Community mobilisation approaches to preventing adolescent multiple risk behaviour: a realist review.

BACKGROUND: Adolescent multiple risk behaviour (MRB) is a global health issue. Most interventions have focused on the proximal causes of adolescent MRB such as peer or family influence, with systematic reviews reporting mixed evidence of effectiveness. There is increasing recognition that community mobilisation approaches could be beneficial for adolescent health. There are gaps in the current literature, theory and implementation that would benefit from a realist approach. We use a theory-driven evidence synthesis to assess how and why community mobilisation interventions work/do not work to prevent adolescent MRB and in what contexts. METHODS: This realist review used a six-stage iterative process, guided by the RAMESES framework. We systematically searched PubMed, MEDLINE, PsycINFO, Web of Science, CINAHL and Sociological Abstracts, from their inception to 2021. Studies were screened for relevance to the programme theory, assessed for rigour and included based on a priori criteria. Two independent reviewers selected, screened and extracted data from included studies. A realist logic of analysis was used to develop context-mechanism-outcome configurations that contributed to our programme theory. FINDINGS: We reviewed 35 documents describing 22 separate community mobilisation intervention studies. Most studies (n = 17) had a quality assessment score of three or four (out of four). We analysed the studies in relation to three middle range theories. To uphold our theory that these interventions work by creating a social environment where adolescents are less likely to engage in MRB, interventions should: (1) embed a framework of guiding principles throughout the community, (2) establish community readiness with population data and (3) ensure a diverse coalition with the support of intervention champions. Mechanisms such as empowerment through coalition ownership over the delivery of the intervention, cohesion across the community and motivation to work collaboratively to improve adolescent health are triggered to achieve social environment shifts. However, certain contexts (e.g. limited funding) restrict intervention success as these mechanisms are not fired. CONCLUSIONS: For community mobilisation interventions to reduce adolescent MRB, the coalitions within them must seek to alter the social environment in which these behaviours occur. Mechanisms including empowerment, cohesion and motivation lead to this shift, but only under certain contexts. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020205342.

Twenty years of network meta-analysis: Continuing controversies and recent developments.

Network meta-analysis (NMA) is an extension of pairwise meta-analysis (PMA) which combines evidence from trials on multiple treatments in connected networks. NMA delivers internally consistent estimates of relative treatment efficacy, needed for rational decision making. Over its first 20 years NMA's use has grown exponentially, with applications in both health technology assessment (HTA), primarily re-imbursement decisions and clinical guideline development, and clinical research publications. This has been a period of transition in meta-analysis, first from its roots in educational and social psychology, where large heterogeneous datasets could be explored to find effect modifiers, to smaller pairwise meta-analyses in clinical medicine on average with less than six studies. This has been followed by narrowly-focused estimation of the effects of specific treatments at specific doses in specific populations in sparse networks, where direct comparisons are unavailable or informed by only one or two studies. NMA is a powerful and well-established technique but, in spite of the exponential increase in applications, doubts about the reliability and validity of NMA persist. Here we outline the continuing controversies, and review some recent developments. We suggest that heterogeneity should be minimized, as it poses a threat to the reliability of NMA which has not been fully appreciated, perhaps because it has not been seen as a problem in PMA. More research is needed on the extent of heterogeneity and inconsistency in datasets used for decision making, on formal methods for making recommendations based on NMA, and on the further development of multi-level network meta-regression.

Pharmacological treatments in panic disorder in adults: a network meta-analysis.

