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A Cross-sectional study of all emergency ambulance runs reported by licensed Emergency Medical Services (EMS) providers between 2013 and 2019 was undertaken to determine if the sex of a patient exp...

BACKGROUND Compared with non-Veterans, Veterans are at higher risk of experiencing homelessness, which is associated with opioid overdose. OBJECTIVE To understand how homelessness and Veteran status are related to risks of nonfatal and fatal opioid overdose in Massachusetts. DESIGN A cross-sectional study. PARTICIPANTS All residents aged 18 years and older during 2011-2015 in the Massachusetts Department of Public Health's Data Warehouse (Veterans: n=144,263; non-Veterans: n=6,112,340). A total of 40,036 individuals had a record of homelessness, including 1307 Veterans and 38,729 non-Veterans. MAIN MEASURES The main independent variables were homelessness and Veteran status. Outcomes included nonfatal and fatal opioid overdose. RESULTS A higher proportion of Veterans with a record of homelessness were older than 45 years (77% vs. 48%), male (80% vs. 62%), or receiving high-dose opioid therapy (23% vs. 15%) compared with non-Veterans. The rates of nonfatal and fatal opioid overdose in Massachusetts were 85 and 16 per 100,000 residents, respectively. Among individuals with a record of homelessness, these rates increased 31-fold to 2609 and 19-fold to 300 per 100,000 residents. Homelessness and Veteran status were independently associated with higher odds of nonfatal and fatal opioid overdose. There was a significant interaction between homelessness and Veteran status in their effects on risk of fatal overdose. CONCLUSIONS Both homelessness and Veteran status were associated with a higher risk of fatal opioid overdoses. An understanding of health care utilization patterns can help identify treatment access points to improve patient safety among vulnerable individuals both in the Veteran population and among those experiencing homelessness.

STUDY OBJECTIVE: Prehospital use of naloxone for presumed opioid overdose has increased markedly in recent years because of the current opioid overdose epidemic. In this study, we determine the one-year mortality of suspected opioid overdose patients who were treated with naloxone by EMS and initially survived. METHODS: This was a retrospective observational study of patients using three linked statewide datasets in Massachusetts: emergency medical services (EMS), a master demographics file, and death records. We included all suspected opioid overdose patients who were treated with naloxone by EMS. The primary outcome measures were death within 3 days of treatment and between 4 days and 1 year of treatment. RESULTS: Between July 1, 2013 and December 31, 2015, there were 9,734 individuals who met inclusion criteria and were included for analysis. Of these, 807 (8.3% (95% confidence interval (CI) 7.7%-8.8%)) died in the first 3 days, 668 (6.9% (95% CI 6.4%-7.4%)) died between 4 days and 1 year, and 8,259 (84.8% (95% CI 84.1%-85.6%)) were still alive at one year. Excluding those who died within 3 days, 668 of the remaining 8,927 individuals (7.5% (95% CI 6.9%-8.0%)) died within one year. CONCLUSION: The one-year mortality of those who are treated with naloxone for opioid overdose by EMS is high. Communities should focus both on primary prevention and interventions for this patient population, including strengthening regional treatment centers and expanding access to medication for opioid use disorder.

Background and aim Medically managed opioid withdrawal (detox) can increase the risk of subsequent opioid overdose. We assessed the association between mortality following detox and receipt of medications for opioid use disorder (MOUD) and residential treatment after detox. Design Cohort study generated from individually linked public health data sets. Setting Massachusetts, USA. Participants A total of 30 681 opioid detox patients with 61 819 detox episodes between 2012 and 2014. Measurements Treatment categories included no post-detox treatment, MOUD, residential treatment or both MOUD and residential treatment identified at monthly intervals. We classified treatment exposures in two ways: (a) 'on-treatment' included any month where a treatment was received and (b) 'with-discontinuation' individuals were considered exposed through the month following treatment discontinuation. We conducted multivariable Cox proportional hazards analyses and extended Kaplan-Meier estimator cumulative incidence for all-cause and opioid-related mortality for the treatment categories as monthly time-varying exposure variables. Findings Twelve months after detox, 41% received MOUD for a median of 3 months, 35% received residential treatment for a median of 2 months and 13% received both for a median of 5 months. In on-treatment analyses for all-cause mortality compared with no treatment, adjusted hazard ratios (AHR) were 0.34 [95% confidence interval (CI) = 0.27-0.43] for MOUD, 0.63 (95% CI = 0.47-0.84) for residential treatment and 0.11 (95% CI = 0.03-0.43) for both. In with-discontinuation analyses for all-cause mortality, compared with no treatment, AHRs were 0.52 (95% CI = 0.42-0.63) for MOUD, 0.76 (95% CI = 0.59-0.96) for residential treatment and 0.21 (95% CI = 0.08-0.55) for both. Results were similar for opioid-related overdose mortality. Conclusions Among people who have undergone medically managed opioid withdrawal, receipt of medications for opioid use disorder, residential treatment or the combination of medications for opioid use disorder and residential treatment were associated with substantially reduced mortality compared with no treatment.

BACKGROUND: As stimulant use increases across the United States, emergency medical services (EMS) are crucial touchpoints in the health care system. To better measure the prevalence of stimulant use, misuse, and EMS incidents related to stimulant intoxication, definitions for stimulant-related incidents (SRIs) are needed. METHODS: We used the Massachusetts Ambulance Trip Record Information System (MATRIS) from 2013 to 2020 to develop definitions of stimulant-related incidents. EMS runs reported to MATRIS were categorized based on stimulant-related words and symptoms. The three tiers were “any stimulant use” (class 1), “problematic stimulant use” (class 2), and “acute stimulant-related incidents” (class 3). A group of four reviewers studied over 650 cases in eight rounds to refine the search terms, achieving definitions with a correct characterization of over 80% of cases that the code selected. RESULTS: SRI definitions were applied against all EMS runs within Massachusetts between 2013 and 2020 (n = 6,584,836 runs). Of these, 43,538 (0.7%) met the class 1 definition, 38,669 (0.6%) met the class 2 definition, and 19,157 (0.3%) met the class 3 definition. Incidents at all tiers of severity increased over time and were more likely to occur among younger adults and males. Race and ethnicity data indicated that Hispanic/Latinx and Black non-Hispanic/non-Latinx residents formed a disproportionately large percentage of SRIs relative to their total percentage of EMS runs. CONCLUSIONS: The prevalence of all three tiers of SRIs are increasing in Massachusetts, and this protocol provides a source of administrative data on stimulant use that complements sources such as hospital, treatment-based, and/or prescribing records.

