Calculating Within-Pair Difference Scores in the Co-twin Control Design. Effects of Alternative Strategies.

Co-twin studies are an elegant and powerful design that allows controlling for the effect of confounding variables, including genetic and a range of environmental factors. There are several approaches to carry out this design. One of the methods commonly used, when contrasting continuous variables, is to calculate difference scores between members of a twin pair on two associated variables, in order to analyse the covariation of such differences. However, information regarding whether and how the different ways of estimating within-pair difference scores may impact the results is scant. This study aimed to compare the results obtained by different methods of data transformation when performing a co-twin study and test how the magnitude of the association changes using each of those approaches. Data was simulated using a direction of causation model and by fixing the effect size of causal path to low, medium, and high values. Within-pair difference scores were calculated as relative scores for diverse within-pair ordering conditions or absolute scores. Pearson's correlations using relative difference scores vary across the established scenarios (how twins were ordered within pairs) and these discrepancies become larger as the within-twin correlation increases. Absolute difference scores tended to produce the lowest correlation in every condition. Our results show that both using absolute difference scores or ordering twins within pairs, may produce an artificial decrease in the magnitude of the studied association, obscuring the ability to detect patterns compatible with causation, which could lead to discrepancies across studies and erroneous conclusions.

Depressive symptoms in adolescence and adult educational and employment outcomes: a structured life course analysis.

BACKGROUND: Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including 'Not in Education, Employment or Training' (NEET) status. METHODS: We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms. RESULTS: Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012-1.019) for an increase of 1 unit in depression at any age between 11 and 24 years. CONCLUSIONS: Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.

Assessment of metal and organic pollutants in combination with stable isotope analysis in tunas from the Gulf of Cadiz (east Atlantic).

Bioaccumulation patterns of heavy metals (Pb, Cd, Cr, Ni, Fe and Cu) and organic (priority and emerging) pollutants, in combination with stable isotope analysis (SIA), were assessed in muscle and liver of three tuna species from the Gulf of Cadiz (Atlantic bluefin tuna, Thunnus thynnus; Atlantic bonito, Sarda sarda, and skipjack tuna, Katsuwonus pelamis). SIA and contaminant (heavy metal and organic) profiles separately discriminated between species. There was no significant overlap between the trophic niches estimated from isotopic data, suggesting that there are diet differences which may determine differential bioaccumulation patterns. The levels of heavy metals and persistent organic pollutants in muscle of all the individuals analyzed were below the allowable limits established by the current legislation. Concentrations of most contaminants were higher in liver than in muscle, underlining the powerful detoxifying capacity of the liver in tunas. In addition to diet, other factors such as size and age (exposure time to environmental chemicals) explain differences in pollutant accumulation patterns in tissues between species, each with varying degrees of involvement depending on the pollutant class. Our results show that combining contaminant profile data with trophic features based on SIA may help understand pollutant bioaccumulation patterns in upper levels of marine food webs.

Early parenting interventions to prevent internalising problems in children and adolescents: a global systematic review and network meta-analysis.

QUESTION: We compared the effectiveness of different types of parenting interventions based on an a priori taxonomy, and the impact of waitlists versus treatment as usual (TAU), in reducing child internalising problems. STUDY SELECTION AND ANALYSIS: We conducted a systematic review and network meta-analysis of published and unpublished randomised controlled trials (RCTs) until 1 October 2022 that investigated parenting interventions with children younger than 4 years. EXCLUSION CRITERIA: studies with children born preterm, with intellectual disabilities, or families receiving support for current abuse, neglect, and substance misuse. We assessed the certainty of evidence using the Confidence in Network Meta-Analysis framework. We used random-effects network meta-analysis to estimate standardised mean differences (SMDs) with 95% credible intervals (CrIs). FINDINGS: Of 20 520 citations identified, 59 RCTs (18 349 participants) were eligible for the network meta-analysis. Parenting interventions focusing on the dyadic relationship (SMD: -0.26, 95% CrI: -0.43 to -0.08) and those with mixed focus (-0.09, -0.17 to -0.02) were more effective in reducing internalising problems than TAU at the first time point available. All interventions were more effective than waitlist, which increased the risk of internalising problems compared with TAU (0.36, 0.19 to 0.52). All effects attenuated at later follow-ups. Most studies were rated as with 'high risk' or 'some concerns' using the Risk of Bias Assessment Tool V.2. There was no strong evidence of effect modification by theoretically informed components or modifiers. CONCLUSIONS: We found preliminary evidence that relationship-focused and mixed parenting interventions were effective in reducing child internalising problems, and the waitlist comparator increased internalising problems with implications for waiting times between referral and support. Considering the high risk of bias of most studies included, the findings from this meta-analysis should be interpreted with caution. PROSPERO registration number CRD42020172251.

