2019 we searched Cochrane Drugs and Alcohol's Specialised Register, CENTRAL, PubMed, Embase and Web of Science. We also searched for ongoing and unpublished studies via ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and Trialsjournal.com. All searches included non-English language literature. We handsearched references of topic-related systematic reviews and the included studies. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effect of DHC for detoxification and maintenance substitution therapy for adolescent (aged 15 years and older) and adult illicit opiate users. The primary outcomes were abstinence from illicit opiate use following detoxification or maintenance therapy measured by self-report or urinalysis. The secondary outcomes were treatment retention and other health and behaviour outcomes. DATA COLLECTION AND ANALYSIS: We followed the standard methodological procedures that are outlined by Cochrane. This includes the GRADE approach to appraise the quality of evidence. MAIN RESULTS: We included three trials (in five articles) with 385 opiate-using participants that measured outcomes at different follow-up periods in this review. Two studies with 150 individuals compared DHC with buprenorphine for detoxification, and one study with 235 participants compared DHC to methadone for maintenance substitution therapy. We downgraded the quality of evidence mainly due to risk of bias and imprecision. For the two studies that compared DHC to buprenorphine, we found low-quality evidence of no significant difference between DHC and buprenorphine for detoxification at six-month follow-up (risk ratio (RR) 0.59, 95% confidence interval (CI) 0.25 to 1.39; P = 0.23) in the meta-analysis for the primary outcome of abstinence from illicit opiates. Similarly, low-quality evidence indicated no difference for treatment retention (RR 1.29, 95% CI 0.99 to 1.68; P = 0.06). In the single trial that compared DHC to methadone for maintenance substitution therapy, the evidence was also of low quality, and there may be no difference in effects between DHC and methadone for reported abstinence from illicit opiates (mean difference (MD) -0.01, 95% CI -0.31 to 0.29). For treatment retention at six months' follow-up in this single trial, the RR calculated with an intention-to-treat analysis also indicated that there may be no difference between DHC and methadone (RR 1.04, 95% CI 0.94 to 1.16). The studies that compared DHC to buprenorphine reported no serious adverse events, while the DHC versus methadone study reported one death due to methadone overdose. AUTHORS' CONCLUSIONS: We found low-quality evidence that DHC may be no more effective than other commonly used pharmacological interventions in reducing illicit opiate use. It is therefore premature to make any conclusive statements about the effectiveness of DHC, and it is suggested that further high-quality studies are conducted, especially in low- to middle-income countries.

Psychosocial interventions for people with both severe mental illness and substance misuse.

BACKGROUND: Even low levels of substance misuse by people with a severe mental illness can have detrimental effects. OBJECTIVES: To assess the effects of psychosocial interventions for reduction in substance use in people with a serious mental illness compared with standard care. SEARCH METHODS: The Information Specialist of the Cochrane Schizophrenia Group (CSG) searched the CSG Trials Register (2 May 2018), which is based on regular searches of major medical and scientific databases. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing psychosocial interventions for substance misuse with standard care in people with serious mental illness. DATA COLLECTION AND ANALYSIS: Review authors independently selected studies, extracted data and appraised study quality. For binary outcomes, we calculated standard estimates of risk ratio (RR) and their 95% confidence intervals (CIs) on an intention-to-treat basis. For continuous outcomes, we calculated the mean difference (MD) between groups. Where meta-analyses were possible, we pooled data using a random-effects model. Using the GRADE approach, we identified seven patient-centred outcomes and assessed the quality of evidence for these within each comparison. MAIN RESULTS: Our review now includes 41 trials with a total of 4024 participants. We have identified nine comparisons within the included trials and present a summary of our main findings for seven of these below. We were unable to summarise many findings due to skewed data or because trials did not measure the outcome of interest. In general, evidence was rated as low- or very-low quality due to high or unclear risks of bias because of poor trial methods, or inadequately reported methods, and imprecision due to small sample sizes, low event rates and wide confidence intervals. 1. Integrated models of care versus standard care (36 months) No clear differences were found between treatment groups for loss to treatment (RR 1.09, 95% CI 0.82 to 1.45; participants = 603; studies = 3; low-quality evidence), death (RR 1.18, 95% CI 0.39 to 3.57; participants = 421; studies = 2; low-quality evidence), alcohol use (RR 1.15, 95% CI 0.84 to 1.56; participants = 143; studies = 1; low-quality evidence), substance use (drug) (RR 0.89, 95% CI 0.63 to 1.25; participants = 85; studies = 1; low-quality evidence), global assessment of functioning (GAF) scores (MD 0.40, 95% CI -2.47 to 3.27; participants = 170; studies = 1; low-quality evidence), or general life satisfaction (QOLI) scores (MD 0.10, 95% CI -0.18 to 0.38; participants = 373; studies = 2; moderate-quality evidence). 2. Non-integrated models of care versus standard care There was no clear difference between treatment groups for numbers lost to treatment at 12 months (RR 1.21, 95% CI 0.73 to 1.99; participants = 134; studies = 3; very low-quality evidence). 3. Cognitive behavioural therapy (CBT) versus standard care There was no clear difference between treatment groups for numbers lost to treatment at three months (RR 1.12, 95% CI 0.44 to 2.86; participants = 152; studies = 2; low-quality evidence), cannabis use at six months (RR 1.30, 95% CI 0.79 to 2.15; participants = 47; studies = 1; very low-quality evidence) or mental state insight (IS) scores by three months (MD 0.52, 95% CI -0.78 to 1.82; participants = 105; studies = 1; low-quality evidence). 4. Contingency management versus standard care We found no clear differences between treatment groups for numbers lost to treatment at three months (RR 1.55, 95% CI 1.13 to 2.11; participants = 255; studies = 2; moderate-quality evidence), number of stimulant positive urine tests at six months (RR 0.83, 95% CI 0.65 to 1.06; participants = 176; studies = 1) or hospitalisations (RR 0.21, 95% CI 0.05 to 0.93; participants = 176; studies = 1); both low-quality evidence. 5. Motivational interviewing (MI) versus standard care We found no clear differences between treatment groups for numbers lost to treatment at six months (RR 1.71, 95% CI 0.63 to 4.64; participants = 62; studies = 1). A clear difference, favouring MI, was observed for abstaining from alcohol (RR 0.36, 95% CI 0.17 to 0.75; participants = 28; studies = 1) but not other substances (MD -0.07, 95% CI -0.56 to 0.42; participants = 89; studies = 1), and no differences were observed in mental state general severity (SCL-90-R) scores (MD -0.19, 95% CI -0.59 to 0.21; participants = 30; studies = 1). All very low-quality evidence. 6. Skills training versus standard care At 12 months, there were no clear differences between treatment groups for numbers lost to treatment (RR 1.42, 95% CI 0.20 to 10.10; participants = 122; studies = 3) or death (RR 0.15, 95% CI 0.02 to 1.42; participants = 121; studies = 1). Very low-quality, and low-quality evidence, respectively. 7. CBT + MI versus standard care At 12 months, there was no clear difference between treatment groups for numbers lost to treatment (RR 0.99, 95% CI 0.62 to 1.59; participants = 327; studies = 1; low-quality evidence), number of deaths (RR 0.60, 95% CI 0.20 to 1.76; participants = 603; studies = 4; low-quality evidence), relapse (RR 0.50, 95% CI 0.24 to 1.04; participants = 36; studies = 1; very low-quality evidence), or GAF scores (MD 1.24, 95% CI -1.86 to 4.34; participants = 445; studies = 4; very low-quality evidence). There was also no clear difference in reduction of drug use by six months (MD 0.19, 95% CI -0.22 to 0.60; participants = 119; studies = 1; low-quality evidence). AUTHORS' CONCLUSIONS: We included 41 RCTs but were unable to use much data for analyses. There is currently no high-quality evidence to support any one psychosocial treatment over standard care for important outcomes such as remaining in treatment, reduction in substance use or improving mental or global state in people with serious mental illnesses and substance misuse. Furthermore, methodological difficulties exist which hinder pooling and interpreting results. Further high-quality trials are required which address these concerns and improve the evidence in this important area.

