The effects of opium on the cardiovascular system: a review of side effects, uses, and potential mechanisms.

BACKGROUND: In Iran, as in many other Asian and Middle Eastern countries, some believe that opium has beneficial effects on cardiovascular system. Dependent patients suppose that opium has positive effects on cardiovascular function and can prevent or improve cardiovascular diseases; however, only few comprehensive studies evaluating such effects have been performed. OBJECTIVES: In this study, we sought to clarify the effect of opium on cardiovascular problems by incorporating the previous findings and the current information on the issue and to explain the possible mechanisms of this effect. METHODS: The available human studies published up to October 30, 2019, were searched in different databases. Case-control, cohort, and cross-sectional studies were retrieved. Papers published in English or those with an English abstract were included. The risk of bias for each included study was assessed based on the Newcastle-Ottawa Scale (NOS). We then categorized the effects of opium on cardiovascular problems along with its probable underlying mechanisms of action. RESULTS: In this study, most of the published articles suggested the adverse effects of opium on the cardiovascular system, including atherosclerosis, myocardial infarction, arrhythmia, low ejection fraction, and cardiovascular mortality; however, some articles reported the beneficial or impartial effects of opium on the cardiovascular system. In this article, we have categorized all the effects of opium on cardiovascular system; also, the proposed mechanisms of action of opium in each of the above-mentioned disorders are summarized. CONCLUSION: Although the available evidences were incoherent, it was mostly suggested that opium use does not protect against or improve cardiovascular problems.

A Clinical Nurse Specialist-Led Emergency Department Naloxone Distribution Program.

PURPOSE: This article describes the implementation of a clinical nurse specialist-led emergency department overdose education and naloxone distribution program. The program's purpose is to increase naloxone availability to reduce opiate overdose mortality rates within the local community. DESCRIPTION OF PROGRAM: The program distributes naloxone kits to patients in the emergency department after an opioid overdose. The kits are designed to help recipients prevent, recognize, and respond to an opioid overdose. OUTCOME: The program, which includes naloxone take-home kits and clinical guidelines outlining a standard of care for naloxone distribution and coprescribing, was successfully implemented across 11 emergency departments within an integrated health system. More than 250 kits were dispensed within the first year of program implementation along with an online patient education video that received more than 1600 views. In 2017, the county reported an opioid-related overdose death rate of 16.5 (per 100 000 residents). From January 2018 to June 2019, the opioid-related death rate per 100 000 residents was reported at 9.6. CONCLUSION: Although emergency department naloxone distribution programs are feasible in the acute care setting, it was critical for clinical nurse specialists to enlist an interdisciplinary team and engage executive leadership to ensure program success. For others considering such a program, early consideration should be given to determining financial support and evaluating the compliance and regulatory aspects of dispensing medications from emergency settings.

Risk of death associated with kratom use compared to opioids.

Kratom use appears to be increasing across the United States, increasing attention to deaths in which kratom use was detected. Most such deaths have been ascribed to fentanyl, heroin, benzodiazepines, prescription opioids, cocaine and other causes (e.g., homicide, suicide and various preexisting diseases). Because kratom has certain opioid-like effects (e.g., pain relief), and is used by some people as a substitute for opioids for pain or addiction, kratom has been compared to "narcotic-like opioids" (e.g., morphine) with respect to risk of death despite evidence that its primary alkaloid, mitragynine, carries little of the signature respiratory depressing effects of morphine-like opioids. This commentary summarizes animal toxicology data, surveys and mortality data associated with opioids and kratom to provide a basis for estimating relative mortality risk. Population-level mortality estimates attributed to opioids as compared to kratom, and the per user mortality risks of opioids as compared to kratom are provided. By any of our assessments, it appears that the risk of overdose death is >1000 times greater for opioids than for kratom. The limitations of the mortality risk estimate warrants caution in individuals with unknown factors such as use of other substances and medications, or other preexisting conditions. More research on kratom safety and risks is needed, as is regulation of commercial kratom products to ensure that consumers are informed by FDA labeling and that kratom products are not contaminated or adulterated with other substances.

The Opioid Epidemic: Moving Toward an Integrated, Holistic Analytical Response.