Improvement of Advanced Sample Preparation Systems for the Determination of Trace Ni in Seawater by Electro-Membranes.

Due to its important environmental role, the analysis of trace metals in natural waters is attracting increasing attention; consequently, faster and more accurate analytical methods are now needed to reach even lower limits of detection. In this work, we propose the use of electro-membrane extraction (EME) to improve analytical methods based on hollow fiber liquid phase micro-extraction (HFLPME). Specifically, an EME-based method for the determination of trace Ni in seawater has been developed, using an HFLPME system with di-2-ethylhexyl phosphoric acid (DEHPA) in kerosene as a chemical carrier, followed by instrumental determination by graphite furnace atomic absorption spectroscopy (GFAAS). Under optimum conditions, Ni was pre-concentrated 180 ± 17 times after 15 min, using sample pH = 5.5, the concentration of DEHPA 0.9 M in the liquid membranes, and 1.9 M HNO3 in the acceptor solution, as well as an electric potential of 25 V with the sample being stirred at 500 rpm. When compared with other HFLPME systems for pre-concentration of trace Ni in seawater in the absence of electric potential, the enrichment factor was improved 2.2 times, while the time of extraction was reduced an 89%. The limit of detection of the new method was 23.3 ng L-1, and both its applicability and accuracy were successfully evaluated by analyzing Ni concentration in a seawater-certified reference material (BCR-403), showing the reliability of EME for sample preparation in the determination of trace metals in marine water samples.

A liquid micro-extraction based one-step method for the chemical fractionation of copper in seawater.

In this work, the reagent Cyanex® 272 has been incorporated in a three-phase solvent bar micro-extraction system to selectively separate the inorganic and organic fractions of copper in seawater. Optimized conditions for micro-extraction of Cu fractions were 0.2 M Cyanex® 272 in the organic solution contained into the fiber pores, 0.5 M HCl as acceptor solution within the fiber, stirring rate of 500 rpm, and 60 min time of extraction, providing an enrichment factor of 51.6 ± 2.3. Experimental results for selective extraction of organic and inorganic Cu showed a good correlation with theoretical data for Cu speciation, and the relationship between enrichment factor and dissolved organic carbon (DOC) concentration in the samples was used to predict total Cu concentration. Instrumental determination of Cu presented a linear response within the range 0.1-20 µg L-1, obtaining a limit of detection of 0.03 µg L-1. Finally, the method was successfully applied to the study of Cu fractions in real seawater samples collected from the Bay of Cádiz (Spain).

Overviews of Reviews: Concept and Development.

BACKGROUND: In the last years, overviews of systematic reviews, or umbrella reviews, have seen a dramatic increase in their use. An overview aims to provide a summary of the included reviews and will often examine research questions beyond those addressed in the systematic reviews being synthesised. The purpose of this article is to provide some recommendations on how overviews should be conducted and reported. METHOD: A literature review was performed to identify relevant papers on both methodological and applied overviews. RESULTS: The current literature recommends carrying out overviews by following similar steps to those of systematic reviews: (a) Defining the overview research question; (b) inclusion and exclusion criteria; (c) literature search; (d) data extraction; (e) assessment of risk of bias and reporting quality; (f) overview results; and (g) reporting the overview. Of special interest is how to address dependencies between the systematic reviews. CONCLUSIONS: Overviews allow evidence to be efficiently combined from multiple systematic reviews. This offers the possibility of translating and summarizing large amounts of information. As in primary studies and systematic reviews, conducting and reporting of overviews must meet appropriate quality standards.

