Interventions to prevent obesity in school-aged children 6-18 years: An update of a Cochrane systematic review and meta-analysis including studies from 2015-2021.

Background: Childhood obesity remains a global public health priority due to the enormous burden it generates. Recent surveillance data suggests there has been a sharp increase in the prevalence of childhood obesity during the COVID-19 pandemic. The Cochrane review of childhood obesity prevention interventions (0-18 years) updated to 2015 is the most rigorous and comprehensive review of randomised controlled trials (RCTs) on this topic. A burgeoning number of high quality studies have been published since that are yet to be synthesised. Methods: An update of the Cochrane systematic review was conducted to include RCT studies in school-aged children (6-18 years) published to 30 June 2021 that assessed effectiveness on child weight (PROSPERO registration: CRD42020218928). Available cost-effectiveness and adverse effect data were extracted. Intervention effects on body mass index (BMI) were synthesised in random effects meta-analyses by setting (school, after-school program, community, home), and meta-regression examined the association of study characteristics with intervention effect. Findings: Meta-analysis of 140 of 195 included studies (183,063 participants) found a very small positive effect on body mass index for school-based studies (SMD -0·03, 95%CI -0·06,-0·01; trials = 93; participants = 131,443; moderate certainty evidence) but not after-school programs, community or home-based studies. Subgroup analysis by age (6-12 years; 13-18 years) found no differential effects in any setting. Meta-regression found no associations between study characteristics (including setting, income level) and intervention effect. Ten of 53 studies assessing adverse effects reported presence of an adverse event. Insufficient data was available to draw conclusions on cost-effectiveness. Interpretation: This updated synthesis of obesity prevention interventions for children aged 6-18 years, found a small beneficial impact on child BMI for school-based obesity prevention interventions. A more comprehensive assessment of interventions is required to identify mechanisms of effective interventions to inform future obesity prevention public health policy, which may be particularly salient in for COVID-19 recovery planning. Funding: This research was funded by the National Health and Medical Research Council (NHMRC), Australia (Application No APP1153479).

Hope, Agency, and the Lived Experience of Violence: A Qualitative Systematic Review of Children's Perspectives on Domestic Violence and Abuse.

There is a large body of research on the impact of domestic violence and abuse (DVA) on children, mostly reporting survey data and focusing largely on psychological outcomes. Qualitative research on the views of children has the potential to enable a child-centered understanding of their experience of DVA, so their needs can be better met by professionals. This systematic review reports general findings from the ViOlence: Impact on Children Evidence Synthesis (VOICES) project that synthesized published qualitative research on the experiences of DVA from the perspective of children and young people. A thematic synthesis of 33 reports identified six themes: lived experience of DVA, children's agency and coping, turning points and transitions, managing relationships postseparation, impact of DVA on children, and children's expressions of hope for the future. We conclude that professionals working with children affected by DVA should be mindful of the diversity in children's experiences and listen carefully to children's own accounts.

Evidence of detrimental effects of prenatal alcohol exposure on offspring birthweight and neurodevelopment from a systematic review of quasi-experimental studies.

BACKGROUND: Systematic reviews of prenatal alcohol exposure effects generally only include conventional observational studies. However, estimates from such studies are prone to confounding and other biases. OBJECTIVES: To systematically review the evidence on the effects of prenatal alcohol exposure from randomized controlled trials (RCTs) and observational designs using alternative analytical approaches to improve causal inference. SEARCH STRATEGY: Medline, Embase, Web of Science, PsychINFO from inception to 21 June 2018. Manual searches of reference lists of retrieved papers. SELECTION CRITERIA: RCTs of interventions to stop/reduce drinking in pregnancy and observational studies using alternative analytical methods (quasi-experimental studies e.g. Mendelian randomization and natural experiments, negative control comparisons) to determine the causal effects of prenatal alcohol exposure on pregnancy and longer-term offspring outcomes in human studies. DATA COLLECTION AND ANALYSIS: One reviewer extracted data and another checked extracted data. Risk of bias was assessed using customized risk of bias tools. A narrative synthesis of findings was carried out and a meta-analysis for one outcome. MAIN RESULTS: Twenty-three studies were included, representing five types of study design, including 1 RCT, 9 Mendelian randomization and 7 natural experiment studies, and reporting on over 30 outcomes. One study design-outcome combination included enough independent results to meta-analyse. Based on evidence from several studies, we found a likely causal detrimental role of prenatal alcohol exposure on cognitive outcomes, and weaker evidence for a role in low birthweight. CONCLUSION: None of the included studies was judged to be at low risk of bias in all domains, results should therefore be interpreted with caution. SYSTEMATIC REVIEW REGISTRATION: This study is registered with PROSPERO, registration number CRD42015015941.

