Transcutaneous bilirubinometry for detecting jaundice in term or late preterm neonates.

BACKGROUND: The American Academy of Pediatrics and the Canadian Paediatric Society both advise that all newborns should undergo bilirubin screening before leaving the hospital, and this has become the standard practice in both countries. However, the US Preventive Task Force has found no strong evidence to suggest that this practice of universal screening for bilirubin reduces the occurrence of significant outcomes such as bilirubin-induced neurologic dysfunction or kernicterus. OBJECTIVES: To evaluate the effectiveness of transcutaneous screening compared to visual inspection for hyperbilirubinemia to prevent the readmission of newborns (infants greater than 35 weeks' gestation) for phototherapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, ICTRP, and ISRCTN in June 2023. We also searched conference proceedings, and the reference lists of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, or prospective cohort studies with control arm that evaluated the use of transcutaneous bilirubin (TcB) screening for hyperbilirubinemia in newborns before hospital discharge. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) and 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to evaluate the certainty of evidence. MAIN RESULTS: We identified one RCT (1858 participants) that met our inclusion criteria. The study included 1858 African newborns at 35 weeks' gestation or greater who were receiving routine care at a well-baby nursery, and were randomly recruited prior to discharge to undergo TcB screening. The study had good methodologic quality. TcB screening versus visual assessment of hyperbilirubinemia in newborns: - may reduce readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - probably has little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - may increase the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - probably has little or no effect on the rate of acute bilirubin encephalopathy (RR 0.33, 95% CI 0.01 to 8.18; low-certainty evidence). The study did not evaluate or report cost of care. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that TcB screening may reduce readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening probably has little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening may increase the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening probably has little or no effect on the rate of acute bilirubin encephalopathy compared to visual inspection. Given that we have only identified one RCT, further studies are necessary to determine whether TcB screening can help to reduce readmission and complications related to neonatal hyperbilirubinemia. In settings with limited newborn follow-up after hospital discharge, identifying newborns at risk of severe hyperbilirubinemia before hospital discharge will be important to plan targeted follow-up of these infants.

Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns.

BACKGROUND: Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels. OBJECTIVES: To determine the diagnostic accuracy of transcutaneous bilirubin measurement for detecting hyperbilirubinaemia in newborns. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies. SELECTION CRITERIA: We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients. DATA COLLECTION AND ANALYSIS: Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis. MAIN RESULTS: We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%. AUTHORS' CONCLUSIONS: The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement.

A Network Meta-Analysis of Intravenous Versus Oral Acetaminophen for Patent Ductus Arteriosus.

The use of acetaminophen to close a PDA in preterm infants is increasing; however, the most effective route of administration is not yet known. This network meta-analysis compares the efficacy of IV versus PO routes of acetaminophen administration on clinical outcomes related to the presence of a PDA in preterm neonates. Medline, Embase, Cochrane Central Register of Controlled Trials, Embase, Web of Science, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched from inception to October 2020. A total 21 randomized controlled trials in neonates less than 37 weeks at birth, comparing oral or intravenously administered acetaminophen to close a PDA based on study criteria were included. Two authors extracted data independently and in duplicate. All outcomes were binary, and a frequentist network meta-analysis was performed. After one or two courses, both PO and IV acetaminophen were efficacious in closing a PDA with oral ranking higher than IV (low confidence). Neither medication was better than no treatment for secondary outcomes of NEC or BPD (moderate and low confidence respectively). We did not test the rectal route of acetaminophen administration and cannot make generalized statements. This study suggests oral acetaminophen increases the odds of being able to close a PDA in preterm neonates when compared to IV acetaminophen.

Noninvasive methods for bilirubin measurements in newborns: A report.

New technologies have become available for noninvasive assessments of neonatal hyperbilirubinemia. Our objective is to review the noninvasive methods for measuring bilirubin in the newborn. We searched relevant literature from 1966 to January 1, 2020, which included cross-sectional studies to define the accuracy of any noninvasive methods for measuring or estimating total serum/plasma bilirubin (TB) levels in newborns. We identified and included 83 relevant studies of direct visual assessment, icterometry, mobile phone applications, and transcutaneous bilirubinometry (TcB). Compared with laboratory TB measurements, visual assessment was the least accurate and least reliable (r: 0.37 to 074), while TcB was the most accurate, but not always near-equivalent (r: 0.45 to 0.99). The sensitivity and specificity of TcB cut-off values to detect significant hyperbilirubinemia (TB>95th percentile for age in hours) ranged from 74% to 100% and 18% to 89%, respectively.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal haemoglobin polymerisation leading to a symptomatic disorder. Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. OBJECTIVES: The objectives of this review are: - to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease; - to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries, Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 September 2020. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Ultrasound imaging versus palpation method for diagnostic lumbar puncture in neonates and infants: a systematic review and meta-analysis.