Comparative clinical effectiveness and safety of tobacco cessation pharmacotherapies and electronic cigarettes: a systematic review and network meta-analysis of randomized controlled trials.

AIM: To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety. METHOD: Systematic reviews and Bayesian network meta-analyses of randomized controlled trials, in any setting, of varenicline, bupropion, NRT and e-cigarettes (in high, standard and low doses, alone or in combination) in adult smokers and smokeless tobacco users with follow-up duration of 24 weeks or greater (effectiveness) or any duration (safety). Nine databases were searched until 19 February 2019. Primary outcomes were sustained tobacco abstinence and serious adverse events (SAEs). We estimated odds ratios (ORs) and treatment rankings and conducted meta-regression to explore covariates. RESULTS: We identified 363 trials for effectiveness and 355 for safety. Most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence; the most effective of these, estimated with some imprecision, were varenicline standard [OR = 2.83, 95% credible interval (CrI) = 2.34-3.39] and varenicline standard + NRT standard (OR = 5.75, 95% CrI = 2.27-14.88). Estimates were higher in smokers receiving counselling than in those without and in studies with higher baseline nicotine dependence scores than in those with lower scores. Varenicline standard + NRT standard showed a high probability of being ranked best or second-best. For safety, only bupropion at standard dose increased the odds of experiencing SAEs compared with placebo (OR = 1.27, 95% CrI = 1.04-1.58), and we found no evidence of effect modification. CONCLUSIONS: Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence, with varenicline appearing to be most effective based on current evidence. There does not appear to be strong evidence of associations between most tobacco cessation pharmacotherapies and adverse events; however, the data are limited and there is a need for improved reporting of safety data.

Effects of Robotic-Assisted Gait Training in Children and Adolescents with Cerebral Palsy: A Network Meta-Analysis.

Gait disturbances are common in children and adolescents with cerebral palsy (CP). Robotic-assisted gait training (RAGT) is becoming increasingly widespread, and hence it is important to examine its effectiveness. A network meta-analysis (NMA) of clinical trials comparing treatments with RAGT vs. other physical therapy treatments was carried out. This study was conducted according to the NMA version of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA-NMA) guidelines and following the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The outcome variables used were the D and E dimensions of the Gross Motor Function Measure (GMFM), gait speed, resistance, and stride length. Among 120 records, 8 trials were included. This NMA did not find statistically significant results for any of the comparisons examined in any of the outcomes studied and the magnitude of the effect size estimates was low or very low. Our NMA results should be interpreted with caution due to the high clinical heterogeneity of the studies included.

The role of school enjoyment and connectedness in the association between depressive and externalising symptoms and academic attainment: Findings from a UK prospective cohort study.

BACKGROUND: Previous research on the relationship between children's depressive and externalising symptoms, experience of school, and academic attainment is inconclusive. The aims of this study were (i) to test bidirectional associations between children's school experience and depressive and externalising symptoms at age 10-11 and 13-14, (ii) to ascertain whether school experience age 13-14 is associated with academic attainment age 16, and (iii) to test whether school experience mediates the relationship between depressive or externalising symptoms and attainment. METHODS: Data was used from the Avon Longitudinal Study of Parents and Children (n=6,409). A cross-lagged model was used to investigate bidirectional associations between school experience (enjoyment and connectedness) and depression and externalising at age 10-11 and 13-14. The same framework was used to test if school experience aged 13-14 mediated associations of depressive and externalising symptoms with later attainment. RESULTS: Depressive and externalising symptoms at 10-11 were negatively associated with school connectedness (depressive: standardised ß=-0.06, CI: -0.11, 0.01; externalizing: ß=-0.13, CI: -0.17, -0.08), and school enjoyment at 13-14 (depressive ß=-0.04, -0.08, 0.03; externalising: ß=-0.08, CI: -0.13, -0.03). School enjoyment at 13-14 was positively associated with attainment at 16 (ß=0.10, CI: 0.04, 0.15), and partially mediated associations between depressive and externalising symptoms at 10-11 and attainment at 16 (depressive: proportion mediated 2.2%, CI: -1.5, 5.9; externalising: proportion mediated; 4.7%, CI: 0.7, 10.1,). LIMITATIONS: Results may be subject to residual confounding. CONCLUSIONS: School enjoyment is a potentially modifiable risk factor that may affect educational attainment of adolescents with depressive or externalising symptoms.

