Caracterización clínica y epidemiológica de los pacientes con trastorno por uso de opioides atendidos en una institución de cuarto nivel en la ciudad de Medellín, entre 2017 y 2022 / Clinical and epidemiological characterization of patients with opioid use disorder treated at a fourth level institution in the city of Medellín, between 2017 and 2022

Los analgésicos opioides son una opción importante en el manejo del dolor agudo grave, crónico e intratable, sin embargo, sus efectos euforizantes y gratificantes han motivado a que algunos pacientes continúen su uso una vez resuelta la condición médica inicial, haciendo entonces un uso indebido de opioides (UIO) y con el potencial riesgo de desarrollar un trastorno por uso de opioides (TUO). El objetivo del presente trabajo fue caracterizar clínica y epidemiológicamente a los pacientes con trastorno por uso de opioides atendidos en una institución de cuarto nivel de Medellín. Para ello, se realizó un estudio observacional, descriptivo, transversal de fuente secundaria; se incluyeron 309 registros de pacientes adultos, con diagnóstico CIE-10, trastornos causados por opiáceos. TUO e UIO constituyeron las variables de interés, se procesó la información en Jamovi® versión 2.2 y se analizaron los datos de variables cuantitativas con test de Sahpiro Wilk y análisis bivariado exploratorio de las variables clínicas y sociodemográficas. Resultados: El TUO obtuvo una prevalencia del 39.9% frente al 25,6 % del UIO. De los pacientes con TUO el 50% tenían 35 años o menos, el 57.7% fueron mujeres, 58.7% solteros, y predominaron los niveles de educación secundaria y universitaria. En cuanto al UIO, el 50% fueron menores de 37 años el 54% de sexo femenino, en su mayoría solteros (61.5%), y predominó el nivel de educación secundaria (48.7%). En el 71% de los pacientes con TUO hay antecedentes de enfermedad mental predominando los trastornos del afecto: ansiedad y depresión. El opioide más usado fue tramadol (17.04%), seguido de morfina e hidromorfona. Conclusión: Ante el aumento en la prevalencia de UIO y TUO es necesario nuevas políticas salud pública que permitan ejercer un control más estricto en la formulación, comercialización y administración segura de este tipo de medicamentos.(AU)

Opioids analgesics are an important option in the management of severe acute, chronic, and intractable pain; however, their euphoric and rewarding effects have motivated some patients to continue their use once the initial medical condition has resolved, thus misusing them. these (UIO) and with the potential risk of developing an opioid use disorder (OUD).Objectives: to clinically and epidemiologically characterize patients with opioid use disorder treated at a fourth-level institution in Medellín.Methodology: Observational, descriptive, cross-sectional study of secondary source; 309 records of adult patients with ICD-10, diagnosis caused by opioids agents were included. TUO and IOU were the variables of interest, the information was processed in Jamovi® version 2.2 and the data of quantitative variables were analyzed with the Sahpiro Wilk test and exploratory bivariate analysis of the clinical and sociodemographic variables.Results: The TUO obtained a prevalence of 39.9% compared to 25.6% of the UIO. Of the patients with OT, 50% were 35 years of age or younger, 57.7% were women, 58.7% were single, and secondary and university education levels predominated. Regarding the UIO, 50% were under 37 years of age, 54% female, mostly single (61.5%), and the secondary education level predominated (48.7%).In 71% of patients with OLW there is a history of mental illness, predominantly affective disorders: anxiety and depression. The most used opioid was tramadol (17.04%), followed by morphine and hydromorphone. Conclusion: Given the increase in the prevalence of UIO and OTU, new public health policies are necessary to exercise stricter control in the formulation, marketing and safe administration of this type of medication.(AU)

Novel treatments for chronic pain: moving beyond opioids.

It is essential that safe and effective treatment options be available to patients suffering from chronic pain. The emergence of an opioid epidemic has shaped public opinions and created stigmas surrounding the use of opioids for the management of pain. This reality, coupled with high risk of adverse effects from chronic opioid use, has led chronic pain patients and their healthcare providers to utilize nonopioid treatment approaches. In this review, we will explore a number of cellular reorganizations that are associated with the development and progression of chronic pain. We will also discuss the safety and efficacy of opioid and nonopioid treatment options for chronic pain. Finally, we will review the evidence for adenylyl cyclase type 1 (AC1) as a novel target for the treatment of chronic pain.