Study objective Despite the increased availability of naloxone, death rates from opioid overdose continue to increase. The goal of this study is to determine the 1-year mortality of patients who were treated for a nonfatal opioid overdose in Massachusetts emergency departments (EDs). Methods This was a retrospective observational study of patients from 3 linked statewide Massachusetts data sets: a master demographics list, an acute care hospital case-mix database, and death records. Patients discharged from the ED with a final diagnosis of opioid overdose were included. The primary outcome measure was death from any cause within 1 year of overdose treatment. Results During the study period, 17,241 patients were treated for opioid overdose. Of the 11,557 patients who met study criteria, 635 (5.5%) died within 1 year, 130 (1.1%) died within 1 month, and 29 (0.25%) died within 2 days. Of the 635 deaths at 1 year, 130 (20.5%) occurred within 1 month and 29 (4.6%) occurred within 2 days. Conclusion The short-term and 1-year mortality of patients treated in the ED for nonfatal opioid overdose is high. The first month, and particularly the first 2 days after overdose, is the highest-risk period. Patients who survive opioid overdose should be considered high risk and receive interventions such as being offered buprenorphine, counseling, and referral to treatment before ED discharge.

Aims To examine how the risks of incident opioid use disorder (OUD), non-fatal and fatal overdose have changed over time among opioid-naive individuals receiving an initial opioid prescription. Design Retrospective, longitudinal study using the Massachusetts Chapter 55 data set, which linked multiple administrative data sets to study the opioid epidemic. We identified the cumulative incidence of OUD, non-fatal and fatal overdose among the opioid-naive initiating opioid treatment in Massachusetts from 2011 to 2014 and estimated rates of these outcomes at 6 months and at 1, 2, 3 and 4 years to 2015. We used Cox regression to examine the association between characteristics of the initial prescription and risk of these outcomes. Setting Massachusetts, USA. Participants Massachusetts residents aged ≥ 11 years in 2011-15 who were opioid-naive (no opioid prescriptions or evidence of OUD in the 6 months prior to the index prescription) (n = 2 154 426). The mean age was 49.1 years, 55.3% were female and 47.3% had commercial insurance. Measurements Opioid prescriptions were identified in the Prescription Monitoring Program (PMP) database, as were the characteristics of the initial prescription database. The outcomes of OUD and non-fatal overdose were identified from claims in the All Payer Claims Database (APCD) and hospital encounters in the acute hospital case mix files. Fatal overdoses were identified using Registry of Vital Records and Statistics (RVRS) death certificates and the Office of the Chief Medical Examiner (OCME) circumstances of death and toxicology reports. Findings Among opioid-naive individuals receiving an initial opioid prescription, the risk of incident OUD appears to have declined between 2011 and 2014, while rates of overdose were largely unchanged. For example, the 1-year OUD rate was 1.18% in 2011, 1.11% in 2012, 1.26% in 2013 and 0.94% in 2014. Longer therapy duration was associated with higher risk of OUD [hazard ratio (HR) = 2.24, 95% confidence interval (CI) = 2.19-2.29 for duration of 3 or more months], non-fatal (HR = 1.67, 95% CI = 1.53-1.82) and fatal opioid overdose (HR = 2.24, 95% CI = 1.91-2.61). Concurrent benzodiazepine treatment was also associated with higher risk of OUD (HR = 1.14, 95% CI = 1.12-1.17), non-fatal (HR = 1.20, 95% CI = 1.10-1.30) and fatal overdose (HR = 1.86, 95% CI = 1.61-2.16). Conclusions Among opioid-naive individuals in Massachusetts receiving an initial opioid prescription, the risk of incident opioid use disorder appears to have declined between 2011 and 2014, while rates of overdose were largely unchanged. Longer therapy duration and concurrent benzodiazepines were associated with higher rates of opioid use disorder and opioid overdose.

Objectives: Opioid-related overdoses are commonly attributed to prescription opioids. We examined data on opioid-related overdose decedents in Massachusetts. For each decedent, we determined which opioid medications had been prescribed and dispensed and which opioids were detected in postmortem medical examiner toxicology specimens. Methods: Among opioid-related overdose decedents in Massachusetts during 2013-2015, we analyzed individually linked postmortem opioid toxicology reports and prescription drug monitoring program records to determine instances of overdose in which a decedent had a prescription active on the date of death for the opioid(s) detected in the toxicology report. We also calculated the proportion of overdoses for which prescribed opioid medications were not detected in decedents’ toxicology reports. Results: Of 2916 decedents with complete toxicology reports, 1789 (61.4%) had heroin and 1322 (45.3%) had fentanyl detected in postmortem toxicology reports. Of the 491 (16.8%) decedents with ≥1 opioid prescription active on the date of death, prescribed opioids were commonly not detected in toxicology reports, specifically: buprenorphine (56 of 97; 57.7%), oxycodone (93 of 176; 52.8%), and methadone prescribed for opioid use disorder (36 of 112; 32.1%). Only 39 (1.3%) decedents had an active prescription for each opioid detected in toxicology reports on the date of death. Conclusion: Linking overdose toxicology reports to prescription drug monitoring program records can help attribute overdoses to prescribed opioids, diverted prescription opioids, heroin, and illicitly made fentanyl.

Background and aims While prescribed and illicit opioid use are primary drivers of the national surges in overdose deaths, opioid overdose deaths in which stimulants are also present are increasing in the U.S. We determined the social determinants and sociodemographic factors associated with opioid-only versus polysubstance opioid overdose deaths in Massachusetts. Particular attention was focused on the role of stimulants in opioid overdose deaths. Methods We analyzed all opioid-related overdose deaths from 2014 to 2015 in an individually-linked population database in Massachusetts. We used linked postmortem toxicology data to identify drugs present at the time of death. We constructed a multinomial logistic regression model to identify factors associated with three mutually exclusive overdose death groups based on toxicological results: opioid-related deaths with (1) opioids only present, (2) opioids and other substances not including stimulants, and (3) opioids and stimulants with or without other substances. Results Between 2014 and 2015, there were 2,244 opioid-related overdose deaths in Massachusetts that had accompanying toxicology results. Toxicology reports indicated that 17% had opioids only, 36% had opioids plus stimulants, and 46% had opioids plus another non-stimulant substance. Persons older than 24 years, non-rural residents, those with comorbid mental illness, non-Hispanic black residents, and persons with recent homelessness were more likely than their counterparts to die with opioids and stimulants than opioids alone. Conclusions Polysubstance opioid overdose is increasingly common in the US. Addressing modifiable social determinants of health, including barriers to mental health services and homelessness, is important to reduce polysubstance use and overdose deaths.

