Suicide risk and prevention during the COVID-19 pandemic:one year on

Emerging data from high and upper-middle-income countries indicate that suicide rates generally did not increase during the initial months of the COVID-19 pandemic, yet the pandemic's impact on suicide is complex. We discuss the nuances of this relationship, how it may evolve over time, and describe the specific steps that governments and societies must take to mitigate harm and prevent suicides in the late stages and aftermath of the pandemic

Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion

The SARS-coronavirus (SARS-CoV) is the etiological agent of severe acute respiratory syndrome (SARS). The SARS-CoV spike (S) glycoprotein mediates membrane fusion events during virus entry and virus-induced cell-to-cell fusion. To delineate functional domains of the SARS-CoV S glycoprotein, single point mutations, cluster-to-lysine and cluster-to-alanine mutations, as well as carboxyl-terminal truncations were investigated in transient expression experiments. Mutagenesis of either the coiled-coil domain of the S glycoprotein amino terminal heptad repeat, the predicted fusion peptide, or an adjacent but distinct region, severely compromised S-mediated cell-to-cell fusion, while intracellular transport and cell-surface expression were not adversely affected. Surprisingly, a carboxyl-terminal truncation of 17 amino acids substantially increased S glycoprotein-mediated cell-to-cell fusion suggesting that the terminal 17 amino acids regulated the S fusogenic properties. In contrast, truncation of 26 or 39 amino acids eliminating either one or both of the two endodomain cysteine-rich motifs, respectively, inhibited cell fusion in comparison to the wild-type S. The 17 and 26 amino-acid deletions did not adversely affect S cell-surface expression, while the 39 amino-acid truncation inhibited S cell-surface expression suggesting that the membrane proximal cysteine-rich motif plays an essential role in S cell-surface expression. Mutagenesis of the acidic amino-acid cluster in the carboxyl terminus of the S glycoprotein as well as modification of a predicted phosphorylation site within the acidic cluster revealed that this amino-acid motif may play a functional role in the retention of S at cell surfaces. This genetic analysis reveals that the SARS-CoV S glycoprotein contains extracellular domains that regulate cell fusion as well as distinct endodomains that function in intracellular transport, cell-surface expression, and cell fusion. © 2005 Elsevier Inc. All rights reserved

Risk factors for deliberate self-harm in young people in rural Sri Lanka: a prospective cohort study of 22,000 individuals

Background: Over 90% of youth suicide deaths occur in low- and middle-income countries. Despite this relatively little is known about risk factors in this context. Aims: Investigate risk factors for deliberate self-harm (non-fatal) in young people in rural Sri Lanka. Methods: A prospective cohort study of 22,401 individuals aged 12-18 years with complete data on sex, student status, household asset score, household access to pesticides and household problematic alcohol use. Deliberate self-harm was measured prospectively by reviewing hospital records. Poisson regression estimated incidence rate ratios (IRRs) for the association of risk factors with deliberate self-harm. Results: Females were at higher risk of deliberate self-harm compared to males (IRR 2.05; 95%CI 1.75 – 2.40). Lower asset scores (low compared to high: IRR 1.46, 95%CI 1.12 - 2.00) and having left education (IRR 1.61 95%CI 1.31 – 1.98) were associated with higher risks of deliberate self-harm, with evidence that the effect of not being in school was more pronounced in males (IRR 1.94; 95%CI 1.40 – 2.70) than females. There was no evidence of an association between household pesticide access and deliberate self-harm risk, but problematic household alcohol use was associated with increased risk (IRR 1.23; 95%CI 1.04 – 1.45), with evidence that this was more pronounced in females than males (IRR for females 1.42; 95%CI 1.17 – 1.72). There was no evidence of deliberate self-harm risk being higher at times of school exam stress. Conclusion: Indicators of lower socioeconomic status, not being in school, and problematic alcohol use in households, were associated with increased deliberate self-harm risk in young people

Risk of suicide and repeat self-harm after hospital attendance for non-fatal self-harm in Sri Lanka: a cohort study