Evaluation of Opioid Prescribing Patterns and Drivers of Variation Following Endoscopic Procedures for Benign Prostatic Hyperplasia Across an Integrated Academic Health System.

OBJECTIVES: To evaluate patient, provider, and facility factors associated with variation in opioid prescribing after endoscopic procedures for benign prostatic hyperplasia across a large academic health system to drive improvement efforts. METHODS: Opioids prescribed at discharge for patients who underwent an endoscopic prostate procedure March 2018-November 2019 were analyzed. Multivariable logistic and linear regression were used to evaluate the relationship between patient, provider, and facility factors and the receipt of any opioid prescription and the quantity prescribed. RESULTS: We included 724 patients who had surgery with one of 26 urologists across five facilities. 222 (30.7%) received an opioid prescription, and the average morphine milligram equivalents (MMEs) prescribed was 97.9±33.5. We found wide variation in the proportion of patients who received an opioid prescription across surgeons (range 0%-88.9%) and facilities (range 19.9%-66.7%) and the average MMEs prescribed (range 25-188.5). Outpatient surgery (OR 2.32; 95% confidence interval [CI] 1.22-4.40, P = .010) and preoperative opioid use (OR 15.04; CI 9.65-23.45, P < .001) were associated with higher rates of opioid prescribing, while prescribing decreased with increasing patient age (OR 0.97; CI 0.95-0.99, P = 0.016). Multivariable linear regression analysis demonstrated an association between surgery at satellite facilities, having a surgeon in practice for at least 20 years, and higher surgeon volume with increased MMEs prescribed. CONCLUSIONS: Opioid prescribing following endoscopic prostate procedures varied widely. Targeted interventions tailored to younger patients, those taking opioids preoperatively, recipients of outpatient surgery and those undergoing surgery at satellite facilities may be particularly high yield given the association between these factors and increased postoperative prescribing.

Short-acting and Long-acting Opioids Utilization among Women Diagnosed with Endometriosis in the United States: A Population-based Claims Study.

STUDY OBJECTIVE: To determine the prevalence and pattern of opioid use in endometriosis and the characteristics of patients prescribed an opioid using medical insurance claims data. DESIGN: We performed a retrospective cohort analysis of data from the Truven MarketScan Commercial database for the period of January 1, 2011 to December 31, 2016. SETTING: The Truven database includes inpatient, outpatient, and prescription claims covering more than 115 million unique individuals and over 36 million inpatient hospital discharges across multiple payer types and all 50 states. PATIENTS: Women with endometriosis were defined as those with 1 inpatient or 2 outpatient codes for endometriosis. INTERVENTIONS: No interventions were assigned. Women who filled an opioid prescription within 12 months of diagnosis were placed in the opioid cohort and women who did not fill an opioid prescription were placed in the nonopioid cohort. MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were evaluated 12 months preindex (date of the first diagnosis) and opioid use was assessed for 12 months after the index date. The dataset included 58 472 women with endometriosis. Of these, 61.7% filled an opioid prescription during the study period. More than 95% filled prescriptions for short-acting opioids (SAOs) only, 4.1% filled prescriptions for both SAOs and extended-release/long-acting opioids (LAOs), and 0.6% filled prescriptions for LAOs only. Patients who filled an opioid prescription had higher baseline comorbidities (especially gynecologic and chronic pain comorbidities) and endometriosis-related medication use compared with patients who did not fill an opioid prescription during the study period. Patients who filled both LAO and SAO prescriptions had the highest total days' supply of opioids, the proportion of days covered by prescriptions, and morphine equivalent daily dose. These patients also had the highest proportions of opioid switching and dose augmentation. Statistical trends in data were not substantially altered when analyses excluded patients with chronic pain comorbidities or surgical opioid prescriptions. CONCLUSION: Although opioids are not a recommended treatment for endometriosis, more than half of our cohort filled an opioid prescription within 1 year after a first recorded diagnosis of endometriosis. Patients who filled an opioid prescription tended to use more endometriosis-related medications and have a higher comorbidity burden. Additional research is necessary to better understand the reasons and outcomes associated with opioid utilization in endometriosis and to determine if there is a more effective pain management treatment plan for patients taking opioids.