Smoking cessation medicines and e-cigarettes: a systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Cigarette smoking is one of the leading causes of early death. Varenicline [Champix (UK), Pfizer Europe MA EEIG, Brussels, Belgium; or Chantix (USA), Pfizer Inc., Mission, KS, USA], bupropion (Zyban; GlaxoSmithKline, Brentford, UK) and nicotine replacement therapy are licensed aids for quitting smoking in the UK. Although not licensed, e-cigarettes may also be used in English smoking cessation services. Concerns have been raised about the safety of these medicines and e-cigarettes. OBJECTIVES: To determine the clinical effectiveness, safety and cost-effectiveness of smoking cessation medicines and e-cigarettes. DESIGN: Systematic reviews, network meta-analyses and cost-effectiveness analysis informed by the network meta-analysis results. SETTING: Primary care practices, hospitals, clinics, universities, workplaces, nursing or residential homes. PARTICIPANTS: Smokers aged ≥ 18 years of all ethnicities using UK-licensed smoking cessation therapies and/or e-cigarettes. INTERVENTIONS: Varenicline, bupropion and nicotine replacement therapy as monotherapies and in combination treatments at standard, low or high dose, combination nicotine replacement therapy and e-cigarette monotherapies. MAIN OUTCOME MEASURES: Effectiveness - continuous or sustained abstinence. Safety - serious adverse events, major adverse cardiovascular events and major adverse neuropsychiatric events. DATA SOURCES: Ten databases, reference lists of relevant research articles and previous reviews. Searches were performed from inception until 16 March 2017 and updated on 19 February 2019. REVIEW METHODS: Three reviewers screened the search results. Data were extracted and risk of bias was assessed by one reviewer and checked by the other reviewers. Network meta-analyses were conducted for effectiveness and safety outcomes. Cost-effectiveness was evaluated using an amended version of the Benefits of Smoking Cessation on Outcomes model. RESULTS: Most monotherapies and combination treatments were more effective than placebo at achieving sustained abstinence. Varenicline standard plus nicotine replacement therapy standard (odds ratio 5.75, 95% credible interval 2.27 to 14.90) was ranked first for sustained abstinence, followed by e-cigarette low (odds ratio 3.22, 95% credible interval 0.97 to 12.60), although these estimates have high uncertainty. We found effect modification for counselling and dependence, with a higher proportion of smokers who received counselling achieving sustained abstinence than those who did not receive counselling, and higher odds of sustained abstinence among participants with higher average dependence scores. We found that bupropion standard increased odds of serious adverse events compared with placebo (odds ratio 1.27, 95% credible interval 1.04 to 1.58). There were no differences between interventions in terms of major adverse cardiovascular events. There was evidence of increased odds of major adverse neuropsychiatric events for smokers randomised to varenicline standard compared with those randomised to bupropion standard (odds ratio 1.43, 95% credible interval 1.02 to 2.09). There was a high level of uncertainty about the most cost-effective intervention, although all were cost-effective compared with nicotine replacement therapy low at the £20,000 per quality-adjusted life-year threshold. E-cigarette low appeared to be most cost-effective in the base case, followed by varenicline standard plus nicotine replacement therapy standard. When the impact of major adverse neuropsychiatric events was excluded, varenicline standard plus nicotine replacement therapy standard was most cost-effective, followed by varenicline low plus nicotine replacement therapy standard. When limited to licensed interventions in the UK, nicotine replacement therapy standard was most cost-effective, followed by varenicline standard. LIMITATIONS: Comparisons between active interventions were informed almost exclusively by indirect evidence. Findings were imprecise because of the small numbers of adverse events identified. CONCLUSIONS: Combined therapies of medicines are among the most clinically effective, safe and cost-effective treatment options for smokers. Although the combined therapy of nicotine replacement therapy and varenicline at standard doses was the most effective treatment, this is currently unlicensed for use in the UK. FUTURE WORK: Researchers should examine the use of these treatments alongside counselling and continue investigating the long-term effectiveness and safety of e-cigarettes for smoking cessation compared with active interventions such as nicotine replacement therapy. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016041302. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 59. See the NIHR Journals Library website for further project information.