IMPORTANCE: Lumbar puncture (LP) failure rates vary and can be as high as 65%. Ultrasound guidance could increase the success of performing LP. OBJECTIVE: To summarise the evidence on the use of ultrasound guidance versus palpation method for LP. DATA SOURCES: We searched computerised databases and published indexes, registries and references identified from bibliographies of pertinent articles without any language restrictions to find studies that compared ultrasound guidance to palpation method for performing an LP. STUDY SELECTION: Studies were included if they were randomised or quasirandomised trials in neonates and infants that compared ultrasound guidance with palpation method for performing an LP. DATA EXTRACTION AND SYNTHESIS: Standardised data collection tool was used for data extraction, and two reviewers independently assessed the quality of the studies. MAIN OUTCOMES AND MEASURES: The primary outcome was the risk of LP failure, while the risk of traumatic tap, needle redirections/reinsertions and procedure durations were secondary outcomes. RESULTS: Data from four studies and 308 participants is included in the analysis. Ultrasound imaging reduced the risk of LP failure, risk ratio of 0.58 (95% CI 0.15 to 2.28), but it was not statistically significant (p=0.44). Ultrasound imaging significantly reduced the risk of a traumatic tap risk ratio of 0.33 (95% CI 0.13 to 0.82) and p=0.02. The included studies had low to moderate quality; the studies differed based on mean age and with variability on outcome definition. CONCLUSIONS AND RELEVANCE: This meta-analysis suggests that ultrasound imaging has no effect in increasing lumbar success but is beneficial in reducing the risk of traumatic taps in neonates and infants. TRIAL REGISTRATION NUMBER: CRD42017055800.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings. We also searched online trial registries,Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 19 July 2018. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Newborn follow-up after discharge from a tertiary care hospital in the Western Cape region of South Africa: a prospective observational cohort study.

BACKGROUND: Current practice in the Western Cape region of South Africa is to discharge newborns born in-hospital within 24 h following uncomplicated vaginal delivery and two days after caesarean section. Mothers are instructed to bring their newborn to a clinic after discharge for a health assessment. We sought to determine the rate of newborn follow-up visits and the potential barriers to timely follow-up. METHODS: Mother-newborn dyads at Tygerberg Hospital in Cape Town, South Africa were enrolled from November 2014 to April 2015. Demographic data were obtained via questionnaire and medical records. Mothers were contacted one week after discharge to determine if they had brought their newborns for a follow-up visit, and if not, the barriers to follow-up. Factors associated with follow-up were analyzed using logistic regression. RESULTS: Of 972 newborns, 794 (82%) were seen at a clinic for a follow-up visit within one week of discharge. Mothers with a higher education level or whose newborns were less than 37 weeks were more likely to follow up. The follow-up rate did not differ based on hospital length of stay. Main reported barriers to follow-up included maternal illness, lack of money for transportation, and mother felt follow-up was unnecessary because newborn was healthy. CONCLUSIONS: Nearly 4 in 5 newborns were seen at a clinic within one week after hospital discharge, in keeping with local practice guidelines. Further research on the outcomes of this population and those who fail to follow up is needed to determine the impact of postnatal healthcare policy.

Governance arrangements for health systems in low-income countries: an overview of systematic reviews.