In many jurisdictions, public safety and public health entities are working together to enhance the timeliness and accuracy of the analytical characterization and toxicology testing of novel synthetic opioids. The improved sharing and early detection of these analytical data are intended to inform surveillance, interdiction efforts, patient intervention and treatment, all of which are critical to curbing the opioid epidemic. Forensic practitioners working to identify novel synthetic opioids struggle to provide timely results when encountering new or unknown substances, such as the fentanyl analogs. These compounds, which mimic heroin in pharmacologic effect but can be far more potent, are inconsistently present in chemical identification libraries, and are currently largely unavailable as reference materials for analytical comparison. Additionally, federal, state and local governments as well as nongovernmental organizations require potency, toxicity and potential-for-abuse data to evaluate the potential health risks of emerging drug threats. Subsequent scheduling efforts and criminal prosecutions also require these thorough drug characterization studies. Pilot programs have demonstrated that early communication of real-time drug toxicity and analytical data significantly impacts the successful response to emerging opioids. High-quality, real-time, national-level data on chemical composition, toxicological test data, drug toxicity and overdoses, and analysis of seized materials by law enforcement are needed to track drug trends. However, the USA still lacks a national system to coordinate and communicate toxicology, medical and medical examiner and coroner data with the broader medical and law enforcement communities. Opportunities to address these gaps as well as recent advancements collected through interagency efforts and technical workshops in the toxicology and analytical chemistry communities are presented here. Opportunities for partnership, increased communication and expanding best practices to move toward an integrated, holistic analytical response are also explored.

Development and applications of the Veterans Health Administration's Stratification Tool for Opioid Risk Mitigation (STORM) to improve opioid safety and prevent overdose and suicide.

Concerns about opioid-related adverse events, including overdose, prompted the Veterans Health Administration (VHA) to launch an Opioid Safety Initiative and Overdose Education and Naloxone Distribution program. To mitigate risks associated with opioid prescribing, a holistic approach that takes into consideration both risk factors (e.g., dose, substance use disorders) and risk mitigation interventions (e.g., urine drug screening, psychosocial treatment) is needed. This article describes the Stratification Tool for Opioid Risk Mitigation (STORM), a tool developed in VHA that reflects this holistic approach and facilitates patient identification and monitoring. STORM prioritizes patients for review and intervention according to their modeled risk for overdose/suicide-related events and displays risk factors and risk mitigation interventions obtained from VHA electronic medical record (EMR)-data extracts. Patients' estimated risk is based on a predictive risk model developed using fiscal year 2010 (FY2010: 10/1/2009-9/30/2010) EMR-data extracts and mortality data among 1,135,601 VHA patients prescribed opioid analgesics to predict risk for an overdose/suicide-related event in FY2011 (2.1% experienced an event). Cross-validation was used to validate the model, with receiver operating characteristic curves for the training and test data sets performing well (>.80 area under the curve). The predictive risk model distinguished patients based on risk for overdose/suicide-related adverse events, allowing for identification of high-risk patients and enrichment of target populations of patients with greater safety concerns for proactive monitoring and application of risk mitigation interventions. Results suggest that clinical informatics can leverage EMR-extracted data to identify patients at-risk for overdose/suicide-related events and provide clinicians with actionable information to mitigate risk. (PsycINFO Database Record

Predictors of Opioid-Related Death During Methadone Therapy.

We aimed to examine pharmacologic, demographic and medical comorbidity risk factors for opioid-related mortality among patients currently receiving methadone for an opioid use disorder. We conducted a population-based, nested case-control study linking healthcare and coroner's records in Ontario, Canada, from January 31, 1994 to December 31, 2010. We included social assistance recipients receiving methadone for an opioid use disorder. Within this group, cases were those who died of opioid-related causes. For each case, we identified up to 5 controls matched on calendar quarter. The primary analysis examined the association between use of psychotropic drugs (benzodiazepines, antidepressants or antipsychotics) and opioid-related mortality. Secondary analyses examined the associations between baseline characteristics, health service utilization, comorbidities and opioid-related mortality. Among 43,545 patients receiving methadone for an opioid use disorder, we identified 175 (0.4%) opioid-related deaths, along with 873 matched controls. Psychotropic drug use was associated with a two fold increased risk of opioid-related death (adjusted odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2 to 3.5). Specifically, benzodiazepines (adjusted OR 1.6; 95% CI 1.1 to 2.5) and antipsychotics (adjusted OR 2.3; 95% CI 1.5 to 3.5) were independently associated with opioid-related death. Other associated factors included chronic lung disease (adjusted OR 1.7; 95% CI 1.2 to 2.6), an alcohol use disorder (adjusted OR 1.9; 95% CI 1.2 to 3.2), mood disorders (adjusted OR 1.8; 95% CI 1.0 to 3.2), and a history of heart disease (adjusted OR 5.3; 95% CI 2.0 to 14.0). Psychotropic drug use is associated with opioid-related death in patients receiving methadone. Mindfulness of these factors may reduce the risk of death among methadone recipients.

