The incidence of sudden unexpected death in epilepsy (SUDEP) in the Republic of Ireland.

BACKGROUND: The incidence of sudden unexpected death in epilepsy (SUDEP) in Ireland has previously been studied in only a small geographical area. Our aim was to calculate an incidence rate for the whole of the Republic of Ireland in 2019. METHODS: All deaths referred to the coroner in 2019 were examined. Those with a history of possible epilepsy were noted and subjected to a more detailed assessment. Cases fulfilling the definition of definite SUDEP were identified. The incidence of SUDEP was calculated using the population of the Republic of Ireland in 2019 and the known prevalence of epilepsy in Ireland. RESULTS: Thirty-three cases of definite SUDEP were identified in the Republic of Ireland in 2019. The estimated incidence of SUDEP in the epilepsy population as a whole was 0.7/1000(0.46 - 0.94) person years. This may be a conservative estimate. More men than women were identified, and most individuals were found dead at home. SUDEP was mentioned on the death certificate in only 52 % of cases. CONCLUSION: This is the first nationwide study of SUDEP incidence in Ireland and provides an incidence rate in keeping with other populations. This work demonstrates that the interrogation of coronial records is a useful way to monitor epilepsy mortality albeit with certain limitations.

Factors associated with suicide in people who use drugs: a scoping review.

BACKGROUND: Suicide is a significant contributor to global mortality. People who use drugs (PWUD) are at increased risk of death by suicide relative to the general population, but there is a lack of information on associated candidate factors for suicide in this group. The aim of this study was to provide a comprehensive overview of existing evidence on potential factors for death by suicide in PWUD. METHODS: A scoping review was conducted according to the Arksey and O'Malley framework. Articles were identified using Medline, CINAHL, PsycINFO, SOCIndex, the Cochrane Database of Systematic Reviews and the Campbell Collaboration Database of Systematic Reviews; supplemented by grey literature, technical reports, and consultation with experts. No limitations were placed on study design. Publications in English from January 2000 to December 2021 were included. Two reviewers independently screened full-text publications for inclusion. Extracted data were collated using tables and accompanying narrative descriptive summaries. The review was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. RESULTS: The initial search identified 12,389 individual publications, of which 53 met the inclusion criteria. The majority (87%) of included publications were primary research, with an uncontrolled, retrospective study design. The most common data sources were drug treatment databases or national death indexes. Eleven potential factors associated with death by suicide among PWUD were identified: sex; mental health conditions; periods of heightened vulnerability; age profile; use of stimulants, cannabis, or new psychoactive substances; specific medical conditions; lack of dual diagnosis service provision; homelessness; incarceration; intravenous drug use; and race or ethnicity. Opioids, followed by cannabis and stimulant drugs were the most prevalent drugs of use in PWUD who died by suicide. A large proportion of evidence was related to opioid use; therefore, more primary research on suicide and explicit risk factors is required. CONCLUSIONS: The majority of studies exploring factors associated with death by suicide among PWUD involved descriptive epidemiological data, with limited in-depth analyses of explicit risk factors. To prevent suicide in PWUD, it is important to consider potential risk factors and type of drug use, and to tailor policies and practices accordingly.

Comparing characteristics of suicide to non-suicide drug poisoning deaths, by sex, in Ireland.