Risperidone versus other antipsychotics for people with severe mental illness and co-occurring substance misuse.

BACKGROUND: Up to 75% of people with serious mental illness (SMI) such as schizophrenia and bipolar disorder have co-occurring substance use disorders (dual diagnosis). Dual diagnosis can have an adverse effect on treatment and prognosis of SMI. OBJECTIVES: To evaluate the effects of risperidone compared to treatment with other antipsychotics (first-generation and other second-generation antipsychotics) used in people with serious mental illness and co-occurring substance misuse. SEARCH METHODS: On 6 January 2016 and 9 October 2017, we searched the Cochrane Schizophrenia Group's Study-Based Register of Trials (including trial registers). SELECTION CRITERIA: We selected randomised trials of risperidone versus any other antipsychotic in people with SMI and substance abuse (dual diagnosis). We included trials meeting our inclusion criteria and reporting useable data. We excluded trials that either did not meet our inclusion criteria or met our inclusion criteria but did not report any useable data. DATA COLLECTION AND ANALYSIS: We independently inspected citations and selected studies. For included studies, we independently extracted data and appraised study quality. For binary outcomes we calculated the risk ratios (RRs) and their 95% confidence intervals. For continuous outcomes we calculated the mean differences (MDs) and their 95% confidence intervals. We pooled data using random-effects meta-analyses and assessed the quality of evidence, creating a 'Summary of findings' table using the GRADE approach. MAIN RESULTS: We identified eight randomised trials containing a total of 1073 participants with SMI and co-occurring substance misuse. Seven of these contributed useable data to the review. There was heterogeneity in trial design and measurement. Risperidone was compared to clozapine, olanzapine, perphenazine, quetiapine and ziprasidone. Few trials compared risperidone with first-generation agents. Few trials examined participants with a dual diagnosis from the outset and most trials only contained separate analyses of subgroups with a dual diagnosis or were secondary data analyses of subgroups of people with a dual diagnosis from existing larger trials.For risperidone versus clozapine we found no clear differences between these two antipsychotics in the reduction of positive psychotic symptoms (1 randomised controlled trial (RCT), n = 36, mean difference (MD) 0.90, 95% CI -2.21 to 4.01, very low quality evidence), or reduction in cannabis use (1 RCT, n = 14, risk ratio (RR) 1.00, 95% CI 0.30 to 3.35, very low quality evidence), improvement in subjective well-being (1 RCT, n = 36, MD -6.00, 95% CI -14.82 to 2.82, very low quality evidence), numbers discontinuing medication (1 RCT, n = 36, RR 4.05, 95% CI 0.21 to 78.76, very low quality evidence), extrapyramidal side-effects (2 RCTs, n = 50, RR 2.71, 95% CI 0.30 to 24.08; I² = 0%, very low quality evidence), or leaving the study early (2 RCTs, n = 45, RR 0.49, 95% CI 0.10 to 2.51; I² = 34%, very low quality evidence). Clozapine was associated with lower levels of craving for cannabis (1 RCT, n = 28, MD 7.00, 95% CI 2.37 to 11.63, very low quality evidence).For risperidone versus olanzapine we found no clear differences in the reduction of positive psychotic symptoms (1 RCT, n = 37, MD -1.50, 95% CI -3.82 to 0.82, very low quality evidence), reduction in cannabis use (1 RCT, n = 41, MD 0.40, 95% CI -4.72 to 5.52, very low quality evidence), craving for cannabis (1 RCT, n = 41, MD 5.00, 95% CI -4.86 to 14.86, very low quality evidence), parkinsonism (1 RCT, n = 16, MD -0.08, 95% CI -1.21 to 1.05, very low quality evidence), or leaving the study early (2 RCT, n = 77, RR 0.68, 95% CI 0.34 to 1.35; I² = 0%, very low quality evidence).For risperidone versus perphenazine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 281, RR 1.05, 95% CI 0.92 to 1.20, low-quality evidence).For risperidone versus quetiapine, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 294, RR 0.96, 95% CI 0.86 to 1.07, low-quality evidence).For risperidone versus ziprasidone, we found no clear differences in the number of participants leaving the study early (1 RCT, n = 240, RR 0.96, 95% CI 0.85 to 1.10, low-quality evidence).For many comparisons, important outcomes were missing; and no data were reported in any study for metabolic disturbances, global impression of illness severity, quality of life or mortality. AUTHORS' CONCLUSIONS: There is not sufficient good-quality evidence available to determine the effects of risperidone compared with other antipsychotics in people with a dual diagnosis. Few trials compared risperidone with first-generation agents, leading to limited applicability to settings where access to second-generation agents is limited, such as in low- and middle-income countries. Moreover, heterogeneity in trial design and measurement of outcomes precluded the use of many trials in our analyses. Future trials in this area need to be sufficiently powered but also need to conform to consistent methods in study population selection, use of measurement scales, definition of outcomes, and measures to counter risk of bias. Investigators should adhere to CONSORT guidelines in the reporting of results.

