Relative Age Within School Grade, Including Delayed and Accelerated School Start: Associations With Midlife Psychiatric Disorders, Suicide, and Alcohol- and Drug-Related Mortality.

Within a school grade, children who are young for grade are at increased risk of psychiatric diagnoses, but the long-term implications remain understudied, and associations with students who delay or accelerate entry underexplored. We used Norwegian birth cohort records (birth years: 1967-1976, n = 626,928) linked to records in midlife. On-time school entry was socially patterned; among those born in December, 23.0% of children in the lowest socioeconomic position (SEP) delayed school entry, compared with 12.2% among the highest SEP. Among those who started school on time, there was no evidence for long-term associations between birth month and psychiatric/behavioral disorders or mortality. Controlling for SEP and other confounders, delayed school entry was associated with increased risk of psychiatric disorders and mortality. Children with delayed school entry were 1.31 times more likely to die by suicide (95% confidence interval: 1.07, 1.61) by midlife, and 1.96 times more likely to die from drug-related death (95% confidence interval: 1.59, 2.40) by midlife than those born late in the year who started school on time. Associations with delayed school entry are likely due to selection, and results thus underscore that long-term health risks can be tracked early in life, including through school entry timing, and are highly socially patterned.

A national survey of law enforcement post-overdose response efforts.

Background: Law enforcement agencies in the US have provided naloxone to officers and developed initiatives to follow-up after a non-fatal overdose. However, the prevalence and characteristics of these efforts have yet to be documented in research literature.Objectives: We sought to understand the national prevalence of naloxone provision among law enforcement and examine the implementation of post-overdose follow-up.Methods: We administered a survey on drug overdose response initiatives using a multimodal approach (online and mail) to a nationally representative sample of law enforcement agencies (N = 2,009; 50.1% response rate) drawn from the National Directory of Law Enforcement Administrators database. We further examine a subsample of agencies (N = 1,514) that equipped officers with naloxone who were also asked about post-overdose follow-up.Results: We found 81.7% of agencies reported officers were equipped with naloxone; among these, approximately one-third (30.3%) reported follow-up after an overdose. More than half (56.8%) of agencies indicated partnership in follow-up with emergency medical services as the most common partner (68.8%). There were 21.4% of agencies with a Quick Response Team, a popular national post-overdose model, and were more likely to indicate partnership with a substance use disorder treatment provider than when agencies were asked generally about partners in follow-up (74.5% and 26.2% respectively).Conclusion: Many law enforcement agencies across the US have equipped officers with naloxone, and about one-third of those are conducting follow-up to non-fatal overdose events. Post-overdose follow-up models and practices vary in ways that can influence treatment engagement and minimize harms against persons who use drugs.

High-potency benzodiazepine misuse in opioid-dependent patients: use naloxone with care.

The misuse of highly potent benzodiazepines is increasing in the UK, particularly among the opioid-using population in Scotland. Differentiating opioid from benzodiazepine toxicity is not always straightforward in patients with reduced level of consciousness following drug overdose. Patients on long-term opioid substitution who present with acute benzodiazepine intoxication and are given naloxone may develop severe opioid withdrawal while still obtunded from benzodiazepines. This situation can be difficult to manage, and these patients may be at increased risk of vomiting while still unable to protect their airway. Fortunately, the short half-life of naloxone means that the situation is generally short-lived. Naloxone should never be withheld from patients with life-threatening respiratory depression where opioids may be contributing, particularly in community and prehospital settings; however, where appropriate clinical experience exists, naloxone should ideally be administered in small incremental intravenous doses with close monitoring of respiratory function. Increased awareness of the potential risks of naloxone in opioid-dependent patients acutely intoxicated with benzodiazepines may reduce the risk of iatrogenic harm in an already very vulnerable population.

Prospective study of retention in opioid agonist treatment and contact with emergency healthcare following release from prisons in Victoria, Australia.

