Fatal Drug Research Articles

Emergency department visits, inpatient hospitalizations, and non-fatal and fatal drug overdoses during COVID-19 among Veterans with opioid use disorder.

The COVID-19 pandemic had dramatic adverse impacts on people with opioid use disorder (OUD), as evidenced by significant disruptions to care and unprecedented increases in drug overdoses. In this study, we evaluated the impacts of COVID-19 on utilization of emergency and inpatient care, and fatal and non-fatal overdoses among veterans with OUD. We used Veterans Health Administration (VHA) electronic medical record and mortality data to compare emergency department (ED) visits, inpatient hospitalizations, and fatal and non-fatal overdoses between a pandemic-exposed cohort of veterans with OUD observed both pre- and post-pandemic onset (n = 53,803; observed January 2019-March 2021) to a matched pre-pandemic control group (n = 53,803; observed October 2017-December 2019). Compared to pre-pandemic trends, there were significant decreases in the odds of ED and inpatient admissions and total number of ED and inpatient admissions during COVID-19. There was a significant decrease in the odds of having a recorded non-fatal overdose. The odds of overdose death increased during the pandemic compared to pre-pandemic trends. We observed significant decreases in the utilization of ED and inpatient care services, and fewer non-fatal overdoses, post-pandemic onset. Healthcare disruptions limiting access to emergency and inpatient care could account for the lower number of recorded non-fatal overdoses, potentially reflecting an underestimate of risk. In contrast, fatal overdoses increased during the pandemic compared to pre-pandemic trends. Lower utilization of emergency and inpatient care, and higher rates of fatal overdoses during the pandemic, suggest an exacerbation of unmet treatment need post-pandemic onset.

Prevalence, Reasons, and Prevention for Drug Related Death After Release from Prisons: A Systematic Review and Meta-analysis

Context: Drug-related mortality is a major concern in public and global health discussions. Objectives: Therefore, the aim of this study was to investigate the prevalence, causes, and prevention of death after individuals are released from prison. Methods: This study was conducted systematically using MeSH keywords with no language or time restrictions. PubMed, Scopus, and Web of Science databases were extensively searched for observational studies from 1980/1/1 to 2023/12/30, following the PRISMA checklist. Fourteen research studies were ultimately included in the systematic review process. The CRD code is CRD42024571756. Results: The two-week period following release, with an 18% prevalence, was identified as the time when most overdose deaths occurred. The leading causes of death included prior heroin use, previous experiences with drug withdrawal, drug injection, and sedative use within six months before death. Compared to other unnatural causes of death, there was an increased risk of fatal drug overdose for individuals who died within the first two months of release. Men had higher death rates from all causes compared to women. Most studies reported that substance abuse treatment during imprisonment and providing take-home naloxone for emergencies protected against mortality from all causes. Conclusions: In conclusion, evidence from these systematic investigations highlights the urgent need for targeted interventions to address substance use disorders and overdose prevention among individuals recently released from prison. Efforts to bridge the gap between incarceration and community reintegration should prioritize comprehensive substance abuse treatment programs to reduce the heightened risk of mortality in this vulnerable population.

Naloxone Access Laws and Opioid-Related Overdose Deaths in Youths

This cross-sectional study assesses fatal drug overdoses in youths associated with implementation of state-level naloxone access expansions.

Antipyretic effect of oral dipyrone (Metamizole) compared to oral ibuprofen in febrile children: a systematic review and meta-analysis