Cigarette smoking is one of the main causes of early death both in the UK and worldwide. Three medicines, varenicline, bupropion and nicotine replacement therapy, are licensed in the UK to help people stop smoking. E-cigarettes can also be used as a stop smoking aid. We combined information from previous studies, including clinical trials, to determine which product was the safest, most effective and best value for money for the NHS. We compared treatments that were given alone as well as treatments that were combined with others, such as combination nicotine replacement therapy, varenicline combined with nicotine replacement therapy, varenicline combined with bupropion and bupropion combined with nicotine replacement therapy. The last three combined treatments are not currently licensed in the UK for smoking cessation. We also compared different treatment doses (low, high and standard doses). We found that most treatments were more effective than placebo in helping people to quit smoking. One of the combination treatments (varenicline at standard dose combined with nicotine replacement therapy at standard dose) was the most effective at getting people to quit smoking, followed by e-cigarette at low dose, varenicline at standard dose combined with bupropion at standard dose, and e-cigarette at high dose. We also found that smokers with higher tobacco dependence and smokers treated with counselling alongside medicines achieved a higher proportion of continuous quitting. We also found evidence that the standard dose of bupropion was associated with an increased risk of serious side effects compared with placebo. There was inconclusive evidence that any of the treatments increased the risk of major cardiovascular side effects. There was some evidence that smokers who received a standard dose of varenicline had an increased risk of major neurological and psychiatric side effects compared with those receiving a standard dose of bupropion. E-cigarette at low dose, varenicline standard plus nicotine replacement therapy standard and varenicline standard plus bupropion standard were the best value for money interventions, but further clinical trials comparing treatments against each other are needed to increase confidence in these findings.

Examining how meta-analytic methods perform in the presence of bias: A simulation study.

Standard meta-analysis methods are vulnerable to bias from incomplete reporting of results (both publication and outcome reporting bias) and poor study quality. Several alternative methods have been proposed as being less vulnerable to such biases. To evaluate these claims independently we simulated study results under a broad range of conditions first with no bias, then introducing simulated publication bias, outcome reporting bias, and bias from poor study quality. We then implemented common and the proposed bias robust meta-analysis methods and compared the mean bias and mean squared error (MSE) for four estimates of effect and the coverage probability of seven confidence intervals. We found that no methods perform well in the presence of any substantial bias. A regression based extension to Egger's test gave an estimate of effect with lower mean bias than standard methods in the presence of publication bias or poor study quality, but had a substantially worse MSE except in very specific conditions. Coverage of all 95% confidence intervals was very poor with increasing numbers of studies in biased conditions, often falling below 50%. The Knapp-Hartung interval performed closest to nominal coverage with fewer than 10 studies in most conditions, and the Henmi-Copas interval generally performed best with more than 10 studies. There was no evidence that a multiplicative term for heterogeneity improved coverage. Multiple forms of bias remain problematic for all meta-analysis methods, with very poor performance under conceivable conditions.

