Association between opioid use disorder and palliative care: a cohort study using linked health administrative data in Ontario, Canada.

BACKGROUND: People with opioid use disorder (OUD) are at risk of premature death and can benefit from palliative care. We sought to compare palliative care provision for decedents with and without OUD. METHODS: We conducted a cohort study using health administrative databases in Ontario, Canada, to identify people who died between July 1, 2015, and Dec. 31, 2021. The exposure was OUD, defined as having emergency department visits, hospital admissions, or pharmacologic treatments suggestive of OUD within 3 years of death. Our primary outcome was receipt of 1 or more palliative care services during the last 90 days before death. Secondary outcomes included setting, initiation, and intensity of palliative care. We conducted a secondary analysis excluding sudden deaths (e.g., opioid toxicity, injury). RESULTS: Of 679 840 decedents, 11 200 (1.6%) had OUD. Compared with people without OUD, those with OUD died at a younger age and were more likely to live in neighbourhoods with high marginalization indices. We found people with OUD were less likely to receive palliative care at the end of their lives (adjusted relative risk [RR] 0.84, 95% confidence interval [CI] 0.82-0.86), but this difference did not exist after excluding people who died suddenly (adjusted RR 0.99, 95% CI 0.96-1.01). People with OUD were less likely to receive palliative care in clinics and their homes regardless of cause of death. INTERPRETATION: Opioid use disorder can be a chronic, life-limiting illness, and people with OUD are less likely to receive palliative care in communities during the 90 days before death. Health care providers should receive training in palliative care and addiction medicine to support people with OUD.

Cause-Specific Mortality among Patients in Treatment for Opioid Use Disorder in Multiple Settings: A Prospective Comparative Cohort Study.

INTRODUCTION: Among people receiving current or previous opioid maintenance treatment (OMT), the leading cause of premature death is an opioid overdose. However, other causes of mortality remain high in this group. An understanding of causes of deaths across multiple settings can be useful in informing more comprehensive prevention responses. The aim of this study was to describe all non-overdose causes of death in three national cohorts (Czechia, Denmark, and Norway) among OMT patients and to explore associations of non-overdose mortality with age and gender. METHODS: This prospective comparative cohort study used national mortality registry databases for OMT patients from Czechia (2000-2019), Denmark (2000-2018), and Norway (2010-2019). Crude mortality rates and age-standardized mortality rates (ASMRs) were calculated as deaths per 1,000 person years for cause-specific mortality. RESULTS: In total, 29,486 patients were included, with 5,322 deaths recorded (18%). We found variations in causes of death among the cohorts and within gender and age groups. The leading non-overdose causes of death were accidents in Czechia and Denmark, and neoplasms in Norway. Cardiovascular deaths were highest in Czechia, particularly for women in OMT (ASMR 3.59 vs. 1.24 in Norway and 1.87 in Denmark). CONCLUSION: This study found high rates of preventable death among both genders and all age groups. Different demographic structures, variations in risk exposure, as well as variations in coding practices can explain the differences. The findings support increased efforts towards screening and preventative health initiatives among OMT patients specific to the demographic characteristics in different settings.

Factors Affecting Inpatient Mortality and Length of Stay in Nonmetastatic Colorectal Cancer: Insights from the National Inpatient Sample.

OBJECTIVE: The objective of this study was to assess the effect of opioid use and other factors on inpatient length of stay (LOS) and mortality among patients hospitalized with nonmetastatic colorectal cancer (NMCRC). MATERIALS AND METHODS: We analyzed discharge encounters collected from the 2016 to 2017 National Inpatient Sample (NIS) to evaluate the effect of long-term opioid use (90 d or longer) and cancer-related complications on LOS and mortality among hospitalized patients with NMCRC. RESULTS: A total of 94,535 patients with NMCRC were included in the analysis. Long-term opioid users had a shorter average LOS and reduced inpatient mortality as compared with nonopioid users (5.97±5.75 vs. 6.66±6.92 d, P<0.01; and adjusted odds ratio=0.72, 95% confidence interval: 0.56-0.93, respectively). Factors that significantly increased both LOS and mortality included infection, venous thromboembolism, and chemotherapy-induced neutropenia; the average LOS was 2.7, 2.6, and 0.7 days longer, and the adjusted odds ratio for risk of inpatient mortality was 3.7, 1.2, and 1.2, respectively (P<0.05), for patients admitted with these cancer-related complications. CONCLUSIONS: Long-term opioid use is associated with decreased LOS and inpatient mortality among patients with NMCRC. Individuals admitted for cancer-related complications face a longer LOS and increased mortality as compared with those admitted without these morbidities.