Background: Evidence from high income countries (HICs) suggests that individuals who present to hospital after self-harm are an important target for suicide prevention, but evidence from low and middle-income countries (LMICs) is lacking. We aimed to investigate the risk of repeat self-harm and suicide, and factors associated with these outcomes, in a large cohort of patients presenting to hospital with self-harm in rural Sri Lanka. Methods: In this cohort study, hospital presentations for self-harm at 13 hospitals in a rural area of North Central Province (population 224and#8200;000), Sri Lanka, were followed up with a self-harm surveillance system, established as part of a community randomised trial, and based on data from all hospitals, coroners, and police stations in the study area. We estimated the risk of repeat non-fatal and fatal self-harm and risk factors for repetition with Kaplan-Meier methods and Cox proportional hazard models. Sociodemographic (age, sex, and socioeconomic position) and clinical (past self-harm and method of self-harm) characteristics investigated were drawn from a household survey in the study area and data recorded at the time of index hospital presentation. We included all individuals who had complete data for all variables in the study in our primary analysis. Outcomes: Between July 29, 2011, and May 12, 2016, we detected 3073 episodes of self-harm (fatal and non-fatal) in our surveillance system, of which 2532 (82and#183;3%) were linked back to an individual in the baseline survey. After exclusion of 145 ineligible episodes, we analysed 2259 index episodes of self-harm. By use of survival models, the estimated risk of repeat self-harm (12 months: 3and#183; 1%, 95% CI 2and#183;4-3and#183;9; 24 months: 5and#183;2%, 4and#183;3-6and#183;4) and suicide (12 months: 0and#183;6%, 0and#183;4-1and#183;1; 24 months: 0and#183;8%, 0and#183;5-1and#183;3) in our study was considerably lower than that in HICs. A higher risk of repeat self-harm was observed in men than in women (fatal and non-fatal; hazard ratio 2and#183;0, 95% CI 1and#183;3-3and#183;2; p=0and#183;0021), in individuals aged 56 years and older compared with those aged 10-25 years (fatal; 16and#183;1, 4and#183;3-59and#183;9; p=0and#183;0027), and those who used methods other than poisoning in their index presentation (fatal and non-fatal; 3and#183;9, 2and#183;0-7and#183;6; p=0and#183;00027). We found no evidence of increased risk of repeat self-harm or suicide in those with a history of self-harm before the index episode. Interpretation: Although people who self-harm are an important high-risk group, focusing suicide prevention efforts on those who self-harm might be somewhat less important in LMICs compared with HICs given the low risk of repeat self-harm and subsequent suicide death. Strategies that focus on other risk factors for suicide might be more effective in reducing suicide deaths in LMICs in south Asia. A better understanding of the low incidence of repeat self-harm is also needed, as this could contribute to prevention strategies in nations with a higher incidence of repetition and subsequent suicide death. FUNDING:Wellcome Trust.</p

Herpesvirus Replication Compartments Originate with Single Incoming Viral Genomes

Previously we described a method to estimate the average number of virus genomes expressed in an infected cell. By analyzing the color spectrum of cells infected with a mixture of isogenic pseudorabies virus (PRV) recombinants expressing three fluorophores, we estimated that fewer than seven incoming genomes are expressed, replicated, and packaged into progeny per cell. In this report, we expand this work and describe experiments demonstrating the generality of the method, as well as providing more insight into herpesvirus replication. We used three isogenic PRV recombinants, each expressing a fluorescently tagged VP26 fusion protein (VP26 is a capsid protein) under the viral VP26 late promoter. We calculated a similar finite limit on the number of expressed viral genomes, indicating that this method is independent of the promoter used to transcribe the fluorophore genes, the time of expression of the fluorophore (early versus late), and the insertion site of the fluorophore gene in the PRV genome (UL versus US). Importantly, these VP26 fusion proteins are distributed equally in punctate virion assembly structures in each nucleus, which improves the signal-to-noise ratio when determining the color spectrum of each cell. To understand how the small number of genomes are distributed among the replication compartments, we used a two-color fluorescent in situ hybridization assay. Most viral replication compartments in the nucleus occupy unique nuclear territories, implying that they arose from single genomes. Our experiments suggest a correlation between the small number of expressed viral genomes and the limited number of replication compartments

Bans of WHO Class I Pesticides in Bangladesh –Suicide Prevention without Hampering Agricultural Output