BackgroundDipyrone (Metamizole) is a potent pain reliever and fever reducer with muscle relaxant properties, most commonly used as an analgesic and antipyretic agent. Despite the fact that it has been banned in many high-income countries following confirmed studies of fatal agranulocytosis and adverse drug reactions, it is still widely used in various countries of the world. However, the antipyretic therapeutic indications of dipyrone in febrile children are currently unknown, and there is little information on the advantages and disadvantages of using dipyrone in febrile children. In febrile children, we expected that dipyrone’s antipyretic effectiveness wouldn’t be any more effective than ibuprofen. Therefore, the purpose of this research is to evaluate the effectiveness of oral dipyrone and oral ibuprofen as antipyretics in febrile children.MethodsSeveral databases, including PubMed, Scopus, Web of Science, and Cochrane Library, were searched thoroughly using a pre-established search strategy for potential research. The studies included in this analysis comprised randomized controlled trials that compared the antipyretic effects of oral ibuprofen and oral dipyrone in febrile children. Data analysis was carried out using RevMan 5.4 software.ResultsThree studies were selected among the 27 publications we discovered to be applicable, and they underwent qualitative and quantitative analysis. The pooled analysis revealed no discernible difference between oral dipyrone and oral ibuprofen in terms of their antipyretic effects (Mean difference (MD) = 0.06; 95% confidence interval (CI): -0.08, 0.20).ConclusionBoth oral dipyrone and ibuprofen are effective in reducing high-temperature levels in febrile children without any significant difference.

Drug-induced hypersensitivity syndrome due to phenytoin: Case report and review of the literature.

Drug hypersensitivity syndrome (DIHS) is a rare but potentially fatal adverse drug reaction characterized by fever, rash, and visceral organ damage, particularly affecting the liver. Early recognition and appropriate management are crucial to prevent serious complications. However, there is limited information on the clinical presentation and management of DIHS, especially in the context of antiepileptic drugs. This case report aims to highlight the importance of recognizing subtle clinical signs and symptoms of DIHS, which can be easily overlooked, particularly in the context of antiepileptic drug use. We report a case of a 15-year-old male patient who developed DIHS after being prescribed phenytoin sodium for epilepsy. The patient presented with symptoms of fever, sore throat, rash, jaundice, and liver dysfunction. Initially, the patient did not receive glucocorticoids and experienced additional reactions to cefoxitin and phosphatidylcholine, likely due to cross-reactivity. The diagnosis of DIHS was made based on the patient's clinical presentation, including fever, extensive rash, organ involvement, and hematological abnormalities. The temporal association with the use of phenytoin sodium, along with the exclusion of other causes of fever and rash, supported the diagnosis. Upon initiation of glucocorticoid therapy with dexamethasone, the patient's symptoms significantly improved. The rash and pruritus decreased, and laboratory values showed improvement, with a decrease in liver enzymes and normalization of white blood cell counts. The patient's fever resolved within 48 hours of starting corticosteroids, and there was no evidence of ongoing inflammation as indicated by a decrease in C-reactive protein levels. Furthermore, the patient's 30-month follow-up revealed no recurrence of rash, liver dysfunction, or organic damage, indicating the long-term effectiveness of the treatment administered. This case highlights the importance of recognizing the subtle clinical signs and symptoms of DIHS, especially in the context of antiepileptic drug use. It underscores the potential benefits of early initiation of glucocorticoid therapy in managing DIHS. The case also serves as a reminder of the potential for drug cross-reactivity in DIHS and the need for cautious drug selection during the acute phase of the syndrome.

"Before medically advised" departure from hospital and subsequent drug overdose: a population-based cohort study.

A substantial number of hospital admissions end in patient-initiated departure before medical treatment is complete. Whether "before medically advised" (BMA) discharge increases the risk of subsequent drug overdose remains uncertain. We performed a retrospective cohort study using administrative health data from a 20% random sample of residents of British Columbia, Canada. We focused on nonelective, nonobstetric hospital stays occurring between 2015 and 2019. We used survival analysis to compare the rate of fatal or nonfatal illicit drug overdose in the first 30 days after BMA discharge versus the rate after physician-advised discharge. Overall, 6440 of 189 808 (3.4%) hospital stays ended in BMA discharge. Among 820 overdoses occurring in the first 30 days after any hospital discharge, 755 (92%) involved patients with a history of substance use disorder. Unadjusted overdose rates were 10-fold higher after BMA discharge than after physician-advised discharge, and BMA discharge was associated with subsequent overdose even after adjustment for potential confounders (crude incidence, 2.8% v. 0.3%; adjusted hazard ratio [HR] 1.58; 95% confidence interval [CI] 1.31-1.89). Before medically advised discharge was associated with increases in subsequent emergency department visits (adjusted HR 1.92; 95% CI 1.83-2.02) and unplanned hospital readmissions (adjusted HR 2.07; 95% CI 1.96-2.19), but there was no significant association with the uncommon outcomes of fatal overdose and all-cause mortality. Before medically advised departure is associated with an increased risk of drug overdose in the first 30 days after discharge. Improved treatment of substance use disorder, expanded access to overdose prevention services, and new means of postdeparture outreach should be explored to reduce this risk.