The association between initial opioid type and long-term opioid use after hip fracture surgery in elderly opioid-naïve patients.

Objectives Long-term opioid use after hip fracture surgery has been demonstrated in previously opioid-naïve elderly patients. It is unknown if the opioid type redeemed after hip surgery is associated with long-term opioid use. The aim of this study was to examine the association between the opioid type redeemed within the first three months after hip fracture surgery and opioid use 3-12 months after the surgery. Methods A nationwide population-based cohort study was conducted using data from Danish health registries (2005-2015). Previously opioid-naïve patients registered in the Danish Multidisciplinary Hip Fracture Registry, aged ≥65 years, who redeemed ≥1 opioid prescription within three months after the surgery, were included. Long-term opioid use was defined as ≥1 redeemed prescription within each of three three-month periods within the year after hip fracture surgery. The proportion with long-term opioid use after surgery, conditioned on nine-month survival, was calculated according to opioid types within three months after surgery. Adjusted odds ratios (aOR) for different opioid types were computed by logistic regression analyses with 95% confidence intervals (CI) using morphine as reference. Subgroup analyses were performed according to age, comorbidity and calendar time before and after 2010. Results The study included 26,790 elderly, opioid-naïve patients with opioid use within three months after hip fracture surgery. Of these patients, 21% died within nine months after the surgery. Among the 21,255 patients alive nine months after surgery, 15% became long-term opioid users. Certain opioid types used within the first three months after surgery were associated with long-term opioid use compared to morphine (9%), including oxycodone (14%, aOR; 1.76, 95% CI 1.52-2.03), fentanyl (29%, aOR; 4.37, 95% CI 3.12-6.12), codeine (13%, aOR; 1.55, 95% CI 1.14-2.09), tramadol (13%, aOR; 1.56, 95% CI 1.35-1.80), buprenorphine (33%, aOR; 5.37, 95% CI 4.14-6.94), and >1 opioid type (27%, aOR; 3.83, 95% CI 3.31-4.44). The proportion of long-term opioid users decreased from 18% before 2010 to 13% after 2010. Conclusions The findings suggest that use of certain opioid types after hip fracture surgery is more associated with long-term opioid use than morphine and the proportion initiating long-term opioid use decreased after 2010. The findings suggest that some elderly, opioid-naïve patients appear to be presented with untreated pain conditions when seen in the hospital for a hip fracture surgery. Decisions regarding the opioid type prescribed after hospitalization for hip fracture surgery may be linked to different indication for pain treatment, emphasizing the likelihood of careful and conscientious opioid prescribing behavior.

Diseñando opioides más seguros: ¿opioides atípicos o «multigésicos»? / Designing safer opioids: atypical or «multigesic» opioids?

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Brief Report: Opioid-Involved Overdose Mortality in United States Veterans.

BACKGROUND AND OBJECTIVES: The purpose of this study is to assess trends in opioid-involved overdose mortality among US Veterans. METHODS: Age-adjusted drug overdose mortality rates, overall and by opioid subtype, were assessed from National Death Index data for US Veterans; statistical significance of trends was assessed for 2010 to 2015 and 2015 to 2016. RESULTS: Veteran age-adjusted overdose mortality rates increased 23.7% from 2010 to 2015 (19.7-24.4 of 100 000) and a further 20.4% through 2016 (29.3 of 100 000). Opioid involvement increased from 51.3% in 2010 to 62.1% in 2016, as opioid overdose rates increased from 10.9 to 19.5 of 100 000. Overdose mortality varied substantially by opioid subtype and demographics. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This report provides the first-ever description of trends and characteristics of overdose mortality and opioid-involved deaths among US Veterans of military service for the period 2010 to 2016. With the exception of female Veterans and Veterans in Western States, it has been found that trends in Veteran overdose mortality paralleled rising rates of drug overdose observed in the United States more broadly. Published 2020. This article is a U.S. Government work and is in the public domain in the USA. (Am J Addict 2020;00:00-00).

Changes in Australian prescription opioid use following codeine rescheduling: A retrospective study using pharmaceutical benefits data.