Antidepressants for depression in adults with HIV infection.

BACKGROUND: Rates of major depression among people living with HIV (PLWH) are substantially higher than those seen in the general population and this may adversely affect antiretroviral treatment outcomes. Several unique clinical and psychosocial factors may contribute to the development and persistence of depression in PLWH. Given these influences, it is unclear if antidepressant therapy is as effective for PLWH as the general population. OBJECTIVES: To assess the efficacy of antidepressant therapy for treatment of depression in PLWH. SEARCH METHODS: We searched The Cochrane Common Mental Disorders Group's specialised register (CCMD-CTR), the Cochrane Library, PubMed, Embase and ran a cited reference search on the Web of Science for reports of all included studies. We conducted additional searches of the international trial registers including; ClinicalTrials.gov, World Health Organization Trials Portal (ICTRP), and the HIV and AIDS - Clinical trials register. We searched grey literature and reference lists to identify additional studies and contacted authors to obtain missing data. We applied no restrictions on date, language or publication status to the searches, which included studies conducted between 1 January 1980 and 18 April 2017. SELECTION CRITERIA: We included randomized controlled trials of antidepressant drug therapy compared to placebo or another antidepressant drug class. Participants eligible for inclusion had to be aged 18 years and older, from any setting, and have both HIV and depression. Depression was defined according to Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the inclusion criteria and extracted data. We presented categorical outcomes as risk ratios (RR) with 95% confidence intervals (CIs). Continuous outcomes were presented mean (MD) or standardized mean differences (SMD) with standard deviations (SD). We assessed quality of evidence using the GRADE approach. MAIN RESULTS: We included 10 studies with 709 participants in this review. Of the 10 studies, eight were conducted in high income countries (USA and Italy), seven were conducted prior to 2000 and seven had predominantly men. Seven studies assessed antidepressants versus placebo, two compared different antidepressant classes and one had three arms comparing two antidepressant classes with placebo.Antidepressant therapy may result in a greater improvement in depression compared to placebo. There was a moderate improvement in depression when assessed with the Hamilton Depression Rating Scale (HAM-D) score as a continuous outcome (SMD 0.59, 95% CI 0.21 to 0.96; participants = 357; studies = 6; I2 = 62%, low quality evidence). However, there was no evidence of improvement when this was assessed with HAM-D score as a dichotomized outcome (RR 1.10, 95% CI 0.89 to 1.35; participants = 434; studies = 5; I2 = 0%, low quality evidence) or Clinical Global Impression of Improvement (CGI-I) score (RR 1.28, 95% CI 0.93 to 1.77; participants = 346; studies = 4; I2 = 29%, low quality evidence). There was little to no difference in the proportion of study dropouts between study arms (RR 1.28, 95% CI 0.91 to 1.80; participants = 306; studies = 4; I2 = 0%, moderate quality evidence).The methods of reporting adverse events varied substantially between studies, this resulted in very low quality evidence contributing to a pooled estimate (RR 0.88, 95% CI 0.64 to 1.21; participants = 167; studies = 2; I2 = 34%; very low quality evidence). Based on this, we were unable to determine if there was a difference in the proportion of participants experiencing adverse events in the antidepressant versus placebo arms. However, sexual dysfunction was reported commonly in people receiving selective serotonin reuptake inhibitors (SSRIs). People receiving tricyclic antidepressants (TCAs) frequently reported anticholinergic adverse effects such as dry mouth and constipation. There were no reported grade 3 or 4 adverse events in any study group.There was no evidence of a difference in follow-up CD4 count at study termination (MD -6.31 cells/mm3, 95% CI -72.76 to 60.14; participants = 176; studies = 3; I2 = 0%; low quality evidence). Only one study evaluated quality of life score (MD 3.60, 95% CI -0.38 to 7.58; participants = 87; studies = 1; very low quality evidence), due to the poor quality evidence we could not draw conclusions for this outcome.There were few studies comparing different antidepressant classes. We are uncertain if SSRIs differ from TCAs with regard to improvement in depression as evaluated by HAM-D score (MD -3.20, 95% CI -10.87 to 4.47; participants = 14; studies = 1; very low quality evidence). There was some evidence that mirtazapine resulted in a greater improvement in depression compared to an SSRI (MD 9.00, 95% CI 3.61 to 14.39; participants = 70; studies = 1; low quality evidence); however, this finding was not consistent for all measures of improvement in depression for this comparison.No studies reported on virological suppression or any other HIV specific outcomes.The studies included in this review had an overall unclear or high risk of bias due to under-reporting of study methods, high risk of attrition bias and inadequate sequence generation methods. Heterogeneity between studies and the limited number of participants, and events lead to downgrading of the quality of the evidence for several outcomes. AUTHORS' CONCLUSIONS: This review demonstrates that antidepressant therapy may be more beneficial than placebo for the treatment of depression in PLWH. The low quality of the evidence contributing to this assessment and the lack of studies representing PLWH from generalized epidemics in low- to middle-income countries make the relevance of these finding in today's context limited. Future studies that evaluate the effectiveness of antidepressant therapy should be designed and conducted rigorously. Such studies should incorporate evaluation of stepped care models and health system strengthening interventions in the study design. In addition, outcomes related to HIV care and antiretroviral therapy should be reported.

Using GRADE as a framework to guide research on the sexual and reproductive health and rights (SRHR) of women living with HIV - methodological opportunities and challenges.

In March 2016, WHO reviewed evidence to develop global recommendations on the sexual and reproductive health and rights (SRHR) of women living with HIV. Systematic reviews and a global survey of women living with HIV informed the guideline development decision-making process. New recommendations covered abortion, Caesarean section, safe disclosure, and empowerment and self-efficacy interventions. Identification of key research gaps is part of the WHO guidelines development process, but consistent methods to do so are lacking. Our method aimed to ensure consistency and comprised the systematic application of a framework based on GRADE (Grading of Recommendations, Assessment, Development and Evaluation) to the process. The framework incorporates the strength and quality rating of recommendations and the priorities reported by women in the survey to inform research prioritisation. For each gap, we also articulated: (1) the most appropriate and robust study design to answer the question; (2) alternative pragmatic designs if the ideal design is not feasible; and (3) the methodological challenges facing researchers through identifying potential biases. We found 12 research gaps and identified five appropriate study designs to address the related questions: (1) Cross-sectional surveys; (2) Qualitative interview-driven studies; (3) Registries; (4) Randomised controlled trials; and (5) Medical record audit. Methodological challenges included selection, recruitment, misclassification, measurement and contextual biases, and confounding. In conclusion, a framework based on GRADE can provide a systematic approach to identifying research gaps from a WHO guideline. Incorporation of the priorities of women living with HIV into the framework systematically ensures that women living with HIV can shape future policy decisions affecting their lives. Implementation science and participatory research are appropriate over-arching approaches to enhance uptake of interventions and to ensure inclusion of women living with HIV at all stages of the research process.

