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1.
BMJ Open ; 9(8): e027766, 2019 08 18.
Article in English | MEDLINE | ID: mdl-31427319

ABSTRACT

INTRODUCTION: Childhood adversity (CA) has been suggested as a key risk factor for suicidal behaviour, but evidence from low/middle-income countries is lacking. In Sri Lanka, CA, in the form of child maltreatment or as a consequence of maternal separation, has been highlighted in primarily qualitative or case series work, as a potentially important determinant of suicidal behaviour. To date, there have been no quantitative studies to investigate CA as a key exposure associated with suicidal behaviour in Sri Lanka. The aim of the research is to understand the association between CA and suicidal behaviour in Sri Lanka and to identify potentially modifiable factors to reduce any observed increased risk of suicidal behaviour associated with CA. METHODS AND ANALYSIS: This is a hospital-based case-control study. Cases (n=200) will be drawn from individuals admitted to the medical toxicology ward of the Teaching Hospital Peradeniya, Sri Lanka, for medical management of intentional self-poisoning. Sex and age frequency-matched controls (n=200) will be recruited from either patients or accompanying visitors presenting at the outpatient department and clinic of the same hospital for conditions unrelated to the outcome of interest. Conditional logistic regression will be used to investigate the association between CA and deliberate self-poisoning and whether the association is altered by other key factors including socioeconomic status, psychiatric morbidity, current experiences of domestic violence and social support. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Ethical Review Committee of the Faculty of Medicine, University of Peradeniya, Sri Lanka. Researchers have been trained in administering the questionnaire and a participant safety and distress protocol has been designed to guide researchers in ensuring participant safety and how to deal with a distressed participant. Results will be disseminated in local policy fora and peer-reviewed articles, local media, and national and international conferences.


Subject(s)
Adult Survivors of Child Abuse/statistics & numerical data , Hospitalization/statistics & numerical data , Poisoning/epidemiology , Self-Injurious Behavior/epidemiology , Suicide, Attempted/statistics & numerical data , Adult , Adult Survivors of Child Abuse/psychology , Case-Control Studies , Hospitals, Teaching , Humans , Research Design , Risk Factors , Sri Lanka/epidemiology , Suicide, Attempted/psychology
3.
Br J Clin Pharmacol ; 84(10): 2303-2310, 2018 10.
Article in English | MEDLINE | ID: mdl-29911343

ABSTRACT

AIMS: Recreational use of novel psychoactive substance (NPS) has become increasingly common. We aimed to assess the association of national legislation and local trading standards activity with hospital presentations. METHODS: We established observational cohorts of patients with recreational drug toxicity presenting to Edinburgh Royal Infirmary and dying with detectable recreational drugs in Edinburgh. We assessed associations with two temporary class drug-orders (April 2015: methylphenidates, Nov 2015: methiopropamine), the Psychoactive Substances Act (June 2016), and trading standards forfeiture orders (October 2015). RESULTS: The methylphenidate temporary class drug-order was associated with rapid 46.7% (P = 0.002) and 21.0% (P = 0.003) reductions in presentations and admissions, respectively, for NPS drug toxicity, comparing 12 months before with 6 months after. The change was greatest for ethylphenidate toxicity (96.7% reduction in admissions, P < 0.001) that was partly offset by a tripling in synthetic cannabinoid receptor agonist cases (P < 0.001) over the next 6 months. This increase reversed following trading standards activity removing all NPS drugs from local shops in October 2015, associated with 64.3% (P < 0.001) and 83.7% (P < 0.001) reductions in presentations and admissions, respectively, for all NPS drugs over the next 12 months. The effect was sustained and associated with a reduced postmortem detection of stimulant NPS drugs. The two interventions prevented an estimated 557 (95% confidence interval 327-934) NPS admissions during 2016, saving an estimated £303 030 (£177 901-508 133) in hospital costs. CONCLUSIONS: We show here that drug legislation and trading standards activity may be associated with effective and sustained prevention. Widespread adoption of trading standards enforcement, together with focused legislation, may turn the tide against these highly-damaging drugs.


