Automated data analysis of unstructured grey literature in health research: A mapping review.

The amount of grey literature and 'softer' intelligence from social media or websites is vast. Given the long lead-times of producing high-quality peer-reviewed health information, this is causing a demand for new ways to provide prompt input for secondary research. To our knowledge, this is the first review of automated data extraction methods or tools for health-related grey literature and soft data, with a focus on (semi)automating horizon scans, health technology assessments (HTA), evidence maps, or other literature reviews. We searched six databases to cover both health- and computer-science literature. After deduplication, 10% of the search results were screened by two reviewers, the remainder was single-screened up to an estimated 95% sensitivity; screening was stopped early after screening an additional 1000 results with no new includes. All full texts were retrieved, screened, and extracted by a single reviewer and 10% were checked in duplicate. We included 84 papers covering automation for health-related social media, internet fora, news, patents, government agencies and charities, or trial registers. From each paper, we extracted data about important functionalities for users of the tool or method; information about the level of support and reliability; and about practical challenges and research gaps. Poor availability of code, data, and usable tools leads to low transparency regarding performance and duplication of work. Financial implications, scalability, integration into downstream workflows, and meaningful evaluations should be carefully planned before starting to develop a tool, given the vast amounts of data and opportunities those tools offer to expedite research.

Evaluating high-cost technologies - no need to throw the baby out with the bathwater.

INTRODUCTION: Evidence generation for the health technology assessment (HTA) of a new technology is a long and expensive process with no guarantees that the health technology will be adopted and implemented into a health-care system. This would suggest that there is a greater risk of failure for a company developing a high-cost technology and therefore incentives (such as increasing the funding available for research or additional market exclusivity) may be needed to encourage development of such technologies as has been seen with many high-cost orphan drugs. AREAS COVERED: This paper discusses some of the key issues relating to the evaluation of high-cost technologies through the use of existing HTA processes and what the challenges will be going forward. EXPERT OPINION: We propose that while the current HTA process is robust, its evolution into accommodating the incorporation of real-world data and evidence alongside a life-cycle HTA approach should better enable developers to produce the evidence required on effectiveness and cost-effectiveness. This should lead to reduced decision uncertainty for HTA agencies to make adoption decisions in a more timely and efficient manner. Furthermore, budget impact analysis remains important in understanding the actual financial impact on health-care systems and budgets outside of the cost-effectiveness framework used to aid decision-making.

The association between maternal and paternal substance use and child substance use, internalizing and externalizing problems: a systematic review and meta-analysis.

AIMS: There is substantial evidence showing an association between parental substance use and child substance use and/or mental health problems. Most research focuses upon maternal substance use, with the influence of paternal substance use often being overlooked. We aimed to investigate the differential effects of maternal and paternal substance use upon children aged 0-18 years. METHODS: We used systematic review methods to identify observational studies examining the association between either maternal or paternal substance use and child substance use and/or mental health problems. The odds ratio (OR) effect measure was used, for ease of computation. We used a random-effects model with the inverse variance method to meta-analyse the findings from eligible studies. RESULTS: We included 17 unique studies with a total of 47 374 child participants. Maternal and paternal substance use were both associated with increased odds of child any drug use [OR = 2.09; 95% confidence interval (CI) = 1.53, 2.86; n = 12 349 participants; three studies and OR = 2.86; 95% CI = 1.25, 6.54; n = 5692 participants; three studies, respectively], child alcohol problem use (OR = 2.16; 95% CI = 1.73, 2.71; n = 7339 participants; four studies and OR = 1.70; 95% CI = 1.36, 2.12; n = 14 219 participants; six studies), child externalizing problems (OR = 1.81; 95% CI = 1.01, 3.22; n = 1748 participants; three studies and OR = 1.60; 95% CI = 1.18, 2.17; n = 2508 participants; six studies) and child internalizing problems (OR = 1.60; 95% CI = 1.25, 2.06; n = 1748 participants; three studies and OR = 1.42; 95% CI = 1.12, 1.81; n = 2248 participants; five studies). Child any alcohol use was associated with maternal substance use only (OR = 2.26; 95% CI = 1.08, 4.70; n = 28 691 participants; five studies). CONCLUSIONS: Both maternal and paternal substance use are associated with child substance use and mental health problems.

