The Role of Risk or Contributory Death Factors in Methadone-Related Fatalities: A Review and Pooled Analysis.
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ABSTRACT:
SUBMITTER: Giorgetti A
PROVIDER: S-EPMC8004630 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Cytochrome P450 (CYP) enzyme 2B6 plays a significant role in the stereo-selective metabolism of (S)-methadone to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine, an inactive methadone metabolite. Elevated (S)-methadone can cause cardiotoxicity by prolonging the QT interval of the heart's electrical cycle. Large inter-individual variability of methadone pharmacokinetics causes discordance in the relationship between dose, plasma concentrations and side effects. The purpose of this study was to determine if one or more single nucleotide polymorphisms (SNPs) located within the CYP2B6 gene contributes to a poor metabolizer phenotype for methadone in these fatal cases. The genetic analysis was conducted on 125 Caucasian methadone-only fatalities obtained from the West Virginia and Kentucky Offices of the Chief Medical Examiner. The frequency of eight exonic and intronic SNPs (rs2279344, rs3211371, rs3745274, rs4803419, rs8192709, rs8192719, rs12721655 and rs35979566) was determined. The frequencies of SNPs rs3745274 (*9, c516G > T, Q172H), and rs8192719 (21563 C > T) were enhanced in the methadone-only group. Higher blood methadone concentrations were observed in individuals who were genotyped homozygous for SNP rs3211371 (*5, c1459C > T, R487C). These results indicate that these three CYP2B6 SNPs are associated with methadone fatalities.
| S-EPMC5412025 | biostudies-literature
Project description:AimSnorkelling is a popular aquatic activity which may result in fatal and non-fatal drowning. However, little is known about the scale of injury, factors impacting risk and strategies for prevention. This review assesses the current literature on snorkelling-related drowning with the aim of assessing available data, improving safety recommendations and reducing the global mortality burden.MethodsA systematic review of peer-reviewed literature in English, Spanish and Portuguese language published between 1 January 1980 and 31 October 2020 was conducted using the PRISMA guidelines. CINAHL Complete, Embase, Medline (Ovid), PubMed, SafetyLit, SportDiscus and grey literature were searched to identify studies reporting the incidence of fatal and non-fatal snorkelling-related drowning, or associated risk factors, prevention strategies, treatments or casualty characteristics. Quality was assessed using the NIH Quality Assessment Tool.ResultsForty-three studies were included (26 reporting population data, 17 case series), of which 27 (62.8%) studies reported data from Australia. Incidence was reported as about 8% of total ocean-related drownings. Case series documented 144 fatalities over 17 years. Frequent casualty characteristics include male (82.6%), pre-existing heart disease (59.4%), tourists (73%) who were inexperienced (71.0%), and lack of a buddy system (89.6%). Two at-risk profiles identified were older adult tourists with pre-existing medical conditions and local, experienced spearfishers. Twenty-two expert recommendations were developed to improve the safety of snorkellers related to individuals, tourism companies, government agencies and diving organisations.ConclusionSnorkelling-related drownings are not infrequent, and there are many opportunities to improve the safety of this activity based on available data.
| S-EPMC8244300 | biostudies-literature
Project description:BackgroundAvalanches are a significant cause of winter recreational fatalities in mountain regions. The purpose of this study was to determine the relative contributions of trauma and asphyxia to avalanche deaths.MethodsWe reviewed all avalanche fatalities between 1984 and 2005 that had been investigated by the offices of the British Columbia Coroners Service and the Chief Medical Examiner of Alberta. In addition, we searched the database of the Canadian Avalanche Centre for fatal avalanche details. We calculated injury severity scores for all victims who underwent autopsy.ResultsThere were 204 avalanche fatalities with mortality information over the 21-year study period. Of these, 117 victims underwent autopsy, and 87 underwent forensic external examination. Asphyxia caused 154 (75%) deaths. Trauma caused 48 (24%) deaths, with the rate of death from trauma ranging from 9% (4/44) for snowmobilers to 42% (5/12) for ice climbers. In addition, 13% (12/92) of the asphyxia victims who underwent autopsy had major trauma, defined as an injury severity score of greater than 15. Only 48% (23/48) of victims for whom trauma was the primary cause of death had been completely buried.InterpretationAsphyxia and severe trauma caused most avalanche fatalities in western Canada. The relative rates differed between snowmobilers and those engaged in other mountain activities. Our findings should guide recommendations for safety devices, safety measures and resuscitation.