Subject(s)
Central Nervous System Stimulants/poisoning , Drug and Narcotic Control/legislation & jurisprudence , Illicit Drugs/poisoning , Psychotropic Drugs/poisoning , Substance Abuse, Oral/epidemiology , Adult , Female , Hospital Costs/statistics & numerical data , Hospitalization/economics , Hospitalization/statistics & numerical data , Humans , Illicit Drugs/legislation & jurisprudence , Male , Methamphetamine/analogs & derivatives , Methamphetamine/poisoning , Methylphenidate/analogs & derivatives , Methylphenidate/poisoning , Program Evaluation , Scotland/epidemiology , Substance Abuse, Oral/economics , Substance Abuse, Oral/etiology , Thiophenes/poisoning , Young Adult
4.
Int J Epidemiol ; 47(1): 175-184, 2018 02 01.
Article in English | MEDLINE | ID: mdl-29024951

ABSTRACT

Background: 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. Methods: 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. Results: 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. Conclusions: 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.


Subject(s)
Agriculture/legislation & jurisprudence , Commerce/legislation & jurisprudence , Pesticides/poisoning , Suicide Prevention , Suicide/statistics & numerical data , Bangladesh , Female , Humans , Incidence , Linear Models , Male , Risk Factors , Suicide/trends , World Health Organization
5.
Lancet ; 390(10105): 1863-1872, 2017 Oct 21.
Article in English | MEDLINE | ID: mdl-28807536

ABSTRACT

BACKGROUND: Agricultural pesticide self-poisoning is a major public health problem in rural Asia. The use of safer household pesticide storage has been promoted to prevent deaths, but there is no evidence of effectiveness. We aimed to test the effectiveness of lockable household containers for prevention of pesticide self-poisoning. METHODS: We did a community-based, cluster-randomised controlled trial in a rural area of North Central Province, Sri Lanka. Clusters of households were randomly assigned (1:1), with a sequence computer-generated by a minimisation process, to intervention or usual practice (control) groups. Intervention households that had farmed or had used or stored pesticide in the preceding agricultural season were given a lockable storage container. Further promotion of use of the containers was restricted to community posters and 6-monthly reminders during routine community meetings. The primary outcome was incidence of pesticide self-poisoning in people aged 14 years or older during 3 years of follow-up. Identification of outcome events was done by staff who were unaware of group allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT1146496. FINDINGS: Between Dec 31, 2010, and Feb 2, 2013, we randomly assigned 90 rural villages to the intervention group and 90 to the control group. 27 091 households (114 168 individuals) in the intervention group and 26 291 households (109 693 individuals) in the control group consented to participate. 20 457 household pesticide storage containers were distributed. In individuals aged 14 years or older, 611 cases of pesticide self-poisoning had occurred by 3 years in the intervention group compared with 641 cases in the control group; incidence of pesticide self-poisoning did not differ between groups (293·3 per 100 000 person-years of follow-up in the intervention group vs 318·0 per 100 000 in the control group; rate ratio [RR] 0·93, 95% CI 0·80-1·08; p=0·33). We found no evidence of switching from pesticide self-poisoning to other forms of self-harm, with no significant difference in the number of fatal (82 in the intervention group vs 67 in the control group; RR 1·22, 0·88-1·68]) or non-fatal (1135 vs 1153; RR 0·97, 0·86-1·08) self-harm events involving all methods. INTERPRETATION: We found no evidence that means reduction through improved household pesticide storage reduces pesticide self-poisoning. Other approaches, particularly removal of highly hazardous pesticides from agricultural practice, are likely to be more effective for suicide prevention in rural Asia. FUNDING: Wellcome Trust, with additional support from the American Foundation for Suicide Prevention, Lister Institute of Preventive Medicine, Chief Scientist Office of Scotland, University of Copenhagen, and NHMRC Australia.


Subject(s)
Agriculture , Pesticides/poisoning , Security Measures , Suicide Prevention , Adult , Female , Humans , Male , Poisoning/prevention & control , Rural Population , Sri Lanka/epidemiology , Suicide/statistics & numerical data
8.
PLoS One ; 12(3): e0172893, 2017.
Article in English | MEDLINE | ID: mdl-28264041