Can we mitigate the psychological impacts of social isolation using behavioural activation? Long-term results of the UK BASIL urgent public health COVID-19 pilot randomised controlled trial and living systematic review.

BACKGROUND: Behavioural and cognitive interventions remain credible approaches in addressing loneliness and depression. There was a need to rapidly generate and assimilate trial-based data during COVID-19. OBJECTIVES: We undertook a parallel pilot RCT of behavioural activation (a brief behavioural intervention) for depression and loneliness (Behavioural Activation in Social Isolation, the BASIL-C19 trial ISRCTN94091479). We also assimilate these data in a living systematic review (PROSPERO CRD42021298788) of cognitive and/or behavioural interventions. METHODS: Participants (≥65 years) with long-term conditions were computer randomised to behavioural activation (n=47) versus care as usual (n=49). Primary outcome was PHQ-9. Secondary outcomes included loneliness (De Jong Scale). Data from the BASIL-C19 trial were included in a metanalysis of depression and loneliness. FINDINGS: The 12 months adjusted mean difference for PHQ-9 was -0.70 (95% CI -2.61 to 1.20) and for loneliness was -0.39 (95% CI -1.43 to 0.65).The BASIL-C19 living systematic review (12 trials) found short-term reductions in depression (standardised mean difference (SMD)=-0.31, 95% CI -0.51 to -0.11) and loneliness (SMD=-0.48, 95% CI -0.70 to -0.27). There were few long-term trials, but there was evidence of some benefit (loneliness SMD=-0.20, 95% CI -0.40 to -0.01; depression SMD=-0.20, 95% CI -0.47 to 0.07). DISCUSSION: We delivered a pilot trial of a behavioural intervention targeting loneliness and depression; achieving long-term follow-up. Living meta-analysis provides strong evidence of short-term benefit for loneliness and depression for cognitive and/or behavioural approaches. A fully powered BASIL trial is underway. CLINICAL IMPLICATIONS: Scalable behavioural and cognitive approaches should be considered as population-level strategies for depression and loneliness on the basis of a living systematic review.

The development and validation of a prognostic model to PREDICT Relapse of depression in adult patients in primary care: protocol for the PREDICTR study.

BACKGROUND: Most patients who present with depression are treated in primary care by general practitioners (GPs). Relapse of depression is common (at least 50% of patients treated for depression will relapse after a single episode) and leads to considerable morbidity and decreased quality of life for patients. The majority of patients will relapse within 6 months, and those with a history of relapse are more likely to relapse in the future than those with no such history. GPs see a largely undifferentiated case-mix of patients, and once patients with depression reach remission, there is limited guidance to help GPs stratify patients according to risk of relapse. We aim to develop a prognostic model to predict an individual's risk of relapse within 6-8 months of entering remission. The long-term objective is to inform the clinical management of depression after the acute phase. METHODS: We will develop a prognostic model using secondary analysis of individual participant data drawn from seven RCTs and one longitudinal cohort study in primary or community care settings. We will use logistic regression to predict the outcome of relapse of depression within 6-8 months. We plan to include the following established relapse predictors in the model: residual depressive symptoms, number of previous depressive episodes, co-morbid anxiety and severity of index episode. We will use a "full model" development approach, including all available predictors. Performance statistics (optimism-adjusted C-statistic, calibration-in-the-large, calibration slope) and calibration plots (with smoothed calibration curves) will be calculated. Generalisability of predictive performance will be assessed through internal-external cross-validation. Clinical utility will be explored through net benefit analysis. DISCUSSION: We will derive a statistical model to predict relapse of depression in remitted depressed patients in primary care. Assuming the model has sufficient predictive performance, we outline the next steps including independent external validation and further assessment of clinical utility and impact. STUDY REGISTRATION: ClinicalTrials.gov ID: NCT04666662.