BACKGROUND: A panic attack is a discrete period of fear or anxiety that has a rapid onset and reaches a peak within 10 minutes. The main symptoms involve bodily systems, such as racing heart, chest pain, sweating, shaking, dizziness, flushing, churning stomach, faintness and breathlessness. Other recognised panic attack symptoms involve fearful cognitions, such as the fear of collapse, going mad or dying, and derealisation (the sensation that the world is unreal). Panic disorder is common in the general population with a prevalence of 1% to 4%. The treatment of panic disorder includes psychological and pharmacological interventions, including antidepressants and benzodiazepines. OBJECTIVES: To compare, via network meta-analysis, individual drugs (antidepressants and benzodiazepines) or placebo in terms of efficacy and acceptability in the acute treatment of panic disorder, with or without agoraphobia. To rank individual active drugs for panic disorder (antidepressants, benzodiazepines and placebo) according to their effectiveness and acceptability. To rank drug classes for panic disorder (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), mono-amine oxidase inhibitors (MAOIs) and benzodiazepines (BDZs) and placebo) according to their effectiveness and acceptability. To explore heterogeneity and inconsistency between direct and indirect evidence in a network meta-analysis. SEARCH METHODS: We searched the Cochrane Common Mental Disorders Specialised Register, CENTRAL, CDSR, MEDLINE, Ovid Embase and PsycINFO to 26 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people aged 18 years or older of either sex and any ethnicity with clinically diagnosed panic disorder, with or without agoraphobia. We included trials that compared the effectiveness of antidepressants and benzodiazepines with each other or with a placebo. DATA COLLECTION AND ANALYSIS: Two authors independently screened titles/abstracts and full texts, extracted data and assessed risk of bias. We analysed dichotomous data and continuous data as risk ratios (RRs), mean differences (MD) or standardised mean differences (SMD): response to treatment (i.e. substantial improvement from baseline as defined by the original investigators: dichotomous outcome), total number of dropouts due to any reason (as a proxy measure of treatment acceptability: dichotomous outcome), remission (i.e. satisfactory end state as defined by global judgement of the original investigators: dichotomous outcome), panic symptom scales and global judgement (continuous outcome), frequency of panic attacks (as recorded, for example, by a panic diary; continuous outcome), agoraphobia (dichotomous outcome). We assessed the certainty of evidence using threshold analyses. MAIN RESULTS: Overall, we included 70 trials in this review. Sample sizes ranged between 5 and 445 participants in each arm, and the total sample size per study ranged from 10 to 1168. Thirty-five studies included sample sizes of over 100 participants. There is evidence from 48 RCTs (N = 10,118) that most medications are more effective in the response outcome than placebo. In particular, diazepam, alprazolam, clonazepam, paroxetine, venlafaxine, clomipramine, fluoxetine and adinazolam showed the strongest effect, with diazepam, alprazolam and clonazepam ranking as the most effective. We found heterogeneity in most of the comparisons, but our threshold analyses suggest that this is unlikely to impact the findings of the network meta-analysis. Results from 64 RCTs (N = 12,310) suggest that most medications are associated with either a reduced or similar risk of dropouts to placebo. Alprazolam and diazepam were associated with a lower dropout rate compared to placebo and were ranked as the most tolerated of all the medications examined. Thirty-two RCTs (N = 8569) were included in the remission outcome. Most medications were more effective than placebo, namely desipramine, fluoxetine, clonazepam, diazepam, fluvoxamine, imipramine, venlafaxine and paroxetine, and their effects were clinically meaningful. Amongst these medications, desipramine and alprazolam were ranked highest. Thirty-five RCTs (N = 8826) are included in the continuous outcome reduction in panic scale scores. Brofaromine, clonazepam and reboxetine had the strongest reductions in panic symptoms compared to placebo, but results were based on either one trial or very small trials. Forty-one RCTs (N = 7853) are included in the frequency of panic attack outcome. Only clonazepam and alprazolam showed a strong reduction in the frequency of panic attacks compared to placebo, and were ranked highest. Twenty-six RCTs (N = 7044) provided data for agoraphobia. The strongest reductions in agoraphobia symptoms were found for citalopram, reboxetine, escitalopram, clomipramine and diazepam, compared to placebo. For the pooled intervention classes, we examined the two primary outcomes (response and dropout). The classes of medication were: SSRIs, SNRIs, TCAs, MAOIs and BDZs. For the response outcome, all classes of medications examined were more effective than placebo. TCAs as a class ranked as the most effective, followed by BDZs and MAOIs. SSRIs as a class ranked fifth on average, while SNRIs were ranked lowest. When we compared classes of medication with each other for the response outcome, we found no difference between classes. Comparisons between MAOIs and TCAs and between BDZs and TCAs also suggested no differences between these medications, but the results were imprecise. For the dropout outcome, BDZs were the only class associated with a lower dropout compared to placebo and were ranked first in terms of tolerability. The other classes did not show any difference in dropouts compared to placebo. In terms of ranking, TCAs are on average second to BDZs, followed by SNRIs, then by SSRIs and lastly by MAOIs. BDZs were associated with lower dropout rates compared to SSRIs, SNRIs and TCAs. The quality of the studies comparing antidepressants with placebo was moderate, while the quality of the studies comparing BDZs with placebo and antidepressants was low. AUTHORS' CONCLUSIONS: In terms of efficacy, SSRIs, SNRIs (venlafaxine), TCAs, MAOIs and BDZs may be effective, with little difference between classes. However, it is important to note that the reliability of these findings may be limited due to the overall low quality of the studies, with all having unclear or high risk of bias across multiple domains. Within classes, some differences emerged. For example, amongst the SSRIs paroxetine and fluoxetine seem to have stronger evidence of efficacy than sertraline. Benzodiazepines appear to have a small but significant advantage in terms of tolerability (incidence of dropouts) over other classes.