BACKGROUND: People recently released from prison engage with emergency healthcare at greater rates than the general population. While retention in opioid agonist treatment (OAT) is associated with substantial reductions in the risk of opioid-related mortality postrelease, it is unknown how OAT affects contact with emergency healthcare. In a cohort of men who injected drugs regularly prior to imprisonment, we described rates of contact with ambulance services and EDs, and their associations with use of OAT, in the 3 months after release from prison. METHODS: Self-report data from a prospective observational cohort of men who regularly injected drugs before a period of sentenced imprisonment, recruited between September 2014 and May 2016, were linked to state-wide ambulance and ED records over a 3-month postrelease period in Victoria, Australia. We used generalised linear models to estimate associations between OAT use (none/interrupted/retained) and contact with ambulance and EDs postrelease, adjusted for other covariates. RESULTS: Among 265 participants, we observed 77 ambulance contacts and 123 ED contacts over a median of 98 days of observation (IQR 87-125 days). Participants who were retained in OAT between prison release and scheduled 3-month postrelease follow-up interviews had lower rates of contact with ambulance (adjusted incidence rate ratio (AIRR) 0.33, 95% CI 0.14 to 0.76) and ED (AIRR 0.43, 95% CI 0.22 to 0.83), compared with participants with no OAT use postrelease. Participants with interrupted OAT use did not differ from those with no OAT use in rates of contact with ambulance or ED. CONCLUSION: We found lower rates of contact with emergency healthcare after release among people retained in OAT, but not among people reporting interrupted OAT use, underscoring the benefits of postrelease OAT retention. Strategies to improve accessibility and support OAT retention after leaving prison are important for men who inject drugs.

Coroner county systems are associated with a higher likelihood of unclassified drug overdoses compared to medical examiner county systems.

Background: There is a striking geographic variation in drug overdose deaths without a specific drug recorded, many of which likely involve opioids. Knowledge of the reasons underlying this variation is limited.Objectives: We sought to understand the role of medicolegal death investigation (MDI) systems in unclassified drug overdose mortality.Methods: This is an observational study of 2014 and 2018 fatal drug overdoses and U.S. county-level MDI system type (coroner vs medical examiner). Mortality data are from the CDC's National Center for Health Statistics. We estimated multivariable logistic regressions to quantify associations between MDI system type and several outcome variables: whether the drug overdose was unclassified and whether involvement of any opioid, synthetic opioid, methadone, and heroin was recorded (vs unclassified), for 2014 (N = 46,996) and 2018 (N = 67,359).Results: In 2018, drug overdose deaths occurring in coroner counties were almost four times more likely to be unclassified (OR 3.87, 95% CI 2.32, 6.46) compared to medical examiner counties. These odds ratios are twice as large as in 2014 (difference statistically significant, P < .001), indicating that medical examiner counties are improving identification of opioids in drug overdoses faster than coroner counties.Conclusions: Accurate reporting of drug overdose deaths depends on MDI systems. When developing state policies and local interventions aimed to decrease opioid overdose mortality, decision-makers should understand the role their MDI system is playing in underestimating the extent of the opioid overdose crisis. Improvements to state and county MDI systems are desirable if accurate reporting and appropriate policy response are to be achieved.

Are we Truly "Safer-At-Home"? A Test of Contextual Effects on Mental Health and Drug Overdose Incidents During the COVID-19 Pandemic.

This study examined whether the social restrictions stemming from COVID-19 impacted the locations of mental health and drug overdose incidents, while controlling for immediate and community contextual indices. Addresses for mental health/overdose calls to law enforcement or emergency medical services between January 1, 2018 and August 13, 2020 were collected from one police department in the Midwestern United States. Businesses and previous victimization/offending were joined with parcels (level-1; N = 20,019), whereas local services and socioeconomic indicators were joined with block groups (level-2; N = 32), to allow for a multi-level (HLM7) examination of context on mental health/overdose incidents. Event Rate Ratios (ERR) revealed the greatest contextual effects took place following social distancing mandates. Findings highlight the importance of allocating to areas with the highest likelihood of reporting incidents and suggest that parcels with a history of sex offenses, drug offenses, and prior mental health calls may benefit the greatest from preventative resources.