BACKGROUND: Governance arrangements include changes in rules or processes that determine authority and accountability for health policies, organisations, commercial products and health professionals, as well as the involvement of stakeholders in decision-making. Changes in governance arrangements can affect health and related goals in numerous ways, generally through changes in authority, accountability, openness, participation and coherence. A broad overview of the findings of systematic reviews can help policymakers, their technical support staff and other stakeholders to identify strategies for addressing problems and improving the governance of their health systems. OBJECTIVES: To provide an overview of the available evidence from up-to-date systematic reviews about the effects of governance arrangements for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on governance arrangements and informing refinements of the framework for governance arrangements outlined in the overview. METHODS: We searched Health Systems Evidence in November 2010 and PDQ Evidence up to 17 December 2016 for systematic reviews. We did not apply any date, language or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of governance arrangements on patient outcomes (health and health behaviours), the quality or utilisation of healthcare services, resource use (health expenditures, healthcare provider costs, out-of-pocket payments, cost-effectiveness), healthcare provider outcomes (such as sick leave), or social outcomes (such as poverty, employment) and that were published after April 2005. We excluded reviews with limitations that were important enough to compromise the reliability of the findings of the review. Two overview authors independently screened reviews, extracted data and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence) and assessments of the relevance of findings to low-income countries. MAIN RESULTS: We identified 7272 systematic reviews and included 21 of them in this overview (19 primary reviews and 2 supplementary reviews). We focus here on the results of the 19 primary reviews, one of which had important methodological limitations. The other 18 were reliable (with only minor limitations).We grouped the governance arrangements addressed in the reviews into five categories: authority and accountability for health policies (three reviews); authority and accountability for organisations (two reviews); authority and accountability for commercial products (three reviews); authority and accountability for health professionals (seven reviews); and stakeholder involvement (four reviews).Overall, we found desirable effects for the following interventions on at least one outcome, with moderate- or high-certainty evidence and no moderate- or high-certainty evidence of undesirable effects. Decision-making about what is covered by health insurance- Placing restrictions on the medicines reimbursed by health insurance systems probably decreases the use of and spending on these medicines (moderate-certainty evidence). Stakeholder participation in policy and organisational decisions- Participatory learning and action groups for women probably improve newborn survival (moderate-certainty evidence).- Consumer involvement in preparing patient information probably improves the quality of the information and patient knowledge (moderate-certainty evidence). Disclosing performance information to patients and the public- Disclosing performance data on hospital quality to the public probably encourages hospitals to implement quality improvement activities (moderate-certainty evidence).- Disclosing performance data on individual healthcare providers to the public probably leads people to select providers that have better quality ratings (moderate-certainty evidence). AUTHORS' CONCLUSIONS: Investigators have evaluated a wide range of governance arrangements that are relevant for low-income countries using sound systematic review methods. These strategies have been targeted at different levels in health systems, and studies have assessed a range of outcomes. Moderate-certainty evidence shows desirable effects (with no undesirable effects) for some interventions. However, there are important gaps in the availability of systematic reviews and primary studies for the all of the main categories of governance arrangements.

Delivery arrangements for health systems in low-income countries: an overview of systematic reviews.

BACKGROUND: Delivery arrangements include changes in who receives care and when, who provides care, the working conditions of those who provide care, coordination of care amongst different providers, where care is provided, the use of information and communication technology to deliver care, and quality and safety systems. How services are delivered can have impacts on the effectiveness, efficiency and equity of health systems. This broad overview of the findings of systematic reviews can help policymakers and other stakeholders identify strategies for addressing problems and improve the delivery of services. OBJECTIVES: To provide an overview of the available evidence from up-to-date systematic reviews about the effects of delivery arrangements for health systems in low-income countries. Secondary objectives include identifying needs and priorities for future evaluations and systematic reviews on delivery arrangements and informing refinements of the framework for delivery arrangements outlined in the review. METHODS: We searched Health Systems Evidence in November 2010 and PDQ-Evidence up to 17 December 2016 for systematic reviews. We did not apply any date, language or publication status limitations in the searches. We included well-conducted systematic reviews of studies that assessed the effects of delivery arrangements on patient outcomes (health and health behaviours), the quality or utilisation of healthcare services, resource use, healthcare provider outcomes (such as sick leave), or social outcomes (such as poverty or employment) and that were published after April 2005. We excluded reviews with limitations important enough to compromise the reliability of the findings. Two overview authors independently screened reviews, extracted data, and assessed the certainty of evidence using GRADE. We prepared SUPPORT Summaries for eligible reviews, including key messages, 'Summary of findings' tables (using GRADE to assess the certainty of the evidence), and assessments of the relevance of findings to low-income countries. MAIN RESULTS: We identified 7272 systematic reviews and included 51 of them in this overview. We judged 6 of the 51 reviews to have important methodological limitations and the other 45 to have only minor limitations. We grouped delivery arrangements into eight categories. Some reviews provided more than one comparison and were in more than one category. Across these categories, the following intervention were effective; that is, they have desirable effects on at least one outcome with moderate- or high-certainty evidence and no moderate- or high-certainty evidence of undesirable effects. Who receives care and when: queuing strategies and antenatal care to groups of mothers. Who provides care: lay health workers for caring for people with hypertension, lay health workers to deliver care for mothers and children or infectious diseases, lay health workers to deliver community-based neonatal care packages, midlevel health professionals for abortion care, social support to pregnant women at risk, midwife-led care for childbearing women, non-specialist providers in mental health and neurology, and physician-nurse substitution. Coordination of care: hospital clinical pathways, case management for people living with HIV and AIDS, interactive communication between primary care doctors and specialists, hospital discharge planning, adding a service to an existing service and integrating delivery models, referral from primary to secondary care, physician-led versus nurse-led triage in emergency departments, and team midwifery. Where care is provided: high-volume institutions, home-based care (with or without multidisciplinary team) for people living with HIV and AIDS, home-based management of malaria, home care for children with acute physical conditions, community-based interventions for childhood diarrhoea and pneumonia, out-of-facility HIV and reproductive health services for youth, and decentralised HIV care. Information and communication technology: mobile phone messaging for patients with long-term illnesses, mobile phone messaging reminders for attendance at healthcare appointments, mobile phone messaging to promote adherence to antiretroviral therapy, women carrying their own case notes in pregnancy, interventions to improve childhood vaccination. Quality and safety systems: decision support with clinical information systems for people living with HIV/AIDS. Complex interventions (cutting across delivery categories and other health system arrangements): emergency obstetric referral interventions. AUTHORS' CONCLUSIONS: A wide range of strategies have been evaluated for improving delivery arrangements in low-income countries, using sound systematic review methods in both Cochrane and non-Cochrane reviews. These reviews have assessed a range of outcomes. Most of the available evidence focuses on who provides care, where care is provided and coordination of care. For all the main categories of delivery arrangements, we identified gaps in primary research related to uncertainty about the applicability of the evidence to low-income countries, low- or very low-certainty evidence or a lack of studies.