Interventions for adults with a history of complex traumatic events: the INCiTE mixed-methods systematic review.

BACKGROUND: People with a history of complex traumatic events typically experience trauma and stressor disorders and additional mental comorbidities. It is not known if existing evidence-based treatments are effective and acceptable for this group of people. OBJECTIVE: To identify candidate psychological and non-pharmacological treatments for future research. DESIGN: Mixed-methods systematic review. PARTICIPANTS: Adults aged ≥ 18 years with a history of complex traumatic events. INTERVENTIONS: Psychological interventions versus control or active control; pharmacological interventions versus placebo. MAIN OUTCOME MEASURES: Post-traumatic stress disorder symptoms, common mental health problems and attrition. DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 onwards); Cochrane Central Register of Controlled Trials (CENTRAL) (from inception); EMBASE (1974 to 2017 week 16); International Pharmaceutical Abstracts (1970 onwards); MEDLINE and MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations (1946 to present); Published International Literature on Traumatic Stress (PILOTS) (1987 onwards); PsycINFO (1806 to April week 2 2017); and Science Citation Index (1900 onwards). Searches were conducted between April and August 2017. REVIEW METHODS: Eligible studies were singly screened and disagreements were resolved at consensus meetings. The risk of bias was assessed using the Cochrane risk-of-bias tool and a bespoke version of a quality appraisal checklist used by the National Institute for Health and Care Excellence. A meta-analysis was conducted across all populations for each intervention category and for population subgroups. Moderators of effectiveness were assessed using metaregression and a component network meta-analysis. A qualitative synthesis was undertaken to summarise the acceptability of interventions with the relevance of findings assessed by the GRADE-CERQual checklist. RESULTS: One hundred and four randomised controlled trials and nine non-randomised controlled trials were included. For the qualitative acceptability review, 4324 records were identified and nine studies were included. The population subgroups were veterans, childhood sexual abuse victims, war affected, refugees and domestic violence victims. Psychological interventions were superior to the control post treatment for reducing post-traumatic stress disorder symptoms (standardised mean difference -0.90, 95% confidence interval -1.14 to -0.66; number of trials = 39) and also for associated symptoms of depression, but not anxiety. Trauma-focused therapies were the most effective interventions across all populations for post-traumatic stress disorder and depression. Multicomponent and trauma-focused interventions were effective for negative self-concept. Phase-based approaches were also superior to the control for post-traumatic stress disorder and depression and showed the most benefit for managing emotional dysregulation and interpersonal problems. Only antipsychotic medication was effective for reducing post-traumatic stress disorder symptoms; medications were not effective for mental comorbidities. Eight qualitative studies were included. Interventions were more acceptable if service users could identify benefits and if they were delivered in ways that accommodated their personal and social needs. LIMITATIONS: Assessments about long-term effectiveness of interventions were not possible. Studies that included outcomes related to comorbid psychiatric states, such as borderline personality disorder, and populations from prisons and humanitarian crises were under-represented. CONCLUSIONS: Evidence-based psychological interventions are effective and acceptable post treatment for reducing post-traumatic stress disorder symptoms and depression and anxiety in people with complex trauma. These interventions were less effective in veterans and had less of an impact on symptoms associated with complex post-traumatic stress disorder. FUTURE WORK: Definitive trials of phase-based versus non-phase-based interventions with long-term follow-up for post-traumatic stress disorder and associated mental comorbidities. STUDY REGISTRATION: This study is registered as PROSPERO CRD42017055523. 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. 24, No. 43. See the NIHR Journals Library website for further project information.