This study aimed to compare trends and characteristics of assisted reproductive technology (ART) and non-ART perinatal deaths and to evaluate the association of perinatal mortality and method of conception (ART vs. non-ART) among ART and non-ART deliveries in Florida, Massachusetts, and Michigan from 2006 to 2011. Retrospective cohort study using linked ART surveillance and vital records data from Florida, Massachusetts, and Michigan. During 2006 to 2011, a total of 570 ART-conceived perinatal deaths and 25,158 non-ART conceived perinatal deaths were identified from the participating states. Overall, ART perinatal mortality rates were lower than non-ART perinatal mortality rates for both singletons (7.0/1,000 births vs. 10.2/1,000 births) and multiples (22.8/1,000 births vs. 41.2/1,000 births). At28 weeks of gestation, the risk of perinatal death among ART singletons was significantly lower than non-ART singletons (adjusted risk ratio [aRR] = 0.46, 95% confidence interval [CI]: 0.26-0.85). Similar results were observed among multiples at28 weeks of gestation (aRR = 0.64, 95% CI: 0.45-0.89). Our findings suggest that ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation, which may be explained by earlier detection and management of fetal and maternal conditions among ART-conceived pregnancies. These findings provide valuable information for health care providers, including infertility specialists, obstetricians, and pediatricians when counseling ART users on risk of treatment.· ART use is associated with a decreased risk of perinatal deaths prior to 28 weeks of gestation.. · ART perinatal mortality rates were lower than that for non-ART perinatal mortality.. · This study used linked data to examine associations between use of ART and perinatal deaths..

A major driver of the U.S. opioid crisis is limited access to effective medications for opioid use disorder (MOUD) that reduce overdose risks. Traditionally, jails and prisons in the U.S. have not initiated or maintained MOUD for incarcerated individuals with OUD prior to their return to the community, which places them at high risk for fatal overdose. A 2018 law (Chapter 208) made Massachusetts (MA) the first state to mandate that five county jails deliver all FDA-approved MOUDs (naltrexone [NTX], buprenorphine [BUP], and methadone). Chapter 208 established a 4-year pilot program to expand access to all FDA-approved forms of MOUD at five jails, with two more MA jails voluntarily joining this initiative. The law stipulates that MOUD be continued for individuals receiving it prior to detention and be initiated prior to release among sentenced individuals where appropriate. The jails must also facilitate continuation of MOUD in the community on release. The Massachusetts Justice Community Opioid Innovation Network (MassJCOIN) partnered with these seven diverse jails, the MA Department of Public Health, and community treatment providers to conduct a Type 1 hybrid effectiveness-implementation study of Chapter 208. We will: (1) Perform a longitudinal treatment outcome study among incarcerated individuals with OUD who receive NTX, BUP, methadone, or no MOUD in jail to examine postrelease MOUD initiation, engagement, and retention, as well as fatal and nonfatal opioid overdose and recidivism; (2) Conduct an implementation study to understand systemic and contextual factors that facilitate and impede delivery of MOUDs in jail and community care coordination, and strategies that optimize MOUD delivery in jail and for coordinating care with community partners; (3) Calculate the cost to the correctional system of implementing MOUD in jail, and conduct an economic evaluation from state policy-maker and societal perspectives to compare the value of MOUD prior to release from jail to no MOUD among matched controls. MassJCOIN made significant progress during its first six months until the COVID-19 pandemic began in March 2020. Participating jail sites restricted access for nonessential personnel, established other COVID-19 mitigation policies, and modified MOUD programming. MassJCOIN adapted research activities to this new reality in an effort to document and account for the impacts of COVID-19 in relation to each aim. The goal remains to produce findings with direct implications for policy and practice for OUD in criminal justice settings.

This cohort study assess the association of receipt of medication for opioid use disorder and mortality after hospitalization for injection drug use–associated infective endocarditis in Massachusetts., Key Points Question Is there an association between receipt of medication for opioid use disorder (MOUD) and mortality after hospitalization for injection drug use–associated infective endocarditis? Findings In this cohort study 679 individuals hospitalized with injection drug use–associated endocarditis, 24% received MOUD within 3 months of discharge. MOUD receipt within 3 months of discharge was not associated with reduced mortality but was associated with a reduction in mortality in the month received. Meaning In this study, treatment with MOUD was uncommon and was associated with reduced mortality in the time-varying analysis but not the main analysis, possibly owing to poor treatment retention., Importance Although hospitalizations for injection drug use–associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown. Objective To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality. Design, Setting, and Participants This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use treatment data from Massachusetts between January 1, 2011, and December 31, 2015; IDU-IE–related discharges between July 1, 2011, and June, 30, 2015, were analyzed. All Massachusetts residents aged 18 to 64 years with a first hospitalization for IDU-IE were included; IDU-IE was defined as any hospitalization with a diagnosis of endocarditis and at least 1 claim in the prior 6 months for OUD, drug use, or hepatitis C and with 2-month survival after hospital discharge. Data were analyzed from November 11, 2018, to June 23, 2020. Exposure Receipt of MOUD, defined as any treatment with methadone, buprenorphine, or naltrexone, within 3 months after hospital discharge excluding discharge month for IDU-IE. Main Outcomes and Measures The main outcome was all-cause mortality. The proportion of patients who received MOUD in the 3 months after hospital discharge was calculated. Multivariable Cox proportional hazard regression models were used to examine the association of MOUD receipt with mortality, adjusting for sex, age, medical and psychiatric comorbidities, and homelessness. In the secondary analysis, receipt of MOUD was considered as a monthly time-varying exposure. Results Of 679 individuals with IDU-IE, 413 (60.8%) were male, the mean (SD) age was 39.2 (12.1) years, 298 (43.9%) were aged 18 to 34 years, 419 (72.3) had mental illness, and 209 (30.8) experienced homelessness. A total of 134 individuals (19.7%) received MOUD in the 3 months before hospitalization and 165 (24.3%) in the 3 months after hospital discharge. Of those who received MOUD after discharge, 112 (67.9%) received buprenorphine. The crude mortality rate was 9.2 deaths per 100 person-years. MOUD receipt within 3 months after discharge was not associated with reduced mortality (adjusted hazard ratio, 1.29; 95% CI, 0.61-2.72); however, MOUD receipt was associated with reduced mortality in the month that MOUD was received (adjusted hazard ratio, 0.30; 95% CI, 0.10-0.89). Conclusions and Relevance In this cohort study, receipt of MOUD was associated with reduced mortality after hospitalization for injection drug use–associated endocarditis only in the month it was received. Efforts to improve MOUD initiation and retention after IDU-IE hospitalization may be beneficial.