Micronutrient supplementation in adults with HIV infection.

BACKGROUND: Micronutrient deficiencies are common among adults living with HIV disease, particularly in low-income settings where the diet may be low in essential vitamins and minerals. Some micronutrients play critical roles in maintenance of the immune system, and routine supplementation could therefore be beneficial. This is an update of a Cochrane Review previously published in 2010. OBJECTIVES: To assess whether micronutrient supplements are effective and safe in reducing mortality and HIV-related morbidity of HIV-positive adults (excluding pregnant women). SEARCH METHODS: We performed literature searches from January 2010 to 18 November 2016 for new randomized controlled trials (RCTs) of micronutrient supplements since the previous review included all trials identified from searches prior to 2010. We searched the CENTRAL (the Cochrane Library), Embase, and PubMed databases. Also we checked the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and the ClinicalTrials.gov trials registers. We also checked the reference lists of all new included trials. SELECTION CRITERIA: We included RCTs that compared supplements that contained either single, dual, or multiple micronutrients with placebo, no treatment, or other supplements. We excluded studies that were primarily designed to investigate the role of micronutrients for the treatment of HIV-positive participants with metabolic morbidity related to highly active antiretroviral therapy (HAART). Primary outcomes included all-cause mortality, morbidity, and disease progression. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, and appraised trial quality for risk of bias. Where possible, we presented results as risk ratios (RR) for dichotomous variables, as hazard ratios (HRs) for time-to-event data, and as mean differences (MD) for continuous variables, each with 95% confidence intervals (CIs). Since we were often unable to pool the outcome data, we tabulated it for each comparison. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 33 trials with 10,325 participants, of which 17 trials were new trials. Ten trials compared a daily multiple micronutrient supplement to placebo in doses up to 20 times the dietary reference intake, and one trial compared a daily standard dose with a high daily dose of multivitamins. Nineteen trials compared supplementation with single or dual micronutrients (such as vitamins A and D, zinc, and selenium) to placebo, and three trials compared different dosages or combinations of micronutrients. Multiple micronutrientsWe conducted analyses across antiretroviral therapy (ART)-naive adults (3 trials, 1448 participants), adults on antiretroviral therapy (ART) (1 trial, 400 participants), and ART-naive adults with concurrent active tuberculosis (3 trials, 1429 participants). Routine multiple micronutrient supplementation may have little or no effect on mortality in adults living with HIV (RR 0.91, 95% CI 0.72 to 1.15; 7 trials, 2897 participants, low certainty evidence).Routine supplementation for up to two years may have little or no effect on the average of mean CD4+ cell count (MD 26.40 cells/mm³, 95% CI -22.91 to 75.70; 6 trials, 1581 participants, low certainty evidence), or the average of mean viral load (MD -0.1 log10viral copies, 95% CI -0.26 to 0.06; 4 trials, 840 participants, moderate certainty evidence). One additional trial in ART-naïve adults did report an increase in the time to reach a CD4+ cell count < 250 cells/mm³ after two years of high dose supplementation in Botswana (HR 0.48, 95% CI 0.26 to 0.88; 1 trial, 439 participants). However, the trial authors reported this effect only in the trial arm that received multiple micronutrients plus selenium (not either supplementation alone), which is inconsistent with the findings of other trials that used similar combinations of micronutrients and selenium.In one additional trial that compared high-dose multiple micronutrient supplementation with standard doses in people on ART, peripheral neuropathy was lower with high dose supplements compared to standard dose (incidence rate ratio (IRR) 0.81, 95% CI 0.7 to 0.94; 1 trial, 3418 participants), but the trial was stopped early due to increased adverse events (elevated alanine transaminase (ALT) levels) in the high dose group. Single or dual micronutrientsNone of the trials of single or dual micronutrient supplements were adequately powered to assess for effects on mortality or morbidity outcomes. No clinically significant changes in CD4 cell count (data not pooled, 14 trials, 2370 participants, very low or low certainty evidence) or viral load (data not pooled, seven studies, 1334 participants, very low or low certainty evidence), were reported. Supplementation probably does increase blood concentrations of vitamin D and zinc (data not pooled, vitamin D: 4 trials, 299 participants, zinc: 4 trials, 484 participants, moderate certainty evidence) and may also increase blood concentrations of vitamin A (data not pooled, 3 trials, 495 participants, low certainty evidence), especially in those who are deficient. AUTHORS' CONCLUSIONS: The analyses of the available trials have not revealed consistent clinically important benefits with routine multiple micronutrient supplementation in people living with HIV. Larger trials might reveal small but important effects.These findings should not be interpreted as a reason to deny micronutrient supplements for people living with HIV where specific deficiencies are found or where the person's diet is insufficient to meet the recommended daily allowance of vitamins and minerals.

HIV-free survival at 12-24 months in breastfed infants of HIV-infected women on antiretroviral treatment.

OBJECTIVE: To provide estimates of HIV-free survival at 12-24 months in breastfed children by maternal ART (6 months or lifelong) to inform WHO HIV and Infant Feeding guidelines. METHODS: Eighteen studies published 2005-2015 were included in a systematic literature review (1295 papers identified, 156 abstracts screened, 55 full texts); papers were analysed by narrative synthesis and meta-analysis of HIV-free survival by maternal ART regimen in a random effects model. We also grouped studies by feeding modality. Study quality was assessed using a modified Newcastle-Ottawa Scale (NOS) and GRADE. RESULTS: The pooled estimates for 12-month HIV-free survival were 89.8% (95% confidence interval, CI: 86.5%, 93.2%) for infants of mothers on ART for 6 months post-natally (six studies) and 91.4% (95% CI 87.5%, 95.4%) for infants of mothers on lifelong ART (three studies). Eighteen-month HIV-free survival estimates were 89.0% (95% CI 83.9%, 94.2%) with 6 months ART (five studies) and 96.1% (95% CI 92.8%, 99.0%) with lifelong ART (three studies). Twenty-four-month HIV-free survival for infants whose mothers were on ART to 6 months post-natally (two studies) was 89.2% (95% CI 79.9%, 98.5%). Heterogeneity was considerable throughout. In four studies, HIV-free survival in breastfed infants ranged from 87% (95% CI 78%, 92%) to 96% (95% CI 91%, 98%) and in formula-fed infants from 67% (95% CI 35.5%, 87.9%) to 97.6% (95% CI 93.0%, 98.2%). CONCLUSION: Our results highlight the importance of breastfeeding for infant survival and of ART in reducing the risk of mother-to-child HIV transmission and support the WHO recommendation to initiate ART for life immediately after HIV diagnosis.