BACKGROUND: Suicide by drug poisoning is potentially preventable; however, evidence on associated risk factors by sex is limited. AIM: To assist in understanding how individual and social contextual factors, and specific drugs, influence risk of suicide compared to non-suicide drug poisoning deaths, and how this differs by sex. METHODS: Data were extracted from the National Drug-Related Deaths Index. Analysis included univariable and multivariable logistic regression to estimate unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for factors associated with suicide drug poisoning deaths (SDPD) (primary outcome) compared with non-suicide drug poisoning deaths (NSDPD) and stratified by sex. RESULTS: SDPD accounted for 240 (22%) of 1114 poisoning deaths, the majority among men (n = 147, 61%). Increasing age, mental ill health (AOR 7.85, 95% CI: 5.46-11.28), chronic pain (AOR 5.57, 95% CI: 3.28-9.46), and history of previous overdose (AOR 5.06, 95% CI: 3.39-7.56) were associated with increased odds of SDPD, with similar results for both sexes. The main drugs associated with SDPD were non-opioid analgesics (OR 4.06 [95% CI 2.66-6.18]), antipsychotics (OR 2.42 [95% CI 1.63-3.60]) and antidepressants (OR 2.18 [95% CI 1.59-2.97]). Pregabalin was associated with SDPD among women only. LIMITATIONS: Secondary analysis of coronial data on drug poisoning deaths therefore findings may not be relevant to suicide deaths in general. CONCLUSIONS: Ongoing monitoring for signs of suicidal intent in individuals with mental illness, chronic pain, overdose, and/or prescribed mental health medications may identify individuals in need of additional intervention.

Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017.

OBJECTIVE: To examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017. DESIGN: Repeated cross-sectional study. SETTING: Drug poisoning deaths in Ireland. PARTICIPANTS: National Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017. OUTCOME MEASURES: The primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004-2017), change points over time and average annual percentage changes (AAPCs) with 95% CI. RESULTS: Increased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3). CONCLUSION: Drugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.

Drug Poisoning Deaths Among Women: A Scoping Review.

OBJECTIVE: Drug poisoning deaths among women remain a challenge for public health policy and have increased at a higher rate relative to men. Although biological, social, and psychological differences between men and women can have an influence on drug poisoning deaths, sex is rarely considered. The objective of this study is to explore the extent, range, and nature of evidence in relation to drug poisoning deaths among women. METHOD: A scoping review was conducted according to the Arksey and O'Malley framework. A comprehensive search was performed using MEDLINE, Embase, CINAHL, and Web of Science, supplemented by gray literature, including national and international reports and government documents and consultation with experts. Publications in English from June 1, 1998, to November 2, 2019, were included. Two reviewers independently screened publications for inclusion. RESULTS: The search identified 5,316 individual publications, and 61 met the inclusion criteria (46% from Europe; n = 28). The main candidate factors identified as contributing factors to drug poisoning deaths among women included age; opioid drugs, especially prescription opioids; other prescription drugs, particularly antidepressants; mental health issues; barriers to treatment; victim of violence; alcohol use; polydrug use; and history of imprisonment. CONCLUSIONS: The majority of studies on drug poisoning deaths among women involved descriptive epidemiological data, primarily prevalence estimates, with limited in-depth analyses of factors explaining these trends. To inform policies and practices to prevent drug poisoning deaths among women, more evidence is required on risk factors specifically related to women.

A repeated cross-sectional study of factors associated with pregabalin-positive poisoning deaths in Ireland.

BACKGROUND: The increasing use of pregabalin and the presence of pregabalin in poisoning deaths, particularly with opioids, highlight it as a potential drug of abuse. In this study we examined factors associated with pregabalin-positive poisoning deaths (PPPD) between 2013 and 2016 in Ireland. METHODS: Data were extracted from the National Drug-Related Deaths Index (NDRDI). Analysis included univariate and multivariate logistic regression to estimate unadjusted and adjusted odds ratios (OR) and 95 % confidence intervals (CI) for factors associated with PPPD (primary outcome) by logistic regression models for the total sample and stratified by gender. RESULTS: Pregabalin was present on 240 (16 %) toxicology reports of 1489 poisoning deaths; significantly rising from 15 (4.5 %) in 2013 to 94 (26 %) in 2016. Women (AOR 2.69, 95 % CI: 1.95-3.70), opioid misuse (AOR 1.74, 95 % CI: 1.17-2.59), in receipt of treatment for problem drug use (AOR 1.95, 95 % CI: 1.33-2.86) and year of death (2016 vs 2013) (AOR 7.95, 95 % CI: 4.58-13.79) were associated with increased odds of PPPD. Alcohol dependence was associated with reduced odds of PPPD (AOR 0.59, 95 % CI: 0.41-0.85). For men, opioid misuse, in receipt of treatment for problem drug use, and year of death were associated with increased odds of PPPD, while alcohol dependence was associated with reduced odds of PPPD. For women, in receipt of treatment for problem drug use and year of death were associated with increased odds of PPPD. CONCLUSIONS: Enhanced training to prescribers and treatment providers on the potential risks associated with pregabalin, particularly among people who use drugs, is required.