Synthesising quantitative evidence in systematic reviews of complex health interventions.

Public health and health service interventions are typically complex: they are multifaceted, with impacts at multiple levels and on multiple stakeholders. Systematic reviews evaluating the effects of complex health interventions can be challenging to conduct. This paper is part of a special series of papers considering these challenges particularly in the context of WHO guideline development. We outline established and innovative methods for synthesising quantitative evidence within a systematic review of a complex intervention, including considerations of the complexity of the system into which the intervention is introduced. We describe methods in three broad areas: non-quantitative approaches, including tabulation, narrative and graphical approaches; standard meta-analysis methods, including meta-regression to investigate study-level moderators of effect; and advanced synthesis methods, in which models allow exploration of intervention components, investigation of both moderators and mediators, examination of mechanisms, and exploration of complexities of the system. We offer guidance on the choice of approach that might be taken by people collating evidence in support of guideline development, and emphasise that the appropriate methods will depend on the purpose of the synthesis, the similarity of the studies included in the review, the level of detail available from the studies, the nature of the results reported in the studies, the expertise of the synthesis team and the resources available.

Transthoracic clamp versus endoaortic balloon occlusion in minimally invasive mitral valve surgery: a systematic review and meta-analysis.

This systematic review and meta-analysis aims to determine outcomes following aortic occlusion with the transthoracic clamp (TTC) versus endoaortic balloon occlusion (EABO) in patients undergoing minimally invasive mitral valve surgery. A subgroup analysis compares TTC to EABO with femoral cannulation separately from EABO with aortic cannulation. We searched Medline and Embase up to December 2018. Two people independently and in duplicate screened title and abstracts, full-text reports, extracted data and assessed the risk of bias using the Cochrane risk-of-bias tool for non-randomized studies. We identified 1564 reports from which 11 observational studies with 4181 participants met the inclusion criteria. We found no evidence of difference in the risk of postoperative death or cerebrovascular accident (CVA) between the 2 techniques. Evidence for a reduction in aortic dissection with TTC was found: 4 of 1590 for the TTC group vs 19 of 2492 for the EABO group [risk ratio 0.33, 95% confidence interval (CI) 0.12-0.93; P = 0.04]. There was no difference in aortic cross-clamp (AoX) time between TTC and EABO [mean difference (MD) -5.17 min, 95% CI -12.40 to 2.06; P = 0.16]. TTC was associated with a shorter AoX time compared to EABO with femoral cannulation (MD -9.26 min, 95% CI -17.00 to -1.52; P = 0.02). EABO with aortic cannulation was associated with a shorter AoX time compared to TTC (MD 7.77 min, 95% CI 3.29-12.26; P < 0.001). There was no difference in cardiopulmonary bypass (CPB) time between TTC and EABO with aortic cannulation (MD -4.98 min, 95% CI -14.41 to 4.45; P = 0.3). TTC was associated with a shorter CPB time compared to EABO with femoral cannulation (MD -10.08 min, 95% CI -19.93 to -0.22; P = 0.05). Despite a higher risk of aortic dissection with EABO, the rates of survival and cerebrovascular accident across the 2 techniques are similar in minimally invasive mitral valve surgery.

Use of emergency contraception among women with experience of domestic violence and abuse: a systematic review.