ABSTRACT

OBJECTIVE: To investigate the effect of 3-year phased bans of the pesticides dimethoate and fenthion in 2008-2010, and paraquat in 2009-2011, on suicide mortality in Sri Lanka. METHODS: Age-standardised overall, sex-specific, and method-specific suicide rates were calculated using Sri Lankan police data (1989-2015). Using negative binomial regression models, we estimated the change in the rate and number of suicide deaths in post-ban years (2011-15) compared to those expected based on pre-ban trends (2001-10). FINDINGS: Overall suicide mortality dropped by 21% between 2011 and 2015, from 18.3 to 14.3 per 100,000. The decline in pesticide suicides during this same period was larger than for overall suicides: from 8.5 to 4.2 per 100,000, a 50% reduction. This was accompanied by a smaller concurrent rise in non-pesticide suicide mortality with a 2% increase (9.9 to 10.1 per 100,000). In 2015, the ratio between the observed and expected pesticide suicide rates was 0.49 (95% confidence interval [CI] 0.40, 0.62), corresponding to an estimated 937 (95% CI 574, 1389) fewer pesticide suicides than expected from pre-ban suicide rates. Findings were similar in sensitivity analyses using 2008 or 2012 as commencement of the post intervention period. CONCLUSION: Bans of paraquat, dimethoate and fenthion in Sri Lanka were associated with a reduction in pesticide suicide mortality and in overall suicide mortality despite a small rise in other methods. This study provides further evidence for the effectiveness of pesticide regulation in limiting the availability of highly hazardous pesticides and thereby reducing the number of global suicides.

9.
BMC Public Health ; 17(1): 193, 2017 02 14.
Article in English | MEDLINE | ID: mdl-28196502

ABSTRACT

BACKGROUND: Between 1955 and 2011 there were marked fluctuations in suicide rates in Sri Lanka; incidence increased six-fold between 1955 and the 1980s, and halved in the early 21st century. Changes in access to highly toxic pesticides are thought to have influenced this pattern. This study investigates variation in suicide rates across Sri Lanka's 25 districts between 1955 and 2011. We hypothesised that changes in the incidence of suicide would be most marked in rural areas due to the variation in availability of highly toxic pesticides in these locations during this time period. METHODS: We mapped district-level suicide rates in 1955, 1972, 1980 and 2011. These periods preceded, included and postdated the rapid rise in Sri Lanka's suicide rates. We investigated the associations between district-level variations in suicide rates and census-derived measures of rurality (population density), unemployment, migration and ethnicity using Spearman's rank correlation and negative binomial models. RESULTS: The rise and fall in suicide rates was concentrated in more rural areas. In 1980, when suicide rates were at their highest, population density was inversely associated with area variation in suicide rates (r = -0.65; p < 0.001), i.e. incidence was highest in rural areas. In contrast the association was weakest in 1950, prior to the rise in pesticide suicides (r = -0.10; p = 0.697). There was no strong evidence that levels of migration or ethnicity were associated with area variations in suicide rates. The relative rates of suicide in the most rural compared to the most urban districts before (1955), during (1980) and after (2011) the rise in highly toxic pesticide availability were 1.1 (95% CI 0.5 to 2.4), 3.7 (2.0 to 6.9) and 2.1 (1.6 to 2.7) respectively. CONCLUSIONS: The findings provide some support for the hypothesis that changes in access to pesticides contributed to the marked fluctuations in Sri Lanka's suicide rate, but the impact of other factors cannot be ruled out.


Subject(s)
Pesticides/poisoning , Suicide/statistics & numerical data , Ethnicity , Female , Humans , Incidence , Male , Pesticides/supply & distribution , Poisoning/epidemiology , Poisoning/prevention & control , Rural Population , Spatio-Temporal Analysis , Sri Lanka/epidemiology , Suicide Prevention
10.
BMC Public Health ; 16: 270, 2016 Mar 15.
Article in English | MEDLINE | ID: mdl-26979534

ABSTRACT

BACKGROUND: In 2010, the "Tackling Suicide on the Railways" programme was launched as a joint initiative among Network Rail, the Samaritans and other key organisations such as the British Transport Police and train operators to achieve a 20% reduction in railway suicides from 2010 to 2015 in Great Britain. We report the most recent age and sex specific trends in railway suicide in England and Wales from 2000 to 2013 and examine whether the initiative's target reduction in railway suicides is likely to be achieved. METHODS: Population data and suicide mortality data (all methods combined and railway) for England and Wales were obtained from the Office for National Statistics (ONS) and used to calculate age and gender specific rates for deaths registered from 2000 to 2013. Data on railway suicides were also obtained from the Rail Safety and Standards Board (RSSB) and compared with ONS data. We used joinpoint regression to identify changes in suicide trends across the study period. RESULTS: The railway was used in 4.1% of all suicides in England and Wales (RSSB data were similar to ONS data for most years). Suicides in all persons from all causes decreased from 2000 to 2007, with small increases from 2008 until 2013; this rise was entirely due to an increase in male suicides. Railway suicide rates increased over the entire study period; the proportion of railway suicides in all persons increased from 3.5 to 4.9% during the study period. This trend was also mainly driven by increases in male suicides as female railway suicide rates remained steady over time. The highest age specific railway suicide rates were observed in middle aged men and women. Although there was no conclusive evidence of an increase in ONS railway suicides, RSSB data showed a statistically significant increase in railway suicides in males from 2009 onwards. CONCLUSION: The continued rise in male railway suicide in England and Wales is concerning, particularly due to the high economic costs and psychological trauma associated with these deaths. The initiative's target of a 20% reduction in railway suicide is unlikely to be achieved.