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.

Data visualisation approaches for component network meta-analysis: visualising the data structure.

BACKGROUND: Health and social care interventions are often complex and can be decomposed into multiple components. Multicomponent interventions are often evaluated in randomised controlled trials. Across trials, interventions often have components in common which are given alongside other components which differ across trials. Multicomponent interventions can be synthesised using component NMA (CNMA). CNMA is limited by the structure of the available evidence, but it is not always straightforward to visualise such complex evidence networks. The aim of this paper is to develop tools to visualise the structure of complex evidence networks to support CNMA. METHODS: We performed a citation review of two key CNMA methods papers to identify existing published CNMA analyses and reviewed how they graphically represent intervention complexity and comparisons across trials. Building on identified shortcomings of existing visualisation approaches, we propose three approaches to standardise visualising the data structure and/or availability of data: CNMA-UpSet plot, CNMA heat map, CNMA-circle plot. We use a motivating example to illustrate these plots. RESULTS: We identified 34 articles reporting CNMAs. A network diagram was the most common plot type used to visualise the data structure for CNMA (26/34 papers), but was unable to express the complex data structures and large number of components and potential combinations of components associated with CNMA. Therefore, we focused visualisation development around representing the data structure of a CNMA more completely. The CNMA-UpSet plot presents arm-level data and is suitable for networks with large numbers of components or combinations of components. Heat maps can be utilised to inform decisions about which pairwise interactions to consider for inclusion in a CNMA model. The CNMA-circle plot visualises the combinations of components which differ between trial arms and offers flexibility in presenting additional information such as the number of patients experiencing the outcome of interest in each arm. CONCLUSIONS: As CNMA becomes more widely used for the evaluation of multicomponent interventions, the novel CNMA-specific visualisations presented in this paper, which improve on the limitations of existing visualisations, will be important to aid understanding of the complex data structure and facilitate interpretation of the CNMA results.

Comparative effectiveness of psychological interventions for treating the psychological consequences of sexual abuse in children and adolescents: a network meta-analysis.

