Trends in drug overdose deaths in Mexico (1999-2019). A national descriptive analysis and interstate comparison.

BACKGROUND: We assess trends in overdose mortality rates in Mexico from 1999 to 2019 and identify the states with the highest overdose mortality rates over time. METHODS: The analysis using mortality statistics examined deaths related to drug use. We estimated general overdose mortality rates at the national and state levels and calculated specific mortality rates associated with opioid and stimulant use using central rate estimation. We used joinpoint regression to analyse national and state-specific trends in overdose mortality from 1999 to 2019. FINDINGS: Nationally, the general overdose mortality rate increased annually by 10.49 % (p < 0.01, CI=11.4-18.9) from 2015 to 2019. The northern states of Baja California and Chihuahua were the states with the higher annual increases (18.6 %, p < 0.01, CI=4.2-29.6; and 15.6 %, p < 0.01, CI=12.9-19.7, respectively). By substance type, the national opioid-related mortality rate increased by 29.82 % per year from 2014 to 2019 (p < 0.01; CI=20.1-40.3), compared with an annual decrease of 11.43 % in the previous period (2005-2014) (p < 0.01; CI=-14.7- 8.0). Baja California was the state with the highest rise in opioid-related mortality from 2013 to 2019, with an annual increase of 15.84 % (p < 0.01; CI=1.4-32.3). Stimulant-related mortality increased by 21.79 % per year since 2013 (p < 0.01; CI=16.9-26.9), but it was not possible to calculate state-level trends. CONCLUSIONS: Drug-related mortality rates have increased in Mexico since 2015, particularly in the northern states of Baja California, Chihuahua, Sonora and Sinaloa. Improving harm reduction programmes and local surveillance of fatal and non-fatal overdoses is essential to address the silent escalation of overdose mortality.

Changes in Opioid and Benzodiazepine Poisoning Deaths After Cannabis Legalization in the US: A County-level Analysis, 2002-2020.

BACKGROUND: Cannabis legalization for medical and recreational purposes has been suggested as an effective strategy to reduce opioid and benzodiazepine use and deaths. We examined the county-level association between medical and recreational cannabis laws and poisoning deaths involving opioids and benzodiazepines in the US from 2002 to 2020. METHODS: Our ecologic county-level, spatiotemporal study comprised 49 states. Exposures were state-level implementation of medical and recreational cannabis laws and state-level initiation of cannabis dispensary sales. Our main outcomes were poisoning deaths involving any opioid, any benzodiazepine, and opioids with benzodiazepines. Secondary analyses included overdoses involving natural and semi-synthetic opioids, synthetic opioids, and heroin. RESULTS: Implementation of medical cannabis laws was associated with increased deaths involving opioids (rate ratio [RR] = 1.14; 95% credible interval [CrI] = 1.11, 1.18), benzodiazepines (RR = 1.19; 95% CrI = 1.12, 1.26), and opioids+benzodiazepines (RR = 1.22; 95% CrI = 1.15, 1.30). Medical cannabis legalizations allowing dispensaries was associated with fewer deaths involving opioids (RR = 0.88; 95% CrI = 0.85, 0.91) but not benzodiazepine deaths; results for recreational cannabis implementation and opioid deaths were similar (RR = 0.81; 95% CrI = 0.75, 0.88). Recreational cannabis laws allowing dispensary sales was associated with consistent reductions in opioid- (RR = 0.83; 95% CrI = 0.76, 0.91), benzodiazepine- (RR = 0.79; 95% CrI = 0.68, 0.92), and opioid+benzodiazepine-related poisonings (RR = 0.83; 95% CrI = 0.70, 0.98). CONCLUSIONS: Implementation of medical cannabis laws was associated with higher rates of opioid- and benzodiazepine-related deaths, whereas laws permitting broader cannabis access, including implementation of recreational cannabis laws and medical and recreational dispensaries, were associated with lower rates. The estimated effects of the expanded availability of cannabis seem dependent on the type of law implemented and its provisions.

Prevalence and Characteristics of Pediatric Opioid Exposures and Poisonings in the United States.