Síndrome Dress por uso de Trimetropin Sulfametoxazol

The term DRESS was introduced in 1996 to describe a drug reaction with eosinophilia, skin eruption and systemic symptoms. Potentially fatal drug reactions include three distinct entities: DRESS syndrome, acute generalized exanthem and Stevens-Johnson syndrome/toxic epidermal necrolysis. We report a case of DRESS syndrome in a female patient who attended Hospital de San José in Bogotá, for presenting a cutaneous reaction induced by trimethroprim/sulfamethoxazole. The physiopathology, diagnosis, clinical features and treatment, are outlined herein.

Modeling Changes of Fatal Xylazine-Involved Drug Overdoses in Connecticut Across Time

Background Fatal drug overdoses have involved both xylazine and fentanyl. Xylazine is a non-opioid substance used in veterinary medicine. This study aimed to model changes in fatal xylazine-involved drug overdose deaths from 2019 to 2023 in Connecticut using overdose death data from the Office of the Chief Medical Examiner. Methods Xylazine-involved drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2019 to 2023. We used joinpoint regression modeling to evaluate quarterly overdose rates across age, number of drugs, and drug types with a significance level of p < 0.05. Results From 2019 to 2023, there were 1116 xylazine-involved fatal overdoses with a cumulative rate of 31.3 deaths per 100,000. Xylazine-involved overdose death rates were significantly higher in Hispanic populations compared to both non-Hispanic White and Black populations (p < 0.05). The joinpoint analyses showed that xylazine-fentanyl mortality rates significantly increased by 0.18 per 100,000 per quarter from 2019 to 2022. Xylazine-fentanyl overdoses involving at least 4 or 5 substances significantly increased. Windham, Hartford, New London, and New Haven counties had the highest xylazine-involved death rates. Conclusion Xylazine-fentanyl deaths increased from 2019 to 2023, and often involved multiple substances (e.g., cocaine, ethanol, benzodiazepines, and oxycodone). Results show Hispanic populations, those aged 35–49, and 50+ experienced high rates of xylazine-fentanyl overdose deaths. Vulnerable populations in Connecticut for special consideration for future intervention and local resource allocation are recommended.

Improving Estimates of the Prevalence of Opioid Use Disorder in the United States: Revising Keyes et al.

The United States faces an ongoing drug overdose crisis, but accurate information on the prevalence of opioid use disorder (OUD) remains limited. A recent analysis by Keyes et al used a multiplier approach with drug poisoning mortality data to estimate OUD prevalence. Although insightful, this approach made stringent and partly inconsistent assumptions in interpreting mortality data, particularly synthetic opioid (SO)-involved and non-opioid-involved mortality. We revise that approach and resulting estimates to resolve inconsistencies and examine several alternative assumptions. We examine 4 adjustments to Keyes and colleagues' estimation approach: (A) revising how the equations account for SO effects on mortality, (B) incorporating fentanyl prevalence data to inform estimates of SO lethality, (C) using opioid-involved drug poisoning data to estimate a plausible range for OUD prevalence, and (D) adjusting mortality data to account for underreporting of opioid involvement. Revising the estimation equation and SO lethality effect (adj. A and B) while using Keyes and colleagues' original assumption that people with OUD account for all fatal drug poisonings yields slightly higher estimates, with OUD population reaching 9.3 million in 2016 before declining to 7.6 million by 2019. Using only opioid-involved drug poisoning data (adj. C and D) provides a lower range, peaking at 6.4 million in 2014-2015 and declining to 3.8 million in 2019. The revised estimation equation presented is feasible and addresses limitations of the earlier method and hence should be used in future estimations. Alternative assumptions around drug poisoning data can also provide a plausible range of estimates for OUD population.