BACKGROUND: Following sexual abuse, children and young people may develop a range of psychological problems, including anxiety, depression, post-traumatic stress disorder (PTSD), and a range of behaviour problems. Those working with children and young people experiencing these problems may use one or more of a range of psychological approaches. OBJECTIVES: To assess the relative effectiveness of psychological interventions compared to other treatments or no treatment controls, to overcome psychological consequences of sexual abuse in children and young people up to 18 years of age. Secondary objectives To rank psychotherapies according to their effectiveness. To compare different 'doses' of the same intervention. SEARCH METHODS: In November 2022 we searched CENTRAL, MEDLINE, Embase, PsycINFO, 12 other databases and two trials registers. We reviewed the reference lists of included studies, alongside other work in the field, and communicated with the authors of included studies. SELECTION CRITERIA: We included randomised controlled trials comparing psychological interventions for sexually abused children and young people up to 18 years old with other treatments or no treatments. Interventions included: cognitive behavioural therapy (CBT), psychodynamic therapy, family therapy, child centred therapy (CCT), and eye movement desensitisation and reprocessing (EMDR). We included both individual and group formats. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias for our primary outcomes (psychological distress/mental health, behaviour, social functioning, relationships with family and others) and secondary outcomes (substance misuse, delinquency, resilience, carer distress and efficacy). We considered the effects of the interventions on all outcomes at post-treatment, six months follow-up and 12 months follow-up. For each outcome and time point with sufficient data, we performed random-effects network and pairwise meta-analyses to determine an overall effect estimate for each possible pair of therapies. Where meta-analysis was not possible, we report the summaries from single studies. Due to the low number of studies in each network, we did not attempt to determine the probabilities of each treatment being the most effective relative to the others for each outcome at each time point. We rated the certainty of evidence with GRADE for each outcome. MAIN RESULTS: We included 22 studies (1478 participants) in this review. Most of the participants were female (range: 52% to 100%), and were mainly white. Limited information was provided on socioeconomic status of participants. Seventeen studies were conducted in North America, with the remaining studies conducted in the UK (N = 2), Iran (N = 1), Australia (N = 1) and Democratic Republic of Congo (N = 1). CBT was explored in 14 studies and CCT in eight studies; psychodynamic therapy, family therapy and EMDR were each explored in two studies. Management as usual (MAU) was the comparator in three studies and a waiting list was the comparator in five studies. For all outcomes, comparisons were informed by low numbers of studies (one to three per comparison), sample sizes were small (median = 52, range 11 to 229) and networks were poorly connected. Our estimates were all imprecise and uncertain. Primary outcomes At post-treatment, network meta-analysis (NMA) was possible for measures of psychological distress and behaviour, but not for social functioning. Relative to MAU, there was very low certainty evidence that CCT involving parent and child reduced PTSD (standardised mean difference (SMD) -0.87, 95% confidence intervals (CI) -1.64 to -0.10), and CBT with only the child reduced PTSD symptoms (SMD -0.96, 95% CI -1.72 to -0.20). There was no clear evidence of an effect of any therapy relative to MAU for other primary outcomes or at any other time point. Secondary outcomes Compared to MAU, there was very low certainty evidence that, at post-treatment, CBT delivered to the child and the carer might reduce parents' emotional reactions (SMD -6.95, 95% CI -10.11 to -3.80), and that CCT might reduce parents' stress. However, there is high uncertainty in these effect estimates and both comparisons were informed only by one study. There was no evidence that the other therapies improved any other secondary outcome. We attributed very low levels of confidence for all NMA and pairwise estimates for the following reasons. Reporting limitations resulted in judgements of 'unclear' to 'high' risk of bias in relation to selection, detection, performance, attrition and reporting bias; the effect estimates we derived were imprecise, and small or close to no change; our networks were underpowered due to the low number of studies informing them; and whilst studies were broadly comparable with regard to settings, the use of a manual, the training of the therapists, the duration of treatment and number of sessions offered, there was considerable variability in the age of participants and the format in which the interventions were delivered (individual or group). AUTHORS' CONCLUSIONS: There was weak evidence that both CCT (delivered to child and carer) and CBT (delivered to the child) might reduce PTSD symptoms at post-treatment. However, the effect estimates are uncertain and imprecise. For the remaining outcomes examined, none of the estimates suggested that any of the interventions reduced symptoms compared to management as usual. Weaknesses in the evidence base include the dearth of evidence from low- and middle-income countries. Further, not all interventions have been evaluated to the same extent, and there is little evidence regarding the effectiveness of interventions for male participants or those from different ethnicities. In 18 studies, the age ranges of participants ranged from 4 to 16 years old or 5 to 17 years old. This may have influenced the way in which the interventions were delivered, received, and consequently influenced outcomes. Many of the included studies evaluated interventions that were developed by members of the research team. In others, developers were involved in monitoring the delivery of the treatment. It remains the case that evaluations conducted by independent research teams are needed to reduce the potential for investigator bias. Studies addressing these gaps would help to establish the relative effectiveness of interventions currently used with this vulnerable population.

A systematic review of communication interventions for countering vaccine misinformation.

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

Commentary/Response: Economic evidence should be routinely collected and reported for studies of intervention effectiveness in mental health. A commentary on Vartiainen et al. (2022).