Traumatic events that happen often and that are difficult to escape from, such as childhood abuse, are sometimes known as complex traumatic events. People who have a history of complex traumatic events can develop post-traumatic stress disorder and can also suffer from other mental health problems. It is not known if people who experience complex traumatic events can benefit from existing psychological treatments or medications, or if these treatments are acceptable. This review aimed to find out which treatments are most effective and acceptable for mental health problems in people with complex trauma histories, and to identify the frontrunners for future research. We searched electronic databases for evidence about treatment effectiveness and acceptability in adults with a history of complex traumatic events. We found 104 randomised controlled trials and nine non-randomised controlled trials that tested the effectiveness of psychological and/or medications, as well as nine studies that used interviews and focus groups to describe the acceptability of psychological treatments. The studies were split across different populations that included veterans, refugees, people who had experienced childhood sexual abuse and domestic violence, and civilians affected by war. We found that psychological treatments that focused on improving symptoms associated with trauma were effective for reducing post-traumatic stress disorder symptoms and depression across all populations and fewer people dropped out of these treatments, suggesting that they are acceptable. However, trauma-focused treatments were less effective among veterans than among other groups and less effective for reducing other psychological symptoms commonly experienced by people with complex trauma histories. Phased treatments that first start with helping people to feel safe before focusing on trauma symptoms might be beneficial for both post-traumatic stress disorder and additional psychological symptoms. There was little evidence that medications, other than antipsychotics, were effective for post-traumatic stress disorder symptoms. Future work should test if phased treatments are more effective than non-phased treatments over the long term.

Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis.

BACKGROUND: Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse, and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at risk of not only posttraumatic stress disorder (PTSD) but also other mental health comorbidities. Whereas evidence-based psychological and pharmacological treatments are effective for single-event PTSD, it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events. METHODS AND FINDINGS: We searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised controlled trials (RCTs) and non-RCTs of psychological and pharmacological treatments for PTSD symptoms in people exposed to complex traumatic events, published up to 25 October 2019. We adopted a nondiagnostic approach and included studies of adults who have experienced complex trauma. Complex-trauma subgroups included veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web-based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs, for a total of 6,158 participants, were included in meta-analyses across the primary and secondary outcomes; 18 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ± 9.3 years, and 42% were male. Nine non-RCTs were included. The mean age of participants in the non-RCTs was 40.6 ± 9.4 years, and 47% were male. The average length of follow-up across all included studies at posttreatment for the primary outcome was 11.5 weeks. The pairwise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k = 46; n = 3,389; standardised mean difference [SMD] = -0.82, 95% confidence interval [CI] -1.02 to -0.63) and active control (k-9; n = 662; SMD = -0.35, 95% CI -0.56 to -0.14) at posttreatment and also compared with inactive control at 6-month follow-up (k = 10; n = 738; SMD = -0.45, 95% CI -0.82 to -0.08). Psychological interventions reduced depressive symptoms (k = 31; n = 2,075; SMD = -0.87, 95% CI -1.11 to -0.63; I2 = 82.7%, p = 0.000) and anxiety (k = 15; n = 1,395; SMD = -1.03, 95% CI -1.44 to -0.61; p = 0.000) at posttreatment compared with inactive control. Sleep quality was significantly improved at posttreatment by psychological interventions compared with inactive control (k = 3; n = 111; SMD = -1.00, 95% CI -1.49 to -0.51; p = 0.245). There were no significant differences between psychological interventions and inactive control group at posttreatment for quality of life (k = 6; n = 401; SMD = 0.33, 95% CI -0.01 to 0.66; p = 0.021). Antipsychotic medicine (k = 5; n = 364; SMD = -0.45; -0.85 to -0.05; p = 0.085) and prazosin (k = 3; n = 110; SMD = -0.52; -1.03 to -0.02; p = 0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills-based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions, we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower dropout, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma-focused interventions across trauma subgroups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multicomponent interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k = 17; n = 1,077; mean difference = -37.95, 95% CI -60.84 to -15.16). Our use of a non-diagnostic inclusion strategy may have overlooked certain complex-trauma populations with severe and enduring mental health comorbidities. Additionally, the relative contribution of skills-based intervention components was not feasibly evaluated in the network meta-analysis. CONCLUSIONS: In this systematic review and meta-analysis, we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multicomponent interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority.

Assessment of C-Reactive Protein Diagnostic Test Accuracy for Late-Onset Infection in Newborn Infants: A Systematic Review and Meta-analysis.