WITHDRAWN: Dental fillings for the treatment of caries in the primary dentition.

BACKGROUND: Childhood caries (tooth decay) consists of a form of tooth decay that affects the milk teeth (also known as baby or primary teeth) of children. This may range from tooth decay in a single tooth to rampant caries affecting all the teeth in the mouth. Primary teeth in young children are vital to their development and every effort should be made to retain these teeth for as long as is possible. Dental fillings or restorations have been used as an intervention to repair these damaged teeth. Oral health professionals need to make astute decisions about the type of restorative (filling) material they choose to best manage their patients with childhood caries. This decision is by no means an easy one as remarkable advances in dental restorative materials over the last 10 years has seen the introduction of a multitude of different filling materials claiming to provide the best performance in terms of durability, aesthetics, symptom relief, etc when placed in the mouth. This review sought to compare the different types of dental materials against each other for the same outcomes. OBJECTIVES: The objective of this review was to compare the outcomes (including pain relief, survival and aesthetics) for restorative materials used to treat caries in the primary dentition in children.  Additionally, the restoration of teeth was compared with extraction and no treatment. SEARCH METHODS: Electronic searches of the following databases were undertaken: the Cochrane Oral Health Group's Trials Register (up to January 2009); CENTRAL (The Cochrane Library 2009, Issue1); MEDLINE (1966 to January 2009); EMBASE (1996 to January 2009); SIGLE (1976 to 2004); and conference proceedings on early childhood caries, restorative materials for paediatric dentistry, and material sciences conferences for dental materials used for children's dentistry (1990 to 2008). The searches attempted to identify all relevant studies irrespective of language.Additionally, the reference lists from articles of eligible papers were searched, handsearching of key journals was undertaken, and personal communication with authors and manufacturers of dental materials was initiated to increase the pool of suitable trials (both published and unpublished) for inclusion into this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) or quasi-randomised controlled trials with a minimum period of 6 months follow up were included. Both parallel group and split-mouth study designs were considered. The unit of randomisation could be the individual, group (school, school class, etc), tooth or tooth pair. Included studies had a drop-out rate of less than 30%. The eligible trials consisted of young children (children less than 12 years) with tooth decay involving at least one tooth in the primary dentition which was symptomatic or symptom free at the start of the study. DATA COLLECTION AND ANALYSIS: Data were independently extracted, in duplicate, by two review authors. Disagreements were resolved by consultation with a third review author. Authors were contacted for missing or unclear information regarding randomisation, allocation sequence, presentation of data, etc. A quality assessment of included trials was undertaken. The Cochrane Collaboration statistical guidelines were followed for data analysis. MAIN RESULTS: Only three studies were included in this review. The Fuks 1999 study assessed the clinical performance of aesthetic crowns versus conventional stainless steel crowns in 11 children who had at least two mandibular primary molars that required a crown restoration. The outcomes assessed at 6 months included gingival health (odds ratio (OR) 0.3; 95% confidence interval (CI) 0.01 to 8.32), restoration failure (OR 3.29; 95% CI 0.12 to 89.81), occlusion, proximal contact and marginal integrity. The odds ratios for occlusion, proximal contact and marginal integrity could not be estimated as no events were recorded at the 6-month evaluation. The Donly 1999 split-mouth study compared a resin-modified glass ionomer (Vitremer) with amalgam over a 36-month period. Forty pairs of Class II restorations were placed in 40 patients (21 males; 19 females; mean age 8 years +/- 1.17; age range 6 to 9 years). Although the study period was 3 years (36 months), only the 6- and 12-month results are reported due to the loss to follow up of patients being greater than 30% for the 24- and 36-month data. Marks 1999a recruited 30 patients (age range 4 to 9 years; mean age 6.7 years, standard deviation 2.3) with one pair of primary molars that required a Class II restoration. The materials tested were Dyract (compomer) and Tytin (amalgam). Loss to follow up at 24 and 36 months was 20% and 43% respectively. This meant that only the 24-month data were useable. For all of the outcomes compared in all three studies, there were no significant differences in clinical performance between the materials tested.No studies were found that compared restorations versus extractions or no treatment as an intervention in children with childhood caries. AUTHORS' CONCLUSIONS: It was disappointing that only three trials that compared three different types of materials were suitable for inclusion into this review. There were no significant differences found in all three trials for all of the outcomes assessed. Well designed, randomised controlled trials comparing the different types of filling materials for similar outcomes are urgently needed in dentistry. There was insufficient evidence from the three included trials to make any recommendations about which filling material to use.

Efavirenz or nevirapine in three-drug combination therapy with two nucleoside or nucleotide-reverse transcriptase inhibitors for initial treatment of HIV infection in antiretroviral-naïve individuals.