Zinc supplementation for the treatment of measles in children.

BACKGROUND: Measles is an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. This is an update of a review first published in 2015. OBJECTIVES: To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles. SEARCH METHODS: We searched CENTRAL (03 February 2017, Issue 2), MEDLINE (1946 to 03 February 2017), Embase (1974 to 03 February 2017), CINAHL (1981 to 03 February 2017), LILACS (1982 to 03 February 2017), Web of Science (1985 to 03 February 2017), and BIOSIS Previews (1985 to 27 June 2014). We also searched ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 03 February 2017 to identify unpublished and ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions, and other study characteristics using a standardised data extraction form. We used risk ratio (RR) and hazard ratio (HR) as measures of effect with 95% confidence intervals (CI). We included only one study, and did not conduct meta-analysis. MAIN RESULTS: We did not identify any new studies for inclusion in this update. One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed no significant difference in mortality between children with measles and pneumonia who received zinc supplements and those who received placebo (RR 0.34, 95% CI 0.01 to 8.14). There was no significant difference in time to absence of fever between children who received zinc supplements and those who did not (HR 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. We assessed the overall quality of the evidence as very low. AUTHORS' CONCLUSIONS: We could not draw any definitive conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in children with measles.

Interleukin-2 as an adjunct to antiretroviral therapy for HIV-positive adults.