Importance: Rapid and accurate diagnosis of late-onset infection in newborn infants could inform treatment decisions and avoid unnecessary administration of antibiotics. Objective: To compare the accuracy of serum C-reactive protein (CRP) with that of microbiological blood culture for diagnosing late-onset infection in newborns. Data Sources: MEDLINE (1946-2019), Embase (1946-2019), and Science Citation Index (1900-2019) databases were searched for references (any language). The MeSH search terms included were "exp infant, newborn/" or "premature birth/" plus free text synonyms; and "C-reactive protein/" plus free text synonyms; and "exp sepsis/" or "exp bacterial infections/" plus free text synonyms. The proceedings from relevant conferences and references of identified papers were scrutinized. Authors were contacted to request missing data. Study Selection: Cohort and cross-sectional studies were included that compared the accuracy of serum CRP levels with microbiological culture results to diagnose late-onset (>72 hours after birth) infection in newborns (any gestational age) hospitalized after birth. Two reviewers assessed study eligibility. Among 10 394 records, 148 studies were assessed as full texts. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline extension for Diagnostic Test Accuracy (DTA) reviews was followed. Two reviewers assessed the method quality of each study using guidance from the Cochrane Screening and Diagnostic Test Methods Group (adapted from the Quality Assessment of Diagnostic Accuracy Studies 2). Main Outcomes and Measures: The primary meta-analysis outcome was diagnostic test accuracy of serum CRP level taken at initial investigation of an infant with suspected late-onset infection. The median specificity (proportion of true-negative results) and calculated pooled sensitivity (proportion of true-positive results) were determined by generating hierarchical summary receiver characteristic operating curves. Results: In total, 22 studies with 2255 infants were included (sample size range, 11-590 infants). Participants in most studies were preterm (<37 weeks) or very low-birth weight (<1500 g) infants. Two studies additionally enrolled infants born at term. Most studies (16) used a prespecified CRP level cutoff for a "positive" index test (5-10 mg/L), and most studies (17) used the culture of a pathogenic microorganism from blood as the reference standard. Risk of bias was low with independent assessment of index and reference tests. At median specificity (0.74), pooled sensitivity was 0.62 (95% CI, 0.50-0.72). Adding serum CRP level to the assessment of an infant with a 40% pretest probability of late-onset infection (the median for the included studies) generated posttest probabilities of 26% for a negative test result and 61% for a positive test result. Conclusions and Relevance: The findings suggest that determination of serum CRP level at initial evaluation of an infant with suspected late-onset infection is unlikely to aid early diagnosis or to select infants to undergo further investigation or treatment with antimicrobial therapy or other interventions.

A systematic review and meta-analysis of the prevalence of common mental disorders in people with non-communicable diseases in Bangladesh, India, and Pakistan.

BACKGROUND: The prevalence of mental and physical comorbidities is unknown in South Asia, as estimates of mental ill health in patients with non-communicable diseases (NCDs) have predominantly come from studies based in the United States, Europe and Australasia. This systematic review and meta-analysis summarises evidence and provides pooled estimates of the prevalence of common mental disorders in adults with non-communicable diseases in South Asia. METHODS: We included prevalence studies of depression and anxiety in adults with diabetes, cancer, cardiovascular disease, and chronic respiratory conditions in Bangladesh, India, and Pakistan, published from 1990 onwards in international and country-specific databases. RESULTS: Out of 96 included studies, 83 provided data for random effects meta-analyses. The pooled prevalence of depression was 44% (95% confidence interval (CI) = 26 to 62) for patients with COPD, 40% (95% CI = 34 to 45) for diabetes, 39% (95% CI = 23 to 56) for stroke, 38% (95% CI = 32 to 45) for hypertension, and 37% (95% CI = 30 to 45) for cancer. The pooled prevalence of anxiety based on 28 studies was 29% (95% CI = 22 to 36). Many quality issues were identified in a critical appraisal of included studies, mostly relating to the sampling frame and selection process, the description of the methods and basic data, and the description of non-responders. CONCLUSIONS: Depression and anxiety are prevalent and underdiagnosed in people with physical comorbidities in Bangladesh, India, and Pakistan.