Cost-Effectiveness Analysis of Smoking Cessation Interventions in the United Kingdom Accounting for Major Neuropsychiatric Adverse Events.

OBJECTIVES: Smoking is a leading cause of death worldwide. Cessation aids include varenicline, bupropion, nicotine replacement therapy (NRT), and e-cigarettes at various doses (low, standard and high) and used alone or in combination with each other. Previous cost-effectiveness analyses have not fully accounted for adverse effects nor compared all cessation aids. The objective was to determine the relative cost-effectiveness of cessation aids in the United Kingdom. METHODS: An established Markov cohort model was adapted to incorporate health outcomes and costs due to depression and self-harm associated with cessation aids, alongside other health events. Relative efficacy in terms of abstinence and major adverse neuropsychiatric events was informed by a systematic review and network meta-analysis. Base case results are reported for UK-licensed interventions only. Two sensitivity analyses are reported, one including unlicensed interventions and another comparing all cessation aids but removing the impact of depression and self-harm. The sensitivity of conclusions to model inputs was assessed by calculating the expected value of partial perfect information. RESULTS: When limited to UK-licensed interventions, varenicline standard-dose and NRT standard-dose were most cost-effective. Including unlicensed interventions, e-cigarette low-dose appeared most cost-effective followed by varenicline standard-dose + bupropion standard-dose combined. When the impact of depression and self-harm was excluded, varenicline standard-dose + NRT standard-dose was most cost-effective, followed by varenicline low-dose + NRT standard-dose. CONCLUSION: Although found to be most cost-effective, combined therapy is currently unlicensed in the United Kingdom and the safety of e-cigarettes remains uncertain. The value-of-information analysis suggested researchers should continue to investigate the long-term effectiveness and safety outcomes of e-cigarettes in studies with active comparators.

Correction: Childhood adversity and self-poisoning: A hospital case control study in Sri Lanka.

[This corrects the article DOI: 10.1371/journal.pone.0242437.].

Depressive symptoms and academic achievement in UK adolescents: a cross-lagged analysis with genetic covariates.

BACKGROUND: The relationship between adolescent depressive symptoms and academic achievement remains poorly understood. The aim of this study was to help clarify the nature and directionality of this association. METHODS: We used a sample of 13,599 British adolescents (main sample of N=3,809 participants). We fitted cross-lagged panel models using four repeated measures of self-reported depressive symptoms and four measures of academic achievement based on British national records between 11-18 years, separately for male and female adolescents and considering polygenic risk scores (PRS) for educational attainment and depression, alongside other child and parental covariates. RESULTS: We found evidence of an overall negative association that was stronger in boys (R=-0.21, 95% CI -0.31 to -0.11) than in girls (-0.13, -0.31 to 0.05). Higher depressive symptoms were associated with lower academic achievement at a later stage up to the end of compulsory education (16 years), when the direction of the association reversed, although girls with lower achievement also appeared vulnerable to depressive symptoms at previous stages. The genetic variables derived for this study showed stronger associations for academic achievement, but the PRS for depression also showed a negative association with academic achievement in girls. Child intelligence quotient and peer victimization also showed relevant associations. LIMITATIONS: Observational design, variation around measurement times, missing data. CONCLUSIONS: Depressive symptoms and academic achievement should be considered jointly when designing school-based programmes for children and adolescents, alongside gender, child ability and school experience. Including genetic information in research can help to disentangle average from time-varying effects.

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

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

Childhood adversity and self-poisoning: A hospital case control study in Sri Lanka.