BACKGROUND: Human immunodeficiency virus (HIV) continues to be a leading cause of morbidity and mortality, particularly in sub-Saharan Africa. Although antiretroviral drugs have helped to improve the quality of life and life expectancy of HIV-positive individuals, there is still a need to explore other interventions that will help to further reduce the disease burden. One potential strategy is the use of interleukin-2 (IL-2) in combination with antiretroviral therapy (ART). IL-2 is a cytokine that regulates the proliferation and differentiation of lymphocytes and may help to boost the immune system. OBJECTIVES: To assess the effects of interleukin-2 (IL-2) as an adjunct to antiretroviral therapy for HIV-positive adults. SEARCH METHODS: We searched the following sources up to 26 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; Embase; the Web of Science; LILACS; the World Health Organization (WHO) International Clinical Trial Registry Platform (ICTRP); and ClinicalTrials.gov. We also checked conference abstracts, contacted experts and relevant organizations in the field, and checked the reference list of all studies identified by the above methods for any other potentially eligible studies. SELECTION CRITERIA: Randomized controlled trials (RCTs) that evaluated the effects of IL-2 as an adjunct to ART in reducing the morbidity and mortality in HIV-positive adults. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records and selected trials that met the inclusion criteria, extracted data, and assessed the risk of bias in the included trials. Where possible, we compared the effects of interventions using risk ratios (RR), and presented them with 95% confidence intervals (CI). We assessed the overall certainty of the evidence using the GRADE approach. MAIN RESULTS: Following a comprehensive literature search up to 26 May 2016, we identified 25 eligible trials. The interventions involved the use of IL-2 in combination with ART compared with ART alone. There was no difference in mortality apparent between the IL-2 group and the ART alone group (RR 0.97, 95% CI 0.80 to 1.17; 6 trials, 6565 participants, high certainty evidence). Seventeen of 21 trials reported an increase in the CD4 cell count with the use of IL-2 compared to control using different measures (21 trials, 7600 participants). Overall, there was little or no difference in the proportion of participants with a viral load of less than 50 cells/mL or less than 500 cells/mL by the end of the trials (RR 0.97, 95% CI 0.81 to 1.15; 5 trials, 805 participants, high certainty evidence) and (RR 0.96, 95% CI 0.82 to 1.12; 4 trials, 5929 participants, high certainty evidence) respectively. Overall there may be little or no difference in the occurrence of opportunistic infections (RR 0.79, 95% CI 0.55 to 1.13; 7 trials, 6141 participants, low certainty evidence). There was probably an increase in grade 3 or 4 adverse events (RR 1.47, 95% CI 1.10 to 1.96; 6 trials, 6291 participants, moderate certainty evidence). None of the included trials reported adherence. AUTHORS' CONCLUSIONS: There is high certainty evidence that IL-2 in combination with ART increases the CD4 cell count in HIV-positive adults. However, IL-2 does not confer any significant benefit in mortality, there is probably no difference in the incidence of opportunistic infections, and there is probably an increase in grade 3 or 4 adverse effects. Our findings do not support the use of IL-2 as an adjunct to ART in HIV-positive adults. Based on our findings, further trials are not justified.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. This is an update of a previously published Cochrane Review. OBJECTIVES: The objectives of this review are:to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 15 August 2016. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Brief school-based interventions and behavioural outcomes for substance-using adolescents.

BACKGROUND: Adolescent substance use is a major problem in and of itself, and because it acts as a risk factor for other problem behaviours. As substance use during adolescence can lead to adverse and often long-term health and social consequences, it is important to intervene early in order to prevent progression to more severe problems. Brief interventions have been shown to reduce problematic substance use among adolescents and are especially useful for individuals who have moderately risky patterns of substance use. Such interventions can be conducted in school settings. This review set out to evaluate the effectiveness of brief school-based interventions for adolescent substance use. OBJECTIVES: To evaluate the effectiveness of brief school-based interventions in reducing substance use and other behavioural outcomes among adolescents compared to another intervention or assessment-only conditions. SEARCH METHODS: We conducted the original literature search in March 2013 and performed the search update to February 2015. For both review stages (original and update), we searched 10 electronic databases and six websites on evidence-based interventions, and the reference lists of included studies and reviews, from 1966 to February 2015. We also contacted authors and organisations to identify any additional studies. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effects of brief school-based interventions for substance-using adolescents.The primary outcomes were reduction or cessation of substance use. The secondary outcomes were engagement in criminal activity and engagement in delinquent or problem behaviours related to substance use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures outlined by The Cochrane Collaboration, including the GRADE approach for evaluating the quality of evidence. MAIN RESULTS: We included six trials with 1176 adolescents that measured outcomes at different follow-up periods in this review. Three studies with 732 adolescents compared brief interventions (Bls) with information provision only, and three studies with 444 adolescents compared Bls with assessment only. Reasons for downgrading the quality of evidence included risk of bias of the included studies, imprecision, and inconsistency. For outcomes that concern substance abuse, the retrieved studies only assessed alcohol and cannabis. We generally found moderate-quality evidence that, compared to information provision only, BIs did not have a significant effect on any of the substance use outcomes at short-, medium-, or long-term follow-up. They also did not have a significant effect on delinquent-type behaviour outcomes among adolescents. When compared to assessment-only controls, we found low- or very low-quality evidence that BIs reduced cannabis frequency at short-term follow-up in one study (standardised mean difference (SMD) -0.83; 95% confidence interval (CI) -1.14 to -0.53, n = 269). BIs also significantly reduced frequency of alcohol use (SMD -0.91; 95% CI -1.21 to -0.61, n = 242), alcohol abuse (SMD -0.38; 95% CI -0.7 to -0.07, n = 190) and dependence (SMD -0.58; 95% CI -0.9 to -0.26, n = 190), and cannabis abuse (SMD -0.34; 95% CI -0.65 to -0.02, n = 190) at medium-term follow-up in one study. At long-term follow-up, BIs also reduced alcohol abuse (SMD -0.72; 95% CI -1.05 to -0.40, n = 181), cannabis frequency (SMD -0.56; 95% CI -0.75 to -0.36, n = 181), abuse (SMD -0.62; 95% CI -0.95 to -0.29, n = 181), and dependence (SMD -0.96; 95% CI -1.30 to -0.63, n = 181) in one study. However, the evidence from studies that compared brief interventions to assessment-only conditions was generally of low quality. Brief interventions also had mixed effects on adolescents' delinquent or problem behaviours, although the effect at long-term follow-up on these outcomes in the assessment-only comparison was significant (SMD -0.78; 95% CI -1.11 to -0.45). AUTHORS' CONCLUSIONS: We found low- or very low-quality evidence that brief school-based interventions may be more effective in reducing alcohol and cannabis use than the assessment-only condition and that these reductions were sustained at long-term follow-up. We found moderate-quality evidence that, when compared to information provision, brief interventions probably did not have a significant effect on substance use outcomes. It is premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use. Further high-quality studies examining the relative effectiveness of BIs for substance use and other problem behaviours need to be conducted, particularly in low- and middle-income countries.