OBJECTIVE: To examine the prevalence and characteristics of pediatric opioid exposures and poisonings in the US. STUDY DESIGN: This was a retrospective, cross-sectional analysis using the National Poison Data System from January 1, 2010 to December 31, 2014. Records of children aged <18 years with exposure to opioid-containing medications were identified. Standardized prevalence rates were calculated, and the annual trend was examined. Pediatric opioid exposures were characterized descriptively, and logistic regression was performed to estimate the association between various clinical and sociodemographic characteristics and exposures with serious (ie, moderate, major, or death) outcomes. The association of pediatric opioid exposures and area-level socioeconomic status factors at 5-digit ZIP code level was examined descriptively. RESULTS: The prevalence of opioid exposures was 22.6 per 100 000 children and was particularly high among ≤5-year-olds. Prevalence declined from 25.5 to 20 per 100 000 children from 2010 to 2014. There were 83 418 pediatric opioid exposures over the 5-year period and nearly one-half resulted in poisoning. Over 60% of exposures were among children ≤5 years of age, 73.4% were unintentional, and over 90% occurred at home. One in every 2 pediatric opioid exposures was evaluated in a healthcare facility. Annually 4912 children aged ≤5 years were treated in the emergency department or admitted for care. Older age, nonaccidental intent, and single-substance opioid, especially buprenorphine and methadone, were associated with serious outcomes (P < .05). Positive correlations were observed for area-level socioeconomic status factors including proportion of adults and pediatric opioid exposures. CONCLUSIONS: Pediatric opioid exposures and poisonings decreased from 2010 to 2014 but morbidity remains high. The epidemiology of opioid exposures differed considerably by age.

An Examination of Claims-based Predictors of Overdose from a Large Medicaid Program.

BACKGROUND: Health systems may play an important role in identification of patients at-risk of opioid medication overdose. However, standard measures for identifying overdose risk in administrative data do not exist. OBJECTIVE: Examine the association between opioid medication overdose and 2 validated measures of nonmedical use of prescription opioids within claims data. RESEARCH DESIGN: A longitudinal retrospective cohort study that estimated associations between overdose and nonmedical use. SUBJECTS: Adult Pennsylvania Medicaid program 2007-2012 patients initiating opioid treatment who were: nondual eligible, without cancer diagnosis, and not in long-term care facilities or receiving hospice. MEASURES: Overdose (International Classification of Disease, ninth edition, prescription opioid poisonings codes), opioid abuse (opioid use disorder diagnosis while possessing an opioid prescription), opioid misuse (a composite indicator of number of opioid prescribers, number of pharmacies, and days supplied), and dose exposure during opioid treatment episodes. RESULTS: A total of 372,347 Medicaid enrollees with 583,013 new opioid treatment episodes were included in the cohort. Opioid overdose was higher among those with abuse (1.5%) compared with those without (0.2%, P<0.001). Overdose was higher among those with probable (1.8%) and possible (0.9%) misuse compared with those without (0.2%, P<0.001). Abuse [adjusted rate ratio (ARR), 1.52; 95% confidence interval (CI), 1.10-2.10), probable misuse (ARR, 1.98; 95% CI, 1.46-2.67), and possible misuse (ARR, 1.76; 95% CI, 1.48-2.09) were associated with significantly more events of opioid medication overdose compared with those without. CONCLUSIONS: Claims-based measures can be used by health systems to identify individuals at-risk of overdose who can be targeted for restrictions on opioid prescribing, dispensing, or referral to treatment.

Recognition and response to opioid overdose deaths-New Mexico, 2012.

PURPOSE: Drug overdose deaths are epidemic in the U.S. Prescription opioid pain relievers (OPR) and heroin account for the majority of drug overdoses. Preventing death after an opioid overdose by naloxone administration requires the rapid identification of the overdose by witnesses. This study used a state medical examiner database to characterize fatal overdoses, evaluate witness-reported signs of overdose, and identify opportunities for intervention. METHODS: We reviewed all unintentional drug overdose deaths that occurred in New Mexico during 2012. Data were abstracted from medical examiner records at the New Mexico Office of the Medical Investigator. We compared mutually exclusive groups of OPR and heroin-related deaths. RESULTS: Of the 489 overdose deaths reviewed, 49.3% involved OPR, 21.7% involved heroin, 4.7% involved a mixture of OPR and heroin, and 24.3% involved only non-opioid substances. The majority of OPR-related deaths occurred in non-Hispanic whites (57.3%), men (58.5%), persons aged 40-59 years (55.2%), and those with chronic medical conditions (89.2%). Most overdose deaths occurred in the home (68.7%) and in the presence of bystanders (67.7%). OPR and heroin deaths did not differ with respect to paramedic dispatch and CPR delivery, however, heroin overdoses received naloxone twice as often (20.8% heroin vs. 10.0% OPR; p<0.01). CONCLUSION: OPR overdose deaths differed by age, health status, and the presence of bystanders, yet received naloxone less often when compared to heroin overdose deaths. These findings suggest that naloxone education and distribution should be targeted in future prevention efforts.