Association of Opioid Agonist Treatment With All-Cause Mortality and Specific Causes of Death Among People With Opioid Dependence: A Systematic Review and Meta-analysis.

Importance: Mortality among people with opioid dependence is higher than that of the general population. Opioid agonist treatment (OAT) is an effective treatment for opioid dependence; however, there has not yet been a systematic review on the relationship between OAT and specific causes of mortality. Objective: To estimate the association of time receiving OAT with mortality. Data Sources: The Embase, MEDLINE, and PsycINFO databases were searched through February 18, 2020, including clinical trial registries and previous Cochrane reviews. Study Selection: All observational studies that collected data on all-cause or cause-specific mortality among people with opioid dependence while receiving and not receiving OAT were included. Randomized clinical trials (RCTs) were also included. Data Extraction and Synthesis: This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Data on study, participant, and treatment characteristics were extracted; person-years, all-cause mortality, and cause-specific mortality were calculated. Crude mortality rates and rate ratios (RRs) were pooled using random-effects meta-analyses. Main Outcomes and Measures: Overall all-cause and cause-specific mortality both by setting and by participant characteristics. Methadone and buprenorphine OAT were evaluated specifically. Results: Fifteen RCTs including 3852 participants and 36 primary cohort studies including 749 634 participants were analyzed. Among the cohort studies, the rate of all-cause mortality during OAT was more than half of the rate seen during time out of OAT (RR, 0.47; 95% CI, 0.42-0.53). This association was consistent regardless of patient sex, age, geographic location, HIV status, and hepatitis C virus status and whether drugs were taken through injection. Associations were not different for methadone (RR, 0.47; 95% CI, 0.41-0.54) vs buprenorphine (RR, 0.34; 95% CI, 0.26-0.45). There was lower risk of suicide (RR, 0.48; 95% CI, 0.37-0.61), cancer (RR, 0.72; 95% CI, 0.52-0.98), drug-related (RR, 0.41; 95% CI, 0.33-0.52), alcohol-related (RR, 0.59; 95% CI, 0.49-0.72), and cardiovascular-related (RR, 0.69; 95% CI, 0.60-0.79) mortality during OAT. In the first 4 weeks of methadone treatment, rates of all-cause mortality and drug-related poisoning were almost double the rates during the remainder of OAT (RR, 2.01; 95% CI, 1.55-5.09) but not for buprenorphine (RR, 0.58; 95% CI, 0.18-1.85). All-cause mortality was 6 times higher in the 4 weeks after OAT cessation (RR, 6.01; 95% CI, 4.32-8.36), remaining double the rate for the remainder of time not receiving OAT (RR, 1.81; 95% CI, 1.50-2.18). Opioid agonist treatment was associated with a lower risk of mortality during incarceration (RR, 0.06; 95% CI, 0.01-0.46) and after release from incarceration (RR, 0.09; 95% CI, 0.02-0.56). Conclusions and Relevance: This systematic review and meta-analysis found that OAT was associated with lower rates of mortality. However, access to OAT remains limited, and coverage of OAT remains low. Work to improve access globally may have important population-level benefits.

Effect of Opioids on All-cause Mortality and Opioid Addiction in Total Hip Arthroplasty: a Korea Nationwide Cohort Study.

BACKGROUND: The purpose of this study was to investigate the use of opioids before and after total hip arthroplasty (THA), to find out the effect of opioid use on mortality in patients with THA, and to analyze whether preoperative opioid use is a risk factor for sustained opioid use after surgery using Korean nationwide cohort data. METHODS: This retrospective nationwide study identified subjects from the Korean National Health Insurance Service-Sample cohort (NHIS-Sample) compiled by the Korean NHIS. The index date (time zero) was defined as 90 days after an admission to a hospital to fulfill the eligibility criteria of the THA. RESULTS: In the comparison of death risk according to current use and the defined daily dose of tramadol and strong opioids in each patient group according to past opioid use, there were no statistically significant differences in the adjusted hazard ratio for death compared to the current non-users in all groups (P > 0.05). Past tramadol and strong opioid use in current users increased the risk of the sustained use of tramadol and strong opioids 1.45-fold (adjusted rate ratio [aRR]; 95% confidence interval [CI], 1.12-1.87; P = 0.004) and 1.65-fold (aRR; 95% CI, 1.43-1.91; P < 0.001), respectively, compared to past non-users. CONCLUSION: In THA patients, the use of opioids within 6 months before surgery and within 3 months after surgery does not affect postoperative mortality, but a past-use history of opioid is a risk factor for sustained opioid use. Even after THA, the use of strong opioids is observed to increase compared to before surgery.