PURPOSE: In February 2018, Australia up-scheduled the 'weak' opioid codeine to a prescription only medication. This study aimed to analyse the change in prescribing trends for codeine and other commonly prescribed opioids in Australia following this policy change to determine if removal of over-the-counter codeine resulted in an increase in opioid prescribing. METHODS: Data was obtained through the Australian Government Department of Human Services statistics website, and contained monthly data about subsidised national prescription numbers for codeine, oxycodone, oxycodone-naloxone, tapentadol, tramadol, morphine, and fentanyl, from January 2016 to December 2018. Segmented linear regression accounting for autocorrelation was used to assess the effect of codeine rescheduling on the supply trends of these opioids. RESULTS: Rescheduling codeine to remove over-the-counter (non-prescription) supply does not appear to have had an immediate effect on the prescription rates of codeine, and there is no significant change in these rates in the months following. Analysis of data showed decreasing trends for codeine and most other schedule 8 prescription opioids, with no increase in any prescribed opioids associated with codeine up scheduling. CONCLUSIONS: Despite concerns, substitution of over-the-counter codeine with higher strength prescribed codeine has not been observed at a population level, nor has a shift to other prescribed opioids occurred. Overall, opioid prescribing in Australia has been decreasing since 2016, both for strong and weak opioids.

Prescription opioid dispensing in Australian children and adolescents: a national population-based study.

BACKGROUND: There are few population-based studies of paediatric opioid use. We aimed to investigate the prevalence of opioid dispensing in Australian children and adolescents. METHODS: In this population-based study, we used data from a random sample of 15% of the children and adolescents who had received any medicines between Feb 1, 2013, and Dec 31, 2017, through the Australian Pharmaceutical Benefits Scheme (PBS). We identified children younger than 18 years who had been dispensed at least one PBS-listed opioid in the study period. We calculated the annual prevalence of children being dispensed one or more opioid presciptions, by age group and by opioid characteristics (such as strength and mode of action), and we assessed trends over time with negative binomial regression. We also identified new treatment episodes and quantified the number of opioid prescriptions dispensed in the ensuing year. FINDINGS: During the study period, 78 320 opioid prescriptions were dispensed to 50 730 Australian children, aged 0-17 years, in our sample. In 2017, 135·4 children per 10 000 were dispensed opioids, representing a slight decrease equal to a change of -2·2% (95% CI -3·5 to -0·8) per annum since 2013. The prevalence of opioid dispensing was greater at older ages: in 2017, 5·7 infants per 10 000 younger than 1 year were dispensed opioids, versus 404·8 adolescents per 10 000 aged 13-17 years, meaning that roughly one in 25 adolescents were dispensed opioids. Weak opioids (ie, codeine and tramadol) accounted for 60·7% of the opioids dispensed, and codeine was the most commonly dispensed opioid, accounting for 39 531 (50·5%) prescriptions dispensed. The prevalence of weak opioid dispensing significantly decreased in all age groups (other than infants younger than 1 year), particularly in those younger than 12 years, for whom weak opioids are not recommended. Dispensing of strong opioids, particularly oxycodone, increased in every age group. Of the 29 073 children who received a new course of treatment, 23 318 (80·2%) children were dispensed only one prescription of opioids in that year. Those dispensed two or more opioids were more likely to be adolescents (vs children younger than 13 years), female, and to have been dispensed several unique medicine types in the 3 previous months (vs those receiving one or fewer types). INTERPRETATION: In 2017, one in 74 Australian children, including one in 25 adolescents, were dispensed an opioid. Dispensing of weak opioids decreased between 2013 and 2017, but codeine is still commonly dispensed in younger children and education to reduce this practice is required. Dispensing of strong opioids increased in all age groups. Children and adolescents must receive appropriate pain management, but further evidence on the risks and benefits of opioid use in this young population is needed. FUNDING: Financial Markets Foundation for Children, National Health and Medical Research Council Centre of Research Excellence in Medicines and Ageing, Australian Government Department of Industry, Innovation and Science, Research Foundation of the Cerebral Palsy Alliance (Australia).

Designing traceable opioid material§ kits to improve laboratory testing during the U.S. opioid overdose crisis.