Optimal Timing of Antiretroviral Therapy Initiation for HIV-Infected Adults With Newly Diagnosed Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.

BACKGROUND: Initiation of antiretroviral therapy (ART) during tuberculosis (TB) treatment remains challenging. PURPOSE: To assess evidence from randomized, controlled trials of the timing of ART initiation in HIV-infected adults with newly diagnosed pulmonary TB. DATA SOURCES: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, conference abstracts, and ClinicalTrials.gov (from January 1980 to May 2015). STUDY SELECTION: Randomized, controlled trials evaluating early versus delayed ART initiation (1 to 4 weeks vs. 8 to 12 weeks after initiation of TB treatment) or deferred ART initiation (after the end of TB treatment). DATA EXTRACTION: Three reviewers independently extracted data and assessed risk of bias. The main outcome measures were all-cause mortality and the TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). DATA SYNTHESIS: The 8 included trials (n = 4568) were conducted in Africa, Asia, and the United States and were generally at low risk of bias for the assessed domains. Overall, early ART reduced mortality compared with delayed ART (relative risk [RR], 0.81 [95% CI, 0.66 to 0.99]; I2 = 0%). In a prespecified subgroup analysis, early ART reduced mortality compared with delayed ART among patients with baseline CD4+ T-cell counts less than 0.050 × 109 cells/L (RR, 0.71 [CI, 0.54 to 0.93]; I2 = 0%). However, a mortality benefit from early ART was not found among those with CD4+ T-cell counts greater than 0.050 × 109 cells/L (RR, 1.05 [CI, 0.68 to 1.61]; I2 = 56%). Early ART was associated with a higher incidence of TB-IRIS than delayed ART (RR, 2.31 [CI, 1.87 to 2.86]; I2 = 19%). LIMITATION: Few trials provided sufficient data for subgroup analysis. CONCLUSION: Early ART in HIV-infected adults with newly diagnosed TB improves survival in those with CD4+ T-cell counts less than 0.050 × 109 cells/L, although this is associated with a 2-fold higher frequency of TB-IRIS. In patients with CD4+ T-cell counts greater than 0.050 × 109 cells/L, evidence is insufficient to support or refute a survival benefit conferred by early versus delayed ART initiation. PRIMARY FUNDING SOURCE: None. (PROSPERO registration: CRD42012001884).

Zinc supplementation for the treatment of measles in children.

BACKGROUND: Measles is still an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. OBJECTIVES: To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles. SEARCH METHODS: We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to June week 3, 2014), EMBASE (1974 to June 2014), CINAHL (1981 to June 2014), LILACS (1982 to June 2014), Web of Science (1985 to June 2014) and BIOSIS Previews (1985 to June 2014). We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to identify unpublished and ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions and other study characteristics using a standardised data extraction form. We used the risk ratio (RR) and hazard ratio as measures of effect with 95% confidence intervals (CI). We included only one study and we did not conduct any meta-analysis. MAIN RESULTS: One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed that there was no significant difference in mortality between the two groups (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.01 to 8.14). Also, there was no significant difference in time to absence of fever between the two groups (hazard ratio (HR) 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. The overall quality of the evidence can be described as very low. AUTHORS' CONCLUSIONS: We cannot draw any definite conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in measles.

Gene therapy for sickle cell disease.