Association of prescription opioid use on mortality and hospital length of stay in the intensive care unit.

OBJECTIVE: Several studies show that chronic opioid dependence leads to higher in-hospital mortality, increased risk of hospital readmissions, and worse outcomes in trauma cases. However, the association of outpatient prescription opioid use on morbidity and mortality has not been adequately evaluated in a critical care setting. The purpose of this study was to determine if there is an association between chronic opioid use and mortality after an ICU admission. DESIGN: A single-center, longitudinal retrospective cohort study of all Intensive Care Unit (ICU) patients admitted to a tertiary-care academic medical center from 2001 to 2012 using the MIMIC-III database. SETTING: Medical Information Mart for Intensive Care III database based in the United States. PATIENTS: Adult patients 18 years and older were included. Exclusion criteria comprised of patients who expired during their hospital stay or presented with overdose; patients with cancer, anoxic brain injury, non-prescription opioid use; or if an accurate medication reconciliation was unable to be obtained. Patients prescribed chronic opioids were compared with those who had not been prescribed opioids in the outpatient setting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final sample included a total of 22,385 patients, with 2,621 (11.7%) in the opioid group and 19,764 (88.3%) in the control group. After proceeding with bivariate analyses, statistically significant and clinically relevant differences were identified between opioid and non-opioid users in sex, length of hospital stay, and comorbidities. Opioid use was associated with increased mortality in both the 30-day and 1-year windows with a respective odds ratios of 1.81 (95% CI, 1.63-2.01; p<0.001) and 1.88 (95% CI, 1.77-1.99; p<0.001), respectively. CONCLUSIONS: Chronic opioid usage was associated with increased hospital length of stay and increased mortality at both 30 days and 1 year after ICU admission. Knowledge of this will help providers make better choices in patient care and have a more informed risk-benefits discussion when prescribing opioids for chronic usage.

Cardiovascular Complications of Opioid Use: JACC State-of-the-Art Review.

Opioids are the most potent of all analgesics. Although traditionally used solely for acute self-limited conditions and palliation of severe cancer-associated pain, a movement to promote subjective pain (scale, 0 to 10) to the status of a "fifth vital sign" bolstered widespread prescribing for chronic, noncancer pain. This, coupled with rising misuse, initiated a surge in unintentional deaths, increased drug-associated acute coronary syndrome, and endocarditis. In response, the American College of Cardiology issued a call to action for cardiovascular care teams. Opioid toxicity is primarily mediated via potent µ-receptor agonism resulting in ventilatory depression. However, both overdose and opioid withdrawal can trigger major adverse cardiovascular events resulting from hemodynamic, vascular, and proarrhythmic/electrophysiological consequences. Although natural opioid analogues are devoid of repolarization effects, synthetic agents may be proarrhythmic. This perspective explores cardiovascular consequences of opioids, the contributions of off-target electrophysiologic properties to mortality, and provides practical safety recommendations.

Opioid use as a potential risk factor for pancreatic cancer in the United States: An analysis of state and national level databases.

Pancreatic cancer (PC) rate is increasing in the U.S. The use of prescription and illicit opioids has continued to rise nationally in recent years as well. Opioids have been shown to have a deleterious effect on multiple types of cancer with recent data suggesting opium use as a risk factor for PC. Using national databases, we tested whether opioid usage pattern over time could explain the state and national-based variations in PC rates in the U.S. Opioid death rate (as a surrogate for prescription and illicit opioid use) was extracted from the CDCs Wonder online data through the Vital Statistics Cooperative Program. Incidence of pancreatic cancer was retrieved from the online CDCs data base gathered from the U.S. Cancer Statistics Working Group. Prevalence of obesity, tobacco and alcohol use was collected from Behavioral risk factor surveillance system. Mixed-effects regression models were used to test the association between levels of PC rate and opioid death/use rates during the years 1999-2016. A rise in PC was seen over time at the national and state levels. Similarly, the opioid death rates increased over time. Among other potential PC risk factors, only obesity prevalence showed an increase during the study period. A state's opioid death rate at 4 years prior significantly predicted initial incidence of PC (ß = 0.1848, p<0.0001) and had a significant effect on the estimated annual change in the rate of PC (ß = -.0193,p<0.0001). Opioid use may be an un-identified risk factor contributing to the increasing incidence of PC in the U.S. These novel findings need to be verified by population-based studies.

Opioid Overdose Deaths with Buprenorphine Detected in Postmortem Toxicology: a Retrospective Analysis.