In 2017, the U.S. Department of Health and Human Services and the White House declared a public health emergency to address the opioid crisis (Hargan, 2017). On average, 192 Americans died from drug overdoses each day in 2017; 130 (67%) of those died specifically because of opioids (Scholl et al., 2019). Since 2013, there have been significant increases in overdose deaths involving synthetic opioids - particularly those involving illicitly-manufactured fentanyl. The U.S. Drug Enforcement Administration (DEA) estimates that 75% of all opioid identifications are illicit fentanyls (DEA, 2018b). Laboratories are routinely asked to confirm which fentanyl or other opioids are involved in an overdose or encountered by first responders. It is critical to identify and classify the types of drugs involved in an overdose, how often they are involved, and how that involvement may change over time. Health care providers, public health professionals, and law enforcement officers need to know which opioids are in use to treat, monitor, and investigate fatal and non-fatal overdoses. By knowing which drugs are present, appropriate prevention and response activities can be implemented. Laboratory testing is available for clinically used and widely recognized opioids. However, there has been a rapid expansion in new illicit opioids, particularly fentanyl analogs that may not be addressed by current laboratory capabilities. In order to test for these new opioids, laboratories require reference standards for the large number of possible fentanyls. To address this need, the Centers for Disease Control and Prevention (CDC) developed the Traceable Opioid Material§ Kits product line, which provides over 150 opioid reference standards, including over 100 fentanyl analogs. These kits were designed to dramatically increase laboratory capability to confirm which opioids are on the streets and causing deaths. The kits are free to U.S based laboratories in the public, private, clinical, law enforcement, research, and public health domains.

Analgesic drug use in elderly persons: A population-based study in Southern Italy.

INTRODUCTION: Analgesics such as non-steroidal anti-inflammatory drugs (NSAIDs), weak and strong opioids are commonly used among elderly persons. The aim of this study was to describe the demographic and clinical characteristics of elderly analgesic users and to measure the frequency of analgesic use, including the frequency of potentially inappropriate analgesic use. METHODS: The Arianna database was used to carry out this study. This database contains prescription data with associated indication of use for 1,076,486 inhabitants registered with their general practitioners (GPs) in the Caserta Local Health Unit (Caserta district, Campania region in Italy). A cohort of persons aged ≥65 years old with >1 year of database history having at least one analgesic drug (NSAIDs, strong or weak opioids) between 2010 and 2014 were identified. The date of the first analgesic prescription in the study period was considered the index date (ID). RESULTS: From a source population of 1,076,486 persons, 116,486 elderly persons were identified. Of these, 94,820 elderly persons received at least one analgesic drug: 36.6% were incident NSAID users (N = 36,629), while 13.2% were incident weak opioid users (N = 12,485) and 8.1% were incident strong opioid users (N = 7,658). In terms of inappropriate analgesic use, 9.2% (N = 10,763) of all elderly users were prescribed ketorolac/indomethacin inappropriately, since these drugs should not be prescribed to elderly persons. Furthermore, at least half all elderly persons with chronic kidney disease or congestive heart failure were prescribed NSAIDs, while these drugs should be avoided. CONCLUSION: Analgesics are commonly used inappropriately among elderly persons, suggesting that prescribing practice in the catchment area may yet be improved.

Changes in Opioid-Involved Overdose Deaths by Opioid Type and Presence of Benzodiazepines, Cocaine, and Methamphetamine - 25 States, July-December 2017 to January-June 2018.