Opium use: an emerging risk factor for cancer?

An estimated 16·5 million people worldwide illicitly use opiates, of whom 4 million use raw opium. We did a systematic review to investigate the association between opium use and cancer incidence and mortality. Opium use was associated with an increased risk of cancers of the oesophagus, stomach, larynx, lung, and urinary bladder. Although the present evidence suggests that these associations are possibly causal, further epidemiological studies (particularly prospective studies that collect detailed data about lifetime opium use and control for a broad range of potential confounders) are needed.

Mortality among methadone maintenance clients in China: a six-year cohort study.

OBJECTIVE: To assess the overall mortality of methadone maintenance treatment (MMT) clients in China and its associated factors. METHODS: A total of 1,511 MMT clients, all of whom enrolled in China's first eight MMT clinics between March and December 2004, were included in this cohort study and followed for approximately six years, until June 2010. Mortality and its predictors were examined using Cox proportional hazards regression models. RESULTS: A total of 154 deaths were observed within 5,391 person-years (PY) of follow-up for an all-cause mortality rate of 28.6 per 1,000 PY. The leading causes of death were drug overdose (33.8%), HIV/AIDS-unrelated disease (21.4%), and HIV/AIDS (16.9%). The all-cause mortality rate of clients engaged in MMT for one year or less was roughly three times that of clients who stayed in MMT for four years or more (14.0 vs. 4.6, p<0.0001), HIV-positive subjects was nearly four times mortality rate than that of HIV-negative individuals (28.1 vs.6.8, p<0.0001). ART-naive HIV-positive subjects had approximately two times higher mortality rate than those receiving ART (31.2 vs. 17.3, <0.0001). After adjusting for confounding variables, we found that being male (HR = 1.63, CI: 1.03-2.57, p = 0.0355) and being HIV-positive (HR = 5.16, CI: 3.70-7.10, p<0.0001) were both associated with higher risk of death whereas increased durations of methadone treatment were associated with a lower risk of death (HR = 0.26, CI: 0.18-0.38, p<0.0001 for two to three years, HR = 0.08, CI: 0.05-0.14, p<0.0001 for four or more years). CONCLUSION: Overall mortality was high among MMT clients in China. Specific interventions aimed at decreasing mortality among MMT clients are needed. Our study supports the need for keeping client at MMT longer and for expanding ART coverage and suggests the potential benefits of integrated MMT and ART services for drug users in China.

Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50,000 adults in Iran.

OBJECTIVES: To investigate the association between opium use and subsequent risk of death. DESIGN: Prospective cohort study. SETTING: The Golestan Cohort Study in north-eastern Iran collected detailed validated data on opium use and other exposures at baseline. Participants were enrolled between January 2004 and June 2008 and were followed to May 2011, with a follow-up success rate of over 99%. PARTICIPANTS: 50,045 participants aged 40-75 at baseline. MAIN OUTCOMES: Mortality, all cause and major subcategories. RESULTS: 17% (n = 8487) of the participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 2145 deaths were reported. The adjusted hazard ratio for all cause mortality associated with ever use of opium was 1.86 (95% confidence interval 1.68 to 2.06). Opium consumption was significantly associated with increased risks of deaths from several causes including circulatory diseases (hazard ratio 1.81) and cancer (1.61). The strongest associations were seen with deaths from asthma, tuberculosis, and chronic obstructive pulmonary disease (11.0, 6.22, and 5.44, respectively). After exclusion of people who self prescribed opium after the onset of major chronic illnesses, the associations remained strong with a dose-response relation. CONCLUSION: Opium users have an increased risk of death from multiple causes compared with non-users. Increased risks were also seen in people who used low amounts of opium for a long period and those who had no major illness before use.