Fatalities associated with failure to adjust drug dose in patients with renal insufficiency: A retrospective study at the Institute of Forensic Medicine in Munich (2019-2023)

Comorbidities in the elderly not only make them more susceptible to kidney disease, but also increase the risk of drug interactions due to polypharmacy. Such patients require regular kidney function tests when treated with renally excreted drugs. We conducted a retrospective study of post-mortem cases over a five- year period. Of 3040 toxicologically investigated cases, 3.8% had a history of renal failure. Thirteen deaths were directly attributable to inadequate drug dosing, 46% of which were related to lactic acidosis due to metformin accumulation. Appropriate dose adjustment could prevent fatal drug toxicity in patients with renal insufficiency.

Higher unemployment benefits are associated with reduced drug overdose mortality in the United States before and during the COVID-19 pandemic

ObjectivesOverdose mortality rates in the United States remain critical to population health. Economic , such as unemployment, are noted risk factors for drug overdoses. The COVID-19 pandemic exacerbated economic hardship; as a result, the US government enacted income protection programs in conjunction with existing unemployment insurance (UI) to dampen COVID-19-related economic consequences. We investigate whether UI, operationalized as the weekly benefit allowance (WBA) replacement rate, is negatively associated with drug-related overdoses. MethodsData from the pooled 2014–2020 Detailed Restricted Mortality files for all counties from the Centers for Disease Control and Prevention, restricted to people ≥18 years of age, aggregated at the county-quarter level (n = 89,914). We included any fatal drug, opioid, and stimulant overdose. We modeled the association between WBA replacement rate (e.g., a greater proportion of weekly earnings replaced by UI) on each county-level age-adjusted mortality outcome using separate linear regression models during 2014–2020, pre-COVID (2014–2018), and post-COVID (2019-2020). We conducted sensitivity analyses using multi-level linear regression models. ResultsResults indicated that a more robust WBA replacement rate any drug (Risk Difference [RD]: −0.06, 95 % Confidence Interval [CI]: −0.08, −0.05), opioid (RD: −0.04, 95 % CI: −0.06, −0.03), and stimulant (RD: −0.03, 95 % CI: −0.04, −0.02) across the entire study period (2014–2020). A more robust WBA replacement rate was associated with fewer fatal drug, opioid and stimulant overdoses in the pre-COVID-19 period and on fatal any drug and stimulant overdoses in the COVID-19 period. ConclusionsFindings support the notion that income protection policies, such as robust UI, can have a supportive role in preventing fatal drug overdoses, calling for a broader discussion onthe role of the safety net programs to buffer drug-related harms.

Trends in and characteristics of drug overdose morbidity among pregnant and postpartum individuals in California, 2010-2018.

Fatal drug overdoses among pregnant and postpartum individuals have risen dramatically over the past 10 years. Trends in and characteristics of nonfatal drug overdoses in this population, however, remain unknown, despite the importance of this outcome for maternal and infant health. We used statewide, longitudinally-linked hospital and emergency department administrative claims data from California to characterize the incidence, trends, drug type involvement, and sociodemographic disparities in pregnancy-associated drug overdose between 2010 and 2019. Generalized linear models accounting for multiple deliveries per individual were used to test for trends; descriptive statistics were used for other study analyses. Of California individuals with a live delivery between 2010 and 2018, approximately 0.2% had a pregnancy-associated drug overdose. Nonfatal overdoses were nearly 60 times more common than fatal overdoses. Incidence of overdoses involving stimulants increased in frequency, while incidence of overdoses involving sedative/hypnotic drugs and psychotropic medications decreased in frequency. Risk of overdose was substantially higher among delivering individuals who were young, non-Hispanic Black, Medicaid patients, or who lived in non-metropolitan areas. Ongoing public health surveillance of and clinical interventions to reduce pregnancy-associated nonfatal drug overdose events are critical for prevention efforts.