The postpartum year is a vulnerable period for women with opioid use disorder, with increased rates of fatal and nonfatal overdose; however, data on the continuation of medications for opioid use disorder on a population level are limited.This study aimed to examine the effect of discontinuing methadone and buprenorphine in women with opioid use disorder in the year following delivery and determine the extent to which maternal and infant characteristics are associated with time to discontinuation of medications for opioid use disorder.This population-based retrospective cohort study used linked administrative data of 211,096 deliveries in Massachusetts between 2011 and 2014 to examine the adherence to medications for opioid use disorder. Individuals receiving medications for opioid use disorder after delivery were included in the study. Here, demographic, psychosocial, prenatal, and delivery characteristics are described. Kaplan-Meier survival analysis and Cox regression modeling were used to examine factors associated with medication discontinuation.A total of 2314 women who received medications for opioid use disorder at delivery were included in our study. Overall, 1484 women (64.1%) continued receiving medications for opioid use disorder for a full 12 months following delivery. The rate of continued medication use varied from 34% if women started on medications for opioid use disorder the month before delivery to 80% if the medications were used throughout pregnancy. Kaplan-Meier survival curves differed by maternal race and ethnicity (the 12-month continuation probability was .65 for White non-Hispanic women and .51 for non-White women; P.001) and duration of use of prenatal medications for opioid use disorder (12-month continuation probability was .78 for women with full prenatal engagement and .60 and .44 for those receiving medications for opioid use disorder ≥5 months [but not throughout pregnancy] and ≤4 months prenatally, respectively; P.001). In all multivariable models, duration of receipt of prenatal medications for opioid use disorder (≤4 months vs throughout pregnancy: adjusted hazard ratio, 3.26; 95% confidence interval, 2.72-3.91) and incarceration (incarceration during pregnancy or after delivery vs none: adjusted hazard ratio, 1.79; 95% confidence interval, 1.52-2.12) were most strongly associated with the discontinuation of medications for opioid use disorder.Almost two-thirds of women with opioid use disorder continued using medications for opioid use disorder for a full year after delivery; however, the rates of medication continuation varied significantly by race and ethnicity, degree of use of prenatal medications for opioid use disorder, and incarceration status. Prioritizing medication continuation across the perinatal continuum, enhancing sex-specific and family-friendly recovery supports, and expanding access to medications for opioid use disorder despite being incarcerated can help improve postpartum medication adherence.

Highlights • HEALing Communities Study is a parallel-group cluster randomized controlled trial. • Communities That HEAL intervention’s goal is to reduce opioid overdose deaths. • Structured consensus decision-making strategy guided study measure development. • More than 80 study measure specifications and a common data model were developed. • The study will provide methodology and longitudinal community data for research., Background Opioid overdose deaths remain high in the U.S. Despite having effective interventions to prevent overdose deaths, there are numerous barriers that impede their adoption. The primary aim of the HEALing Communities Study (HCS) is to determine the impact of an intervention consisting of community-engaged, data-driven selection, and implementation of an integrated set of evidence-based practices (EBPs) on reducing opioid overdose deaths. Methods The HCS is a four year multi-site, parallel-group, cluster randomized wait-list controlled trial. Communities (n = 67) in Kentucky, Massachusetts, New York and Ohio are randomized to active intervention (Wave 1), which starts the intervention in Year 1 or the wait-list control (Wave 2), which starts the intervention in Year 3. The HCS will test a conceptually driven framework to assist communities in selecting and adopting EBPs with three components: 1) A community engagement strategy with local coalitions to guide and implement the intervention; 2) A compendium of EBPs coupled with technical assistance; and 3) A series of communication campaigns to increase awareness and demand for EBPs and reduce stigma. An implementation science framework guides the intervention and allows for examination of the multilevel contexts that promote or impede adoption and expansion of EBPs. The primary outcome, number of opioid overdose deaths, will be compared between Wave 1 and Wave 2 communities during Year 2 of the intervention for Wave 1. Numerous secondary outcomes will be examined. Discussion The HCS is the largest community-based implementation study in the field of addiction with an ambitious goal of significantly reducing fatal opioid overdoses.

BACKGROUND: People with a history of incarceration are at high risk for opioid overdose. A variety of factors contribute to this elevated risk though our understanding of these factors is deficient. Research to identify risk and protective factors for overdose is often conducted using administrative data or researcher-derived surveys and without explicit input from people with lived experience. We aimed to understand the scope of U.S. research on factors associated with opioid overdose among previously incarcerated people. We did this by conducting a narrative review of the literature and convening expert panels of people with lived experience. We then categorized these factors using a social determinants of health framework to help contextualize our findings. METHODS: We first conducted a narrative review of the published literature. A search was performed using PubMed and APA PsycInfo. We then convened two expert panels consisting of people with lived experience and people who work with people who were previously incarcerated. Experts were asked to evaluate the literature derived factors for completeness and add factors that were not identified. Finally, we categorized factors as either intermediary or structural according to the World Health Organization’s Social Determinants of Health (SDOH) Framework. RESULTS: We identified 13 papers that met our inclusion criteria for the narrative review. Within these 13 papers, we identified 22 relevant factors for their role in the relationship between overdose and people with a history of incarceration, 16 were risk factors and six were protective factors. Five of these were structural factors (three risk and two protective) and 17 were intermediary factors (13 risk and four protective). The expert panels identified 21 additional factors, 10 of which were structural (six risk and four protective) and 11 of which were intermediary (eight risk and three protective). CONCLUSION: This narrative review along with expert panels demonstrates a gap in the published literature regarding factors associated with overdose among people who were previously incarcerated. Additionally, this review highlights a substantial gap with regard to the types of factors that are typically identified. Incorporating voices of people with lived experience is crucial to our understanding of overdose in this at-risk population.

