Psychological interventions for children and young people affected by armed conflict or political violence: a systematic literature review.

Youths exposed to armed conflict have a higher prevalence of mental health and psychosocial difficulties. Diverse interventions exist that aim to ameliorate the effect of armed conflict on the psychological and psychosocial wellbeing of conflict affected youths. However, the evidence base for the effectiveness of these interventions is limited. Using standard review methodology, this review aims to address the effectiveness of psychological interventions employed among this population. The search was performed across four databases and grey literature. Article quality was assessed using the Downs and Black Quality Checklist (1998). Where possible, studies were subjected to meta-analyses. The remaining studies were included in a narrative synthesis. Eight studies concerned non clinical populations, while nine concerned clinical populations. Review findings conclude that Group Trauma Focused-Cognitive Behavioural Therapy is effective for reducing symptoms of posttraumatic stress disorder, anxiety, depression and improving prosocial behaviour among clinical cohorts. The evidence does not suggest that interventions aimed at non clinical groups within this population are effective. Despite high quality studies, further robust trials are required to strengthen the evidence base, as a lack of replication has resulted in a limited evidence base to inform practice.

Impact of non-pharmacological interventions on prevention and treatment of delirium in critically ill patients: protocol for a systematic review of quantitative and qualitative research

Background: Critically ill patients have an increased risk of developing delirium during their intensive care stay.To date, pharmacological interventions have not been shown to be effective for delirium management but non-pharmacological interventions have shown some promise. The aim of this systematic review is to identify effective non-pharmacological interventions for reducing the incidence or the duration of delirium in critically ill patients.

Methods: We will search MEDLINE, EMBASE, CINAHL, Web of Science, AMED, psycINFO and the Cochrane Library.We will include studies of critically ill adults and children. We will include randomised trials and controlled trials which measure the effectiveness of one or more non-pharmacological interventions in reducing incidence or duration ofdelirium in critically ill patients. We will also include qualitative studies that provide an insight into patients and their families’ experiences of delirium and non-pharmacological interventions. Two independent reviewers will assess studies for eligibility, extract data and appraise quality. We will conduct meta-analyses if possible or present results narratively.Qualitative studies will also be reviewed by two independent reviewers, and a specially designed quality assessment tool incorporating the CASP framework and the POPAY framework will be used to assess quality.

Discussion: Although non-pharmacological interventions have been studied in populations outside of intensive care units and multicomponent interventions have successfully reduced incidence and duration of delirium, no systematic review of non-pharmacological interventions specifically targeting delirium in critically ill patients have been undertaken to date. This systematic review will provide evidence for the development of a multicomponent intervention for delirium management of critically ill patients that can be tested in a subsequent multicentre randomised trial.

Risk factors (excluding hormone therapy) for endometrial hyperplasia: a systematic review.

Objective: To conduct a systematic review of risk factors associated with the development of Endometrial Hyperplasia (EH).

Data sources: Ovid MEDLINE, EMBASE and Web of Science databases were searched from inception to 30 June 2015.

Study eligibility: Fifteen observational studies that reported on EH risk in relation to lifestyle factors (n=14), medical history (n=11), reproductive and menstrual history (n=9) and measures of socio-economic status (n=2) were identified. Pooled relative risk estimates and corresponding 95% confidence intervals (CI) were able to be derived for EH and Body Mass Index (BMI), smoking, diabetes and hypertension, using random effects models comparing high versus low categories.

Results: The pooled relative risk for EH when comparing women with the highest versus lowest BMI was 1.82 (95% CI 1.22–2.71; n=7 studies, I2=90.4%). No significant associations were observed for EH risk for smokers compared with non-smokers (RR 0.88, 95% CI 0.66-1.17; n=3, I2=0.0%), hypertensive versus normotensive women (RR 1.51, 95% CI 0.72–3.15; n=5 studies, I2=79.1%), or diabetic versus non-diabetic women (RR 1.77, 95% CI 0.79–3.96; n=5 studies, I2=31.8%) respectively although the number of included studies was limited. There were mixed reports on the relationship between age and risk of EH. Too few studies reported on other factors to reach any conclusions in relation to EH risk.