BACKGROUND: Buprenorphine is a unique µ-opioid receptor partial agonist with avid receptor binding, nominal euphoric reward, and a ceiling effect on sedation and respiratory depression. Despite a pharmacologic profile that enhances safety, cases of fatal opioid overdose with buprenorphine on postmortem toxicology are reported, but details of these cases in the literature are limited. METHODS: A retrospective review of opioid-involved drug overdose fatalities in Rhode Island (RI) from 2016 to 2018 using the RI Department of Health State Unintentional Drug Overdose Reporting System (SUDORS) database. Deaths with buprenorphine on toxicology testing versus opioid-involved overdose deaths without buprenorphine were compared to assess the type and number of co-exposures. RESULTS: Of 534 opioid-involved deaths, 29 (5.4%) included buprenorphine and/or norbuprenorphine on toxicology. Most frequent co-exposures are as follows: fentanyl (75.9%), norfentanyl (72.4%), cocaine (41.4%), benzoylecgonine (41.4%), cannabinoids (31.0%), ethanol (31.0%), levamisole (31.0%), and free morphine (31.0%). An average number of co-exposures for fatalities with buprenorphine were 9.24 versus 6.68 in those without buprenorphine. In one case buprenorphine was the only drug listed to cause death; all other fatalities with buprenorphine on toxicology reported additional drugs contributing to death. CONCLUSION: Decedents with buprenorphine detected on toxicology testing commonly had documented polysubstance use. Although data are limited, buprenorphine may provide some risk mitigation against full agonist opioid overdose including fentanyl. Further work should explore the use of postmortem concentrations of buprenorphine, norbuprenorphine, and other opioid metabolites to determine the role of buprenorphine in fatal overdose pharmacology.

Association of Treatment With Medications for Opioid Use Disorder With Mortality After Hospitalization for Injection Drug Use-Associated Infective Endocarditis.

Importance: Although hospitalizations for injection drug use-associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown. Objective: To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality. Design, Setting, and Participants: This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE-related discharges between July 1, 2011, and June, 30, 2015, were analyzed. All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge. Data were analyzed from November 11, 2018, to June 23, 2020. Exposure: Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE. Main Outcomes and Measures: The main outcome was all-cause mortality. The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated. Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness. In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure. Results: Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness. A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge. Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine. The crude mortality rate was 9.2 deaths per 100 person-years. MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89). Conclusions and Relevance: In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use-associated endocarditis only in the month it was received. Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial.

Nonmedical Use of Prescription Opioids, Heroin Use, Injection Drug Use, and Overdose Mortality in U.S. Adolescents.

OBJECTIVE: We assessed overdose mortality by opioid types involved as well as interrelationships between nonmedical use of prescription opioids (NUPO) and heroin and injection drug use (IDU) among adolescents. METHOD: We examined 2010 and 2016 overdose data by drug type for decedents in the United States ages 15-19 years from the Multiple Cause of Death Files. We also analyzed data from the 2017 National Youth Risk Behavior Survey, a nationally representative survey of high school students. We assessed lifetime NUPO and calculated heroin use and IDU by frequency of lifetime NUPO. Adjusted prevalence ratios (aPRs) were generated, and linear contrast analysis determined dose-response relationships between frequency of lifetime NUPO and the two outcomes. RESULTS: The percentage of deaths involving prescription opioids that also involved illicit opioids such as heroin or fentanyl was 5.5% in 2010 and 25.0% in 2016. We observed a positive dose-response relationship with frequency of lifetime NUPO; aPRs were highest for 20 or more times of NUPO and heroin use (aPR = 49.49, 95% CI [33.39, 73.34]) and IDU (aPR = 44.37, 95% CI [23.16, 84.99]). However, aPRs for heroin and IDU were high even among those reporting just one or two occasions of NUPO (aPRs = 9.25, 95% CI [5.90, 14.49] and 6.63, 95% CI [3.99, 11.02], respectively). CONCLUSIONS: Adolescent prescription opioid overdose deaths now frequently involve illicit opioids. Heroin use and IDU are higher among students reporting even a few instances of NUPO, indicating that students with any NUPO are an important risk group. Clinical, community, and school-based efforts can address NUPO, noting these associations.

Relationship between opiates and asthma in the determination of death.