Objectives. To estimate the annual prevalence of opioid use disorder (OUD) in Massachusetts from 2011 to 2015. Methods. We performed a multisample stratified capture–recapture analysis to estimate OUD prevalence in Massachusetts. Individuals identified from 6 administrative databases for 2011 to 2012 and 7 databases for 2013 to 2015 were linked at the individual level and included in the analysis. Individuals were stratified by age group, sex, and county of residence. Results. The OUD prevalence in Massachusetts among people aged 11 years or older was 2.72% in 2011 and 2.87% in 2012. Between 2013 and 2015, the prevalence increased from 3.87% to 4.60%. The greatest increase in prevalence was observed among those in the youngest age group (11–25 years), a 76% increase from 2011 to 2012 and a 42% increase from 2013 to 2015. Conclusions. In Massachusetts, the OUD prevalence was 4.6% among people 11 years or older in 2015. The number of individuals with OUD is likely increasing, particularly among young people.

The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons. Population-based assisted reproductive technology surveillance data for 2000–2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses. ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons. PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

To examine outcomes of singleton pregnancies conceived without assisted reproductive technology (non-ART) compared with singletons conceived with ART by elective single-embryo transfer (eSET), nonelective single-embryo transfer (non-eSET), and double-embryo transfer with the establishment of 1 (DET -1) or ≥2 (DET ≥2) early fetal heartbeats.Retrospective cohort using linked ART surveillance data and vital records from Florida, Massachusetts, Michigan, and Connecticut.Not applicable.Singleton live-born infants.None.Preterm birth (PTB37 weeks), very preterm birth (VPTB32 weeks), small for gestational age birth weight (10th percentile), low birth weight (LBW2,500 g), very low birth weight (VLBW1,500 g), 5-minute Apgar score7, and neonatal intensive care unit (NICU) admission.After controlling for maternal characteristics and employing a weighted propensity score approach, we found that singletons conceived after eSET were less likely to have a 5-minute Apgar7 (adjusted odds ratio [aOR] 0.33; 95% CI, 0.15-0.69) compared with non-ART singletons. There were no differences among outcomes between non-ART and non-eSET infants. We found that PTB, VPTB, LBW, and VLBW were more likely among DET -1 and DET ≥2 compared with non-ART infants, with the odds being higher for DET ≥2 (PTB aOR 1.58; 95% CI, 1.09-2.29; VPTB aOR 2.46; 95% CI, 1.20-5.04; LBW aOR 2.17; 95% CI, 1.24-3.79; VLBW aOR 3.67; 95% CI, 1.38-9.77).Compared with non-ART singletons, singletons born after eSET and non-eSET did not have increased risks whereas DET -1 and DET ≥2 singletons were more likely to have adverse perinatal outcomes.

Background and aims Benzodiazepines are commonly prescribed to patients with opioid use disorder receiving buprenorphine treatment, yet may increase overdose risk. However, prescribed benzodiazepines may improve retention in care by reducing buprenorphine discontinuation and thus may prevent relapse to illicit opioid use. We aimed to test the association between benzodiazepine prescription and fatal opioid overdose, non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. Design and setting This was a retrospective cohort study using five individually linked data sets from Massachusetts, United States government agencies. Participants We studied 63 389 Massachusetts residents aged 18 years or older who received buprenorphine treatment between January 2012 and December 2015. Measurements Filled benzodiazepine prescription during buprenorphine treatment was the main independent variable. The primary outcome was time to fatal opioid overdose. Secondary outcomes were time to non-fatal opioid overdose, all-cause mortality and buprenorphine discontinuation. We defined buprenorphine discontinuation as having a 30-day gap without another prescription following the end date of the previous prescription. We used Cox proportional hazards models to calculate hazards ratios that tested the association between receipt of benzodiazepines and all outcomes, restricted to periods during buprenorphine treatment. Findings Of the 63 345 individuals who received buprenorphine, 24% filled at least one benzodiazepine prescription during buprenorphine treatment. Thirty-one per cent of the 183 deaths from opioid overdose occurred when individuals received benzodiazepines during buprenorphine treatment. Benzodiazepine receipt during buprenorphine treatment was associated with an increased risk of fatal opioid overdose adjusted hazard ratio (HR) = 2.92, 95% confidence interval (CI) = 2.10-4.06, non-fatal opioid overdose, adjusted HR = 2.05, 95% CI, 1.68-2.50, all-cause mortality, adjusted HR = 1.90, 95% CI, 1.48-2.44 and a decreased risk of buprenorphine discontinuation, adjusted HR = 0.87, 95% CI, 0.85-0.89. Conclusions Benzodiazepine receipt appears to be associated with both increased risk of opioid overdose and all-cause mortality and decreased risk of buprenorphine discontinuation among people receiving buprenorphine.

Study objective Nonfatal opioid overdose represents an opportunity to engage young adults into using medication for opioid use disorder. We seek to describe characteristics of young adults who experience nonfatal overdose and estimate rates of and time to medication for opioid use disorder for young adults relative to those aged 26 to 45 years. Methods We conducted a cohort study using retrospective administrative data of 15,281 individuals aged 18 to 45 years who survived an opioid-related overdose in Massachusetts between 2012 and 2014, using deidentified, individual-level, linked data sets from Massachusetts government agencies. We described patient characteristics stratified by age (18 to 21, 22 to 25, and 26 to 45 years) and evaluated multivariable Cox proportional hazards models to compare rates of medication for opioid use disorder receipt, controlling for age, sex, history of mental health disorders, and addiction treatment. Results Among 4,268 young adults in the year after nonfatal overdose, 28% (n=336/1,209) of those aged 18 to 21, 36% (n=1,097/3,059) of those aged 22 to 25 years, and 36% (n=3,916/11,013) of those aged 26 to 45 years received medication for opioid use disorder. For individuals aged 18 to 21 and 22 to 25 years, median time to buprenorphine treatment was 4 months (interquartile range 1.7 to 1.8 months); to methadone treatment, 4 months (interquartile range 2.8 to 2.9 months); and to naltrexone treatment, 1 month (interquartile range 1 to 1 month). Individuals aged 18 to 21 years were less likely (adjusted hazard ratio 0.60 [95% confidence interval 0.45 to 0.70]) to receive methadone than those aged 22 to 25 and 26 to 45 years. Individuals aged 18 to 21 years and those aged 22 to 25 years were more likely to receive naltrexone (adjusted hazard ratio 1.65 [95% confidence interval 1.36 to 2.00] and 1.41 [95% confidence interval 1.23 to 1.61], respectively) than those aged 26 to 45 years. Conclusion One in 3 young adults received medication for opioid use disorder in the 12 months after surviving an overdose. Type of medication for opioid use disorder received appeared to be age associated. Future research should focus on how medication choice is made and how to optimize the emergency department for medication for opioid use disorder initiation after nonfatal overdose.