Conclusions: A high BMI was associated with an increased risk of EH, providing additional rationale for women to maintain a normal body weight. No significant associations were detected for other factors and EH risk, however relatively few studies have been conducted and few of the available studies adequately adjusted for relevant confounders. Therefore, further aetiological studies of endometrial hyperplasia are warranted.

Markers of vitamin D exposure and oesophageal cancer risk: a systematic review and meta-analysis.

Vitamin D has been associated with reduced risk of many cancers, but evidence for oesophageal cancer is mixed. To clarify the role of Vitamin D, we performed a systematic review and meta-analysis to evaluate the association of Vitamin D exposures and oesophageal neoplasia, including adenocarcinoma, squamous cell carcinoma (SCC), Barrett's oesophagus and squamous dysplasia. Ovid MEDLINE, EMBASE and Web of Science were searched from inception to September 2015. Fifteen publications in relation to circulating 25-hydroxyvitamin D (n=3), Vitamin D intake (n=4), UVB exposure (n=1), and genetic factors (n=7) were retrieved. Higher 25-OHD was associated with increased risk of cancer (adenocarcinoma or SCC, OR=1.39;95%CI:1.04-1.74), with the majority of participants coming from China. No association was observed between Vitamin D intake and risk of cancer overall (OR=1.03;0.65-1.42); however, a non-significantly increased risk for adenocarcinoma (OR=1.45;0.65-2.24) and non-significantly decreased risk for SCC (OR=0.80;0.48-1.12) were observed. One study reported a decreased risk of adenocarcinoma with higher UVB exposure. A decreased risk was found for VDR haplotype rs2238135(G)/rs1989969(T) carriers, OR=0.45;0.00-0.91, and a suggestive association was observed for rs2107301. No consistent associations were observed between Vitamin D exposures and occurrence of oesophageal lesions. Further adequately powered, well-designed studies are needed before conclusions can be made.

Acid-labile protein-adducted heterocyclic aromatic amines in human blood are not viable biomarkers of dietary exposure: A systematic study.

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of protein-rich foods. HCA residues adducted to blood proteins have been postulated as biomarkers of HCA exposure. However, the viability of quantifying HCAs following hydrolytic release from adducts in vivo and correlation with dietary intake are unproven. To definitively assess the potential of labile HCA-protein adducts as biomarkers, a highly sensitive UPLC-MS/MS method was validated for four major HCAs: 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) and 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMeIQx). Limits of detection were 1e5 pg/ml plasma and recoveries 91e115%. Efficacy of hydrolysis was demonstrated by HCA-protein adducts synthesised in vitro. Plasma and 7-day food diaries were collected from 122 fasting adults consuming their habitual diets. Estimated HCA intakes ranged from 0 to 2.5 mg/day. An extensive range of hydrolysis conditions was examined for release of adducted HCAs in plasma. HCA was detected in only one sample (PhIP, 9.7 pg/ml), demonstrating conclusively for the first time that acid-labile HCA adducts do not reflect dietary HCA intake and are present at such low concentrations that they are not feasible biomarkers of exposure. Identification of biomarkers remains important. The search should concentrate on stabilised HCA peptide markers and use of untargeted proteomic and metabolomic approaches.

Systematic review of interventions to improve the psychological well-being of general practitioners

BACKGROUND: The health of doctors who work in primary care is threatened by workforce and workload issues. There is a need to find and appraise ways in which to protect their mental health, including how to achieve the broader, positive outcome of well-being. Our primary outcome was to evaluate systematically the research evidence regarding the effectiveness of interventions designed to improve General Practitioner (GP) well-being across two continua; psychopathology (mental ill-health focus) and 'languishing to flourishing' (positive mental health focus). In addition we explored the extent to which developments in well-being research may be integrated within existing approaches to design an intervention that will promote mental health and prevent mental illness among these doctors.