Pesticide self-poisoning is a major problem in Bangladesh. Over the past 20-years, the Bangladesh government has introduced pesticide legislation and banned highly hazardous pesticides (HHPs) from agricultural use. We aimed to assess the impacts of pesticide bans on suicide and on agricultural production.We obtained data on unnatural deaths from the Statistics Division of Bangladesh Police, and used negative binomial regression to quantify changes in pesticide suicides and unnatural deaths following removal of WHO Class I toxicity HHPs from agriculture in 2000. We assessed contemporaneous trends in other risk factors, pesticide usage and agricultural production in Bangladesh from 1996 to 2014.Mortality in hospital from pesticide poisoning fell after the 2000 ban: 15.1% vs 9.5%, relative reduction 37.1% [95% confidence interval (CI) 35.4 to 38.8%]. The pesticide poisoning suicide rate fell from 6.3/100 000 in 1996 to 2.2/100 000 in 2014, a 65.1% (52.0 to 76.7%) decline. There was a modest simultaneous increase in hanging suicides [20.0% (8.4 to 36.9%) increase] but the overall incidence of unnatural deaths fell from 14.0/100 000 to 10.5/100 000 [25.0% (18.1 to 33.0%) decline]. There were 35 071 (95% CI 25 959 to 45 666) fewer pesticide suicides in 2001 to 2014 compared with the number predicted based on trends between 1996 to 2000. This reduction in rate of pesticide suicides occurred despite increased pesticide use and no change in admissions for pesticide poisoning, with no apparent influence on agricultural output.Strengthening pesticide regulation and banning WHO Class I toxicity HHPs in Bangladesh were associated with major reductions in deaths and hospital mortality, without any apparent effect on agricultural output. Our data indicate that removing HHPs from agriculture can rapidly reduce suicides without imposing substantial agricultural costs

Challenges and opportunities of a paperless baseline survey in Sri Lanka

BACKGROUND: Personal digital assistants (PDAs) have been shown to reduce costs associated with survey implementation and digitisation, and to improve data quality when compared to traditional paper based data collection. Few studies, however, have shared their experiences of the use of these devices in rural settings in Asia. This paper reports on our experiences of using a PDA device for data collection in Sri Lanka as part of a large cluster randomised control trial. FINDINGS: We found that PDAs were useful for collecting data for a baseline survey of a large randomised control trial (54,000 households). We found that the PDA device and survey format was easy to use by inexperienced field staff, even though the survey was programmed in English. The device enabled the rapid digitisation of survey data, providing a good basis for continuous data quality assurance, supervision of staff and survey implementation. An unexpected advantage was the improved community opinion of the research project as a result of the device, because the use of the technology gave data collectors an elevated status amongst the community. In addition the global positioning system (GPS) functionality of the device allowed precise mapping of households, and hence distinct settlements to be identified as randomisation clusters. Future users should be mindful that to save costs the piloting should be completed before programming. In addition consideration of a local after-care service is important to avoid costs and time delays associated with sending devices back to overseas providers. DISCUSSION: Since the start of this study, PDA devices have rapidly developed and are increasingly used. The use of PDA or similar devices for research is not without its problems; however we believe that the universal lessons learnt as part of this study are even more important for the effective utilisation of these rapidly developing technologies in resource poor settings

Are left-behind families of migrant workers at increased risk of attempted suicide? – A cohort study of 178,000+ individuals in Sri Lanka

Background There are an estimated 258 million international migrants worldwide. In Asia low-skilled workers often emigrate on a temporary basis (2–3 years) without their families. There is significant concern over the mental health and wellbeing of left-behind families in this region. No previous study has examined whether the risk of suicidal behaviour is elevated in left-behind family members. Methods Cohort study using baseline data from a large randomised controlled trial in Sri Lanka (n = 178,730 participants; 8% households had a current temporary foreign migrant) and prospective hospital presentations of suicide attempts. Using multilevel Poisson regression models, we compared the risk of attempted suicide in households with left-behind and non-left-behind family members. We also investigated whether the sex of the migrant or the age/sex of the household member left behind altered any associations. Results The risk of an attempted suicide was elevated in female migrant households (IRR 1.60 95% CI 1.38, 1.85), but not male migrant households (IRR 1.01 95% CI 0.76,1.36)) with strong evidence that risk differed for female vs. male migrant households (p-value = 0.005). We found no evidence that the age or sex of the left-behind household member altered the association observed. Conclusions This analysis suggests that members of households with a temporary female foreign migrant are at an increased risk of attempted suicide, but these findings must be interpreted with caution. The increased risk of suicidal behaviour in these households may be due to factors that were present before the migration and persist post-migration (e.g. household violence, poverty)