Background Medical care, public health, and criminal justice systems encounters could serve as touchpoints to identify and intervene with individuals at high-risk of opioid overdose death. The relative risk of opioid overdose death and proportion of deaths that could be averted at such touchpoints are unknown. Methods We used 8 individually linked data sets from Massachusetts government agencies to perform a retrospective cohort study of Massachusetts residents ages 11 and older. For each month in 2014, we identified past 12-month exposure to 4 opioid prescription touchpoints (high dosage, benzodiazepine co-prescribing, multiple prescribers, or multiple pharmacies) and 4 critical encounter touchpoints (opioid detoxification, nonfatal opioid overdose, injection-related infection, and release from incarceration). The outcome was opioid overdose death. We calculated Standardized Mortality Ratios (SMRs) and Population Attributable Fractions (PAFs) associated with touchpoint exposure. Results The cohort consisted of 6,717,390 person-years of follow-up with 1315 opioid overdose deaths. We identified past 12-month exposure to any touchpoint in 2.7% of person-months and for 51.8% of opioid overdose deaths. Opioid overdose SMRs were 12.6 (95% CI: 11.1, 14.1) for opioid prescription and 68.4 (95% CI: 62.4, 74.5) for critical encounter touchpoints. Fatal opioid overdose PAFs were 0.19 (95% CI: 0.17, 0.21) for opioid prescription and 0.37 (95% CI: 0.34, 0.39) for critical encounter touchpoints. Conclusions Using public health data, we found eight candidate touchpoints were associated with increased risk of fatal opioid overdose, and collectively identified more than half of opioid overdose decedents. These touchpoints are potential targets for development of overdose prevention interventions.

Background Research has shown an association between assisted reproductive technology (ART) and adverse birth outcomes. We identified whether birth outcomes of ART-conceived pregnancies vary across states with different maternal characteristics, insurance coverage for ART services, and type of ART services provided. Methods CDC's National ART Surveillance System data were linked to Massachusetts, Florida, and Michigan vital records from 2000 through 2006. Maternal characteristics in ART- and non-ART-conceived live births were compared between states using chi-square tests. We performed multivariable logistic regression analyses and calculated adjusted odds ratios (aOR) to assess associations between ART use and singleton preterm delivery (

Background The Helping to End Addiction Long-termSM (HEALing) Communities Study (HCS) is a multisite, parallel-group, cluster randomized wait-list controlled trial evaluating the impact of the Communities That HEAL intervention to reduce opioid overdose deaths and associated adverse outcomes. This paper presents the approach used to define and align administrative data across the four research sites to measure key study outcomes. Methods Priority was given to using administrative data and established data collection infrastructure to ensure reliable, timely, and sustainable measures and to harmonize study outcomes across the HCS sites. Results The research teams established multiple data use agreements and developed technical specifications for more than 80 study measures. The primary outcome, number of opioid overdose deaths, will be measured from death certificate data. Three secondary outcome measures will support hypothesis testing for specific evidence-based practices known to decrease opioid overdose deaths: (1) number of naloxone units distributed in HCS communities; (2) number of unique HCS residents receiving Food and Drug Administration-approved buprenorphine products for treatment of opioid use disorder; and (3) number of HCS residents with new incidents of high-risk opioid prescribing. Conclusions The HCS has already made an impact on existing data capacity in the four states. In addition to providing data needed to measure study outcomes, the HCS will provide methodology and tools to facilitate data-driven responses to the opioid epidemic, and establish a central repository for community-level longitudinal data to help researchers and public health practitioners study and understand different aspects of the Communities That HEAL framework.

Key Points Question Do differences by maternal race and ethnicity exist in the use of methadone or buprenorphine medications for the treatment of opioid use disorder during pregnancy? Findings In this cohort study of 5247 women with opioid use disorder who delivered a live infant, black non-Hispanic and Hispanic women with opioid use disorder were significantly less likely to use any medication for treatment and were less likely to consistently use medication for treatment during pregnancy compared with white non-Hispanic women with opioid use disorder. Meaning This study found racial and ethnic disparities in the use of medications for the treatment of opioid use disorder during pregnancy among a large population-level sample of women with opioid use disorder in Massachusetts; further investigation is warranted to explore the factors associated with inequitable access to and receipt of medication., Importance Racial and ethnic disparities persist across key health and substance use treatment outcomes for mothers and infants. The use of medications, such as methadone or buprenorphine, for the treatment of opioid use disorder (OUD) has been associated with improvements in the outcomes of mothers and infants; however, only half of all pregnant women with OUD receive these medications. The extent to which maternal race or ethnicity is associated with the use of medication to treat OUD, the duration of the use of medication to treat OUD, and the type of medication used to treat OUD during pregnancy are unknown. Objective To examine the extent to which maternal race and ethnicity is associated with the use of medications for the treatment of OUD in the year before delivery among pregnant women with OUD. Design, Setting, and Participants This retrospective cohort study used a linked population-level statewide data set of pregnant women with OUD who delivered a live infant in Massachusetts between October 1, 2011, and December 31, 2015. Of 274 234 total deliveries identified, 5247 deliveries among women with indicators of having OUD were included in the analysis. Maternal race and ethnicity were defined as white non-Hispanic, black non-Hispanic, or Hispanic based on self-reported data on birth certificates. Main Outcomes and Measures Main outcomes were the receipt of any medication for OUD, the consistency of the use of medication (at least 6 continuous months of use before delivery, inconsistent use, or no use) for the treatment of OUD, and the type of medication (methadone or buprenorphine) used to treat OUD. Multivariable models were adjusted for maternal sociodemographic characteristics, comorbidities, and any significant interactions between the covariates and race and ethnicity. Results The sample included 5247 pregnant women with OUD who delivered a live infant in Massachusetts during the study period. The mean (SD) maternal age at delivery was 28.7 (5.0) years; 4551 women (86.7%) were white non-Hispanic, 462 women (8.8%) were Hispanic, and 234 women (4.5%) were black non-Hispanic. A total of 3181 white non-Hispanic women (69.9%) received any type of medication for the treatment of OUD in the year before delivery compared with 228 Hispanic women (49.4%) and 108 black non-Hispanic women (46.2%). Compared with white non-Hispanic women, black non-Hispanic and Hispanic women had a substantially lower likelihood (adjusted odds ratio [aOR], 0.37; 95% CI, 0.28-0.49 and aOR, 0.42; 95% CI, 0.35-0.52, respectively) of receiving any medication for the treatment of OUD. Stratification by maternal age identified greater disparities among younger women. Black non-Hispanic and Hispanic women also had a lower likelihood (aOR, 0.24; 95% CI, 0.17-0.35 and aOR, 0.34; 95% CI, 0.27-0.44, respectively) of consistent use of medication for the treatment of OUD compared with white non-Hispanic women. With respect to the type of medication used to treat OUD, black non-Hispanic and Hispanic women had a lower likelihood (aOR, 0.60; 95% CI, 0.40-0.90 and aOR, 0.77; 95% CI, 0.58-1.01, respectively) than white non-Hispanic women of receiving buprenorphine treatment compared with methadone treatment. Conclusions and Relevance This study found racial and ethnic disparities in the use of medications to treat OUD during pregnancy, with black non-Hispanic and Hispanic women significantly less likely to use medications consistently or at all compared with white non-Hispanic women. Further investigation of patient, clinician, treatment program, and system-level factors associated with these findings is warranted., This cohort study assesses the extent to which maternal race and ethnicity is associated with the use of medications for the treatment of opioid use disorder in the year before delivery among pregnant women with opioid use disorder in Massachusetts.