INTRODUCTION: Adverse childhood experiences (ACE) have been recognized as an important risk factor for suicidal behaviour among adults, but evidence from low and middle-income countries is lacking. This study explored associations between ACE and hospital admission due to non-fatal self-poisoning in Sri Lanka. METHODS: This was a case-control study. Adults admitted to a tertiary care hospital for medical management of self-poisoning were included as cases, and age and sex matched controls were recruited from the outpatient department. ACE were measured using the World Health Organization's Childhood Adversity Scale. Logistic regression models adjusting for age, sex, ethnicity, and religion were used to quantify the association between ACE and self-poisoning. RESULTS: The study included 235 cases and 451 controls. Cases were 2.5 times (95% CI 1.8, 3.6) more likely to report an ACE than controls and had higher ACE scores. Childhood physical abuse (OR 4.7, 95% CI 1.2, 19.0) and emotional abuse or neglect (OR 3.7, 95% CI 1.3, 10.1, and 3.7, 95% CI 2.3, 6.0 respectively), increased the risk of self-poisoning in adulthood, as did witnessing household violence (OR 2.2, 95% CI 1.4, 3.4), growing up in a household with a mentally ill or suicidal household member (OR 2.1, 95% CI 1.2, 3.4), and experiencing parental death/separation/divorce (OR 3.1, 95% CI 2.0, 4.9) as a child. CONCLUSIONS: Reducing exposures to ACEs should be a priority for prevention of suicide and self-harm in Sri Lanka. Innovative methods to increase support for children facing adversity should be explored.

A Critical Study of the Effect of Polymeric Fibers on the Performance of Supported Liquid Membranes in Sample Microextraction for Metals Analysis.

Popularity of hollow fiber-supported liquid membranes (HF-SLM) for liquid-phase microextraction (HF-LPME) has increased in the last decades. In particular, HF-SLM are applied for sample treatment in the determination and speciation of metals. Up to the date, optimization of preconcentration systems has been focused on chemical conditions. However, criteria about fiber selection are not reflected in published works. HFs differ in pore size, porosity, wall thickness, etc., which can affect efficiency and/or selectivity of chemical systems in extraction of metals. In this work, Ag+ transport using tri-isobutylphosphine sulfide (TIBPS) has been used as a model to evaluate differences in metal transport due to the properties of three different fibers. Accurel PP 50/280 fibers, with a higher effective surface and smaller wall thickness, showed the highest efficiency for metal transport. Accurel PP Q3/2 exhibited intermediate efficiency but easier handling and, finally, Accurel PP S6/2 fibers, with a higher wall thickness, offered poorer efficiency but the highest stability and capability for metal speciation. Summarizing, selection of the polymeric support of HF-SLM is a key factor in their applicability of LPME for metals in natural waters.

Protocol for a systematic review and network meta-analysis of randomised controlled trials examining the effectiveness of early parenting interventions in preventing internalising problems in children and adolescents.

BACKGROUND: Internalising problems, such as depression and anxiety, are common and represent an important economical and societal burden. The effectiveness of parenting interventions in reducing the risk of internalising problems in children and adolescents has not yet been summarised. The aims of this review are to assess the effectiveness of parenting interventions in the primary, secondary and tertiary prevention of internalising problems in children and adolescents and to determine which intervention components and which intervention aspects are most effective for reducing the risk of internalising problems in children and adolescents. METHODS: Electronic searches in OVID SP versions of MEDLINE, EMBASE and PsycINFO; Cochrane Central Register of Controlled Trials; EBSCO version of ERIC and ClinicalTrials.gov have been performed to identify randomised controlled trials or quasi-randomised controlled trials of parenting interventions. At least two independent researchers will assess studies for inclusion and extract data from each paper. The risk of bias assessment will be conducted independently by two reviewers using the Cochrane Collaboration's Risk of Bias Assessment Tool. Statistical heterogeneity is anticipated given potential variation in participant characteristics, intervention type and mode of delivery, and outcome measures. Random effects models, assuming a common between-study variability, will be used to account for statistical heterogeneity. Results will be analysed using a network meta-analysis (NMA). If appropriate, we will also conduct a component-level NMA, where the 'active ingredients' of interventions are modelled using a network meta-regression approach. DISCUSSION: Preventing and reducing internalising problems could have major beneficial effects at the economic and societal level. Informing policy makers on the effectiveness of parenting interventions and on which intervention's component is driving the effect is important for the development of treatment strategies. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020172251.