Anxiety and related disorders are increasingly widespread amongst children and adolescents. Preventing mental health disorders from developing has the potential to realise long-term benefits for children and adolescents. In their paper, 'Economic evidence of preventive interventions for anxiety disorders in children and adolescents-a systematic review', Vartiainen et al. conducted a systematic review to examine economic evidence of interventions for the primary prevention of anxiety disorders in children and adolescents, under 18 years of age. Five articles were eligible for inclusion in the review, of which two were model-based economic evaluations and three conducted alongside randomised controlled trials (RCTs). All five papers used either a cost-effectiveness analysis (CEA) or cost-utility analysis (CUA) as their main analysis. Vartiainen et al. concluded that, due to the small number of studies and relatively small sample sizes, the evidence for the cost-effectiveness of anxiety prevention interventions is weak. In this commentary, the challenges of conducting economic evaluations for prevention interventions are briefly outlined and Vartiainen et al.'s findings are discussed in the context of two further reviews of economic studies, published in 2021. The first focuses on the prevention of anxiety and depression in children and young people and the second takes a broader perspective and also includes interventions for mental health promotion. Both additional reviews note the small number of published economic evaluations, and all three reviews are united in their call for economic evaluations to be conducted alongside all future mental health prevention intervention trials.

Practitioner and digitally delivered interventions for reducing hazardous and harmful alcohol consumption in people not seeking alcohol treatment: a systematic review and network meta-analysis.

AIM: To compare the effectiveness of practitioner versus digitally delivered interventions for reducing hazardous and harmful alcohol consumption. DESIGN: Systematic review and network meta-analysis comprising comprehensive search for randomised controlled trials, robust screening and selection methods and appraisal with the Cochrane Risk of Bias tool. Network meta-analyses were conducted in Stata using random effects, frequentist models. The confidence in network meta-analysis (CINeMA) tool was used to assess confidence in effect sizes. SETTING: Online or community or health settings where the intervention was immediately accessible without referral. PARTICIPANTS: Non treatment-seeking hazardous or harmful drinkers. MEASUREMENTS: Primary outcome was mean difference in alcohol consumption (g/wk); secondary outcome was number of single high intensity drinking episodes. Baseline consumption was analysed as a covariate. FINDINGS: Of 201 included trials (94 753 participants), 152 reported a consumption outcome that could be converted to grams/week; 104 reported number of single high intensity drinking episodes. At 1 and 6 months, practitioner delivered interventions reduced consumption more than digitally delivered interventions (1 month: -23 g/wk (95% CI, -43 to -2); 6 months: -14 g/wk [95% CI, -25 to -3]). At 12 months there was no evidence of difference between practitioner and digitally delivered interventions (-6 g/wk [95% CI, -24 to 12]). There was no evidence of a difference in single high intensity drinking episodes between practitioner and digitally delivered interventions at any time point. Effect sizes were small, but could impact across a population with relatively high prevalence of hazardous and harmful drinking. Heterogeneity was a concern. Some inconsistency was indicated at 1 and 6 months, but little evidence was apparent at 12 months. CONCLUSION: Practitioner delivered interventions for reducing hazardous and harmful alcohol consumption are more effective than digitally delivered interventions up to 6 months; at 12 months there is no evidence of a difference.

Does provision of antenatal care in Southern Asia improve neonatal survival? A systematic review and meta-analysis.

BACKGROUND: Southern Asia has one of the highest burdens of neonatal mortality worldwide (26/1000 live births). Ensuring that women receive antenatal care from a skilled provider may play an important role in reducing this burden. OBJECTIVE: This study aimed to determine whether antenatal care received from a skilled provider could reduce neonatal mortality in Southern Asia by systematically reviewing existing evidence. STUDY DESIGN: Seven databases were searched (MEDLINE, Embase, Cochrane Library, CINAHL, PubMed, PsycINFO, and International Bibliography of the Social Sciences [IBSS]). The key words included: "neonatal mortality," "antenatal care," and "Southern Asia." Nonrandomized comparative studies conducted in Southern Asia reporting on neonatal mortality in women who received antenatal care compared with those who did not were included. Two authors carried out the screening and data extraction. The Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) was used to assess quality of studies. Results were reported using a random-effects model based on odds ratios with 95% confidence intervals. RESULTS: Four studies were included in a meta-analysis of adjusted results. The pooled odds ratio was 0.46 (95% confidence interval, 0.24 to 0.86) for neonatal deaths among women having at least 1 antenatal care visit during pregnancy compared with women having none. In the final meta-analysis, 16 studies could not be included because of lack of adjustment for confounders, highlighting the need for further higher-quality studies to evaluate the true impact. CONCLUSION: This review suggests that in Southern Asia, neonates born to women who received antenatal care have a lower risk of death in the neonatal period compared with neonates born to women who did not receive antenatal care. This should encourage health policy to strengthen antenatal care programs in Southern Asia.