Background and aimsOpioid-related overdose is increasingly linked to pregnancy-associated deaths, but factors associated with postpartum overdose are unknown. We aimed to estimate the strength of the association between maternal and infant characteristics and postpartum opioid-related overdose.DesignRetrospective cohort study using a linked, population-level data set.SettingMassachusetts, United States.ConclusionAmong women who delivered live infants in Massachusetts, USA between 2012 and 2014, maternal diagnosis of OUD, prior non-fatal overdose, infant diagnosis of NAS and high unscheduled health-care utilization appeared to be positively associated with postpartum opioid overdose. However, more than half of postpartum overdoses in that period were to women without a diagnosis of OUD. Engagement in methadone or buprenorphine treatment in the month prior to delivery was not sufficient to reduce the odds of postpartum overdose.ParticipantsWomen who delivered one or more live births from 2012 to 2014 (n=174 517).MeasurementsThe primary outcome was opioid-related overdose in the postpartum year. We used multivariable logistic regression to explore the independent associations of maternal (demographics, substance use, pregnancy) and infant [gestational age, birthweight, neonatal abstinence syndrome (NAS)] characteristics with postpartum opioid overdose. Findings were stratified by maternal opioid use disorder (OUD) diagnosis.FindingsThere were 189 deliveries to women who experienced ≥1 opioid overdose in the first year postpartum (11 of 10 000 deliveries). Among women with postpartum opioid overdose, 46.6% had an OUD diagnosis within 12months before delivery. In our adjusted model, maternal diagnosis of OUD [adjusted odds ratio (aOR)=3.61, 95% confidence interval (CI)=1.73-7.51] and prior non-fatal overdose (aOR=2.40, 95% CI=1.11-5.17) were most strongly associated with postpartum overdose. After stratifying by OUD status, infant diagnosis of NAS (OUD+ aOR=2.03, 95% CI=1.26-3.27; OUD- aOR=2.79, 95% CI=1.12-6.93) and high unscheduled health-care utilization (OUD+ aOR=2.27, 95% CI=1.38-3.73; OUD- aOR=2.11, 95% CI=1.24-3.58) were positively associated with postpartum overdose in both groups.

The aim of this study was to evaluate whether veterans in Massachusetts receiving opioids and/or benzodiazepines from both Veterans Health Administration (VHA) and non-VHA pharmacies are at higher risk of adverse events compared with those receiving opioids at VHA pharmacies only.A cohort study of veterans who filled a prescription for any Schedule II through V substance at a Massachusetts VHA pharmacy. Prescriptions were recorded in the Massachusetts Department of Public Health Chapter 55 data set.The study sample included 16,866 veterans residing in Massachusetts, of whom 9238 (54.8%) received controlled substances from VHA pharmacies only and 7628 (45.2%) had filled prescriptions at both VHA and non-VHA pharmacies ("dual care users") between October 1, 2013, and December 31, 2015. Our primary outcomes were nonfatal opioid overdose, fatal opioid overdose, and all-cause mortality.Compared with VHA-only users, more dual care users resided in rural areas (12.6% vs 10.6%), received high-dose opioid therapy (26.3% vs 7.3%), had concurrent prescriptions of opioids and benzodiazepines (34.8% vs 8.2%), and had opioid use disorder (6.8% vs 1.6%) (P.0001 for all). In adjusted models, dual care users had higher odds of nonfatal opioid overdose (odds ratio [OR], 1.29; 95% CI, 0.98-1.71) and all-cause mortality (OR, 1.66; 95% CI, 1.43-1.93) compared with VHA-only users. Dual care use was not associated with fatal opioid overdoses.Among veterans in Massachusetts, receipt of opioids from multiple sources was associated with worse outcomes, specifically nonfatal opioid overdose and mortality. Better information sharing between VHA and non-VHA pharmacies and prescribers has the potential to improve patient safety.

BACKGROUND/OBJECTIVES: Potentially inappropriate opioid prescribing (PIP) may contribute to risk for fatal opioid overdose among older adults (age 50+). Our objective was to examine the effect of age on the likelihood of PIP exposure, as well as the effect of PIP exposure on adverse outcomes. DESIGN: Retrospective cohort study SETTING: Data from multiple state agencies in Massachusetts, 2011–2015 PARTICIPANTS: Over 3 million adult Massachusetts residents (3,078,163) who received at least one prescription opioid during the study period; approximately half (1,589,365) were older adults (age 50+). MEASUREMENTS: We measured exposure to five types of PIP: high-dose opioids, co-prescription with benzodiazepines, multiple opioid prescribers, multiple opioid pharmacies, and continuous opioid therapy without a pain diagnosis. We examined three adverse outcomes: non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality. RESULTS: The rate of any PIP exposure increased with age, ranging from 2% among individuals age 18–29 to 14% among those age 50 and older. Older adults also had elevated rates of exposure to two or more different types of PIP, including 5% of adults age 50–69 and 4% of adults age 70 or older, in comparison to 2.5% of age 40–49 and lower percentages in younger age groups. Among covariates assessed, increasing age was the greatest positive predictor of PIP exposure. In analyses stratified by age, exposure to both any PIP and specific types of PIP were associated with non-fatal overdose, fatal overdose, and all-cause mortality among both younger and older adults. CONCLUSION: Older adults are more likely to be exposed to PIP, which elevates their risk for adverse events. Strategies to reduce exposure to PIP, and to improve outcomes among those already exposed, will be instrumental to addressing the opioid crisis as it manifests among older adults.