METHODS: Medline, Embase, Cinahl, PsychINFO, Cochrane Register of Trials and Web of Science were searched from inception to January 2015 for studies where General Practitioners and synonyms were the primary participants. Eligible interventions included mental ill-health prevention strategies (e.g. promotion of early help-seeking) and mental health promotion programmes (e.g. targeting the development of protective factors at individual and organizational levels). A control group was the minimum design requirement for study inclusion and primary outcomes had to be assessed by validated measures of well-being or mental ill-health. Titles and abstracts were assessed independently by two reviewers with 99 % agreement and full papers were appraised critically using validated tools.

RESULTS: Only four studies (with a total of 997 GPs) from 5392 titles met inclusion criteria. The studies reported statistically significant improvement in self-reported mental ill-health. Two interventions used cognitive-behavioural techniques, one was mindfulness-based and one fed-back GHQ scores and self-help information.

CONCLUSION: There is an urgent need for high quality, controlled studies in GP well-being. Research on improving GP well-being is limited by focusing mainly on stressors and not giving systematic attention to the development of positive mental health.

Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis

Background
Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness.

Methods
We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate.

Discussion
While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials.

Systematic review registration
PROSPERO CRD42013005608. (http://​www.​crd.​york.​ac.​uk/​PROSPERO/​)

Alpha-2 agonists for sedation of mechanically ventilated adults in intensive care units: a systematic review

BACKGROUND: Care of critically ill patients in intensive care units (ICUs) often requires potentially invasive or uncomfortable procedures, such as mechanical ventilation (MV). Sedation can alleviate pain and discomfort, provide protection from stressful or harmful events, prevent anxiety and promote sleep. Various sedative agents are available for use in ICUs. In the UK, the most commonly used sedatives are propofol (Diprivan(®), AstraZeneca), benzodiazepines [e.g. midazolam (Hypnovel(®), Roche) and lorazepam (Ativan(®), Pfizer)] and alpha-2 adrenergic receptor agonists [e.g. dexmedetomidine (Dexdor(®), Orion Corporation) and clonidine (Catapres(®), Boehringer Ingelheim)]. Sedative agents vary in onset/duration of effects and in their side effects. The pattern of sedation of alpha-2 agonists is quite different from that of other sedatives in that patients can be aroused readily and their cognitive performance on psychometric tests is usually preserved. Moreover, respiratory depression is less frequent after alpha-2 agonists than after other sedative agents.

OBJECTIVES: To conduct a systematic review to evaluate the comparative effects of alpha-2 agonists (dexmedetomidine and clonidine) and propofol or benzodiazepines (midazolam and lorazepam) in mechanically ventilated adults admitted to ICUs.

DATA SOURCES: We searched major electronic databases (e.g. MEDLINE without revisions, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE and Cochrane Central Register of Controlled Trials) from 1999 to 2014.

METHODS: Evidence was considered from randomised controlled trials (RCTs) comparing dexmedetomidine with clonidine or dexmedetomidine or clonidine with propofol or benzodiazepines such as midazolam, lorazepam and diazepam (Diazemuls(®), Actavis UK Limited). Primary outcomes included mortality, duration of MV, length of ICU stay and adverse events. One reviewer extracted data and assessed the risk of bias of included trials. A second reviewer cross-checked all the data extracted. Random-effects meta-analyses were used for data synthesis.