Fatal opioid overdoses in the U.S. declined more than reported between 2017 and 2018.

Background: In U.S. death records, many drug overdoses do not have classified drug involvement, which challenges surveillance of opioid overdoses across time and space.Objective: To estimate the 2017-2018 change in opioid overdose deaths that accounts for probable opioid involvement in unclassified drug overdose deaths.Methods: In this retrospective design study, data on all drug overdose decedents from 2017-2018 in the U.S. were used to calculate the year-to-year change in known opioid overdoses, predict opioid involvement in unclassified drug overdoses, and estimate the year-to-year change in corrected opioid overdoses, which include both known and predicted opioid deaths. We used the Multiple Cause of Death (MCOD) data from CDC.Results: We estimated that the decrease in the age-adjusted opioid overdose death rate from 2017-2018 was 7.0%. There is a striking variation across states. Age-adjusted opioid overdose death rates decreased by 9.9% in Ohio and more than 5.0% in other Appalachian states (Pennsylvania, West Virginia, Kentucky), while they increased by 6.8% in Delaware.Conclusions: Our models suggest that opioid overdose-related mortality declined from 2017 to 2018 at a higher rate than reported (7.0% versus than the reported 2.0%), potentially indicating that clinical efforts and federal, state, and local government policies designed to control the epidemic have been effective in most states. Our local area estimates can be used by researchers, policy-makers and public health officials to assess effectiveness of state policies and interventions in smaller jurisdictions implemented in response to the crisis.

Geospatial Variations and Neighborhood Deprivation in Drug-Related Admissions and Overdoses.

Drug overdoses are a national and global epidemic. However, while overdoses are inextricably linked to social, demographic, and geographical determinants, geospatial patterns of drug-related admissions and overdoses at the neighborhood level remain poorly studied. The objective of this paper is to investigate spatial distributions of patients admitted for drug-related admissions and overdoses from a large, urban, tertiary care center using electronic health record data. Additionally, these spatial distributions were adjusted for a validated socioeconomic index called the Area Deprivation Index (ADI). We showed spatial heterogeneity in patients admitted for opioid, amphetamine, and psychostimulant-related diagnoses and overdoses. While ADI was associated with drug-related admissions, it did not correct for spatial variations and could not account alone for this spatial heterogeneity.

Association between Adult Attention Deficit/Hyperactivity Disorder and Intravenous Misuse of Opioid and Benzodiazepine in Patients under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study.

BACKGROUND: Intravenous misuse and attention-deficit/hyperactivity disorder (ADHD) are common in patients under opioid maintenance treatment (OMT), who often misuse benzodiazepine (BZD). OBJECTIVES: To explore the rate of adult ADHD among patients under OMT in Italy and whether screening positive for adult ADHD is associated with OMT and BZD misuse and emergency room (ER) admission because of misuse. METHODS: We recruited 1,649 patients from 27 addiction units (AUs) in Italy and collected data on the self-reported rate of OMT intravenous misuse (prevalence, repeated misuse, main reason, temporal pattern in relation to AU access, experience), concurrent intravenous and intranasal BZD misuse (prevalence, type of misused BZD), ADHD and ER admissions because of misuse complications. RESULTS: Screening positive for adult ADHD was found in 11.2% patients (ADHD+), with a significant gender difference (women: 15.3%, men: 10.3%). OMT misuse was reported by 24.4 and 18.5% patients during lifetime and in the previous 6 months respectively. BZD misuse was reported by 20.0 and 8.6% patients for intravenous and intranasal route respectively. Misuse was significantly more common in ADHD+ (OMT 27.4-33.1%, BZD 14.5-31.5%) than ADHD- group (OMT 17.4-23.3%, BZD 7.9-18.3%). The multivariate logistic regression model showed positive screening for ADHD to be significantly associated with intravenous OMT misuse in the previous 6 months, and intravenous/intranasal BZD misuse, independently of age, gender and route of previous heroin administration. CONCLUSIONS: Screening positive for adult ADHD was associated with OMT and BZD misuse. AU physicians and medical personnel should focus on OMT patient's features that are associated with a higher likelihood of misuse, in particular ADHD.