BACKGROUND: The advent of highly active antiretroviral therapy (ART) has reduced the morbidity and mortality due to HIV infection. The World Health Organization (WHO) ART guidelines focus on three classes of antiretroviral drugs, namely nucleoside or nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors. Two of the most common medications given as first-line treatment are the NNRTIs, efavirenz (EFV) and nevirapine (NVP). It is unclear which NNRTI is more efficacious for initial therapy. This systematic review was first published in 2010. OBJECTIVES: To determine which non-nucleoside reverse transcriptase inhibitor, either EFV or NVP, is more effective in suppressing viral load when given in combination with two nucleoside reverse transcriptase inhibitors as part of initial antiretroviral therapy for HIV infection in adults and children. SEARCH METHODS: We attempted to identify all relevant studies, regardless of language or publication status, in electronic databases and conference proceedings up to 12 August 2016. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov to 12 August 2016. We searched LILACS (Latin American and Caribbean Health Sciences Literature) and the Web of Science from 1996 to 12 August 2016. We checked the National Library of Medicine (NLM) Gateway from 1996 to 2009, as it was no longer available after 2009. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared EFV to NVP in people with HIV without prior exposure to ART, irrespective of the dosage or NRTI's given in combination.The primary outcome of interest was virological success. Other primary outcomes included mortality, clinical progression to AIDS, severe adverse events, and discontinuation of therapy for any reason. Secondary outcomes were change in CD4 count, treatment failure, development of ART drug resistance, and prevention of sexual transmission of HIV. DATA COLLECTION AND ANALYSIS: Two review authors assessed each reference for inclusion using exclusion criteria that we had established a priori. Two review authors independently extracted data from each included trial using a standardized data extraction form. We analysed data on an intention-to-treat basis. We performed subgroup analyses for concurrent treatment for tuberculosis and dosage of NVP. We followed standard Cochrane methodological procedures. MAIN RESULTS: Twelve RCTs, which included 3278 participants, met our inclusion criteria. None of these trials included children. The length of follow-up time, study settings, and NRTI combination drugs varied greatly. In five included trials, participants were receiving concurrent treatment for tuberculosis.There was little or no difference between EFV and NVP in virological success (RR 1.04, 95% CI 0.99 to 1.09; 10 trials, 2438 participants; high quality evidence), probably little or no difference in mortality (RR 0.84, 95% CI 0.59 to 1.19; 8 trials, 2317 participants; moderate quality evidence) and progression to AIDS (RR 1.23, 95% CI 0.72 to 2.11; 5 trials, 2005 participants; moderate quality evidence). We are uncertain whether there is a difference in all severe adverse events (RR 0.91, 95% CI 0.71 to 1.18; 8 trials, 2329 participants; very low quality evidence). There is probably little or no difference in discontinuation rate (RR 0.93, 95% CI 0.69 to 1.25; 9 trials, 2384 participants; moderate quality evidence) and change in CD4 count (MD -3.03; 95% CI -17.41 to 11.35; 9 trials, 1829 participants; moderate quality evidence). There may be little or no difference in treatment failure (RR 0.97, 95% CI 0.76 to 1.24; 5 trials, 737 participants; low quality evidence). Development of drug resistance is probably slightly less in the EFV arms (RR 0.76, 95% CI 0.60 to 0.95; 4 trials, 988 participants; moderate quality evidence). No studies were found that looked at sexual transmission of HIV.When we examined the adverse events individually, EFV probably is associated with more people with impaired mental function (7 per 1000) compared to NVP (2 per 1000; RR 4.46, 95% CI 1.65 to 12.03; 6 trials, 2049 participants; moderate quality evidence) but fewer people with elevated transaminases (RR 0.52, 95% CI 0.35 to 0.78; 3 trials, 1299 participants; high quality evidence), fewer people with neutropenia (RR 0.48, 95% CI 0.28 to 0.82; 3 trials, 1799 participants; high quality evidence), and probably fewer people withrash (229 per 100 with NVP versus 133 per 1000 with EFV; RR 0.58, 95% CI 0.34 to 1.00; 7 trials, 2277 participants; moderate quality evidence). We found that there may be little or no difference in gastrointestinal adverse events (RR 0.76, 95% CI 0.48 to 1.21; 6 trials, 2049 participants; low quality evidence), pyrexia (RR 0.65, 95% CI 0.15 to 2.73; 3 trials, 1799 participants; low quality evidence), raised alkaline phosphatase (RR 0.65, 95% CI 0.17 to 2.50; 1 trial, 1007 participants; low quality evidence), raised amylase (RR 1.40, 95% CI 0.72 to 2.73; 2 trials, 1071 participants; low quality evidence) and raised triglycerides (RR 1.10, 95% CI 0.39 to 3.13; 2 trials, 1071 participants; low quality evidence). There was probably little or no difference in serum glutamic oxaloacetic transaminase (SGOT; MD 3.3, 95% CI -2.06 to 8.66; 1 trial, 135 participants; moderate quality evidence), serum glutamic- pyruvic transaminase (SGPT; MD 5.7, 95% CI -4.23 to 15.63; 1 trial, 135 participants; moderate quality evidence) and raised cholesterol (RR 6.03, 95% CI 0.75 to 48.78; 1 trial, 64 participants; moderate quality evidence).Our subgroup analyses revealed that NVP slightly increases mortality when given once daily (RR 0.34, 95% CI 0.13 to 0.90; 3 trials, 678 participants; high quality evidence). There were little or no differences in the primary outcomes for patients who were concurrently receiving treatment for tuberculosis. AUTHORS' CONCLUSIONS: Both drugs have similar benefits in initial treatment of HIV infection when combined with two NRTIs. The adverse events encountered affect different systems, with EFV more likely to cause central nervous system adverse events and NVP more likely to raise transaminases, cause neutropenia and rash.

Formulating the Future Research Agenda for Postexposure Prophylaxis for HIV: Methodological Challenges and Potential Approaches.

BACKGROUND: During a World Health Organization-convened Guideline Development Group meeting, recommendations for postexposure prophylaxis (PEP) for human immunodeficiency virus were made and research gaps identified. METHODS: We used the PEP clinical management pathway and the Grading of Evidence, Assessment, Development and Evaluation (GRADE) system as a framework to formulate future research questions, describe the most feasible study design, and identify potential biases. RESULTS: Three key study design formats were identified to address 12 research questions: (1) survey- and interview-driven research to identify barriers to access to PEP and related clinical care; (2) establishment of a global PEP registry to generate data to inform the choice of an optimal PEP drug regimen, record drug toxicities arising from specific PEP regimens, and track follow-up and linkage to care (including transition from PEP to preexposure prophylaxis); and (3) randomized controlled trials to determine the optimal adherence promotion strategies necessary for successful outcomes following PEP. CONCLUSIONS: Positioning key clinical and programmatic research questions within the GRADE framework facilitates the formulation of an evidence-based research agenda and future revisions of guidelines.

Measuring evidence-based practice knowledge and skills in occupational therapy--a brief instrument.