Several studies have shown an association between asthma and opiate abuse. This retrospective study aims to analyse the demographic, toxicological, and seasonal differences in asthmatic and non-asthmatic subjects who died of opiates. In addition, the relationship between toxicological levels of opiates and histologic grade of lung inflammation is examined. Deaths from 2013 to 2018 involving opiates as the primary cause of death in Cook County, Illinois (USA) were reviewed. Twenty-six cases of opiate deaths of individuals with a history of asthma and lung histology slides available were identified. In comparison, 40 cases of deaths due to opiates only were analysed. A check-list system for the evaluation of the grade of microscopic inflammation in asthma was developed. We found statistically significant differences between the asthmatics and the non-asthmatics regarding demography (age and race) and toxicology (6-MAM presence). In particular, the "opiate and asthma group" was mainly composed of African-American subjects, in contrast with the "opiate group", consisting mostly of Caucasian. The mean age was significantly higher in the "opiate and asthma group" compared with the "opiate group". A greater presence of 6-MAM was detected in the "opiate group" compared with the "opiate and asthma group". While we expected to find that low opiate levels would lead to deaths in asthmatics and, in particular, that lower opiate concentrations would cause deaths in subjects with higher grades of histologic inflammation, our study suggests that the quantity of drug and the level of inflammation are not statistically significant in the determination of death. We, therefore, recommend histologic examination of the lungs to evaluate for asthma, particularly in suspected low-level opiate-related deaths, to help further clarify any relationship between asthma and opiate use.

Estimating the impact of wide scale uptake of screening and medications for opioid use disorder in US prisons and jails.

BACKGROUND: Medications for opioid use disorder (OUD) are the most effective treatment for OUD, but uptake of these life-saving medications has been extremely limited in US prisons and jail settings, and limited data are available to guide policy decisions. The objective of this study was to estimate the impact of screening and treatment with medications for OUD in US prisons and jails on post-release opioid-related mortality. METHODS: We used data from the National Center for Vital Statistics, the Bureau of Justice Statistics, and relevant literature to construct Monte Carlo simulations of a counterfactual scenario in which wide scale uptake of screening and treatment with medications for OUD occurred in US prisons and jails in 2016. RESULTS: Our model predicted that 1840 (95% Simulation Interval [SI]: -2757 - 4959) lives would have been saved nationally if all persons who were clinically indicated had received medications for OUD while incarcerated. The model also predicted that approximately 4400 (95% SI: 2675 - 5557) lives would have been saved nationally if all persons who were clinically indicated had received medications for OUD while incarcerated and were retained in treatment post-release. These estimates correspond to 668 (95% SI: -1008 - 1812) and 1609 (95% SI: 972 - 2037) lives saved per 10,000 persons incarcerated, respectively. CONCLUSIONS: Prison and jail-based programs that comprehensively screen and provide treatment with medications for OUD have the potential to produce substantial reductions in opioid-related overdose deaths in a high-risk population; however, retention on treatment post-release is a key driver of population level impact.

Risk factors and outcomes of chronic opioid use following trauma.

BACKGROUND: The growing problem of opioid misuse has become a serious crisis in many countries. The role of trauma as a gateway to opioid use is currently not determined. The study was undertaken to assess whether traumatic injury might be associated with chronic opioid use and accompanying increased long-term mortality. METHODS: Injured patients and controls from Sweden were matched for age, sex and municipality. After linkage to Swedish health registers, opioid consumption was assessed before and after trauma. Among injured patients, logistic regression was used to investigate factors associated with chronic opioid use, assessed by at least one written and dispensed prescription in the second quarter after trauma. Cox regression was employed to study excess risk of mortality. In addition, causes of death for postinjury opioid users were explored. RESULTS: Some 13 309 injured patients and 70 621 controls were analysed. Exposure to trauma was independently associated with chronic opioid use (odds ratio 3·28, 95 per cent c.i. 3·02 to 3·55); this use was associated with age, low level of education, somatic co-morbidity, psychiatric co-morbidity, pretrauma opioid use and severe injury. The adjusted hazard ratio for death from any cause 6-18 months after trauma for chronic opioid users was 1·82 (95 per cent c.i. 1·34 to 2·48). Findings were similar in a subset of injured patients with no pretrauma opioid exposure. CONCLUSION: Traumatic injury was associated with chronic opioid use. These patients have an excess risk of death in the 6-18 months after trauma.