Exploring the effect of Colorado's recreational marijuana policy on opioid overdose rates.

OBJECTIVES: Opioid overdose death rates have continued to spike exponentially from the start of the 21st century, creating what is known to be one of the worst public health crises in the United States. Simultaneously, as more states began passing medical cannabis laws (MCLs), the idea that marijuana was the solution to the opioid crisis began to spread nationwide. As some states have maintained strict medical marijuana policies, others-such as Colorado-have expanded their statutes to allow recreational marijuana sales within their state. Researchers have been able to provide sense of the public health implications resulting from MCLs, but little is known about the effects of this marijuana policy expansion. This preliminary study will focus on exploring the statewide effects of Colorado's recreational marijuana policy on the state's opioid overdose death rates. STUDY DESIGN: Because Colorado has existing panel data for opioid overdose death rates, we can use statistical software to define and create an optimal control group to adequately resemble Colorado's outcome variable of interest. This process known as the synthetic control method can provide a valid counterfactual for Colorado's opioid overdose outcomes in the absence of this policy-a Colorado that did not expand marijuana policy to the point recreational dispensaries were established. METHODS: Opioid overdose death rate data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (WONDER) will be used to construct a synthetic control unit composed of a donor pool of states resembling Colorado's regulatory environment pertaining to marijuana before legalization. The synthetic control unit allows for a comparative observation of overdose rate trends in Colorado and its synthetic counterpart for the years 1999-2017, all while including a set of predictor variables for robustness checks. A difference-in-difference estimate will then help us observe the effects of the treatment given to Colorado. Inference tests will be conducted to evaluate the method's predictive power and significance of the results. RESULTS: The results of the synthetic control model and its outcomes showed that the estimated negative 5% drop in overdose death rates was deemed insignificant on conducting a placebo in-space analysis, meaning there is not enough evidence to prove that opening recreational dispensaries as a result of recreational marijuana legislation was instrumental in reducing Colorado's ongoing opioid crisis depicted through opioid overdose deaths. CONCLUSION: Owing to the lack of additional post-treatment data and captured lagged effects, it is too soon to dismiss this policy as inadequate in combating the opioid epidemic. Once additional post-treatment data become available, the study can be reproduced to obtain more robust results and achieve a clearer understanding of the policy implications shown.

Drug overdose deaths at work, 2011-2016.

Drug overdose fatalities have risen sharply and the impact on US workplaces has not been described. This paper describes US workplace overdose deaths between 2011 and 2016. Drug overdose deaths were identified from the Census of Fatal Occupational Injuries and fatality rates calculated using denominators from the Current Population Survey. Fatality rates were compared among demographic groups and industries. Negative binomial regression was used to analyse trends. Between 2011 and 2016, 760 workplace drug overdoses occurred for a fatality rate of 0.9 per 1 000 000 full-time equivalents (FTEs). Workplace overdose fatality rates significantly increased 24% annually. Workplace overdose fatality rates were highest in transportation and mining industries (3.0 and 2.6 per 1 000 000 FTEs, respectively). One-third of workplace overdose fatalities occurred in workplaces with fewer than 10 employees. Heroin was the single most frequent drug documented in workplace overdose deaths (17%). Workplace overdose deaths were low, but increased considerably over the six-year period. Workplaces are impacted by the national opioid overdose epidemic.

An 11-year retrospective review of cyproheptadine use in serotonin syndrome cases reported to the California Poison Control System.