BACKGROUND: Exposure to domestic violence and abuse (DVA) results in a reduction of women's use of regular contraceptives. This evidence suggests that women exposed to DVA are more likely to have unprotected sexual intercourse and therefore may use more emergency contraception (EC) than those women who are not exposed to DVA. We aimed to test this hypothesis through evaluating the evidence for an association between exposure to DVA and use of EC. METHODS: We systematically searched eight electronic databases from inception until December 2017, checked references and citations, and contacted corresponding authors. Primary studies that evaluated the association between exposure to DVA and use of EC were included. Two reviewers were involved in screening, data extraction, quality assessment and analysis. We evaluated the quality of included studies with the adapted Newcastle-Ottawa Scale. We used tables and descriptive text to summarise and synthesise the data. Odds ratios (ORs) and 95% confidence intervals (CIs) for each estimate of the association between DVA and use of EC were plotted on a forest plot. RESULTS: Our search retrieved 1216 records of which six studies with 15,297 women were included. Five studies were observational; one study included intervention on the outcome (advance supply of EC). All studies were at high risk of bias. Four studies provided evidence of an association between DVA and EC use - ORs from 1.51 (95% CI 1.13, 2.02) to 6.50 (95% CI 4.15, 10.17). Two studies found no evidence of a such association - ORs 0.46 (95% CI 0.11, 1.96) and 0.76 (95% CI 0.29, 1.98). The latter differed by how the authors recruited participants, measured EC use and adjusted for confounders. CONCLUSIONS: This systematic review provides some evidence of increased use of EC among women exposed to DVA. Request for EC can indicate possible exposure to DVA. Therefore, each consultation for EC could be an appropriate context for clinical enquiry about DVA and signposting/referral to specialist DVA services. PROTOCOL REGISTRATION: PROSPERO CRD42017058221 .

Low alcohol consumption and pregnancy and childhood outcomes: time to change guidelines indicating apparently 'safe' levels of alcohol during pregnancy? A systematic review and meta-analyses.

OBJECTIVES: To determine the effects of low-to-moderate levels of maternal alcohol consumption in pregnancy on pregnancy and longer-term offspring outcomes. SEARCH STRATEGY: Medline, Embase, Web of Science and Psychinfo from inception to 11 July 2016. SELECTION CRITERIA: Prospective observational studies, negative control and quasiexperimental studies of pregnant women estimating effects of light drinking in pregnancy (≤32 g/week) versus abstaining. Pregnancy outcomes such as birth weight and features of fetal alcohol syndrome were examined. DATA COLLECTION AND ANALYSIS: One reviewer extracted data and another checked extracted data. Random effects meta-analyses were performed where applicable, and a narrative summary of findings was carried out otherwise. MAIN RESULTS: 24 cohort and two quasiexperimental studies were included. With the exception of birth size and gestational age, there was insufficient data to meta-analyse or make robust conclusions. Odds of small for gestational age (SGA) and preterm birth were higher for babies whose mothers consumed up to 32 g/week versus none, but estimates for preterm birth were also compatible with no association: summary OR 1.08, 95% CI (1.02 to 1.14), I2 0%, (seven studies, all estimates were adjusted) OR 1.10, 95% CI (0.95 to 1.28), I2 60%, (nine studies, includes one unadjusted estimates), respectively. The earliest time points of exposure were used in the analysis. CONCLUSION: Evidence of the effects of drinking ≤32 g/week in pregnancy is sparse. As there was some evidence that even light prenatal alcohol consumption is associated with being SGA and preterm delivery, guidance could advise abstention as a precautionary principle but should explain the paucity of evidence.

Methodological exemplar of integrating quantitative and qualitative evidence - supportive care for men with prostate cancer: what are the most important components?