From 2013 to 2017, the number of opioid-involved overdose deaths (opioid deaths) in the United States increased 90%, from 25,052 to 47,600.* This increase was primarily driven by substantial increases in deaths involving illicitly manufactured fentanyl (IMF) or fentanyl analogs† mixed with heroin, sold as heroin, or pressed into counterfeit prescription pills (1-3). Methamphetamine-involved and cocaine-involved deaths that co-involved opioids also substantially increased from 2016 to 2017 (4). Provisional 2018§ estimates of the number of opioid deaths suggest a small decrease from 2017. Investigating the extent to which decreases occurred broadly or were limited to a subset of opioid types (e.g., prescription opioids versus IMF) and drug combinations (e.g., IMF co-involving cocaine) can assist in targeting of intervention efforts. This report describes opioid deaths during January-June 2018 and changes from July-December 2017 in 25¶ of 32 states and the District of Columbia participating in CDC's State Unintentional Drug Overdose Reporting System (SUDORS).** Opioid deaths were analyzed by involvement (opioid determined by medical examiner or coroner to contribute to overdose death) of prescription or illicit opioids,†† as well as by the presence (detection of the drug in decedent) of co-occurring nonopioid drugs (cocaine, methamphetamine, and benzodiazepines). Three key findings emerged regarding changes in opioid deaths from July-December 2017 to January-June 2018. First, overall opioid deaths decreased 4.6%. Second, decreases occurred in prescription opioid deaths without co-involved illicit opioids and deaths involving non-IMF illicit synthetic opioids (fentanyl analogs and U-series drugs) (5). Third, IMF deaths, especially those with multiple illicit opioids and common nonopioids, increased. Consequently, IMF was involved in approximately two-thirds of opioid deaths during January-June 2018. Notably, during January-June 2018, 62.6% of all opioid deaths co-occurred with at least one common nonopioid drug. To maintain and accelerate reductions in opioid deaths, efforts to prevent IMF-involved deaths and address polysubstance misuse with opioids must be enhanced. Key interventions include broadening outreach to groups at high risk for IMF or fentanyl analog exposure and overdose. Improving linkage to and engagement in risk-reduction services and evidence-based treatment for persons with opioid and other substance use disorders with attention to polysubstance use or misuse is also needed.

Opioids Prescribed at Discharge or Given During Emergency Department Visits Among Adults in the United States, 2016.

Opioid analgesics are primarily used to treat chronic and acute pain and, when used appropriately, can be an important part of treatment (1). Pain is a major symptom of patients visiting the emergency department (ED), with up to 42% of ED visits being related to pain (2). Opioids may either be administered in the ED as part of treatment, provided post-treatment in the form of a prescription, or both (3). This report compares rates and percentages of ED visits by adults at which opioids were only given in the ED, only prescribed at discharge, or both, by selected characteristics.

Consumption trends and prescription patterns of opioids from 2011 to 2016: a survey in a Chinese city.

OBJECTIVE: Opioid consumption in China has been very less and has varied widely since 1995. The representatively high level of consumption in Mainland China has never been reported. Our aim was to describe the consumption trends and prescription patterns of opioids in Nanjing, a highly developed city of Mainland China, and compare the results with selected worldwide regions. METHODS: Application data of opioids in 2011-2016 were extracted from the Jiangsu Medicine Information Institute. Six opioids were included. Consumption was expressed in terms of defined daily doses (DDDs), morphine equivalents (MEs) and expenditure. The correlation between consumption of opioids and gross domestic product (GDP), Human Development Index (HDI) and cancer incidence was analysed by Pearson's correlation test. RESULTS: DDDs, expenditure and MEs of opioids were, respectively, 256.04, $599.24 and 13.07 g in 2011, and increased to 361.27, $1041.79 and 18.09 g in 2016. DDDs in Nanjing were 2.80-fold that in Mainland China, 1.42-fold that in East and South-East Asia, but only equivalent to 8.89% of the worldwide average level. From 2011 to 2016, the consumption had a linear correlation with GDP, HDI and cancer incidence (p<0.05). However, DDDs varied greatly in countries with similar GDP or HDI. Within 45 Asian countries, the GDP only contributed to 10.47% of change in DDDs, while the HDI contributed to 20.32%. Consumption of non-intravenous opioids or strong opioids always comprised majority of the total consumption. The opioids prescribed predominantly were fentanyl, oxycodone and morphine. Fentanyl and oxycodone account for most of the increase in consumption. CONCLUSION: Opioid consumption has increased >40% from 2011 to 2016, with consumption of fentanyl and oxycodone accounting for most of that increase. The consumption in Nanjing was higher than the average Chinese level, but lower than the global average. An increase in pain control services might be needed, but this need should be highly regulated.

Assessment of Changes in the Geographical Distribution of Opioid-Related Mortality Across the United States by Opioid Type, 1999-2016.