WHAT IS KNOWN: Cyproheptadine is a serotonin and histamine antagonist that has been suggested as a treatment for serotonin syndrome in case reports. OBJECTIVE: We sought to examine the differences between outcomes and treatment recommendations in patients who received and did not receive cyproheptadine for a probable serotonin syndrome. METHODS: A retrospective review of cases reported to the California Poison Control System between 2006 and 2017 involving cyproheptadine administration or consideration for treatment of a probable serotonin syndrome. RESULTS AND DISCUSSION: A total of 1420 cases were identified and 288 cases met the inclusion criteria. Of these, 68 (23.1%) patients received cyproheptadine treatment and were significantly older (mean age 49.7 vs 33.5 years, P < 0.00001), intubated (n = 35, 51% vs n = 62, 28%, P < 0.05) and, although not statistically significant, were more frequently admitted to a critical care unit (n = 56, 82.3% vs n = 154, 70.0%, P = 0.09). There were no significant differences in serious outcomes (moderate or worse effects) or hospitalization rates (OR, 1.09, 95% CI, 0.49-2.64 and OR, 1.99, 95% CI, 0.86-4.58). There were eight fatalities, of which two patients received cyproheptadine. All fatalities were acute polypharmacy ingestions and had manifested severe symptoms (seizures, hypotension or hyperthermia) either prior to the administration or consideration of cyproheptadine therapy. Cyproheptadine was not administered in 138 (48%) cases primarily due to minimal clinical severity and patient improvement (43%), and not recommended in 82 (28%) cases for reasons from waiting for response to other supportive measures (30%), limited evidence of efficacy (28%) and undetermined diagnosis (14.6%). WHAT IS NEW AND CONCLUSION: The benefits of and indications for cyproheptadine are uncertain and questionable for the management of a serotonin syndrome. Future recommendations on its use should be based on diagnostic criteria, severity of symptoms and management in conjunction with other supportive measures.

Ambulance-attended opioid overdoses: An examination into overdose locations and the role of a safe injection facility.

Background: Although the United States and numerous other countries are amidst an opioid overdose crisis, access to safe injection facilities remains limited. Methods: We used prospective data from ambulance journals in Oslo, Norway, to describe the patterns, severity, and outcomes of opioid overdoses and compared these characteristics among various overdose locations. We also examined what role a safe injection facility may have had on these overdoses. Results: Based on 48,825 ambulance calls, 1054 were for opioid overdoses from 465 individuals during 2014 and 2015. The rate of calls for overdoses was 1 out of 48 of the total ambulance calls. Males made up the majority of the sample (n = 368, 79%), and the median age was 35 (range: 18-96). Overdoses occurred in public locations (n = 530, 50.3%), the safe injection facility (n = 353, 33.5%), in private homes (n = 83, 7.9%), and other locations (n = 88, 8.3%). Patients from the safe injection facility and private homes had similarly severe initial clinical symptoms (Glasgow Coma Scale median =3 and respiratory frequency median =4 breaths per minute) when compared with other locations, yet the majority from the safe injection facility did not require further ambulance transport to the hospital (n = 302, 85.6%). Those overdosed in public locations (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.17-2.35), and when the safe injection facility was closed (OR =1.4, 95% CI =1.04-1.89), were more likely to receive transport for further treatment. Conclusions: Our findings suggest that the opening hours at the safe injection facility and the overdose location may impact the likelihood of ambulance transport for further treatment.

Labeling Morphine Milligram Equivalents on Opioid Packaging: a Potential Patient Safety Intervention.

PURPOSE OF REVIEW: Given that the primary cause of overdose death in the USA is related to prescribed opioids, one potential strategy to improve awareness and decrease morbidity and/or mortality could include improved labeling. Specific patient populations which significantly struggle with adverse outcomes related to opioid abuse are seen in palliative care, chronic pain, and acute pain treatment settings. RECENT FINDINGS: An unexplored option for improving the healthcare quality and safety for patients currently prescribed opioids would be to require pharmaceutical companies to provide a morphine milligram equivalent (MME) on opioid packaging. Some limitations to MME conversions include equianalgesic conversions being estimates at best and may not account for variations in genetics and pharmacokinetics. Changing opioid labeling requirements is feasible as it falls under the purview of the US Food and Drug Administration (FDA), which has been mandated to provide mechanisms to reduce or to minimize overdoses related to opioid prescriptions. Labeling opioid packaging with MME per dose will promote clearer communication about opioid strength between patients and physicians. Labeling MME on packaging could help prevent prescriber errors.