ANTECEDENTES: El uso indebido de opioides es un problema creciente que se ha convertido en una grave crisis en muchos países. No se ha analizado el papel de las lesiones traumáticas como puerta de entrada al uso de opioides. Se estableció la hipótesis de que una lesión traumática podría asociarse con el uso crónico de opioides y acompañarse de un aumento de la mortalidad a largo plazo. MÉTODOS: Se ajustaron por edad, sexo y municipio a los pacientes suecos con lesiones traumáticas y sus controles. Después de vincular varios registros de salud suecos, se evaluó el consumo de opioides antes y después de la lesión traumática. En los pacientes con lesiones traumáticas, se utilizó una regresión logística para definir los factores asociados con el uso crónico de opioides, definida como una receta prescrita y dispensada en el segundo trimestre después de la lesión traumática, y ​​una regresión de Cox para estudiar el exceso de riesgo de mortalidad. Además, se exploraron las causas de muerte de los usuarios de opioides postraumáticos. RESULTADOS: Se analizaron 13.309 pacientes con lesiones traumáticas y 70.621 controles. La exposición a una lesión traumática se asoció de forma independiente con el uso crónico de opioides, (razón de oportunidades, odds ratio, OR) OR 3,3 (i.c. del 95% 3,0-3,6), y dicho uso se asoció con la edad, el bajo nivel educativo, las comorbilidad físicas y psiquiátricas, el uso previo de opioides y la gravedad de las lesiones. El cociente de riesgos instantáneos, hazard ratio, HR ajustado de muerte por cualquier causa a los 6-18 meses de la lesión traumática para los consumidores crónicos de opioides fue de 1,8 (i.c. del 95% 1,3-2,5). En un subconjunto de pacientes con lesiones traumáticas sin exposición previa a los opioides, los hallazgos fueron similares. CONCLUSIÓN: La lesión traumática se asoció con el uso crónico de opioides. Estos pacientes presentan un exceso de riesgo de mortalidad entre los 6 y 8 meses después del trauma.

Preoperative Opioid Prescription Is Associated With Major Complications in Patients With Crohn's Disease Undergoing Elective Ileocolic Resection.

BACKGROUND: Opioid use has grown exponentially over the last decade. The effect of preoperative opioid prescription in patients with Crohn's disease undergoing surgery is unknown. OBJECTIVE: The purpose of this study was to identify whether preoperative opioid prescription is associated with adverse postoperative outcomes in Crohn's disease. DESIGN: This is a single-institution retrospective observational study. SETTINGS: This study was performed at an academic tertiary care center. Details of preoperative opioid prescription were collected from the Kentucky All-Schedule Prescription Electronic Reporting database and the electronic databases of bordering states. PATIENTS: Consecutive patients undergoing ileocolic resection for Crohn's disease from 2014 to 2018 were included. MAIN OUTCOME MEASURES: The outcomes examined were major complications (Clavien-Dindo ≥3a), length of stay, and 30-day hospital readmission. RESULTS: Fifty one of 118 patients were prescribed opioids within 6 months preoperatively (range, 0-33,760 morphine milligram equivalents). Patients with preoperative opioid prescription compared with no preoperative opioid prescription required more daily opioids during hospital admission (p = 0.024). Nineteen patients had a major postoperative complication (preoperative opioid prescription: 26% (13/51) vs no preoperative opioid prescription: 9% (6/67)). On multivariable analysis, preoperative opioid prescription (OR = 2.994 (95% CI, 1.024-8.751); p = 0.045) was a significant