Toxic Epidermal Necrolysis by Lamotrigine - A Case Report of Fatality

Toxic epidermal necrolysis (TEN) is an immune mediated fatal adverse muco-cutaneous drug reaction characterized by extensive exfoliation of the epidermis and mucous membrane. It may result in sepsis and death. In most cases, TEN is caused by certain drugs &amp; vaccines. TEN involves more than 30% of body surface area. Steven Johnson Syndrome also shows the same disease process and same spectrum of drug-induced epidermolysis. A 37-year-old patient who was on Lamotrigine, Escitalopram &amp; Clonazepam for multiple somatoform disorder developed generalized vesicular rash with fever after 2 weeks of initiation of lamotrigine. The patient was admitted to the hospital and Lamotrigine was taken off. Patient was given conservative management. Adverse drug reaction was reported to Adverse drug reaction monitoring centre (AMC) and severity was assessed by WHO-UMC Scale. Patient died after 5 days of admission. Score of Toxic epidermal necrolysis (SCORTEN Scale) is used to assess severity of the illness and to predict mortality rate. Early Diagnosis, withdrawal of offending agent, timely proper supportive management can help in lowering the mortality. Keywords: Toxic epidermal necrolysis, Lamotrigine, Adverse drug reaction, Multiple somatoform disorder, Steven Johnson Syndrome, Score of Toxic epidermal necrolysis

T95 - A Time Series Analysis of Nonfatal and Fatal Drug Overdose Outcomes for the Surveillance of Drug Overdose Outbreaks

T95 - A Time Series Analysis of Nonfatal and Fatal Drug Overdose Outcomes for the Surveillance of Drug Overdose Outbreaks

Evaluation of a Suspected Overdose Form for Timely Surveillance of Fatal Drug Overdoses, Multnomah County, OR, 2020-2021.

There is a significant delay in finalization of drug overdose deaths, and a need to more quickly identify suspected overdoses to improve public health response. The objective of our study was to describe creation of a suspect overdose form and evaluate its use. Evaluation of a suspected overdose form used to record information related to death investigation with matching to state vital records. We calculated the toxicology turnaround time for matched records, and also calculated sensitivity, specificity, positive predictive value, and negative predictive value of the form compared to vital records as the gold standard. Multnomah County, Oregon, deaths investigated by the County Medical Examiner between January 2020 and December 2021. Sensitivity of the suspected overdose form. We analyzed 2818 matched death records in total during the study period. The average turnaround time for the 1673 records with toxicology results was 101days. In 2020, sensitivity of the form was 74%, but this increased to nearly 95% in 2021. Multnomah County's suspected evaluation form provides a timelier indicator of deaths suspected to be from drug overdose, has good sensitivity to detect true overdoses, and can help guide more rapid public health and public safety response activities.

Difficulties associated with the interpretation of postmortem toxicology.

While postmortem (PM) toxicology results provide valuable information towards ascertaining both the cause and manner of death in coronial cases, there are also significant difficulties associated with the interpretation of PM drug levels. Such difficulties are influenced by several pharmacokinetic and pharmacodynamic factors including PM redistribution, diffusion, site-to-site variability in drug levels, different drug properties and metabolism, bacterial activity, genetic polymorphisms, tolerance, resuscitation efforts, underlying conditions, and the toxicity profile of cases (i.e. single- or mixed-drug toxicity). A large body of research has been dedicated for better understanding and even quantifying the influence of these factors on PM drug levels. For example, several investigative matrices have been developed as potential indicators of PM redistribution, but they have limited practical value. Reference tables of clinically relevant therapeutic, toxic, and potentially fatal drug concentrations have also been compiled, but these unfortunately do not provide reliable reference values for PM toxicology. More recent research has focused on developing databases of peripheral PM drug levels for a variety of case-types to increase transferability to real-life cases and improve interpretations. Changes to drug levels after death are inevitable and unavoidable. As such, guidelines and practices will continue to evolve as we further our understanding of such phenomena.