AIMS: To present a methodological exemplar of integrating findings from a quantitative and qualitative review on the same topic to provide insight into components of care that contribute to supportive care that is acceptable to men with prostate cancer. BACKGROUND: Men with prostate cancer are likely to live a long time with the disease, experience side effects from treatment and therefore have ongoing supportive care needs. Quantitative and qualitative reviews have been published but the findings have yet to be integrated. DESIGN: Integration of quantitative and qualitative synthesized evidence. DATA SOURCE: Two previously published systematic reviews. REVIEW METHODS: Synthesized evidence on supportive care for men with prostate cancer was integrated from two previously published systematic reviews: a narrative quantitative review and a qualitative review with thematic synthesis. These two streams of synthesized evidence were synthesized using concurrent narrative summary. Data from both reviews were used to develop a set of propositions from which a summary of components of care that likely to contribute to supportive care acceptable to men with prostate cancer were identified. RESULTS: Nine propositions were developed which covered men's supportive care focusing on the role of health professionals. These propositions were used to compose nine components of care likely to lead to supportive care that is acceptable to men with prostate cancer. Some of these components are no/low cost such as developing a more empathic personalized approach, but more specific approaches need further investigation in randomized controlled trials, for example, online support. CONCLUSION: This methodological exemplar demonstrates the integration of quantitative and qualitative synthesized data to determine components of care likely to lead to provision of supportive care acceptable to men with prostate cancer.

Symptomatic and quality-of-life outcomes after treatment for clinically localised prostate cancer: a systematic review.

To conduct a systematic review of the risks of short-term outcomes after major treatments for clinically localised prostate cancer. MEDLINE, EMBASE and the Cochrane Library were searched from 2004 to January 2013. Study arms that included ≥100 men with localised prostate cancer in receipt of surgery, radiotherapy or active surveillance and reported symptomatic and quality-of-life (QoL) data from 6 to 60 months after treatment were eligible. Data were extracted by one reviewer and checked by another. In all, 64 studies (80 treatment cohorts) were included. Most were single treatment cohorts from the USA or Europe. Radiotherapy was the most common treatment (40 cohorts, including 31 brachytherapy cohorts) followed by prostatectomy (39 cohorts), with only one active surveillance cohort. Most frequently measured symptoms were urinary, followed by sexual, and bowel; QoL was assessed in only 17 cohorts. Most studies used validated measures, although poor data reporting and differences between studies meant that it was not possible to pool data. Data on the precise impact of short-term symptomatic and QoL outcomes after treatment for localised prostate cancer are of insufficient quality for clear guidance to men about the risks to these aspects of their lives. It is important that future studies focus on collecting core outcomes through validated measures and comply with reporting guidelines, so that clear and accurate information can be derived for men considering screening or treatment for prostate cancer.

Behavioural therapies versus other psychological therapies for depression.

BACKGROUND: Behavioural therapies represent one of several categories of psychological therapies that are currently used in the treatment of depression. However, the effectiveness and acceptability of behavioural therapies for depression compared with other psychological therapies remain unclear. OBJECTIVES: 1. To examine the effects of all BT approaches compared with all other psychological therapy approaches for acute depression.2. To examine the effects of different BT approaches (behavioural therapy, behavioural activation, social skills training and relaxation training) compared with all other psychological therapy approaches for acute depression.3. To examine the effects of all BT approaches compared with different psychological therapy approaches (CBT, third wave CBT, psychodynamic, humanistic and integrative psychological therapies) for acute depression. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR, 31/07/2013), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE, (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. SELECTION CRITERIA: Randomised controlled trials that compared behavioural therapies with other psychological therapies for acute depression in adults. DATA COLLECTION AND ANALYSIS: Two or more review authors independently identified studies, assessed trial quality and extracted data. We contacted study authors for additional information. MAIN RESULTS: Twenty-five trials involving 955 participants compared behavioural therapies with one or more of five other major categories of psychological therapies (cognitive-behavioural, third wave cognitive-behavioural, psychodynamic, humanistic and integrative therapies). Most studies had a small sample size and were assessed as being at unclear or high risk of bias. Compared with all other psychological therapies together, behavioural therapies showed no significant difference in response rate (18 studies, 690 participants, risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09) or in acceptability (15 studies, 495 participants, RR of total dropout rate 1.02, 95% CI 0.65 to 1.61). Similarly, in comparison with each of the other classes of psychological therapies, low-quality evidence showed better response to cognitive-behavioural therapies than to behavioural therapies (15 studies, 544 participants, RR 0.93, 95% CI 0.83 to 1.05) and low-quality evidence of better response to behavioural therapies over psychodynamic therapies (2 studies, 110 participants, RR 1.24, 95% CI 0.84 to 1.82).When compared with integrative therapies and humanistic therapies, only one study was included in each comparison, and the analysis showed no significant difference between behavioural therapies and integrative or humanistic therapies. AUTHORS' CONCLUSIONS: We found low- to moderate-quality evidence that behavioural therapies and other psychological therapies are equally effective. The current evidence base that evaluates the relative benefits and harms of behavioural therapies is very weak. This limits our confidence in both the size of the effect and its precision for our key outcomes related to response and withdrawal. Studies recruiting larger samples with improved reporting of design and fidelity to treatment would improve the quality of evidence in this review.