Importance: As the opioid epidemic evolves, it is vital to identify changes in the geographical distribution of opioid-related deaths, and the specific opioids to which those deaths are attributed, to ensure that federal and state public health interventions remain appropriately targeted. Objective: To identify changes in the geographical distribution of opioid-related mortality across the United States by opioid type. Design, Setting, and Participants: Cross-sectional study using joinpoint modeling and life table analysis of individual-level data from the National Center for Health Statistics on 351 630 US residents who died from opioid-related causes from January 1, 1999, to December 31, 2016, for all of the United States and the District of Columbia. The analysis was conducted from September 6 to November 23, 2018. Exposures: Deaths involving any opioid, heroin, synthetic opioids, and natural and semisynthetic opioids. Main Outcomes and Measures: Opioid-related mortality rate, annual percent change in the opioid-related mortality rate, and life expectancy lost at age 15 years by state and opioid type. Results: From 1999 to 2016, a total of 231 264 men and 120 366 women died from opioid-related causes across the whole United States. Sixty-six observations were removed owing to missing data on age; therefore, 351 564 US residents were included in this study. The mean (SD) age at death was 39.8 (12.5) years for men and was 43.5 (12.9) years from women. Opioid-related mortality rates, especially from synthetic opioids, rapidly increased in all of the eastern United States. In most states, mortality associated with natural and semisynthetic opioids (ie, prescription painkillers) remained stable. In contrast, 28 states had mortality rates from synthetic opioids that more than doubled every 2 years (ie, annual percent change, ≥41%), including 12 with high mortality rates from synthetic opioids (>10 per 100 000 people). Among these 28 states, the mortality rate from natural and semisynthetic opioids ranged from 2.0 to 18.7 per 100 000 people (with a mean mortality rate of 6.0 per 100 000 people). The District of Columbia had the fastest rate of increase in mortality from opioids, more than tripling every year since 2013 (annual percent change, 228.3%; 95% CI, 169.7%-299.6%; P < .001), and a high mortality rate from synthetic opioids in 2016 (18.8 per 100 000 people); the mortality rate from natural and semisynthetic opioids was 6.9 per 100 000 people. Nationally, overall opioid-related mortality resulted in 0.36 years of life expectancy lost in 2016, which was 14% higher than deaths due to firearms and 18% higher than deaths due to motor vehicle crashes; 0.17 years of the life expectancy lost was due specifically to synthetic opioids. In 2016, New Hampshire and West Virginia lost more than 1 year of life expectancy due to opioid-related mortality. Conclusions and Relevance: Opioid-related mortality, particularly mortality associated with synthetic opioids, has increased in the eastern United States. These findings indicate that policies focused on reducing opioid-related deaths may need to prioritize synthetic opioids and rapidly expanding epidemics in northeastern states and consider the potential for synthetic opioid epidemics outside of the heroin supply.

Members of the same pharmacological family are not alike: Different opioids, different consequences, hope for the opioid crisis?

Pain management is the specialized medical practice of modulating pain perception and thus easing the suffering and improving the life quality of individuals suffering from painful conditions. Since this requires the modulation of the activity of endogenous systems involved in pain perception, and given the large role that the opioidergic system plays in pain perception, opioids are currently the most effective pain treatment available and are likely to remain relevant for the foreseeable future. This contributes to the rise in opioid use, misuse, and overdose death, which is currently characterized by public health officials in the United States as an epidemic. Historically, the majority of preclinical rodent studies were focused on morphine. This has resulted in our understanding of opioids in general being highly biased by our knowledge of morphine specifically. However, recent in vitro studies suggest that direct extrapolation of research findings from morphine to other opioids is likely to be flawed. Notably, these studies suggest that different opioid analgesics (opioid agonists) engage different downstream signaling effects within the cell, despite binding to and activating the same receptors. This recognition implies that, in contrast to the historical status quo, different opioids cannot be made equivalent by merely dose adjustment. Notably, even at equianalgesic doses, different opioids could result in different beneficial and risk outcomes. In order to foster further translational research regarding drug-specific differences among opioids, here we review basic research elucidating differences among opioids in pharmacokinetics, pharmacodynamics, their capacity for second messenger pathway activation, and their interactions with the immune system and the dopamine D2 receptors.

Poor Identification of Emergency Department Acute Recreational Drug Toxicity Presentations Using Routine Hospital Coding Systems: the Experience in Denmark, Switzerland and the UK.