BACKGROUND: Sickle cell disease encompasses a group of genetic disorders characterized by the presence of at least one hemoglobin S (Hb S) allele, and a second abnormal allele that could allow abnormal hemoglobin polymerisation leading to a symptomatic disorder.Autosomal recessive disorders (such as sickle cell disease) are good candidates for gene therapy because a normal phenotype can be restored in diseased cells with only a single normal copy of the mutant gene. OBJECTIVES: The objectives of this review are:- to determine whether gene therapy can improve survival and prevent symptoms and complications associated with sickle cell disease;- to examine the risks of gene therapy against the potential long-term gain for people with sickle cell disease. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises of references identified from comprehensive electronic database searches and searching relevant journals and abstract books of conference proceedings.Date of the most recent search of the Group's Haemoglobinopathies Trials Register: 21 July 2014. SELECTION CRITERIA: All randomised or quasi-randomised clinical trials (including any relevant phase 1, 2 or 3 trials) of gene therapy for all individuals with sickle cell disease, regardless of age or setting. DATA COLLECTION AND ANALYSIS: No trials of gene therapy for sickle cell disease were found. MAIN RESULTS: No trials of gene therapy for sickle cell disease were reported. AUTHORS' CONCLUSIONS: No randomised or quasi-randomised clinical trials of gene therapy for sickle cell disease were reported. Thus, no objective conclusions or recommendations in practice can be made on gene therapy for sickle cell disease. This systematic review has identified the need for well-designed, randomised controlled trials to assess the benefits and risks of gene therapy for sickle cell disease.

Treatment of severe or progressive Kaposi's sarcoma in HIV-infected adults.

Background Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients.Objectives To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma.Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014.Selection criteria Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens.Data collection and analysis Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens.Main results We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events.Authors' conclusions The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.

Treatment of severe or progressive Kaposi's sarcoma in HIV-infected adults.

BACKGROUND: Kaposi's sarcoma remains the most common cancer in Sub-Saharan Africa and the second most common cancer in HIV-infected patients worldwide. Since the introduction of highly active antiretroviral therapy (HAART), there has been a decline in its incidence.However, Kaposi's sarcoma continues to be diagnosed in HIV-infected patients. OBJECTIVES: To assess the added advantage of chemotherapy plus HAART compared to HAART alone; and the advantages of different chemotherapy regimens in HAART and HAART naive HIV infected adults with severe or progressive Kaposi's sarcoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and , GATEWAY, the WHO Clinical Trials Registry Platform and the US National Institutes of Health's ClinicalTrials.gov for ongoing trials and the Aegis archive of HIV/AIDS for conference abstracts. An updated search was conducted in July 2014. SELECTION CRITERIA: Randomised trials and observational studies evaluating the effects of any chemotherapeutic regimen in combination with HAART compared to HAART alone, chemotherapy versus HAART, and comparisons between different chemotherapy regimens. DATA COLLECTION AND ANALYSIS: Two review authors assessed the studies independently and extracted outcome data.We used the risk ratio (RR) with a 95% confidence interval (CI) as the measure of effect.We did not conduct meta-analysis as none of the included trials assessed identical chemotherapy regimens. MAIN RESULTS: We included six randomised trials and three observational studies involving 792 HIV-infected adults with severe Kaposi's sarcoma.Seven studies included patients with a mix of mild to moderate (T0) and severe (T1) Kaposi's sarcoma. However, this review was restricted to the subset of participants with severe Kaposi's sarcoma disease.Studies comparing HAART plus chemotherapy to HAART alone showed the following: one trial comparing HAART plus doxorubicin,bleomycin and vincristine (ABV) to HAART alone showed a significant reduction in disease progression in the HAART plus ABV group (RR 0.10; 95% CI 0.01 to 0.75, 100 participants); there was no statistically significant reduction in mortality and no difference in adverse events. A cohort study comparing liposomal anthracyclines plus HAART to HAART alone showed a non-statistically significant reduction in Kaposi's sarcoma immune reconstitution inflammatory syndrome in patients that received HAART plus liposomal anthracyclines (RR 0.49; 95% CI 0.16 to 1.55, 129 participants).Studies comparing HAART plus chemotherapy to HAART plus a different chemotherapy regimen showed the following: one trial involving 49 participants and comparing paclitaxel versus pegylated liposomal doxorubicin in patients on HAART showed no difference in disease progression. Another trial involving 46 patients and comparing pegylated liposomal doxorubicin versus liposomal daunorubicin showed no participants with progressive Kaposi's sarcoma disease in either group.Studies comparing different chemotherapy regimens in patients from the pre-HAART era showed the following: in the single RCT comparing liposomal daunorubicin to ABV, there was no significant difference with the use of liposomal daunorubicin compared to ABV in disease progression (RR 0.78; 95% CI 0.34 to 1.82, 227 participants) and overall response rate. Another trial involving 178 participants and comparing oral etoposide versus ABV demonstrated no difference in mortality in either group. A non-randomised trial comparing bleomycin alone to ABV demonstrated a higher median survival time in the ABV group; there was also a non-statistically significant reduction in adverse events and disease progression in the ABV group (RR 11; 95% CI 0.67 to 179.29, 24 participants).An additional non-randomised study showed a non-statistically significant overall mortality benefit from liposomal doxorubicin as compared to conservative management consisting of either bleomycin plus vinblastine, vincristine or single-agent antiretroviral therapy alone (RR 0.93; 95% CI 0.75 to 1.15, 29 participants). The overall quality of evidence can be described as moderate quality. The quality of evidence was downgraded due to the small size of many of the included studies and small number of events. AUTHORS' CONCLUSIONS: The findings from this review suggest that HAART plus chemotherapy may be beneficial in reducing disease progression compared to HAART alone in patients with severe or progressive Kaposi's sarcoma. For patients on HAART, when choosing from different chemotherapy regimens, there was no observed difference between liposomal doxorubicin, liposomal daunorubicin and paclitaxel.