Subject(s)
Railroads/statistics & numerical data , Suicide/trends , Adolescent , Adult , Age Factors , Aged , England/epidemiology , Female , Humans , Male , Middle Aged , Sex Factors , Wales/epidemiology , Young Adult , Suicide Prevention
11.
BMC Public Health ; 15: 1055, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26472204

ABSTRACT

BACKGROUND: Forty percent of the world's suicide deaths occur in low and middle income countries (LAMIC) in Asia. There is a recognition that social factors, such as socioeconomic position (SEP), play an important role in determining suicidal risk in high income countries, but less is known about the association in LAMIC. METHODS: The objective of this systematic review was to synthesise existing evidence of the association between SEP and attempted suicide/suicide risk in LAMIC countries in South and South East Asia. Web of Science, MEDLINE, MEDLINE in Process, EMBASE, PsycINFO, and article reference lists/forward citations were searched for eligible studies. Epidemiological studies reporting on the association of individual SEP with suicide and attempted suicide were included. Study quality was assessed using an adapted rating tool and a narrative synthesis was conducted. RESULTS: Thirty-one studies from nine countries were identified; 31 different measures of SEP were reported, with education being the most frequently recorded. Most studies suggest that lower levels of SEP are associated with an increased risk of suicide/attempted suicide, though findings are not always consistent between and within countries. Over half of the studies included in this review were of moderate/low quality. The SEP risk factors with the most consistent association across studies were asset based measures (e.g. composite measures); education; measures of financial difficulty and subjective measures of financial circumstance. Several studies show a greater than threefold increased risk in lower SEP groups with the largest and most consistent association with subjective measures of financial circumstance. CONCLUSION: The current evidence suggests that lower SEP increases the likelihood of suicide/attempted suicide in LAMIC in South and South East Asia. However, the findings are severely limited by study quality; larger better quality studies are therefore needed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2014: CRD42014006521.


Subject(s)
Suicide/statistics & numerical data , Asia/epidemiology , Female , Humans , Risk Factors , Socioeconomic Factors , Suicide, Attempted/statistics & numerical data
12.
BMJ ; 350: h1109, 2015 Mar 12.
Article in English | MEDLINE | ID: mdl-25767129

ABSTRACT

OBJECTIVE: To determine the risk of neuropsychiatric adverse events associated with use of varenicline compared with placebo in randomised controlled trials. DESIGN: Systematic review and meta-analysis comparing study effects using two summary estimates in fixed effects models, risk differences, and Peto odds ratios. DATA SOURCES: Medline, Embase, PsycINFO, the Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials with a placebo comparison group that reported on neuropsychiatric adverse events (depression, suicidal ideation, suicide attempt, suicide, insomnia, sleep disorders, abnormal dreams, somnolence, fatigue, anxiety) and death. Studies that did not involve human participants, did not use the maximum recommended dose of varenicline (1 mg twice daily), and were cross over trials were excluded. RESULTS: In the 39 randomised controlled trials (10,761 participants), there was no evidence of an increased risk of suicide or attempted suicide (odds ratio 1.67, 95% confidence interval 0.33 to 8.57), suicidal ideation (0.58, 0.28 to 1.20), depression (0.96, 0.75 to 1.22), irritability (0.98, 0.81 to 1.17), aggression (0.91, 0.52 to 1.59), or death (1.05, 0.47 to 2.38) in the varenicline users compared with placebo users. Varenicline was associated with an increased risk of sleep disorders (1.63, 1.29 to 2.07), insomnia (1.56, 1.36 to 1.78), abnormal dreams (2.38, 2.05 to 2.77), and fatigue (1.28, 1.06 to 1.55) but a reduced risk of anxiety (0.75, 0.61 to 0.93). Similar findings were observed when risk differences were reported. There was no evidence for a variation in depression and suicidal ideation by age group, sex, ethnicity, smoking status, presence or absence of psychiatric illness, and type of study sponsor (that is, pharmaceutical industry or other). CONCLUSIONS: This meta-analysis found no evidence of an increased risk of suicide or attempted suicide, suicidal ideation, depression, or death with varenicline. These findings provide some reassurance for users and prescribers regarding the neuropsychiatric safety of varenicline. There was evidence that varenicline was associated with a higher risk of sleep problems such as insomnia and abnormal dreams. These side effects, however, are already well recognised. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2014:CRD42014009224.