risk factor for a major complication. Preoperative opioid prescription was associated with increased length of stay (p < 0.001) and was a risk factor for readmission (OR = 2.978 (95% CI, 1.075-8.246); p = 0.036). Twenty-four patients were readmitted. Using a cutoff for higher opioid prescription of 300 morphine milligram equivalents within 6 months preoperation (eg, 60 tablets of hydrocodone/acetaminophen 5/325), preoperative opioid prescription remained a risk factor for major postoperative complications (OR = 3.148 (95% CI, 1.110-8.928); p = 0.031). LIMITATIONS: This was a retrospective study and could not assess nonprescribed opioid use. CONCLUSIONS: Preoperative opioid prescription was a significant risk factor for adverse outcomes in patients with Crohn's disease undergoing elective ileocolic resection. See Video Abstract at http://links.lww.com/DCR/B113. LA PRESCRIPCIÓN PREOPERATORIA DE OPIOIDES SE ASOCIA CON COMPLICACIONES MAYORES EN PACIENTES CON ENFERMEDAD DE CROHN SOMETIDOS A RESECCIÓN ILEOCÓLICA ELECTIVA: El uso de opioides ha crecido exponencialmente en la última década. Se desconoce el efecto de la prescripción preoperatoria de opioides en pacientes con enfermedad de Crohn sometidos a cirugía.Identificar si la prescripción preoperatoria de opioides está asociada con resultados postoperatorios adversos en la enfermedad de Crohn.Este es un estudio observacional retrospectivo de una sola institución.Este estudio se realizó en un centro académico de atención terciaria. Los detalles de la prescripción preoperatoria de opiáceos se recopilaron de la base de datos de "Kentucky All-Schedule Prescription Electronic Reporting" y de las bases de datos electrónicas de los estados fronterizos.Pacientes consecutivos sometidos a resección ileocólica por enfermedad de Crohn entre 2014-2018.Los resultados examinados fueron complicaciones mayores (Clavien-Dindo ≥3a), duración de la estancia y el reingreso hospitalario de 30 días.A cincuenta y uno de 118 pacientes se le recetaron opioides dentro de los 6 meses preoperatorios (rango, 0 a 33,760 equivalentes de miligramos de morfina). Los pacientes con prescripción preoperatoria de opioides en comparación con ninguna prescripción preoperatoria de opioides requirieron más opioides diarios durante el ingreso hospitalario (p = 0,024). Diecinueve pacientes tuvieron una complicación postoperatoria importante (prescripción preoperatoria de opioides: 26% [13/51] frente a ninguna prescripción preoperatoria de opioides: 9% [6/67]). En el análisis multivariable, la prescripción de opioides preoperatorios (OR = 2.994, IC 95%: 1.024-8.751, p = 0.045) fueron factores de riesgo significativos para una complicación mayor. La prescripción preoperatoria de opioides se asoció con un aumento de la duración de la estadía (p <0.001) y fue un factor de riesgo para el reingreso (OR = 2.978, IC 95%: 1.075-8.246, p = 0.036). Veinticuatro pacientes fueron readmitidos. Utilizando un límite para una mayor prescripción de opioides de 300 miligramos equivalentes de morfina dentro de los 6 meses previos a la operación (p. Ej., 60 tabletas de hidrocodona / acetaminofén 5/325), la prescripción preoperatoria de opioides siguió siendo un factor de riesgo para complicaciones postoperatorias mayores (OR = 3.148 IC 95%: 1.110-8.928, p = 0.031).Este fue un estudio retrospectivo y no pudo evaluar el uso de opioides no prescritos.La prescripción preoperatoria de opioides fue un factor de riesgo significativo para los resultados adversos en pacientes con enfermedad de Crohn sometidos a resección ileocólica electiva. Consulte Video Resumen en http://links.lww.com/DCR/B113.