BACKGROUND: Valid and reliable instruments are required to measure the effect of educational interventions to improve evidence-based practice (EBP) knowledge and skills in occupational therapy. The aims of this paper are to: 1) describe amendments to the Adapted Fresno Test of Competence in EBP (AFT), and 2) report the psychometric properties of the modified instrument when used with South African occupational therapists. METHODS: The clinical utility of the AFT was evaluated for use with South African occupational therapists and modifications made. The modified AFT was used in two studies to assess its reliability and validity. In Study 1 a convenience sample of 26 occupational therapists in private practice or government-funded health facilities in a South African province were recruited to complete the modified AFT on two occasions 1 week apart. Completed questionnaires were scored independently by two raters. Inter-rater, test-retest reliability and internal consistency were determined. Study 2 was a pragmatic randomised controlled trial involving occupational therapists in four Western Cape Department of Health district municipalities (n = 58). Therapists were randomised in matched pairs to one of two educational interventions (interactive or didactic), and completed the modified AFT at baseline and 12 weeks after the intervention. An intention-to-treat analysis was performed. Data were not normally distributed, thus non-parametric statistics were used. RESULTS: In Study 1, 21 of 26 participants completed the questionnaire twice. Test-retest (ICC = 0.95, 95 % CI = 0.88-0.98) and inter-rater reliability (Time 1: ICC = 0.995, 95 % CI = 0.99-0.998; Time 2: ICC = 0.99, 95 % CI = 0.97-0.995) were excellent for total scores. Internal consistency based on time 1 scores was satisfactory (α = 0.70). In Study 2, 28 participants received an interactive educational intervention and completed the modified AFT at baseline and 12 weeks later. Median total SAFT scores increased significantly from baseline to 12-weeks (Z = -4.078, p < 0.001) with a moderate effect size (r = 0.55). CONCLUSION: The modified AFT has demonstrated validity for detecting differences in EBP knowledge between two groups. It also has excellent test-retest and inter-rater reliability. The instrument is recommended for contexts where EBP is an emerging approach and time is at a premium. TRIAL REGISTRATION: Pan African Controlled Trials Register PACTR201201000346141 . Registered 31 January 2012. Clinical Trials NCT01512823 . Registered 1 February 2012. South African National Clinical Trial Register DOH2710093067 . Registered 27 October 2009.

Restricting or banning alcohol advertising to reduce alcohol consumption in adults and adolescents.

BACKGROUND: Alcohol is estimated to be the fifth leading risk factor for global disability-adjusted life years. Restricting or banning alcohol advertising may reduce exposure to the risk posed by alcohol at the individual and general population level. To date, no systematic review has evaluated the effectiveness, possible harms and cost-effectiveness of this intervention. OBJECTIVES: To evaluate the benefits, harms and costs of restricting or banning the advertising of alcohol, via any format, compared with no restrictions or counter-advertising, on alcohol consumption in adults and adolescents. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Specialised Register (May 2014); CENTRAL (Issue 5, 2014); MEDLINE (1966 to 28 May 2014); EMBASE (1974 to 28 May 2014); PsychINFO (June 2013); and five alcohol and marketing databases in October 2013. We also searched seven conference databases and www.clinicaltrials.gov and http://apps.who.int/trialsearch/ in October 2013. We checked the reference lists of all studies identified and those of relevant systematic reviews or guidelines, and contacted researchers, policymakers and other experts in the field for published or unpublished data, regardless of language. SELECTION CRITERIA: We included randomised controlled trials (RCTs), controlled clinical trials, prospective and retrospective cohort studies, controlled before-and-after studies and interrupted time series (ITS) studies that evaluated the restriction or banning of alcohol advertising via any format including advertising in the press, on the television, radio, or internet, via billboards, social media or product placement in films. The data could be at the individual (adults or adolescent) or population level. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included one small RCT (80 male student participants conducted in the Netherlands and published in 2009) and three ITS studies (general population studies in Canadian provinces conducted in the 1970s and 80s).The RCT found that young men exposed to movies with a low-alcohol content drank less than men exposed to movies with a high-alcohol content (mean difference (MD) -0.65 drinks; 95% CI -1.2, -0.07; p value = 0.03, very-low-quality evidence). Young men exposed to commercials with a neutral content compared with those exposed to commercials for alcohol drank less (MD -0.73 drinks; 95% CI -1.30, -0.16; p value = 0.01, very-low-quality evidence). Outcomes were assessed immediately after the end of the intervention (lasting 1.5 hours), so no follow-up data were available. Using the Grading of Recommendations Assessment, Development and Evaluation approach, the quality of the evidence was rated as very low due to a serious risk of bias, serious indirectness of the included population and serious level of imprecision.Two of the ITS studies evaluated the implementation of an advertising ban and one study evaluated the lifting of such a ban. Each of the three ITS studies evaluated a different type of ban (partial or full) compared with different degrees of restrictions or no restrictions during the control period. The results from the three ITS studies were inconsistent. A meta-analysis of the two studies that evaluated the implementation of a ban showed an overall mean non-significant increase in beer consumption in the general population of 1.10% following the ban (95% CI -5.26, 7.47; p value = 0.43; I(2) = 83%, very-low-quality evidence). This finding is consistent with an increase, no difference, or a decrease in alcohol consumption. In the study evaluating the lifting of a total ban on all forms of alcohol advertising to a partial ban on spirits advertising only, which utilised an Abrupt Auto-regressive Integrated Moving Average model, the volume of all forms of alcohol sales decreased by 11.11 kilolitres (95% CI -27.56, 5.34; p value = 0.19) per month after the ban was lifted. In this model, beer and wine sales increased per month by 14.89 kilolitres (95% CI 0.39, 29.39; p value = 0.04) and 1.15 kilolitres (95% CI -0.91, 3.21; p value = 0.27), respectively, and spirits sales decreased statistically significantly by 22.49 kilolitres (95% CI -36.83, -8.15; p value = 0.002). Using the GRADE approach, the evidence from the ITS studies was rated as very low due to a high risk of bias arising from a lack of randomisation and imprecision in the results.No other prespecified outcomes (including economic loss or hardship due to decreased alcohol sales) were addressed in the included studies and no adverse effects were reported in any of the studies. None of the studies were funded by the alcohol or advertising industries. AUTHORS' CONCLUSIONS: There is a lack of robust evidence for or against recommending the implementation of alcohol advertising restrictions. Advertising restrictions should be implemented within a high-quality, well-monitored research programme to ensure the evaluation over time of all relevant outcomes in order to build the evidence base.

Understanding effective post-test linkage strategies for HIV prevention and care: a scoping review.