Subject(s)
Benzazepines/adverse effects , Mental Disorders/chemically induced , Quinoxalines/adverse effects , Sleep Wake Disorders/chemically induced , Tobacco Use Cessation Devices/adverse effects , Aggression/drug effects , Depression/chemically induced , Humans , Risk Factors , Suicide/statistics & numerical data , Suicide, Attempted/statistics & numerical data , Varenicline
13.
BMC Public Health ; 14: 839, 2014 Aug 13.
Article in English | MEDLINE | ID: mdl-25118074

ABSTRACT

BACKGROUND: Sri Lanka has experienced major changes in its suicide rates since the 1970s, and in 1995 it had one of the highest rates in the world. Subsequent reductions in Sri Lanka's suicide rates have been attributed to the introduction of restrictions on the availability of highly toxic pesticides. We investigate these changes in suicide rates in relation to age, gender, method specific trends and birth-cohort and period effects, with the aim of informing preventative strategies. METHODS: Secular trends of suicide in relation to age, sex, method, birth-cohort and period effects were investigated graphically using police data (1975-2012). Poisoning case-fatality was investigated using national hospital admission data (2004-2010). RESULTS: There were marked changes to the age-, gender- and method-specific incidence of suicide over the study period. Year on year declines in rates began in 17-25 year olds in the early 1980s. Reduction in older age groups followed and falls in all age groups occurred after all class I (the most toxic) pesticides were banned. Distinct changes in the age/gender pattern of suicide are observed: in the 1980s suicide rates were highest in 21-35 year old men; by the 2000s, this pattern had reversed with a stepwise increase in male rates with increasing age. Throughout the study period female rates were highest in 17-25 year olds. There has been a rise in suicide by hanging, though this rise is relatively small in relation to the marked decline in self-poisoning deaths. The patterns of suicides are more consistent with a period rather than birth-cohort effect. CONCLUSIONS: The epidemiology of suicide in Sri Lanka has changed noticeably in the last 30 years. The introduction of pesticide regulations in Sri Lanka coincides with a reduction in suicide rates, with evidence of limited method substitution.


Subject(s)
Suicide/statistics & numerical data , Adolescent , Adult , Aged , Child , Cohort Studies , Female , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Middle Aged , Police , Sri Lanka/epidemiology , Suicide/trends
14.
BMC Res Notes ; 7: 452, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-25027231

ABSTRACT

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.


Subject(s)
Community-Based Participatory Research , Computers, Handheld/statistics & numerical data , Data Collection/instrumentation , Software , Data Collection/statistics & numerical data , Family Characteristics , Geographic Information Systems/statistics & numerical data , Humans , Randomized Controlled Trials as Topic , Rural Population , Sri Lanka
15.
Cancer Epidemiol Biomarkers Prev ; 23(7): 1356-1365, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24753544

ABSTRACT

BACKGROUND: Only a minority of the genetic components of prostate cancer risk have been explained. Some observed associations of SNPs with prostate cancer might arise from associations of these SNPs with circulating prostate-specific antigen (PSA) because PSA values are used to select controls. METHODS: We undertook a genome-wide association study (GWAS) of screen-detected prostate cancer (ProtecT: 1,146 cases and 1,804 controls); meta-analyzed the results with those from the previously published UK Genetic Prostate Cancer Study (1,854 cases and 1,437 controls); investigated associations of SNPs with prostate cancer using either "low" (PSA < 0.5 ng/mL) or "high" (PSA ≥ 3 ng/mL, biopsy negative) PSA controls; and investigated associations of SNPs with PSA. RESULTS: The ProtecT GWAS confirmed previously reported associations of prostate cancer at three loci: 10q11.23, 17q24.3, and 19q13.33. The meta-analysis confirmed associations of prostate cancer with SNPs near four previously identified loci (8q24.21,10q11.23, 17q24.3, and 19q13.33). When comparing prostate cancer cases with low PSA controls, alleles at genetic markers rs1512268, rs445114, rs10788160, rs11199874, rs17632542, rs266849, and rs2735839 were associated with an increased risk of prostate cancer, but the effect-estimates were attenuated to the null when using high PSA controls (Pheterogeneity in effect-estimates < 0.04). We found a novel inverse association of rs9311171-T with circulating PSA. CONCLUSIONS: Differences in effect-estimates for prostate cancer observed when comparing low versus high PSA controls may be explained by associations of these SNPs with PSA. IMPACT: These findings highlight the need for inferences from genetic studies of prostate cancer risk to carefully consider the influence of control selection criteria.