Strimvelis® for Treating Severe Combined Immunodeficiency Caused by Adenosine Deaminase Deficiency: An Evidence Review Group Perspective of a NICE Highly Specialised Technology Evaluation.

The Centre for Reviews and Dissemination and Centre for Health Economics Technology Assessment Group at the University of York was commissioned by the National Institute for Health and Care Excellence (NICE) Highly Specialised Technologies (HST) programme to act as the independent Evidence Review Group (ERG) for an appraisal of Strimvelis®, a gene therapy treatment for adenosine deaminase deficiency-severe combined immunodeficiency (ADA-SCID). This paper describes the manufacturing company's submission of clinical and economic evidence, the ERG's review and the resulting NICE guidance. For Strimvelis® compared with haematopoietic stem cell transplant (HSCT) from a matched unrelated donor (MUD) and HSCT from a haploidentical donor, the company base-case deterministic incremental cost-effectiveness ratios (ICERs) were £36,360 and £14,645 per quality-adjusted life-year (QALY) gained, respectively (using a discount rate of 1.5%). Although overall survival in patients receiving Strimvelis® was substantially higher than historical comparator data on HSCT from a MUD or haploidentical donor, the ERG was concerned that the estimated treatment benefit remained highly uncertain. The ERG critiqued some assumptions in the cost-effectiveness model, including that all patients return to general population mortality and morbidity after a successful procedure; that all patients receive a matched sibling donor following an unsuccessful engraftment; and that differences in wait times exist between the treatments. Incorporating a number of changes to the model, the ERG's base-case ICERs were £86,815 per QALY gained for Strimvelis® compared with HSCT from a MUD and £16,704 per QALY gained compared with HSCT from a haploidentical donor (using a discount rate of 1.5%). The ICER for Strimvelis® compared with HSCT from a MUD was highly sensitive to the difference in procedural mortality and could exceed NICE's £100,000 per QALY gained threshold for HSTs, if HSCT survival rates have improved since the most recent data. The evaluation committee concluded that the most plausible ICERs were lower than £100,000 per QALY gained and that Strimvelis® should be recommended for treatment of ADA-SCID where a matched related donor is unavailable.

The public health evidence-base on novel psychoactive substance use: scoping review with narrative synthesis of selected bodies of evidence.

Background: This review aimed to address what was known about the public health burden associated with novel psychoactive substances (NPS) use, and the effectiveness of responses targeting NPS use and/or associated problems. Methods: Relevant literature was identified through a range of searches covering the period from January 2006 to June 2016. Data synthesis was undertaken in three stages. Firstly we mapped the evidence available in order to characterize the literature according to a set of analytic categories developed a priori. Secondly, we identified evidence gaps from a set of a priori research questions. Finally, we then undertook a narrative synthesis of selected bodies of evidence, interpreting data using a conceptual framework specifically designed for use in this review. Results: A total of 995 articles were included in the scoping review with the majority being case reports/series on individual level adverse effects due to NPS use. We synthesized UK data from 29 surveys and 7 qualitative studies, and international data in 10 systematic reviews on harms associated with NPS use, and 17 evaluations of policy responses. We found little data on risk factors, harms associated with long-term NPS use, and interventions. Conclusion: In all cases we found the available evidence to be at an early stage of development.

Sexual orientation and suicidal behaviour in young people.

Lesbian, gay, and bisexual (LGB) young people have been found to be at greater risk of suicidal behaviour. National prevention strategies have identified the need to reduce suicide risk in this population. However, research on specific risk factors for LGB young people that might inform suicide prevention programmes are at an early stage of development.

Prevalence and predictors of post-stroke mood disorders: A meta-analysis and meta-regression of depression, anxiety and adjustment disorder.