Case report of a fatal intoxication by Nucynta.

Tapentadol (Nucynta) is a centrally acting opioid analgesic prescribed for the treatment of moderate to severe acute pain. Its efficacy is believed to be due to µ-opioid receptor agonist activity and inhibition of norepinephrine reuptake resulting in increased norepinephrine concentrations. There is only one other case in the literature relating to the toxicity of this agent or report of a fatality. This case report documents a case in which tapentadol was identified as the cause of death. The tapentadol concentration found in the heart blood submitted in this case was more than 20 times the upper limit of the therapeutic range. Possible mechanisms of death include respiratory depression, central nervous system depression, and serotonin syndrome. Based on the scene investigation and autopsy findings in this case, the medical examiner determined that the cause of death was narcotic (Nucynta) intoxication and the manner of death was undetermined.

Programas de monitoreo de medicamentos de prescripción en los Estados Unidos de América / Prescription drug monitoring programs in the United States of America

Desde finales de la década de los años noventa, el número de muertes por sobredosis que involucran analgésicos opioides se ha cuadriplicado en los Estados Unidos de América (de 4 030 muertes en 1999 a 16 651 en 2010). Los objetivos de este artículo son proporcionar una visión general del problema de sobredosis de medicamentos de prescripción en los Estados Unidos y discutir las acciones que podrían ayudar a reducir el problema, abordando en forma directa las características de los Programas de monitoreo de medicamentos de prescripción (PDMP). Estos programas están compuestos de bases de datos a nivel estatal que vigilan las sustancias controladas. La información recopilada en las bases de datos está a disposición de las personas autorizadas por el Estado (por ejemplo, los médicos, los farmacéuticos y otros proveedores de cuidado médico) y debe ser utilizada solo con propósitos profesionales. Los proveedores pueden utilizar dicha información para evitar la interacción con otros medicamentos, la duplicación terapéutica o la identificación de conductas de búsqueda de drogas. Las agencias del orden público pueden utilizar estos programas para identificar patrones de prescripción inadecuada, dispensación o desviación.

Since the late 1990s, the number of opioid analgesic overdose deaths has quadrupled in the United States of America (from 4 030 deaths in 1999 to 16 651 in 2010). The objectives of this article are to provide an overview of the problem of prescription drug overdose in the United States and to discuss actions that could help reduce the problem, with particular attention to the characteristics of prescription drug monitoring programs (PDMPs). These programs consist of state-level databases that monitor controlled substances. The information compiled in the databases is at the disposal of authorized persons (e.g., physicians, pharmacists, and other health-care providers) and may be used only for professional purposes. Suppliers can use such information to prevent interaction with other drugs or therapeutic duplication, or to identify drug-search behavior. Law enforcement agencies can use these programs to identify improper drug prescription or dispensing patterns, or drug diversion.

Root causes, clinical effects, and outcomes of unintentional exposures to buprenorphine by young children.

OBJECTIVE: To characterize the rates, root causes, and clinical effects of unintentional exposures to buprenorphine sublingual formulations among young children and to determine whether exposure characteristics differ between formulations. STUDY DESIGN: Unintentional exposures to buprenorphine-containing products among children 28 days to less than 6 years old were collected from the Researched Abuse, Diversion, and Addiction-Related Surveillance System Poison Center Program and Reckitt Benckiser Pharmaceuticals' pharmacovigilance system from October 2009-March 2012. After adjustment for drug availability, negative binomial regression was used to estimate average exposure rates. Root cause assessment was conducted, and an expert clinician panel adjudicated causality and severity of moderate to severe adverse events (AEs). RESULTS: A total of 2380 cases were reviewed, including 4 deaths. Exposures to buprenorphine-naloxone combination film were significantly less frequent than exposures to buprenorphine tablets (rate ratio 3.5 [95% CI, 2.7-4.5]) and buprenorphine-naloxone combination tablets (rate ratio 8.8 [7.2-10.6]). The most commonly identified root causes were medication stored in sight, accessed from a bag or purse, and not stored in the original packaging. Among 536 panel review cases, the most common AEs reported for all formulations were lethargy, respiratory depression, miosis, and vomiting. The highest level AE severity did not differ significantly by formulation. CONCLUSIONS: Unintentional exposure to buprenorphine can cause central nervous system depression, respiratory depression, and death in young children. Exposure rates to film formulations are significantly less than to tablet formulations. Package and storage deficiencies contribute to unintentional exposures in young children.