Brief school-based interventions and behavioural outcomes for substance-using adolescents.

BACKGROUND: Adolescent substance use is a major problem, in and of itself and because it acts as a risk factor for other problem behaviours. As substance use during adolescence can lead to adverse and often long-term health and social consequences, it is important to intervene early on in order to prevent progression to more severe problems. Brief interventions have been shown to reduce problematic substance use among adolescents and are especially useful for individuals who have moderately risky patterns of substance use. Such interventions can be conducted in school settings. This review set out to evaluate the effectiveness of brief school-based interventions for adolescent substance use. OBJECTIVES: To evaluate the effectiveness of brief school-based interventions on reducing substance use and other behavioural outcomes among adolescents compared to another intervention or assessment-only conditions. SEARCH METHODS: We searched 10 electronic databases and six websites on evidence-based interventions, and the reference lists of included studies and reviews, from 1966 to March 2013. We also contacted authors and organisations to identify any additional studies. SELECTION CRITERIA: We included randomised controlled trials that evaluated the effects of brief school-based interventions for substance-using adolescents.The primary outcomes were reduction or cessation of substance use. The secondary outcomes were engagement in criminal activity and engagement in delinquent or problem behaviours related to substance use. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures outlined by The Cochrane Collaboration, including the GRADE approach for evaluating the quality of evidence. MAIN RESULTS: Six studies involving 1139 participants were included in this review. Overall the quality of evidence was moderate in the information provision comparison, and low or very low in the assessment only comparison. Reasons for downgrading the quality included risk of bias of the included studies, imprecision and inconsistency. Our findings suggested that compared to information provision only, brief interventions (BIs) did not have a significant effect on any substance use (three studies, 732 participants, standardised mean difference (SMD) -0.06; 95% confidence interval (CI) -0.20 to 0.09) or delinquent-type behaviour outcomes among adolescents (two studies, 531 participants, SMD -0.26; 95% CI -0.54 to 0.02). When compared to assessment-only controls, BIs had some significant effects on substance use and delinquent-type or problem behaviours, but high levels of heterogeneity existed between studies and it was not always possible to pool the results. When the comparison was with assessment-only conditions, studies of individual interventions that measured BI effectiveness reported significantly reduced substance use in general and in two studies reduced frequency of alcohol use specifically. When the data were pooled, BIs reduced cannabis frequency (SMD -0.22; 95% CI -0.45 to -0.02) across three studies (n = 407). Cannabis quantity was also reduced by BIs in comparison to assessment only (SMD -60.27; 95% CI -66.59 to -53.95) in one study (n = 179). However, the evidence for studies that compared brief interventions to assessment-only conditions was generally of low quality. Brief interventions also had mixed effects on participants' delinquent or problem behaviours. AUTHORS' CONCLUSIONS: There was limited quality evidence that brief school-based interventions were more effective in reducing substance use than the assessment-only condition, but were similar to information provision. There is some evidence for the effectiveness of BI in reducing adolescent substance use, particularly cannabis, when compared to assessment only. However, it is premature to make definitive statements about the effectiveness of brief school-based interventions for reducing adolescent substance use. Further high quality studies examining the relative effectiveness of BIs for substance use and other problem behaviours need to be conducted, particularly in low- and middle-income countries.