| S-EPMC2645441 | biostudies-literature
Project description:AimsAs methadone clients age, their drug-related death (DRD) risks increase, more than doubling at 45+ years for methadone-specific DRDs.MethodsUsing Community Health Index (CHI) numbers, mortality to 31 December 2015 was ascertained for 36 347 methadone-prescription clients in Scotland during 2009-2015. Cohort entry, quantity of prescribed methadone and daily dose (actual or recovered by effective, simple rules) were defined by clients' first CHI-identified methadone prescription after 30 June 2009 and used in proportional hazards analysis. As custodian of death records, National Records of Scotland identified non-DRDs from DRDs. Methadone-specific DRD means methadone was implicated but neither heroin nor buprenorphine.ResultsThe cohort's 192 928 person-years included 1857 non-DRDs and 1323 DRDs (42%), 546 of which were methadone specific. Actual/recovered daily dose was available for 26 533 (73%) clients who experienced 420 methadone-specific DRDs. Top quintile for daily dose at first CHI-identified methadone prescription was >90 mg. Age 45+ years at cohort-entry (hazard ratio vs 25-34 years: 3.1, 95% confidence interval: 2.4-4.2), top quintile for baseline daily dose of prescribed methadone (vs 50-70 mg: 1.9, 1.1-3.1) and being female (1.3, 1.0-1.6) significantly increased clients' risk of methadone-specific DRD.ConclusionExtra care is needed when methadone daily dose exceeds 90 mg. Females' higher risk for methadone-specific DRD is new and needs validation. Further analyses of prescribed daily dose linked to mortality for large cohorts of methadone clients are needed internationally, together with greater pharmacodynamic and pharmacokinetic understanding of methadone by age and sex. Balancing age-related risks is challenging for prescribers who manage chronic opiate dependency against additional uncertainty about the nature, strength and pharmacological characteristics of drugs from illegal markets.
| S-EPMC7612180 | biostudies-literature
Project description:BackgroundHeart failure risk factors are diverse and likely to vary among world regions. Systematic review and pooled analysis were used to describe contributions of major underlying risk factors for heart failure in six world regions.MethodsElectronic databases were systematically searched, and 37 clinic-based studies representing 40 countries published in 1980-2008 and reporting underlying risk factors for heart failure were included. Risk factors were classified as ischemic heart disease (IHD), hypertension, rheumatic/other valvular heart disease, cardiopulmonary disease, cardiomyopathy, and "other". Crude and age- and sex-adjusted risk factor prevalences were estimated for each region using a regression analysis, under specifications of overlapping as well as additive contributions.ResultsMany heart failure cases were assigned multiple underlying risk factors, leading to a considerable overlap. Crude IHD prevalence among heart failure patients was >50% in Europe and North America, approximately 30-40% in East Asia and Latin America and the Caribbean, and <10% in Sub-Saharan Africa. Age and sex adjustment attenuated regional differences in IHD-as-risk factor but IHD remained rare in Sub-Saharan Africa. Hypertension prevalence was high in heart failure patients of all regions but the highest in Eastern and Central Europe and Sub-Saharan Africa (age- and sex-adjusted, 35.0% and 32.6%, respectively). Cardiomyopathy was most common in Latin America, the Caribbean and Sub-Saharan Africa (age- and sex-adjusted, 19.8% and 25.7%).ConclusionsHeart failure risk factors vary substantially among world regions. More detailed regional heart failure epidemiology studies are needed in order to quantify the global burden of heart failure and identify regional prevention and treatment strategies.
| S-EPMC3594565 | biostudies-literature
Project description:AimTo quantify gender, age-group and quantity of methadone prescribed as risk factors for drugs-related deaths (DRDs), and for methadone-specific DRDs, in Scotland's methadone-prescription clients.DesignLinkage to death-records for Scotland's methadone-clients with one or more Community Health Index (CHI)-identified methadone prescriptions during July 2009 to June 2013.SettingScotland's Prescribing Information System and National Records of Scotland.MeasurementsCovariates defined at first CHI-identified methadone prescription, and person-years at-risk (pys) thereafter until the earlier of death-date or 31 December 2013. Methadone-specific DRDs were defined as: methadone implicated but neither heroin nor buprenorphine. Hazard ratios (HRs) were assessed using proportional hazards regression.FindingsScotland's CHI-identified methadone-prescription cohort comprised 33,128 clients, 121,254 pys, 1,171 non-DRDs and 760 DRDs (6.3 per 1,000 pys), of which 362 were methadone-specific. Irrespective of gender, methadone-specific DRD-rate, per 1,000 pys, was higher in the 35+ age-group (4.2; 95% CI: 3.6-4.7) than for younger clients (1.9; 95% CI: 1.5-2.2). For methadone-specific DRDs, age-related HRs (e.g., 2.9 at 45+ years; 95% CI: 2.1-3.9) were steeper than for all DRDs (1.9; 95% CI: 1.5-2.4); there was no hazard-reduction for females; no gender by age-group interaction; and, unlike for all DRDs, the highest quintile for quantity of prescribed methadone at cohort-entry (>1960mg) was associated with increased HR (1.8; 95% CI: 1.3-2.5).ConclusionHigher methadone-specific DRD rates in older clients, irrespective of gender, call for better understanding of methadone's pharmaco-dynamics in older, opioid-dependent clients, many with progressive physical or mental ill-health.