Antenatal care in Nepal: a qualitative study into missed opportunities in the first trimester.

BACKGROUND: Use of timely antenatal care has been identified as key to facilitating healthy pregnancies worldwide. Although considerable investment has been made to enhance maternal health services in Nepal, approximately one-third of women do not attend antenatal care until after the first trimester (late). These women miss out on the benefits of screening and interventions that are most effective in the first trimester. OBJECTIVE: This study aimed to identify the missed opportunities of women who do not attend antenatal care in the first trimester, and to explore some of the factors underlying late attendance and consider potential solutions for minimizing these missed opportunities in the future. STUDY DESIGN: This study was conducted in 3 hospitals in Nepal. Focus groups (n=18) with a total of 48 postnatal women and 49 staff members, and 10 individual interviews with stakeholders were conducted. Purposive sampling facilitated the obtainment of a full range of maternity experiences, staff categories, and stakeholder positions. Data were qualitative and analyzed using a thematic approach. RESULTS: Limited awareness among women of the importance of early antenatal care was reported as a key factor behind attendance only after the first trimester. The family and community were described as significant influencers in women's decision-making regarding the timing of antenatal care. The benefits of early ultrasound scanning and effective supplementation in pregnancy were the major missed opportunities. Increasing awareness, reducing cost, and enhancing interprofessional collaboration were suggested as potential methods for improving timely initiation of antenatal care. CONCLUSION: Limited awareness continues to drive late attendance to antenatal care after the first trimester. Investment in services in the first trimester and community health education campaigns are needed to improve this issue and enhance maternal and neonatal outcomes.

Individual-, family- and school-based interventions to prevent multiple risk behaviours relating to alcohol, tobacco and drug use in young people aged 8-25 years: a systematic review and meta-analysis.

BACKGROUND: Engagement in multiple substance use risk behaviours such as tobacco smoking, alcohol and drug use during adolescence can result in adverse health and social outcomes. The impact of interventions that address multiple substance use risk behaviours, and the differential impact of universal versus targeted approaches, is unclear given findings from systematic reviews have been mixed. Our objective was to assess effects of interventions targeting multiple substance use behaviours in adolescents. METHODS: Eight databases were searched to October 2019. Individual and cluster randomised controlled trials were included if they addressed two or more substance use behaviours in individuals aged 8-25 years. Data were pooled in random-effects meta-analyses, reported by intervention and setting. Quality of evidence was assessed using GRADE. Heterogeneity was assessed using between-study variance, τ2 and Ι2, and the p-value of between-study heterogeneity statistic Q. Sensitivity analyses were undertaken using the highest and lowest intra-cluster correlation coefficient (ICC). RESULTS: Of 66 included studies, most were universal (n=52) and school-based (n=41). We found moderate quality evidence that universal school-based interventions are likely to have little or no short-term benefit (up to 12 months) in relation to alcohol use (OR 0.94, 95% CI: 0.84, 1.04), tobacco use (OR 0.98, 95% CI: 0.83, 1.15), cannabis use (OR 1.06, 95% CI: 0.86, 1.31) and other illicit drug use (OR 1.09, 95% CI: 0.85, 1.39). For targeted school-level interventions, there was low quality evidence of no or a small short-term benefit: alcohol use (OR 0.90, 95% CI: 0.74-1.09), tobacco use (OR 0.86, 95% CI: 0.66, 1.11), cannabis use (OR 0.84, 95% CI: 0.66-1.07) and other illicit drug use (OR 0.79, 95% CI 0.62-1.02). There were too few family-level (n=4), individual-level (n=2) and combination level (n=5) studies to draw confident conclusions. Sensitivity analyses of ICC did not change results. CONCLUSIONS: There is low to moderate quality evidence that universal and targeted school-level interventions have no or a small beneficial effect for preventing substance use multiple risk behaviours in adolescents. Higher quality trials and study reporting would allow better evidence syntheses, which is needed given small benefit of universal interventions can have high public health benefit. TRIAL REGISTRATION: Cochrane Database of Systematic Reviews 2014, Issue 11. Art. No.: CD011374. DOI: 10.1002/14651858.CD011374.