BACKGROUND: Understanding emergency department and healthcare utilisation related to acute recreational drug toxicity (ARDT) generally relies on nationally collated data based on ICD-10 coding. Previous UK studies have shown this poorly captures the true ARDT burden. The aim of this study was to investigate whether this is also the case elsewhere in Europe. METHODS: The Euro-DEN Plus database was interrogated for all presentations 1st July to 31st December 2015 to the EDs in (i) St Thomas' Hospital, London, UK; (ii) Universitätsspital Basel, Basel, Switzerland; and (iii) Zealand University Hospital, Roskilde, Denmark. Comparison of the drug(s) involved in the presentation with the ICD-10 codes applied to those presentations was undertaken to determine the proportion of cases where the primary/subsequent ICD-10 code(s) were ARDT related. RESULTS: There were 619 presentations over the 6-month period. Two hundred thirteen (34.4%) of those presentations were coded; 89.7% had a primary/subsequent ARDT-related ICD-10 code. One hundred percent of presentations to Roskilde had a primary ARDT ICD-10 code compared to 9.6% and 18.9% in Basel and London respectively. Overall, only 8.5% of the coded presentations had codes that captured all of the drugs that were involved in that presentation. CONCLUSIONS: While the majority of primary and secondary codes applied related to ARDT, often they did not identify the actual drug(s) involved. This was due to both inconsistencies in the ICD-10 codes applied and lack of ICD-10 codes for the drugs/NPS. Further work and education is needed to improve consistency of use of current ICD-10 and future potential ICD-11 coding systems.

Trends in Opioid Prescribing and Dispensing by Veterinarians in Pennsylvania.

Importance: Veterinarians are a subset of opioid prescribers. Objective: To assess the quantity and trends in prescribing and dispensing of several different opioids in the past 11 years in a large veterinary hospital in Philadelphia, Pennsylvania. Design, Setting, and Participants: This cross-sectional study inventoried all opioid tablets and/or patches dispensed or prescribed by veterinarians practicing in a multispecialty academic veterinary teaching hospital in Philadelphia for small animals and species, such as rabbits, birds, and reptiles, from January 1, 2007, through December 31, 2017. Prescribing data were obtained from all veterinarians who wrote a prescription for opioids by reviewing detailed pharmacy records of controlled substances for the study period. Data included all opioids dispensed, or prescribed to animals (patients) undergoing evaluation at the center or being followed up as outpatients by the veterinarians in the hospital. Statewide veterinarian prescribing data were used for comparison. Data were analyzed from December 24, 2017, through May 15, 2018. Main Outcomes and Measures: The trend in administration and prescribing of 4 specific opioid analgesics (codeine sulfate, hydrocodone bitartrate, and tramadol hydrochloride tablets as well as fentanyl citrate patch) during the 11-year study period. The individual opioids were converted to morphine milligram equivalents (MME) for comparison. Results: The study included 134 veterinarians (70.9% women) with 366 468 patient visits. During the study period, the hospital veterinarians prescribed 105 183 689 tablets of tramadol, 97 547 tablets of hydrocodone, 38 939 tablets of codeine, and 3153 fentanyl patches to dogs (73.0%), cats (22.5%), and exotic animals (4.5%). Overall, MME use increased 41.2%, whereas visits increased by 12.8%. The comparison data for Pennsylvania revealed a predominance of hydrocodone use (688 340 tablets prescribed), although data were not available for comparison with tramadol because it is a Schedule IV drug. Conclusions and Relevance: Results of this study suggest that the large, increasing volume of opioids prescribed at 1 veterinary teaching hospital highlights concerns parallel to those about excessive opioid prescribing in humans. The extent to which these data may represent similar volumes of prescriptions from the general veterinary practices and hospitals across the United States is suggested by the accompanying Pennsylvania state data. These findings highlight an opportunity to assess the risk of veterinarian opioid prescriptions to safeguard public health.

Drug Overdose Deaths in the United States, 1999-2017.

Deaths from drug overdose continue to be a public health burden in the United States (1-5). This report uses the most recent final mortality data from the National Vital Statistics System (NVSS) to update trends in drug overdose deaths, describe demographic and geographic patterns, and identify shifts in the types of drugs involved.