Evidence for sodium valproate toxicity in mitochondrial diseases: a systematic analysis

BackgroundWe aimed to determine whether sodium valproate (VPA) should be contraindicated in all mitochondrial diseases, due to known VPA-induced severe hepatotoxicity in some mitochondrial diseases.MethodsWe systematically reviewed the published literature...

Heparin-Induced Thrombocytopenia

The extensive use of therapeutic doses of heparin to prevent thrombosis in critically ill patients with COVID-19 during the pandemic has led to an increased incidence of bleeding and heparin-induced thrombocytopenia (HIT). In addition, the introduction of the AstraZeneca and Johnson&amp;Johnson vaccines against COVID-19 into clinical practice was associated with the development of a rare but very severe, adverse thrombotic complication, vaccine-induced immune thrombotic thrombocytopenia (VITT). Thrombotic complications of VITT turned out to be similar to HIT both clinically and pathophysiologically. HIT is a potentially fatal immune-mediated adverse drug response that results in emergence of antibodies that activate platelets in the presence of heparin. HIT is characterized by a high incidence of venous and arterial thromboses, often with fatal outcomes. Currently, there are clearly defined international guidelines for the diagnosis, treatment and prevention of HIT. In case of thrombotic complications, non-heparin anticoagulants should be used.

Spatial Heterogeneity in Fatal Overdose Rate Trends in Mexican Cities: 2005-2021.

Objectives. To describe national and city-level fatal drug overdose trends between 2005 and 2021 in Mexico. Methods. We calculated fatal overdose rates at the city level in 3-year periods from 2005 to 2021 and annually at the national level for people aged 15 to 64 years in Mexico. We calculated rate differences and rate ratios for each city between periods. Results. The national fatal overdose rate was 0.53 overdose deaths per 100 000 population and was almost twice as high in urban than in nonurban areas. The national fatal overdose rate was stable over the period 2005 to 2014 and increased monotonically to a peak in 2021. Fatal overdose rates varied across cities. Cities with the 8 highest fatal overdose rates in the period were all in states along the US-Mexico border. Conclusions. Fatal overdoses have doubled over the past 15 years in Mexico. Overdose rates are particularly high and increasing in cities close to the US-Mexico border. Public Health Implications. There is a need for enhanced overdose surveillance data and coordinated harm reduction strategies, particularly in the northern border region of Mexico. (Am J Public Health. 2024;114(7):705-713. https://doi.org/10.2105/AJPH.2024.307650).

Patients presenting to the ED with nonfatal drug overdose: Self-reported history of overdose and naloxone use

BackgroundIn the context of polysubstance use and fentanyl detection in non-opioid drugs supplies (e.g., cocaine, methamphetamine), it is important to re-evaluate and expand our understanding of which populations are at high risk for fatal drug overdoses. The primary objective of this pilot study was to gather data from the ED to characterize the population presenting with drug overdose, including demographics, drug use patterns and comorbidities, to inform upstream overdose prevention efforts. MethodsA consecutive sample of ED patients undergoing treatment for non-fatal overdose were prospectively recruited for study participation at the time of ED visit. Participants reported history of substance use over the past six months, recent and lifetime overdose, and naloxone receipt and administration history. ResultsA total of 76 eligible participants were enrolled over the course of seven months. Participants reported high rates of opioid (56%), stimulant (56%), and cannabis use (59%). Self-reported polysubstance use, defined as self-reported use of more than one substance, was 83%. Of enrolled participants, 64% reported at least one overdose and 39% reported three or more lifetime overdoses prior to their index overdose ED visit. Participants with no self-reported intentional opioid use (n = 32) in the past six months had fentanyl positive urine drug screen 84% of the time versus 89% in the overall study population (n = 74). Participants who did not report opioid use in the past six months were less likely to possess (34% vs. 55%) or to know how to acquire (50% vs. 74%) naloxone compared to participants with self-reported history of opioid use. ConclusionThis study demonstrated high rates of fentanyl exposure on toxicology testing at time of overdose across all participants including study participants without self-reported intentional opioid use. Data gathered in the ED at time of overdose can be used to inform upstream naloxone distribution and public health initiatives.