'Third wave' cognitive and behavioural therapies versus treatment as usual for depression.

BACKGROUND: So-called 'third wave' cognitive and behavioural therapies represent a new generation of psychological therapies that are increasingly being used in the treatment of psychological problems. However, the effectiveness and acceptability of third-wave cognitive and behavioural therapy (CBT) approaches as treatment for acute depression remain unclear. OBJECTIVES: 1. To examine the effects of all third wave CBT approaches compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.2. To examine the effects of different third wave CBT approaches (ACT, compassionate mind training, functional analytic psychotherapy, dialectical behaviour therapy, MBCT, extended behavioural activation and metacognitive therapy) compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.3. To examine the effects of all third wave CBT approaches compared with different types of comparators (treatment as usual, no treatment, waiting list, attention placebo, psychological placebo) for acute depression. SEARCH METHODS: We searched the Cochrane Depression Anxiety and Neurosis Group Trials Specialised Register (CCDANCTR to 01/01/12), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE, (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. An updated search of CCDANCTR restricted to search terms relevant to third wave CBT therapies was conducted in March 2013 (CCDANCTR to 01/02/13). SELECTION CRITERIA: Randomised controlled trials that compared third wave CBT therapies with control conditions for acute depression in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies, assessed trial quality and extracted data. Study authors were contacted for additional information when required. We rated the quality of evidence using GRADE methods. MAIN RESULTS: Four small studies (224 participants) were included in the review. Little information was provided about the process of allocating participants to groups. None of the studies used independent outcome assessors, and evidence suggested researcher allegiance towards the active treatments. The four studies examined a diversity of third wave CBT approaches (extended behavioural activation, acceptance and commitment therapy and competitive memory training) and control conditions. None of the studies conducted follow-up assessments. The results showed a significant difference in clinical response rates in favour of third wave CBT when compared with treatment as usual (TAU) conditions (three studies, 170 participants, risk ratio (RR) 0.51, 95% confidence interval (CI) 0.27 to 0.95; very low quality). No significant difference in treatment acceptability based on dropout rates was found between third wave CBT approaches and TAU (four studies, 224 participants, RR 1.01, 95% CI 0.08 to 12.30; very low quality). Both analyses showed substantial statistical heterogeneity. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that third wave CBT approaches appear to be more effective than treatment as usual in the treatment of acute depression. The very small number of available studies and the diverse types of interventions and control comparators, together with methodological limitations, limit the ability to draw any conclusions on their effect in the short term or over a longer term. The increasing popularity of third wave CBT approaches in clinical practice underscores the importance of completing further studies of third wave CBT approaches in the treatment of acute depression, on a short- and long-term basis, to provide evidence of their effectiveness to policy-makers, clinicians and users of services.

'Third wave' cognitive and behavioural therapies versus other psychological therapies for depression.