Subject(s)
Genetic Predisposition to Disease/genetics , Prostate-Specific Antigen/genetics , Prostatic Neoplasms/genetics , Aged , Genetic Association Studies , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Prostate-Specific Antigen/blood , Prostatic Neoplasms/blood
16.
BMJ Open ; 4(3): e004173, 2014 Mar 19.
Article in English | MEDLINE | ID: mdl-24647446

ABSTRACT

OBJECTIVES: Pregnancy represents a metabolic challenge to women; in a normal pregnancy, transient metabolic changes occur that support the needs of the growing fetus. It is possible that repeating this challenge within a relatively short amount of time may result in lasting damage to the woman's cardiovascular health. Conversely, it is also possible that a long interpregnancy interval (IPI) may reflect subfertility, which has been found to be associated with cardiovascular disease (CVD). We examine the associations of short and long IPI with measures of cardiovascular health. DESIGN: Prospective cohort. SETTING: Mothers of the Avon Longitudinal Study of Parents and Children (ALSPAC). PARTICIPANTS: Women with two live births in order to control for confounding by parity. OUTCOME MEASURES: Arterial distensibility, common carotid intima, adiposity, blood pressure, lipids, glucose, insulin, proinsulin, triglycerides, C reactive protein. RESULTS: 25% (n=3451) of ALSPAC mothers had provided sufficient data to determine full reproductive history-of these, 1477 had two live births, with 54% mothers having non-missing data on all variables required for our analyses. A total of 1268 mothers with IPI (interbirth interval minus 9 months' gestation) had CVD risk factors measured/imputed at mean age 48 years. After adjusting for confounding, we found no association of either short (≤15 months) or long (>27 months) IPI and increased levels of cardiovascular risk factors. There was some suggestion that women with long and short IPIs had a more favourable lipid profile compared with women whose IPI was 16-27 months; however, the differences were small in magnitude and imprecisely estimated. CONCLUSIONS: This study does not support the hypothesis that either long or short IPI is a risk factor for later cardiovascular health.


Subject(s)
Birth Intervals , Cardiovascular Diseases/etiology , Maternal Age , Female , Humans , Live Birth , Middle Aged , Parity , Pregnancy , Prospective Studies , Risk Factors
17.
BMC Public Health ; 11: 879, 2011 Nov 21.
Article in English | MEDLINE | ID: mdl-22104027

ABSTRACT

BACKGROUND: The WHO recognises pesticide poisoning to be the single most important means of suicide globally. Pesticide self-poisoning is a major public health and clinical problem in rural Asia, where it has led to case fatality ratios 20-30 times higher than self-poisoning in the developed world. One approach to reducing access to pesticides is for households to store pesticides in lockable "safe-storage" containers. However, before this approach can be promoted, evidence is required on its effectiveness and safety. METHODS/DESIGN: A community-based cluster randomised controlled trial has been set up in 44,000 households in the North Central Province, Sri Lanka. A census is being performed, collecting baseline demographic data, socio-economic status, pesticide usage, self-harm and alcohol. Participating villages are then randomised and eligible households in the intervention arm given a lockable safe storage container for agrochemicals. The primary outcome will be incidence of pesticide self-poisoning over three years amongst individuals aged 14 years and over. 217,944 person years of follow-up are required in each arm to detect a 33% reduction in pesticide self-poisoning with 80% power at the 5% significance level. Secondary outcomes will include the incidence of all pesticide poisoning and total self-harm. DISCUSSION: This paper describes a large effectiveness study of a community intervention to reduce the burden of intentional poisoning in rural Sri Lanka. The study builds on a strong partnership between provincial health services, local and international researchers, and local communities. We discuss issues in relation to randomisation and contamination, engaging control villages, the intervention, and strategies to improve adherence.


Subject(s)
Pesticides/poisoning , Poisoning/prevention & control , Product Packaging/methods , Rural Population , Cluster Analysis , Housing , Humans , Sri Lanka , Suicide Prevention
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