Assessing the accuracy of opioid overdose and poisoning codes in diagnostic information from electronic health records, claims data, and death records.

PURPOSE: The purpose of this study is to assess positive predictive value (PPV), relative to medical chart review, of International Classification of Diseases (ICD)-9/10 diagnostic codes for identifying opioid overdoses and poisonings. METHODS: Data were obtained from Kaiser Permanente Northwest and Northern California. Diagnostic data from electronic health records, submitted claims, and state death records from Oregon, Washington, and California were linked. Individual opioid-related poisoning codes (e.g., 965.xx and X42), and adverse effects of opioids codes (e.g., E935.xx) combined with diagnoses possibly indicative of overdoses (e.g., respiratory depression), were evaluated by comparison with chart audits. RESULTS: Opioid adverse effects codes had low PPV to detect overdoses (13.4%) as assessed in 127 charts and were not pursued. Instead, opioid poisoning codes were assessed in 2100 individuals who had those codes present in electronic health records in the period between the years 2008 and 2012. Of these, 10/2100 had no available information and 241/2100 were excluded potentially as anesthesia-related. Among the 1849 remaining individuals with opioid poisoning codes, 1495 events were accurately identified as opioid overdoses; 69 were miscodes or misidentified, and 285 were opioid adverse effects, not overdoses. Thus, PPV was 81%. Opioid adverse effects or overdoses were accurately identified in 1780 of 1849 events (96.3%). CONCLUSIONS: Opioid poisoning codes have a predictive value of 81% to identify opioid overdoses, suggesting ICD opioid poisoning codes can be used to monitor overdose rates and evaluate interventions to reduce overdose. Further research to assess sensitivity, specificity, and negative predictive value are ongoing. Copyright © 2017 John Wiley & Sons, Ltd.

Toxicodynetics in nordiazepam and oxazepam overdoses.

OBJECTIVES: Toxicodynetics aims at defining the time-course of major clinical events in drug overdose. We report the toxicodynetics in mono-intoxications with oxazepam and nordiazepam. METHODS: Cases of oxazepam or nordiazepam overdoses collected at the Paris poison control centre from 1999 to 2014 on the basis of self-report. A particular attention was paid to eliminate the concomitant alcohol or psychotropic co-ingestions. The toxicodynetic parameters were assessed as previously described. Results are expressed using 10-90 percentiles. In adults, the dose was normalized (TI, toxic Index) by dividing the supposed ingested dose by the maximal recommended dose. RESULTS: Two hundred and fifty-one and 74 cases of oxazepam and nordiazepam poisonings were included, respectively. The Emax for oxazepam and nordiazepam were sleepiness or obtundation in 106 and 36 cases, respectively. Coma was used to qualify only one oxazepam overdose. The median delay in onset of the Emax was 1.5h (0.33-15) in nordiazepam and 4h (0.5-15) in oxazepam overdose. In both overdoses, the onset of Emax occurred on an "on-off" mode. In adults, the greatest TIs in nordiazepam and oxazepam overdoses were 45 and 26.7, respectively. The TI in the oxazepam-induced coma was 26.7, the largest dose. CONCLUSION: Data collected in PCC allow determining a number of toxicodynetic parameters. Toxicodynetics showed that nordiazepam is not a cause of coma even in large overdose while oxazepam causes coma only at a very high dose. Deep coma in nordiazepam overdose whatever the dose and deep coma in overdose with oxazepam involving TI less than 20 result from unrecognized drug-drug interaction.