BACKGROUND: So-called 'third wave' cognitive and behavioural therapies represents a new generation of psychological therapies that are increasingly being used in the treatment of psychological problems. However, the effectiveness and acceptability of third wave cognitive and behavioural therapy (CBT) approaches as a treatment for depression compared with other psychological therapies remain unclear. OBJECTIVES: 1. To examine the effects of all third wave CBT approaches compared with all other psychological therapy approaches for acute depression.2. To examine the effects of different third wave CBT approaches (ACT, compassionate mind training, functional analytic psychotherapy, extended behavioural activation and metacognitive therapy) compared with all other psychological therapy approaches for acute depression.3. To examine the effects of all third wave CBT approaches compared with different psychological therapy approaches (psychodynamic, behavioural, humanistic, integrative, cognitive-behavioural) for acute depression. SEARCH METHODS: We searched the Cochrane Depression, Anxiety and Neurosis Group Specialised Register (CCDANCTR to 01/01/12), which includes relevant randomised controlled trials from The Cochrane Library (all years), EMBASE (1974-), MEDLINE (1950-) and PsycINFO (1967-). We also searched CINAHL (May 2010) and PSYNDEX (June 2010) and reference lists of the included studies and relevant reviews for additional published and unpublished studies. An updated search of CCDANCTR restricted to search terms relevant to third wave CBT was conducted in March 2013 (CCDANCTR to 01/02/13). SELECTION CRITERIA: Randomised controlled trials that compared various third wave CBT with other psychological therapies for acute depression in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently identified studies, assessed trial quality and extracted data. Study authors were contacted for additional information where required. We rated the quality of evidence using GRADE methods. MAIN RESULTS: A total of three studies involving 144 eligible participants were included in the review. Two of the studies (56 participants) compared an early version of acceptance and commitment therapy (ACT) with CBT, and one study (88 eligible participants) compared extended behavioural activation with CBT. No other studies of third wave CBT were identified. The two ACT studies were assessed as being at high risk of performance bias and researcher allegiance. Post-treatment results, which were based on dropout rates, showed no evidence of any difference between third wave CBT and other psychological therapies for the primary outcomes of efficacy (risk ratio (RR) of clinical response 1.14, 95% confidence interval (CI) 0.79 to 1.64; very low quality) and acceptability. Results at two-month follow-up showed no evidence of any difference between third wave CBT and other psychological therapies for clinical response (2 studies, 56 participants, RR 0.22, 95% CI 0.04 to 1.15). Moderate statistical heterogeneity was indicated in the acceptability analyses (I(2) = 41%). AUTHORS' CONCLUSIONS: Very low quality evidence suggests that third wave CBT and CBT approaches are equally effective and acceptable in the treatment of acute depression. Evidence is limited in quantity, quality and breadth of available studies, precluding us from drawing any conclusions as to their short- or longer-term equivalence. The increasing popularity of third wave CBT approaches in clinical practice underscores the importance of completing further studies to compare various third wave CBT approaches with other psychological therapy approaches to inform clinicians and policymakers on the most effective forms of psychological therapy in treating depression.

Statins for the primary prevention of cardiovascular disease.