Risk factors for completed suicide among people who use drugs: A scoping review protocol.

Background: Research over the past several decades has shown an increased risk for completed suicide among people who use drugs (PWUD). However, no study to date has attempted to summarise the available literature on the variety of risk factors associated with this increased risk. This paper presents a protocol for a scoping review that aims to systematically map and synthesise the extent and nature of published, unpublished and grey literature related to risk factors for suicide among PWUD. Methods: The following six-stage methodological framework for scoping reviews proposed by Arksey and O'Malley with enhancements by Levac and colleagues will be used: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting/mapping the data, (5) collating, summarising and reporting results and (6) expert consultation. The review will be conducted and reported in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR). Key inclusion and exclusion criteria will be developed to guide literature screening and data charting. Three reviewers will conduct the initial screening of published, unpublished and grey literature. Identified risk factors will be collated, summarised and categorised iteratively by two independent reviewers. Stakeholder consultation will occur with experts from a national steering committee, a national advisory group, a national suicide prevention centre and a European drug monitoring centre. Conclusion: Collating and thematically categorising the various risk factors for suicide among this high-risk group will hold important implications for future research, policy and practice. The research will be disseminated through publication in a peer-reviewed academic journal and a conference presentation, and by sharing the findings with key stakeholders working within research, policy-making and professional practice contexts.

Trends in Injector Deaths in Ireland, as Recorded by the National Drug-Related Deaths Index, 1998-2014.

OBJECTIVE: The purpose of this study was to provide trend analysis on all deaths among drug users who injected at or around the time of their death in Ireland between 1998 and 2014. METHOD: A review of the data recorded by the National Drug-Related Deaths Index (NDRDI) was conducted to identify individuals who were known to be injecting at or around the time of their death, from 1998 to 2014. RESULTS: Between 1998 and 2014, 16,500 deaths were recorded by the NDRDI. Of these, 792 (5%) people were known to be injecting at or around the time of death; 90% were poisoning deaths (n = 715) and 10% nonpoisoning deaths (n = 77). The majority of those who died while injecting were male (n = 682; 86%). Most people were living in Dublin city or county (n = 550; 69%). One fifth of those who died were homeless (n = 149; 19%). Opioids, specifically heroin, were implicated in the vast majority of injector poisoning deaths (n = 673; 94%), most commonly in association with polydrug use (n = 417; 62%). Single opioid poisoning resulted in 256 deaths (38%), and two fifths of those who died by single opioid poisoning were not alone at the time of death (n = 105; 41%). CONCLUSIONS: This study is the first to describe the trends in all deaths among drug users who injected at or around the time of their death in Ireland between 1998 and 2014. The analysis provides empirical evidence that can be used by policy makers to support the ongoing improvement of drug treatment services, harm reduction initiatives, and overdose prevention strategies for people who inject drugs.

The role of alcohol dependency in deaths among people with epilepsy recorded by the National Drug-Related Deaths Index (NDRDI) in Ireland, 2004-2013.