Treatment of opioid overdose in a physician-based prehospital EMS: frequency and long-term prognosis.

BACKGROUND: Prehospital treatment of opioid overdose accounts for a significant proportion of the workload of the emergency system in most major cities. Treatment consists of basic life support and administering naloxone. In our physician-manned mobile emergency care unit (MECU), most patients are released and not admitted to hospital. In this study, we aimed to assess the pattern in the number of episodes with opioid overdose treated by MECU in Copenhagen during a 10-year period and to investigate risk factors for mortality of these patients beyond the initial contact. METHODS: Data were collected prospectively in the MECU database covering all cases of opioid overdose in a 10-year period between 1994 and 2003. The pattern in the number of opioid overdose was analysed in Poisson regression models, and mortality was analysed in Kaplan-Meier plots and in Cox regression models. RESULTS: A total of 4762 episodes of opioid overdose were recorded. Patients were identified in 3245 of these episodes. The annual number of episodes decreased significantly over the data-collection period: from 639 overdoses out of 4520 (14.1%) patients treated in 1994 to 311 out of 7263 patients treated (4.3%) in 2003. A total of 352 patients had cardiac arrest at the scene. The MECU released 2246 patients (69.3%) after treatment, while 675 (20.8%) were admitted to hospital and 322 (9.9%) died. Long-term prognosis was poor with 14% mortality at 1 year. Long-term mortality was significantly related to increasing age, time of the year and if the patient had previous episodes of opioid overdose. CONCLUSIONS: There has been a significant decrease in the number of opioid overdoses during this 10-year-period. Long-term mortality is high in these patients and highest in those with advanced age and numerous episodes of opioid overdose.

Prehospital treatment of opioid overdose in Copenhagen--is it safe to discharge on-scene?

INTRODUCTION: In the prehospital setting opioid overdose is often treated with naloxone. In our physician-based medical emergency care unit (MECU) we have adopted a discharge-on-scene policy, where patients are released on scene if no residual signs of opioid intoxication are found after treatment. The aim of this study was to describe our experience with the discharge-on-scene policy used during a 10-year-period with focus on the frequency of rebound opioid toxicity. METHODS: Data were prospectively recorded in our MECU database and we reviewed all cases of opioid overdose between 1994 and 2003. The MECU database was cross-referenced with the Central Personal Registry. For patients who died within 48 h of MECU contact we reviewed the forensic autopsy reports to establish whether rebound opioid toxicity was likely. RESULTS: We found 4762 cases of acute opioid overdose. In 3245 cases positive identification was obtained. Over this ten year period fourteen patients who were released on-scene after having been treated with naloxone died within 48 h, but only in 3 of these we found a rebound opioid toxicity to be the likely cause of death, corresponding to 0.13% of those 2241 released on scene who were identified. CONCLUSION: Prehospital discharge-on-scene after naloxone treatment is associated with a low risk of death due to rebound toxicity.

Mortality among individuals with cannabis, cocaine, amphetamine, MDMA, and opioid use disorders: a nationwide follow-up study of Danish substance users in treatment.

This is a register-based cohort study of 20,581 individuals in treatment for illicit substance use disorders in Denmark between 1996 and 2006. All in all, 1441 deaths were recorded during 111,445 person-years of follow-up. Standardized mortality ratios (SMRs) associated with different primary substance types were calculated and Cox-regression analyses were performed in order to establish hazard ratios (HR) associated with injection drug use and psychiatric comorbidity. SMRs for primary users of specific substances were: cannabis: 4.9 (95% confidence interval (CI): 4.2-5.8), cocaine: 6.4 (CI: 3.9-10.0), amphetamine: 6.0 (CI: 4.2-8.3), heroin: 9.1 (CI: 8.5-9.8), and other opioids 7.7 (CI: 6.6-8.9). For MDMA ('ecstasy') the crude mortality rate was 1.7/1000 person-years (CI: 0.4-7.0) and the SMR was not significantly elevated. Injection drug use was associated with significantly increased hazard ratios in users of opioids and cocaine/amphetamine. Overall, psychiatric comorbidity was not associated with increased mortality (HR: 1.1 [CI: 0.9-1.2], p=.28), but an association was found specifically among cocaine/amphetamine users (HR: 3.6 [CI: 2.1-6.4], p<.001).

Effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery.

PURPOSE: Data regarding the effect of opium use on short-term outcome in patients undergoing coronary artery bypass surgery are limited. We sought to assess the morbidity and in-hospital mortality of current and past users compared the data with those from nonusers of opium after coronary artery bypass grafting (CABG). METHODS: This is a descriptive analytical review of prospectively collected data on 782 consecutive male patients who underwent isolated CABG between January 2005 and December 2007. Of these, 708 (90.5%) were nonusers, 56 (7.1%) were current users, and 18 (2.3%) were former opium users of more than 4 weeks. The effect of opium usage on clinical, admission, and outcome variables were analyzed. RESULTS: Current opium users were younger (P = 0.004) and more likely to be cigarette smokers (P = 0.0004). Other demographic characteristics, major coronary risk factors, rates of postoperative complications, intensive care unit readmission, postoperative length of stay, and in-hospital mortality did not differ among the three groups. Current opium users needed less analgesic postoperatively (P = 0.0001), were significantly less compliant with medical and dietary recommendations after discharge (P < 0.0001), and were more likely to be rehospitalized with cardiovascular causes within 6 months after CABG surgery; these differences were much more pronounced for nonusers versus current users of opium (P < 0.0001). CONCLUSION: Continued use of opium is a significant predictor of rehospitalization with a cardiac cause within 6 months of CABG surgery. This may be partly due to the low compliance of these patients with treatment recommendations.

The association of opium dependence and postoperative complications following coronary artery bypass graft surgery: a propensity-matched study.

OBJECTIVE: Opium is an overwhelming public health problem in some countries. Different studies have suggested this drug as a risk factor for cardiovascular disease. Although the effect of opium on immune system, lung disease, nephropathy, stroke, and cardiac arrhythmia has been found in different studies, its effect on postoperation complications is not clear yet. The authors conducted this study to assess the effect of opium on post operation in hospital complications among patients who underwent coronary artery bypass graft. DESIGN: The authors retrospectively analyzed the data in this study. SETTING: This study has been done at Tehran Heart Center. PATIENTS: A total of 4,398 patients who had undergone isolated CABG were studied. MAIN OUTCOME MEASURE: Patients who fulfilled the DSM-IV-TR criteria for opium dependence (by smoking) were enrolled as Opium Dependent Patients. Also outcome variables were: Perioperative MI, septicemia, UTI, TIA, continuous coma, prolonged ventilation, pulmonary embolism, renal failure, acute limb ischemia, heart block, AF, mortality. RESULTS: The prevalence of opium dependence was 15.6percent among patients. The authors used a propensity matched model to analyze the relationship between opium and post operation complications. The authors adjusted opium and non-opium dependent patients in all of the baseline preoperative risk factors, so all of the matched patients were same and there was no bias in assessment. CONCLUSION: Opium dependent patients had significantly longer resource utilization. However, no significant relationship was found between opium dependence and other cardiac and non cardiac in hospital complications.

Buprenorphine and HIV primary care: new opportunities for integrated treatment.

Drug abuse and infection with human immunodeficiency virus (HIV) are associated with high rates of morbidity and mortality, but, because of medical, social, and legal factors, opiate addiction/dependence is a major obstacle to successful treatment of disease--for example, treatment of acquired immunodeficiency syndrome (AIDS) with highly active antiretroviral therapy. In an effort to improve the opportunity for treatment of drug abuse and HIV infection, the Forum for Collaborative HIV Research, in collaboration with the Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, the Centers for Disease Control and Prevention, and other agencies, presented a workshop entitled "Buprenorphine in the Primary HIV Care Setting." Participants reviewed and discussed current issues, such as the introduction of and sources for the provision of buprenorphine in HIV primary care settings and strategies for integrating treatment of HIV-infected drug abusers, all of which are covered in this supplement.