INTRODUCTION: Following HIV testing services (HTS), the World Health Organization recommends prompt linkage to prevention and treatment. Scale-up of effective linkage strategies is essential to achieving the global 95-95-95 goals for maintaining low HIV incidence by 2030 and reducing HIV-related morbidity and mortality. Whereas linkage to care including same-day antiretroviral therapy (ART) initiation for all people with HIV is now routinely implemented in testing programmes, linkage to HIV prevention interventions including behavioural or biomedical strategies, for HIV-negative individuals remains sub-optimal. This review aims to evaluate effective post-HTS linkage strategies for HIV overall, and highlight gaps specifically in linkage to prevention. METHODS: Using the five-step Arksey and O'Malley framework, we conducted a scoping review searching existing published and grey literature. We searched PubMed, Cochrane Library, CINAHL, Web of Science and EMBASE databases for English-language studies published between 1 January 2010 and 30 November 2023. Linkage interventions included as streamlined interventions-involving same-day HIV testing, ART initiation and point-of-care CD4 cell count/viral load, case management-involving linkage coordinators developing personalized HIV care and risk reduction plans, incentives-financial and non-financial, partner services-including contact tracing, virtual-like social media, quality improvement-like use of score cards, and peer-based interventions. Outcomes of interest were linkage to any form of HIV prevention and/or care including ART initiation. RESULTS: Of 2358 articles screened, 66 research studies met the inclusion criteria. Only nine linkage to prevention studies were identified (n = 9/66, 14%)-involving pre-exposure prophylaxis, voluntary medical male circumcision, sexually transmitted infection and cervical cancer screening. Linkage to care studies (n = 57/66, 86%) focused on streamlined interventions in the general population and on case management among key populations. DISCUSSION: Despite a wide range of HIV prevention interventions available, there was a dearth of literature on HIV prevention programmes and on the use of messaging on treatment as prevention strategy. Linkage to care studies were comparatively numerous except those evaluating virtual interventions, incentives and quality improvement. CONCLUSIONS: The findings give insights into linkage strategies but more understanding of how to provide these effectively for maximum prevention impact is needed.

Whole-of-community and intersectoral interventions that address alcohol-related harms: A scoping review.

Alcohol harms threaten global population health, with youth particularly vulnerable. Low - and middle-income countries (LMIC) are increasingly targeted by the alcohol industry. Intersectoral and whole-of-community actions are recommended to combat alcohol harms, but there is insufficient global evidence synthesis and research examining interventions in LMIC. This paper maps existing literature on whole-of - community and intersectoral alcohol harms reduction interventions in high-income countries (HIC) and LMIC. Systematic searching and screening produced 61 articles from an initial set of 1325: HIC (n = 53), LMIC (n = 8). Data were extracted on geographic location, intersectoral action, reported outcomes, barriers, and enablers. HIC interventions most often targeted adolescents and combined community action with other components. LMIC interventions did not target adolescents or use policy, schools, alcohol outlets, or enforcement components. Programme enablers were a clear intervention focus with high political support and local level leadership, locally appropriate plans, high community motivation, community action and specific strategies for parents. Challenges were sustainability, complexity of interventions, managing participant expectations and difficulty engaging multiple sectors. A learning agenda to pilot, scale and sustain whole-of-community approaches to address alcohol harms in settings is crucial, with consideration of local contexts and capacities, more standardised methods, and a focus on community-driven action.

The medical use of cannabis for reducing morbidity and mortality in patients with HIV/AIDS.

BACKGROUND: The use of cannabis (marijuana) or of its psychoactive ingredient delta-9-tetrahydrocannabinol (THC) as a medicine has been highly contested in many settings.There have been claims that smoked or ingested cannabis, either in its natural form or artificial form (pharmaceutically manufactured drug such as dronabinol), improves the appetites of people with AIDS, results in weight gain and lifts mood, thus improving the quality of life. OBJECTIVES: The objectives of this review were to assess whether cannabis (in its natural or artificially produced form), either smoked or ingested, decreases the morbidity or mortality of patients infected with HIV. SEARCH METHODS: The search strategy was conducted to July 2012 and was based on that of the Cochrane HIV/AIDS Review Group. We searched the following databases: CENTRAL/CCTR, MEDLINE and EMBASE. In addition, searching was performed where necessary of journals, reference lists of articles, and conference proceedings. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) of any cannabis intervention, in any form, and administered by any route, in adults with HIV or AIDS, compared with placebo or with a known effective treatment, and conducted in a hospital, outpatient clinic, or home care setting. Quasi-randomised studies using any form of cannabis as an intervention in patients with HIV or AIDS were also included. DATA COLLECTION AND ANALYSIS: Data from the eligible studies were extracted and coded independently by two researchers, using a standardised data extraction form. Data were then analysed using RevMan 5.0. No meta-analyses were performed. MAIN RESULTS: A total of seven relevant studies were included in the review, reported in eight publications. All were randomised controlled studies, with four utilising a parallel group design, two a within-subject randomisation and two a cross-over design. All of the studies were of a fairly short duration, ranging from 21 days to 84 days. In only four papers (in effect, three studies) were sequence generation and allocation concealment judged to be adequate. The use of cannabis and rapidly acting cannabinoids posed considerable challenges for blinding, as the psychoactive effects are expected to be quickly discernible to study participants, particularly those who have been previous users of such products. Dronabinol was expected to be more easily blinded. The outcomes measured were variable, including change in weight, change in body fat (measured as a percentage of total body weight), change in appetite (measured on a visual analogue scale), change in caloric intake (measured in kcals/kg/24hr), change in nausea and vomiting (measured on a visual analogue scale), change in performance (measured by Karnofsky performance score or specific tests for memory and dexterity) and change in mood (measured on a visual analogue scale).The evidence for substantial effects on morbidity and mortality is currently limited. Data from only one relatively small study (n=139, of which only 88 were evaluable), conducted in the period before access to highly-active antiretroviral therapy (HAART), showed that patients administered dronabinol were twice as likely to gain 2kg or more in body weight (RR 2.09), but the confidence interval for this measure (95% CI 0.72 - 6.06) included unity. The mean weight gain in the dronabinol group was only 0.1kg, compared with a loss of 0.4kg in the placebo group. However, the quality of sequence generation and allocation concealment in this study, in which participants were randomised by centre, could not be assessed. AUTHORS' CONCLUSIONS: Despite dronabinol being registered by at least some medicines regulatory authorities for the treatment of AIDS-associated anorexia, and some jurisdictions making allowances for the "medical" use of marijuana by patients with HIV/AIDS, evidence for the efficacy and safety of cannabis and cannabinoids in this setting is lacking. Such studies as have been performed have been of short duration, in small numbers of patients, and have focused on short-term measures of efficacy. Long-term data, showing a sustained effect on AIDS-related morbidity and mortality and safety in patients on effective antiretroviral therapy, has yet to be presented. Whether the available evidence is sufficient to justify a wide-ranging revisiting of medicines regulatory practice remains unclear.