Maternal use of oxycodone resulting in opioid intoxication in her breastfed neonate.

A 4-day-old breastfed infant presented with opioid intoxication resulting from the maternal use of oxycodone after cesarean delivery. The infant was hypothermic, lethargic, and had pinpoint pupils. A dose of naloxone reversed the symptoms. This report highlights the importance of recognizing the potential effects of maternal oxycodone on the breastfed neonate in the emergency department setting.

A toxicology-based review of fentanyl-related deaths in New Mexico (1986-2007).

Since its approval in the United States, fentanyl has become increasingly popular for the medical management of pain and as a substance of abuse. Fentanyl is unique among the opioids in its widespread use with a transdermal delivery system, which contributes to its unique pharmacokinetics and abuse potential. We examined the demographics of deaths with fentanyl identified on toxicologic analysis and reviewed specific challenges in the laboratory detection of postmortem fentanyl levels. The New Mexico Office of the Medical Investigator database was searched for all cases from January 1986 through December 2007 with fentanyl reported as present or quantified. Those deaths with a cause of death identified as drug overdose were then analyzed separately. From 1986 to 2007, 154 cases were identified with fentanyl present in postmortem samples, with 96 of the cases identified as fentanyl-related drug overdoses. The number of fentanyl-related deaths has increased over the past 20 years, corresponding to both statewide increases in the medical use of fentanyl and the abuse of prescription opioids. The demographics of these fentanyl-related overdoses showed that subjects were more likely to be female, white non-Hispanic, and older than those in previously described overdose deaths. Several cases were identified with central and peripheral blood samples and antemortem and postmortem samples available for fentanyl quantification. Given the uncharacteristic demographics of fentanyl-related deaths and the complexity of the laboratory analysis of fentanyl, forensic scientists must use caution in both the detection and interpretation of fentanyl concentrations.

Unintentional drug overdose death trends in New Mexico, USA, 1990-2005: combinations of heroin, cocaine, prescription opioids and alcohol.

AIMS: To determine the contribution of heroin, prescription opioids, cocaine and alcohol/drug combinations to the total overdose death rate and identify changes in drug overdose patterns among New Mexico subpopulations. DESIGN: We analyzed medical examiner data for all unintentional drug overdose deaths in New Mexico during 1990-2005. Age-adjusted drug overdose death rates were calculated by sex and race/ethnicity; we modeled overall drug overdose death adjusting for age and region. FINDINGS: The total unintentional drug overdose death rate in New Mexico increased from 5.6 per 100 000 in 1990 to 15.5 per 100 000 in 2005. Deaths caused by heroin, prescription opioids, cocaine and alcohol/drug combinations together ranged from 89% to 98% of the total. Heroin caused the most deaths during 1990-2005, with a notable rate increase in prescription opioid overdose death during 1998-2005 (58%). During 1990-2005, the 196% increase in single drug category overdose death was driven by prescription opioids alone and heroin alone; the 148% increase in multi-drug category overdose death was driven by heroin/alcohol and heroin/cocaine. Hispanic males had the highest overdose death rate, followed by white males, white females, Hispanic females and American Indians. The most common categories causing death were heroin alone and heroin/alcohol among Hispanic males, heroin/alcohol among American Indian males and prescription opioids alone among white males and all female subpopulations. CONCLUSIONS: Interventions to prevent drug overdose death should be targeted according to use patterns among at-risk subpopulations. A comprehensive approach addressing both illicit and prescription drug users, and people who use these drugs concurrently, is needed to reduce overdose death.