Evaluating the Potential for Unintentional Occupational Exposure to Fentanyl and Fentanyl Analogues Among Medicolegal Death Investigators and Autopsy Technicians.

Recent increases in deaths in the United States from synthetic opioids such as fentanyl and fentanyl analogues (fentanyls) have raised concerns about possible occupational exposures to these potent agents. Medicolegal death investigators and autopsy suite staff might perform job tasks involving exposure to fentanyls. The potential for exposure to fentanyls among medicolegal death investigators and autopsy technicians at a state medical examiner's office was evaluated through review of caseload characteristics, injury and illness logs, and procedures and policies and discussions with management and employee representatives. The evaluation showed that this medical examiner's office had low potential for work-related exposure to fentanyls; its standard operating procedures and personal protective equipment requirements should reduce the potential for occupational exposure. Medicolegal death investigation agencies can develop and implement guidance to control exposures and provide workforce education and training to reduce the potential for work-related exposure to fentanyls.

Economic burden and clinical impact of preoperative opioid dependence for patients undergoing lower extremity bypass surgery.

OBJECTIVE: Surgeons' prescription practices and the opioid epidemic have received significant attention in the media. Limited data exist, however, on the impact of prior or coexistent opioid use on vascular surgery outcomes. This study aimed to quantify the incidence, economic burden, and clinical impact of pre-existing opioid dependency in patients undergoing lower extremity bypass (LEB) surgery. METHODS: Data were collected from 1,132,645 weighted (230,858 unweighted) patient admissions for LEB in the National Inpatient Sample for the years 2002 to 2015. Patients with a concomitant diagnosis of opioid abuse or dependency were identified using International Classification of Diseases, Ninth Revision codes. Matched cohorts of patients with (n = 606 unweighted) and without (n = 32,343 unweighted) opioid dependence were created using coarsened exact matching to control for patient demographics. Linear regression was used to control for hospital-level factors and to identify differential outcomes for patients with opioid dependency. Our primary end points were hospital cost and length of stay. Our secondary end points were surgical complications and in-hospital mortality. RESULTS: There were 1,132,645 (230,858 unweighted) patient admissions for LEB in the National Inpatient Sample during 2002 to 2015. There were 3190 (0.3%) patients (643 unweighted) who had a diagnosis of pre-existing opioid dependency. The incidence of opioid dependency rose over time (2002, 0.13%; 2015, 0.63%; R2 = 0.90; P < .001). Before matching, opioid-dependent patients were younger (53.9 ± 12.3 years vs 66.7 ± 12.1 years; P < .001) and more likely to be male (65.2% vs 61.9%; P < .001), to be nonwhite (37.9% vs 24.1%; P < .001), to pay with Medicaid (29.6% vs 7.4%; P < .001), and to fall in the lowest income quartile based on ZIP code (39.6% vs 27.5%; P < .001). After matching, opioid-dependent patients (n = 606 unweighted vs n = 32,343 unweighted nonopioid-dependent patients) were at increased risk of surgical site infections (odds ratio [OR], 1.61; P = .006), major bleeding (OR, 1.56; P = .04), acute kidney injury (OR, 1.46; P = .02), and deep venous thrombosis (OR, 2.53; P = .005). Linear regression of matched cohorts revealed that opioid-dependent patients had an increased length of hospital stay (11.76 days vs 9.80 days; P < .001) and an increased mean inflation-adjusted in-hospital cost of U.S. $7032 ($37,522 vs $30,490; P < .001). CONCLUSIONS: The incidence of pre-existing opioid dependency in patients undergoing LEB continues to rise. Patients with opioid use disorder undergoing LEB surgery have substantial increases in length of hospital stay and costs. These findings highlight the importance of early preoperative recognition of this disorder in vascular surgery patients and open the opportunity for early intervention in that cohort.

Health Outcomes Among Long-term Opioid Users With Testosterone Prescription in the Veterans Health Administration.

Importance: Androgen deficiency is common among male opioid users, and opioid use has emerged as a common antecedent of testosterone treatment. The long-term health outcomes associated with testosterone therapy remain unknown, however. Objective: To compare health outcomes between long-term opioid users with testosterone deficiency who filled testosterone prescriptions and those with the same condition but who did not receive testosterone treatment. Design, Setting, and Participants: This cohort study focused on men in the care of the Veterans Health Administration (VHA) facilities throughout the United States from October 1, 2008, to September 30, 2014. It included male veterans who were long-term opioid users, had low testosterone levels (<300 ng/dL), and received either a testosterone prescription or any other prescription. It excluded male patients with HIV infection, gender dysphoria, or prostate cancer and those who received testosterone in fiscal year 2008. Data were analyzed from April 1, 2017, to April 30, 2019. Exposure: Prescription for testosterone. Main Outcomes and Measures: All-cause mortality and incidence of major adverse cardiovascular events (MACE), vertebral or femoral fractures, and anemia during the 6-year follow-up through September 30, 2015. Results: After exclusions, 21 272 long-term opioid users (mean [SD] age, 53 [10] years; n = 16 689 [78.5%] white) with low total or free testosterone levels were included for analysis, of whom 14 121 (66.4%) received testosterone and 7151 (33.6%) did not. At baseline, compared with opioid users who did not receive testosterone, long-term opioid users who received testosterone treatment were more likely to have obesity (43.7% vs 49.0%; P < .001), hyperlipidemia (43.0% vs 48.8%; P < .001), and hypertension (53.9% vs 55.2%; P = .07) but had lower prevalence of coronary artery disease (15.9% vs 12.9%; P < .001) and stroke (2.4% vs 1.3%; P < .001). After adjusting for covariates, opioid users who received testosterone had significantly lower all-cause mortality (hazard ratio [HR] = 0.51; 95% CI, 0.42-0.61) and lower incidence of MACE (HR = 0.58; 95% CI, 0.51-0.67), femoral or hip fractures (HR = 0.68; 95% CI, 0.48-0.96), and anemia (HR = 0.73; 95% CI, 0.68-0.79) during the follow-up period of up to 6 years, compared with their counterparts without a testosterone prescription. In covariate-adjusted models, men who received opioids plus testosterone were more likely to have resolved anemia compared with those who received opioids only during the 6-year follow-up (HR = 1.16; 95% CI, 1.02-1.31). Similar results were obtained in propensity score-matched models and when analyses were restricted to opioid users with noncancer pain or those who did not receive glucocorticoids. Conclusions and Relevance: This study found that, in the VHA system, male long-term opioid users with testosterone deficiency who were treated with opioid and testosterone medications had significantly lower all-cause mortality and significantly lower incidence of MACE, femoral or hip fractures, and anemia after a multiyear follow-up. These results warrant confirmation through a randomized clinical trial to ascertain the efficacy of testosterone in improving health outcomes for opioid users with androgen deficiency.