Behaviour patterns preceding a railway suicide: Explorative study of German Federal Police officers' experiences

<p>Abstract</p> <p>Background</p> <p>Constant high-level numbers of railway suicides indicate that prevention strategies against railway suicides are urgently needed. The main question of the present study was whether pre-crash railway suicide behaviour can be identified, using German Federal Police officers experience with suicidal events in railway related environments.</p> <p>Methods</p> <p>To collect information on pre-crash railway suicide behaviour, a questionnaire was used and made available on the German Federal Police intranet. A total of 202 subjects (mean age: 41 years, sex: 84.9% male) were included in the analysis. Multivariate logistic regression analyses were performed to predict the prevention of suicide (first model) or demand for counselling (second model) as outcomes. Sex, age, years of service, number of experienced suicides, suicides personally observed, information on suicides obtained from witnesses and finally either counselling/debriefing (first model) or whether officers had prevented a suicide (second model) were used as predictors.</p> <p>Results</p> <p>A considerable proportion of police officers reported behavioural patterns preceding a suicide. Half of them observed the dropping or leaving behind of personal belongings or the avoidance of eye contact, more than a third erratic gesture, mimic or movement. Erratic communication patterns and general confusion were each reported by about one quarter. One fifth indicated the influence of alcohol. Less frequently observed behaviour was aimlessly wandering (14.3%) and out of the ordinary clothing (4%). About one third of all railway suicide victims committed suicide in stations. Of those, 70% had chosen an eminent spot. The multivariate logistic regression model using prevented suicides as the outcome identified the number of suicides experienced, counselling/debriefing and having personally observed a suicide as variables with significant impact. The model using counselling/debriefing as the outcome identified age and having prevented a suicide as variables with a significant association.</p> <p>Conclusions</p> <p>Our results provide evidence that railway suicides are preceded by identifiable behavioural patterns. This emphasizes the importance of educational efforts, taking into account the knowledge and skills of experienced police officers.</p

Interventions for behaviour change and self-management in stroke secondary prevention: protocol for an overview of reviews

Abstract Background Stroke secondary prevention guidelines recommend medication prescription and adherence, active education and behavioural counselling regarding lifestyle risk factors. To impact on recurrent vascular events, positive behaviour/s must be adopted and sustained as a lifestyle choice, requiring theoretically informed behaviour change and self-management interventions. A growing number of systematic reviews have addressed complex interventions in stroke secondary prevention. Differing terminology, inclusion criteria and overlap of studies between reviews makes the mechanism/s that affect positive change difficult to identify or replicate clinically. Adopting a two-phase approach, this overview will firstly comprehensively summarise systematic reviews in this area and secondly identify and synthesise primary studies in these reviews which provide person-centred, theoretically informed interventions for stroke secondary prevention. Methods An overview of reviews will be conducted using a systematic search strategy across the Cochrane Database of Systematic Reviews, PubMed and Epistomonikas. Inclusion criteria: systematic reviews where the population comprises individuals post-stroke or TIA and where data relating to person-centred risk reduction are synthesised for evidence of efficacy when compared to standard care or no intervention. Primary outcomes of interest include mortality, recurrent stroke and other cardiovascular events. In phase 1, two reviewers will independently (1) assess the eligibility of identified reviews for inclusion; (2) rate the quality of included reviews using the ROBIS tool; (3) identify unique primary studies and overlap between reviews; (4) summarise the published evidence supporting person-centred behavioural change and self-management interventions in stroke secondary prevention and (5) identify evidence gaps in this field. In phase 2, two independent reviewers will (1) examine person-centred, primary studies in each review using the Template for Intervention Description and Replication (TIDieR checklist), itemising, where present, theoretical frameworks underpinning interventions; (2) group studies employing theoretically informed interventions by the intervention delivered and by the outcomes reported (3) apply GRADE quality of evidence for each intervention by outcome/s identified from theoretically informed primary studies. Disagreement between reviewers at each process stage will be discussed and a third reviewer consulted. Discussion This overview will comprehensively bring together the best available evidence supporting person-centred, stroke secondary prevention strategies in an accessible format, identifying current knowledge gaps

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Rapid Generation of MicroRNA Sponges for MicroRNA Inhibition

MicroRNA (miRNA) sponges are transcripts with repeated miRNA antisense sequences that can sequester miRNAs from endogenous targets. MiRNA sponges are valuable tools for miRNA loss-of-function studies both in vitro and in vivo. We developed a fast and flexible method to generate miRNA sponges and tested their efficiency in various assays. Using a single directional ligation reaction we generated sponges with 10 or more miRNA binding sites. Luciferase and AGO2-immuno precipitation (IP) assays confirmed effective binding of the miRNAs to the sponges. Using a GFP competition assay we showed that miR-19 sponges with central mismatches in the miRNA binding sites are efficient miRNA inhibitors while sponges with perfect antisense binding sites are not. Quantification of miRNA sponge levels suggests that this is at least in part due to degradation of the perfect antisense sponge transcripts. Finally, we provide evidence that combined inhibition of miRNAs of the miR-17∼92 cluster results in a more effective growth inhibition as compared to inhibition of individual miRNAs. In conclusion, we describe and validate a method to rapidly generate miRNA sponges for miRNA loss-of-function studies

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

&lt;p&gt;Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.&lt;/p&gt; &lt;p&gt;Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.&lt;/p&gt; &lt;p&gt;Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p&#60;5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.&lt;/p&gt; &lt;p&gt;Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.&lt;/p&gt

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Weight and metabolic effects of cpap in obstructive sleep apnea patients with obesity

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.</p> <p>Methods</p> <p>In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.</p> <p>Results</p> <p>CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.</p> <p>Conclusions</p> <p>Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.</p