PURPOSE: The aim of this study was to investigate deaths among individuals with epilepsy recorded on the National Drug-Related Deaths Index (NDRDI). METHOD: A descriptive analysis of individuals with a known history of epilepsy in the NDRDI from 2004 to 2013 was undertaken. RESULTS: Between 2004 and 2013, 225 (2%) of the recorded cases had a documented history of epilepsy, 82 (36%) of whom had epilepsy recorded as the cause of death. Of these 82 deaths, the majority were male (60-73%) and half (median age) were aged 47 years or younger. A post mortem toxicology report was available for 65 (79%) of these deaths, of which over two thirds (44-68%) did not have any antiepileptic drugs present on toxicology. Over two thirds of these deaths, (31-70%) were among people known to be alcohol dependent. CONCLUSION: The high percentage of individuals with a diagnosis of alcohol dependency that died as a result of epilepsy and who have no antiepileptic drugs in their system at the time of their death, highlights the need for preventative measures for this at-risk group.

Testing reported associations of genetic risk factors for oral clefts in a large Irish study population.

BACKGROUND: Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) could be confirmed. METHODS: Thirty-one single nucleotide polymorphisms (SNPs) in exons, splice sites, and conserved non-coding regions were studied in 509 patients with cleft lip with or without cleft palate (CLP), 383 with cleft palate only (CP), 838 mothers and 719 fathers of patients with oral clefts, and 902 controls from Ireland. Case-control and family-based statistical tests were performed using isolated oral clefts for the main analyses. RESULTS: In case-control comparisons, the minor allele of PTCH1 A562A (rs2066836) was associated with reduced odds of CLP (odds ratios [OR], 0.29; 95% confidence interval [CI], 0.13-0.64 for homozygotes), whereas the minor allele of PTCH1 L1315P (rs357564) was associated with increased odds of CLP (OR, 1.36; 95% CI, 1.07-1.74 for heterozygotes; and OR, 1.56; 95% CI, 1.09-2.24 for homozygotes). The minor allele of one SUMO1 SNP, rs3769817 located in intron 2, was associated with increased odds of CP (OR, 1.45; 95% CI, 1.06-1.99 for heterozygotes). Transmission disequilibrium was observed for the minor allele of TGFA V159V (rs2166975) which was over-transmitted to CP cases (p = 0.041). CONCLUSIONS: For 10 of the 12 genes, this is the largest candidate gene study of nonsyndromic oral clefts to date. The findings provide further evidence that PTCH1, SUMO1, and TGFA contribute to nonsyndromic oral clefts.

Folate-related gene polymorphisms as risk factors for cleft lip and cleft palate.

BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folate-related genes associated with clefts have, however, often been inconclusive. This study examined four SNPs related to folate metabolism (MTHFR 677 C-->T, MTHFR 1298 A-->C, MTHFD1 1958 G-->A, and TC II 776 C-->G) in a large Irish population to clarify their relationship with clefts. METHODS: Cases and their parents were recruited from major surgical centers performing cleft repairs in Ireland and a support organization. Data on risk factors, medical history, and DNA were collected. Controls were pregnant women from the greater Dublin area (n = 1,599). RESULTS: CLP cases numbered 536 and CPO cases 426 after exclusions. CPO mothers were significantly more likely than controls to be MTHFR 677 TT, OR 1.50 (95% CI: 1.05-2.16; p = .03). Log-linear analysis showed a borderline association (p = .07). Isolated CPO case mothers were significantly more likely than controls to be homozygous for the MTHFD1 1958 G-->A variant, OR 1.50 (95%CI: 1.08-2.09; p = .02). When multiple cases were added, both CPO cases and case mothers were significantly more likely to be AA (p = .02 and p = .007, respectively). The CLP case-control and mother-control analyses also showed significant effects, ORs 1.38 (95% CI: 1.05-1.82; p = .03) and 1.39 (95% CI: 1.04-1.85; p = .03), respectively. CONCLUSIONS: Associations were found for both CPO and CLP and MTHFD1 1958 G-->A in cases and case mothers. MTHFR 677 C-->T could be a maternal risk factor for clefts but the association was not strong. Because multiple comparisons were made, these findings require additional investigation. Given the known association between MTHFD1 1958 G-->A and NTDs, these findings should be explored in more detail.