| S-EPMC5047032 | biostudies-literature
Project description:Since the first cases of the novel corona virus disease (COVID-19) were diagnosed in China, outcomes associated with this infection in terms of total numbers of cases and deaths have varied widely between countries. While some countries had minimal rates of infections and deaths, other countries were hit hard by the pandemic. Countries with highest numbers of cases continued to change over time, but at the time of submission of this article they are: USA, Brazil, Russia, UK, India, Spain, Italy, Peru and Chile. This is in contrary to many countries in the Middle East, Far East, and Africa, which had lower cases or deaths/cases rates. This raised many questions pertaining to this variation. This overview explores the potential factors that contribute to spread, transmission and outcomes of the COVID-19 infection. It also uses an evidence-based approach in reviewing the available most recent literature that tackled the various factors that modify the populations' response to COVID-19, namely, factors pertaining to population characteristics, environmental and geographic factors.
| S-EPMC7551068 | biostudies-literature
Project description:BACKGROUND:The first evidence that the hazard ratio (HR) for methadone-specific death rises more steeply with age-group than for all drug-related deaths (DRDs) came from Scotland's cohort of 33,000 methadone-prescription clients. We aim to examine, for England, whether illicit opioid users' risk of methadone-specific death increases with age; and to pool age-related HRs for methadone-specific deaths with those for Scotland's methadone-prescription clients. METHODS:The setting is all services in England that provide publicly-funded, structured treatment for illicit opioid users, the methodology linkage of the English National Drug Treatment Monitoring System and mortality database, and key measurements are DRDs, methadone-specific DRDs, or heroin-specific DRDs, by age-group and gender, with proportional hazards adjustment for substances used, injecting status and periods in/out of treatment. RESULTS:Linkage was achieved for 129,979 adults receiving prescribing treatment modalities for opioid dependence during April 2005 to March 2009 and followed-up for 378,009 person-years (pys). There were 1,266 DRDs: 271 methadone-specific (7 per 10,000 pys: irrespective of gender) and 473 heroin-specific (15 per 10,000 pys for males, 7 for females). Methadone-specific DRD-rate per 10,000 person-years was 3.5 (95% CI: 2.7-4.4) at 18-34 years, 8.9 (CI: 7.3-10.5) at 35-44 years and 18 (CI: 13.8-21.2) at 45+ years; heroin-specific DRD-rate was unchanged with age. Relative to 25-34 years, pooled HRs for UK clients' methadone-specific deaths were: 0.87 at <25 years (95% CI: 0.56-1.35); 2.14 at 35-44 years (95% CI: 1.76-2.60); 3.75 at 45+ years (95% CI: 2.99-4.70). CONCLUSION:International testing and explanation are needed of UK's sharp age-related increase in the risk of methadone-specific death. Clients should be alerted that their risk of methadone-specific death increases as they age.
| S-EPMC6004035 | biostudies-literature
Project description:PurposeThe number of flood disaster deaths has been on the rise in recent years. The current review investigated and categorized the risk factors of deaths from floods in parallel with preventive and control measures designed to minimize deaths from floods.MethodsIn a systematic review, International electronic databases including PubMed, Scopus, Web of Science, and Google Scholar were investigated for articles published in English language. In addition, Iranian databases including IranMedex, Irandoc, Magiran, and Scientific Information Database (SID) were investigated for studies published in Persian. ProQuest database was also searched for related theses. The studies were selected regardless their methods but based on the inclusion and exclusion criteria. The data were extracted, coded and prepared for further analysis. Finally, descriptive and thematic analyses were conducted.ResultsA total of 114 factors were identified and categorized into the following five category that can influence on flood death.: hazard related factors, and individual, environmental, socio-economic, and managerial categories.ConclusionsThe study identified many factors that affect flood deaths. The variety and the diverse nature of the factors necessitate appropriate interventions for removing or reducing the effects of the identified factors. More quantitative analytical studies are needed to confirm causal relationship between extracted factors and floods death.
| S-EPMC7721754 | biostudies-literature
Project description:How we react to humanitarian crises, epidemics, and other tragic events involving the loss of human lives depends largely on the extent to which we are moved by the size of their associated death tolls. Many studies have demonstrated that people generally exhibit a diminishing sensitivity to the number of human fatalities and, equivalently, a preference for risky (vs. sure) alternatives in decisions under risk involving human losses. However, the reason for this tendency remains unknown. Here we show that the distributions of event-related death tolls that people observe govern their evaluations of, and risk preferences concerning, human fatalities. In particular, we show that our diminishing sensitivity to human fatalities follows from the fact that these death tolls are approximately power-law distributed. We further show that, by manipulating the distribution of mortality-related events that people observe, we can alter their risk preferences in decisions involving fatalities. Finally, we show that the tendency to be risk-seeking in mortality-related decisions is lower in countries in which high-mortality events are more frequently observed. Our results support a model of magnitude evaluation based on memory sampling and relative judgment. This model departs from the utility-based approaches typically encountered in psychology and economics in that it does not rely on stable, underlying value representations to explain valuation and choice, or on choice behavior to derive value functions. Instead, preferences concerning human fatalities emerge spontaneously from the distributions of sampled events and the relative nature of the evaluation process.
| S-EPMC2799776 | biostudies-literature