OBJECTIVE: To ascertain the prevalence and predictors of mood disorders, determined by structured clinical interviews (ICD or DSM criteria) in people after stroke. METHODS: Major electronic databases were searched from inception to June 2016 for studies involving major depression (MDD), minor depression (MnD), dysthymia, adjustment disorder, any depressive disorder (any depressive disorder) and anxiety disorders. Studies were combined using both random and fixed effects meta-analysis and results were stratified as appropriate. RESULTS: Depression was examined on 147 occasions from 2days to 7years after stroke (mean 6.87months, N=33 in acute, N=43 in rehabilitation and N=69 in the community/outpatients). Across 128 analyses involving 15,573 patients assessed for major depressive disorder (MDD), the point prevalence of depression was 17.7% (95% CI=15.6% to 20.0%) 0.65 analyses involving 9720 patients determined MnD was present in 13.1% in all settings (95% CI=10.9% to 15.8%). Dysthymia was present in 3.1% (95% CI=2.1% to 5.3%), adjustment disorder in 6.9% (95% CI=4.6 to 9.7%) and anxiety in 9.8% (95% CI=5.9% to 14.8%). Any depressive disorder was present in 33.5% (95% CI=30.3% to 36.8%). The relative risk of any depressive disorder was higher following left (dominant) hemisphere stroke, aphasia, and among people with a family history and past history of mood disorders. CONCLUSION: Depression, adjustment disorder and anxiety are common after stroke. Risk factors are aphasia, dominant hemispheric lesions and past personal/family history of depression but not time since stroke.

Multiple Risk Behavior Interventions: Meta-analyses of RCTs.

CONTEXT: Multiple risk behaviors are common and associated with developing chronic conditions such as heart disease, cancer, or Type 2 diabetes. A systematic review, meta-analysis, and meta-regression of the effectiveness of multiple risk behavior interventions was conducted. EVIDENCE ACQUISITION: Six electronic databases including MEDLINE, EMBASE, and PsycINFO were searched to August 2016. RCTs of non-pharmacologic interventions in general adult populations were selected. Studies targeting specific at-risk groups (such as people screened for cardiovascular risk factors or obesity) were excluded. Studies were screened independently. Study characteristics and outcomes were extracted and risk of bias assessed by one researcher and checked by another. The Behaviour Change Wheel and Oxford Implementation Index were used to code intervention content and context. EVIDENCE SYNTHESIS: Random-effects meta-analyses were conducted. Sixty-nine trials involving 73,873 individuals were included. Interventions mainly comprised education and skills training and were associated with modest improvements in most risk behaviors: increased fruit and vegetable intake (0.31 portions, 95% CI=0.17, 0.45) and physical activity (standardized mean difference, 0.25; 95% CI=0.13, 0.38), and reduced fat intake (standardized mean difference, -0.24; 95% CI=-0.36, -0.12). Although reductions in smoking were found (OR=0.78, 95% CI=0.68, 0.90), they appeared to be negatively associated with improvement in other behaviors (such as diet and physical activity). Preliminary evidence suggests that sequentially changing smoking alongside other risk behaviors was more effective than simultaneous change. But most studies assessed simultaneous rather than sequential change in risk behaviors; therefore, comparisons are sparse. Follow-up period and intervention characteristics impacted effectiveness for some outcomes. CONCLUSIONS: Interventions comprising education (e.g., providing information about behaviors associated with health risks) and skills training (e.g., teaching skills that equip participants to engage in less risky behavior) and targeting multiple risk behaviors concurrently are associated with small changes in diet and physical activity. Although on average smoking was reduced, it appeared changes in smoking were negatively associated with changes in other behaviors, suggesting it may not be optimal to target smoking simultaneously with other risk behaviors.

Promising evidence for nutrition interventions in people with serious mental illness.

People with serious mental illness (SMI) are more likely to engage in health risk behaviours such as unhealthy eating, physical inactivity and smoking. The review by Teasdale et al in this issue shows the potential for nutrition interventions to help people with SMI to manage their weight.

The effect of Liver Transplantation on the quality of life of the recipient's main caregiver - a systematic review.

Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health-Related Quality of Life (HRQL) of LT patients' main caregivers. We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however, the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data were available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. The current information about LT caregivers' needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients' family and caregivers to understand the importance of caregiver support to maximize outcomes of LT for the patient and their caregivers.

A systematic review on the clustering and co-occurrence of multiple risk behaviours.

BACKGROUND: Risk behaviours, such as smoking and physical inactivity account for up to two-thirds of all cardiovascular deaths, and are associated with substantial increased mortality in many conditions including cancer and diabetes. As risk behaviours are thought to co-occur in individuals we conducted a systematic review of studies addressing clustering or co-occurrence of risk behaviours and their predictors. As the main aim of the review was to inform public health policy in England we limited inclusion to studies conducted in the UK. METHODS: Key databases were searched from 1990 to 2016. We included UK based cross-sectional and longitudinal studies that investigated risk behaviours such as smoking, physical inactivity, unhealthy diet. High heterogeneity precluded meta-analyses. RESULTS: Thirty-seven studies were included in the review (32 cross-sectional and five longitudinal). Most studies investigated unhealthy diet, physical inactivity, alcohol misuse, and smoking. In general adult populations, there was relatively strong evidence of clustering between alcohol misuse and smoking; and unhealthy diet and smoking. For young adults, there was evidence of clustering between sexual risk behaviour and smoking, sexual risk behaviour and illicit drug use, and sexual risk behaviour and alcohol misuse. The strongest associations with co-occurrence and clustering of multiple risk behaviours were occupation (up to 4-fold increased odds in lower SES groups) and education (up to 5-fold increased odds in those with no qualifications). CONCLUSIONS: Among general adult populations, alcohol misuse and smoking was the most commonly identified risk behaviour cluster. Among young adults, there was consistent evidence of clustering found between sexual risk behaviour and substance misuse. Socio-economic status was the strongest predictor of engaging in multiple risk behaviours. This suggests the potential for interventions targeting multiple risk behaviours either sequentially or concurrently particularly where there is evidence of clustering. In addition, there is potential for intervening at the social or environmental level due to the strong association with socio-economic status.

Predicting suicide following self-harm: systematic review of risk factors and risk scales.

BACKGROUND: People with a history of self-harm are at a far greater risk of suicide than the general population. However, the relationship between self-harm and suicide is complex. AIMS: To undertake the first systematic review and meta-analysis of prospective studies of risk factors and risk assessment scales to predict suicide following self-harm. METHOD: We conducted a search for prospective cohort studies of populations who had self-harmed. For the review of risk scales we also included studies examining the risk of suicide in people under specialist mental healthcare, in order to broaden the scope of the review and increase the number of studies considered. Differences in predictive accuracy between populations were examined where applicable. RESULTS: Twelve studies on risk factors and 7 studies on risk scales were included. Four risk factors emerged from the meta-analysis, with robust effect sizes that showed little change when adjusted for important potential confounders. These included: previous episodes of self-harm (hazard ratio (HR) = 1.68, 95% CI 1.38-2.05, K = 4), suicidal intent (HR = 2.7, 95% CI 1.91-3.81, K = 3), physical health problems (HR = 1.99, 95% CI 1.16-3.43, K = 3) and male gender (HR = 2.05, 95% CI 1.70-2.46, K = 5). The included studies evaluated only three risk scales (Beck Hopelessness Scale (BHS), Suicide Intent Scale (SIS) and Scale for Suicide Ideation). Where meta-analyses were possible (BHS, SIS), the analysis was based on sparse data and a high heterogeneity was observed. The positive predictive values ranged from 1.3 to 16.7%. CONCLUSIONS: The four risk factors that emerged, although of interest, are unlikely to be of much practical use because they are comparatively common in clinical populations. No scales have sufficient evidence to support their use. The use of these scales, or an over-reliance on the identification of risk factors in clinical practice, may provide false reassurance and is, therefore, potentially dangerous. Comprehensive psychosocial assessments of the risks and needs that are specific to the individual should be central to the management of people who have self-harmed.