BACKGROUND: Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of CVD is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with CVD. The case for primary prevention was uncertain when the last version of this review was published (2011) and in light of new data an update of this review is required. OBJECTIVES: To assess the effects, both harms and benefits, of statins in people with no history of CVD. SEARCH METHODS: To avoid duplication of effort, we checked reference lists of previous systematic reviews. The searches conducted in 2007 were updated in January 2012. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2022, Issue 4), MEDLINE OVID (1950 to December Week 4 2011) and EMBASE OVID (1980 to 2012 Week 1).There were no language restrictions. SELECTION CRITERIA: We included randomised controlled trials of statins versus placebo or usual care control with minimum treatment duration of one year and follow-up of six months, in adults with no restrictions on total, low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion and extracted data. Outcomes included all-cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), revascularisation, change in total and LDL cholesterol concentrations, adverse events, quality of life and costs. Odds ratios (OR) and risk ratios (RR) were calculated for dichotomous data, and for continuous data, pooled mean differences (MD) (with 95% confidence intervals (CI)) were calculated. We contacted trial authors to obtain missing data. MAIN RESULTS: The latest search found four new trials and updated follow-up data on three trials included in the original review. Eighteen randomised control trials (19 trial arms; 56,934 participants) were included. Fourteen trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (OR 0.86, 95% CI 0.79 to 0.94); as was combined fatal and non-fatal CVD RR 0.75 (95% CI 0.70 to 0.81), combined fatal and non-fatal CHD events RR 0.73 (95% CI 0.67 to 0.80) and combined fatal and non-fatal stroke (RR 0.78, 95% CI 0.68 to 0.89). Reduction of revascularisation rates (RR 0.62, 95% CI 0.54 to 0.72) was also seen. Total cholesterol and LDL cholesterol were reduced in all trials but there was evidence of heterogeneity of effects. There was no evidence of any serious harm caused by statin prescription. Evidence available to date showed that primary prevention with statins is likely to be cost-effective and may improve patient quality of life. Recent findings from the Cholesterol Treatment Trialists study using individual patient data meta-analysis indicate that these benefits are similar in people at lower (< 1% per year) risk of a major cardiovascular event. AUTHORS' CONCLUSIONS: Reductions in all-cause mortality, major vascular events and revascularisations were found with no excess of adverse events among people without evidence of CVD treated with statins.

Effects of cannabis use on outcomes of psychotic disorders: systematic review.

BACKGROUND: It is unclear if research findings support clinical opinion that cannabis use leads to worse outcomes in people with psychosis, or whether this impression is confounded by other factors. AIMS: To systematically review the evidence pertaining to whether cannabis affects outcome of psychotic disorders. METHOD: We searched 10 relevant databases (to November 2006), reference lists of included studies and contacted experts. We included 13 longitudinal studies from 15,303 references. Data extraction and quality assessment were conducted independently and in duplicate. RESULTS: Cannabis use was consistently associated with increased relapse and non-adherence. Associations with other outcome measures were more disparate. Few studies adjusted for baseline illness severity, and most made no adjustment for alcohol, or other potentially important confounders. Adjusting for even a few confounders often resulted in substantial attenuation of results. CONCLUSIONS: Confidence that most associations reported were specifically due to cannabis is low. Despite clinical opinion, it remains important to establish whether cannabis is harmful, what outcomes are particularly susceptible, and how such effects are mediated. Studies to examine this further are eminently feasible.

Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review.

BACKGROUND: Whether cannabis can cause psychotic or affective symptoms that persist beyond transient intoxication is unclear. We systematically reviewed the evidence pertaining to cannabis use and occurrence of psychotic or affective mental health outcomes. METHODS: We searched Medline, Embase, CINAHL, PsycINFO, ISI Web of Knowledge, ISI Proceedings, ZETOC, BIOSIS, LILACS, and MEDCARIB from their inception to September, 2006, searched reference lists of studies selected for inclusion, and contacted experts. Studies were included if longitudinal and population based. 35 studies from 4804 references were included. Data extraction and quality assessment were done independently and in duplicate. FINDINGS: There was an increased risk of any psychotic outcome in individuals who had ever used cannabis (pooled adjusted odds ratio=1.41, 95% CI 1.20-1.65). Findings were consistent with a dose-response effect, with greater risk in people who used cannabis most frequently (2.09, 1.54-2.84). Results of analyses restricted to studies of more clinically relevant psychotic disorders were similar. Depression, suicidal thoughts, and anxiety outcomes were examined separately. Findings for these outcomes were less consistent, and fewer attempts were made to address non-causal explanations, than for psychosis. A substantial confounding effect was present for both psychotic and affective outcomes. INTERPRETATION: The evidence is consistent with the view that cannabis increases risk of psychotic outcomes independently of confounding and transient intoxication effects, although evidence for affective outcomes is less strong. The uncertainty about whether cannabis causes psychosis is unlikely to be resolved by further longitudinal studies such as those reviewed here. However, we conclude that there is now sufficient evidence to warn young people that using cannabis could increase their risk of developing a psychotic illness later in life.