RESULTS: Eighteen RCTs (2489 adult patients) were included. One trial at unclear risk of bias compared dexmedetomidine with clonidine and found that target sedation was achieved in a higher number of patients treated with dexmedetomidine with lesser need for additional sedation. The remaining 17 trials compared dexmedetomidine with propofol or benzodiazepines (midazolam or lorazepam). Trials varied considerably with regard to clinical population, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded outcome assessors. Compared with propofol or benzodiazepines (midazolam or lorazepam), dexmedetomidine had no significant effects on mortality [risk ratio (RR) 1.03, 95% confidence interval (CI) 0.85 to 1.24, I (2) = 0%; p = 0.78]. Length of ICU stay (mean difference -1.26 days, 95% CI -1.96 to -0.55 days, I (2) = 31%; p = 0.0004) and time to extubation (mean difference -1.85 days, 95% CI -2.61 to -1.09 days, I (2) = 0%; p < 0.00001) were significantly shorter among patients who received dexmedetomidine. No difference in time to target sedation range was observed between sedative interventions (I (2) = 0%; p = 0.14). Dexmedetomidine was associated with a higher risk of bradycardia (RR 1.88, 95% CI 1.28 to 2.77, I (2) = 46%; p = 0.001).

LIMITATIONS: Trials varied considerably with regard to participants, type of comparators, dose of sedative agents, outcome measures and length of follow-up. Overall, risk of bias was generally high or unclear. In particular, few trials blinded assessors.

CONCLUSIONS: Evidence on the use of clonidine in ICUs is very limited. Dexmedetomidine may be effective in reducing ICU length of stay and time to extubation in critically ill ICU patients. Risk of bradycardia but not of overall mortality is higher among patients treated with dexmedetomidine. Well-designed RCTs are needed to assess the use of clonidine in ICUs and identify subgroups of patients that are more likely to benefit from the use of dexmedetomidine.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42014014101.

FUNDING: The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates.

Do Cochrane summaries help student midwives understand the findings of Cochrane systematic reviews: the BRIEF randomised trial

BACKGROUND: Abstracts and plain language summaries (PLS) are often the first, and sometimes the only, point of contact between readers and systematic reviews. It is important to identify how these summaries are used and to know the impact of different elements, including the authors' conclusions. The trial aims to assess whether (a) the abstract or the PLS of a Cochrane Review is a better aid for midwifery students in assessing the evidence, (b) inclusion of authors' conclusions helps them and (c) there is an interaction between the type of summary and the presence or absence of the conclusions.

METHODS: Eight hundred thirteen midwifery students from nine universities in the UK and Ireland were recruited to this 2 × 2 factorial trial (abstract versus PLS, conclusions versus no conclusions). They were randomly allocated to one of four groups and asked to recall knowledge after reading one of four summary formats of two Cochrane Reviews, one with clear findings and one with uncertain findings. The primary outcome was the proportion of students who identified the appropriate statement to describe the main findings of the two reviews as assessed by an expert panel.

RESULTS: There was no statistically significant difference in correct response between the abstract and PLS groups in the clear finding example (abstract, 59.6 %; PLS, 64.2 %; risk difference 4.6 %; CI -0.2 to 11.3) or the uncertain finding example (42.7 %, 39.3 %, -3.4 %, -10.1 to 3.4). There was no significant difference between the conclusion and no conclusion groups in the example with clear findings (conclusions, 63.3 %; no conclusions, 60.5 %; 2.8 %; -3.9 to 9.5), but there was a significant difference in the example with uncertain findings (44.7 %; 37.3 %; 7.3 %; 0.6 to 14.1, p = 0.03). PLS without conclusions in the uncertain finding review had the lowest proportion of correct responses (32.5 %). Prior knowledge and belief predicted student response to the clear finding review, while years of midwifery education predicted response to the uncertain finding review.

CONCLUSIONS: Abstracts with and without conclusions generated similar student responses. PLS with conclusions gave similar results to abstracts with and without conclusions. Removing the conclusions from a PLS with uncertain findings led to more problems with interpretation.

Triangular Objects and Systematic K-Theory

We investigate modules over “systematic” rings. Such rings are “almost graded” and have appeared under various names in the literature; they are special cases of the G-systems of Grzeszczuk. We analyse their K-theory in the presence of conditions on the support, and explain how this generalises and unifies calculations of graded and filtered K-theory scattered in the literature. Our treatment makes systematic use of the formalism of idempotent completion and a theory of triangular objects in additive categories, leading to elementary and transparent proofs throughout.