A systematic review and narrative synthesis of antenatal interventions to improve maternal and neonatal health in Nepal.

BACKGROUND: Maternal and neonatal mortality rates remain high in many economically underdeveloped countries, including Nepal, and good quality antenatal care can reduce adverse pregnancy outcomes. However, identifying how to best improve antenatal care can be challenging. OBJECTIVE: To identify the interventions that have been investigated in the antenatal period in Nepal for maternal or neonatal benefit. We wanted to understand their scale, location, cost, and effectiveness. STUDY DESIGN: Online bibliographic databases (Cochrane Central, MEDLINE, Embase, CINAHL Plus, British Nursing Index, PsycInfo, Allied and Complementary Medicine) and trial registries (ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform) were searched from their inception till May 24, 2020. We included all studies reporting any maternal or neonatal outcome after an intervention in the antenatal period. We screened the studies and extracted the data in duplicate. A meta-analysis was not possible because of the heterogeneity of the interventions and outcomes, so we performed a narrative synthesis of the included studies. RESULTS: A total of 25 studies met our inclusion criteria. These studies showed a variety of approaches toward improving antenatal care (eg, educational programs, incentive schemes, micronutrient supplementation) in different settings (home, community, or hospital-based) and with a wide variety of outcomes. Less than a quarter of the studies were randomized controlled trials, and many were single-site or reported only short-term outcomes. All studies reported having made a positive impact on antenatal care in some way, but only 3 provided a cost-benefit analysis to support implementation. None of these studies focused on the most remote communities in Nepal. CONCLUSION: Our systematic review found good quality evidence that micronutrient supplementation and educational interventions can bring important clinical benefits. Iron and folic acid supplementation significantly reduces neonatal mortality and maternal anemia, whereas birth preparedness classes increase the uptake of antenatal and postnatal care, compliance with micronutrient supplementation, and awareness of the danger signs in pregnancy.

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.

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.

Is adolescent multiple risk behaviour associated with reduced socioeconomic status in young adulthood and do those with low socioeconomic backgrounds experience greater negative impact? Findings from two UK birth cohort studies.

BACKGROUND: Adolescent multiple risk behaviour (MRB) is associated with negative outcomes such as police arrests, unemployment and premature mortality and morbidity. What is unknown is whether MRB is associated with socioeconomic status (SES) in adulthood. We test whether adolescent MRB is associated with socioeconomic status (SES) in young adulthood and whether it is moderated by early life SES variables. METHODS: Prospective cohort studies; British Cohort Study 1970 (BCS70) and Avon Longitudinal Study of Parents and Children (ALSPAC), born in 1991-1992, were used and two comparable MRB variables were derived. Logistic regression was used to determine the association between MRB and young adult SES. The moderating effect of three early life SES variables was assessed using logistic regression models with and without interaction parameters. Evidence to support the presence of moderation was determined by likelihood ratio tests ≤p = 0.05. Multiple imputation was used to account for missing data. RESULTS: Adolescents had a median of two risk behaviours in BCS70 and three in ALSPAC. Adolescent MRB was negatively associated with young adult SES (university degree attainment) in BCS70 (OR 0.81, 95% CI: 0.76, 0.86) and ALSPAC (OR 0.85, 95% CI: 0.82, 0.88). There was a dose response relationship, with each additional risk behaviour resulting in reduced odds of university degree attainment. MRB was associated occupational status at age 34 in BCS70 (OR 0.86 95% CI: 0.82, 0.90). In BCS70, there was evidence that maternal education (p = 0.03), parental occupational status (p = 0.009) and household income (p = 0.03) moderated the effect of adolescent MRB on young adult SES in that the negative effect of MRB is stronger for those with low socioeconomic backgrounds. No evidence of moderation was found in the ALSPAC cohort. CONCLUSIONS: Adolescence appears to be a critical time in the life course to address risk behaviours, due to the likelihood that behaviours established here may have effects in adulthood. Intervening on adolescent MRB could improve later SES outcomes and thus affect health outcomes later in life. Evidence for a moderation effect in the BCS70 but not ALSPAC suggests that more detailed measures should be investigated to capture the nuance of contemporary young adult SES.