BACKGROUND: Opioid-related overdoses and deaths among adolescents in the United States continue to increase, but little is known about adolescents who experience opioid-related non-fatal overdose (NFOD). Our objective was to describe (1) the characteristics of adolescents aged 11-17 who experienced NFOD and (2) their receipt of medications for opioid use disorder (MOUD) in the 12 months following NFOD, compared with adults. METHODS: We created a retrospective cohort using six Massachusetts state agency datasets linked at the individual level, with information on 98% of state residents. Individuals entered the cohort if they experienced NFOD between January 1, 2012 and December 31, 2014. We compared adolescents to adults experiencing NFOD, examining individual characteristics and receipt of medications for opioid use disorder (MOUD)—methadone, buprenorphine, or naltrexone. RESULTS: Among 22,506 individuals who experienced NFOD during the study period, 195 (0.9%) were aged 11-17. Fifty-two percent (102/195) of adolescents were female, whereas only 38% of adults were female (P

INTRODUCTION: Opioid overdose deaths quintupled in Massachusetts between 2000 and 2016. Potentially inappropriate opioid prescribing practices (PIP) are associated with increases in overdoses. The purpose of this study was to conduct spatial epidemiological analyses of novel comprehensively linked data to identify overdose and PIP hotspots. METHODS: Sixteen administrative datasets, including prescription monitoring, medical claims, vital statistics, and medical examiner data, covering >98% of Massachusetts residents between 2011–2015, were linked in 2017 to better investigate the opioid epidemic. PIP was defined by six measures: ≥100 morphine milligram equivalents (MMEs), co-prescription of benzodiazepines and opioids, cash purchases of opioid prescriptions, opioid prescriptions without a recorded pain diagnosis, and opioid prescriptions through multiple prescribers or pharmacies. Using spatial autocorrelation and cluster analyses, overdose and PIP hotspots were identified among 538 ZIP codes. RESULTS: More than half of the adult population (n=3,143,817, ages 18 and older) were prescribed opioids. Nearly all ZIP codes showed increasing rates of overdose over time. Overdose clusters were identified in Worcester, Northampton, Lee/Tyringham, Wareham/Bourne, Lynn, and Revere/Chelsea (Getis-Ord Gi*; p< 0.05). Large PIP clusters for ≥100 MMEs and prescription without pain diagnosis were identified in Western Massachusetts; and smaller clusters for multiple prescribers in Nantucket, Berkshire, and Hampden Counties (p

BACKGROUND: Potentially inappropriate prescribing (PIP) may contribute to opioid overdose. OBJECTIVE: To examine the association between PIP and adverse events. DESIGN: Cohort study. PARTICIPANTS: Three million seventy-eight thousand thirty-four individuals age ≥ 18, without disseminated cancer, who received prescription opioids between 2011 and 2015. MAIN MEASURES: We defined PIP as (a) morphine equivalent dose ≥ 100 mg/day in ≥ 3 months; (b) overlapping opioid and benzodiazepine prescriptions in ≥ 3 months; (c) ≥ 4 opioid prescribers in any quarter; (d) ≥ 4 opioid-dispensing pharmacies in any quarter; (e) cash purchase of prescription opioids on ≥ 3 occasions; and (f) receipt of opioids in 3 consecutive months without a documented pain diagnosis. We used Cox proportional hazards models to identify PIP practices associated with non-fatal opioid overdose, fatal opioid overdose, and all-cause mortality, controlling for covariates. KEY RESULTS: All six types of PIP were associated with higher adjusted hazard for all-cause mortality, four of six with non-fatal overdose, and five of six with fatal overdose. Lacking a documented pain diagnosis was associated with non-fatal overdose (adjusted hazard ratio [AHR] 2.21, 95% confidence interval [CI] 2.02–2.41), as was high-dose opioids (AHR 1.68, 95% CI 1.59–1.76). Co-prescription of benzodiazepines was associated with fatal overdose (AHR 4.23, 95% CI 3.85–4.65). High-dose opioids were associated with all-cause mortality (AHR 2.18, 95% CI 2.14–2.23), as was lacking a documented pain diagnosis (AHR 2.05, 95% CI 2.01–2.09). Compared to those who received opioids without PIP, the hazard for fatal opioid overdose with one, two, three, and ≥ four PIP subtypes were 4.24, 7.05, 10.28, and 12.99 (test of linear trend, p

Objective To determine whether assisted reproductive technology (ART) cycles involving cryopreserved-warmed embryos are associated with the development of preeclampsia. Design Retrospective cohort study. Setting IVF clinics and hospitals. Patient(s) A total of 15,937 births from ART: 9,417 singleton and 6,520 twin. Intervention(s) We used linked ART surveillance, birth certificate, and maternal hospitalization discharge data, considering resident singleton and twin births from autologous or donor eggs from 2005–2010. Main Outcome Measure(s) We compared the frequency of preeclampsia diagnosis for cryopreserved-warmed versus fresh ET and used multivariable logistic regression to adjust for confounders. Result(s) Among pregnancies conceived with autologous eggs resulting in singletons, preeclampsia was greater after cryopreserved-warmed versus fresh ET (7.51% vs. 4.29%, adjusted odds ratio=2.17 [95% CI 1.67–2.82]). Preeclampsia without and with severe features, preeclampsia with preterm delivery, and chronic hypertension with superimposed preeclampsia were more frequent after cryopreserved-warmed versus fresh ET (3.99% vs. 2.55%; 2.95% vs. 1.41%; 2.76 vs. 1.48%; and 0.95% vs. 0.43%, respectively). Among pregnancies from autologous eggs resulting in twins, the frequency of preeclampsia with severe features (9.26% vs. 5.70%) and preeclampsia with preterm delivery (14.81% vs. 11.74%) was higher after cryopreserved versus fresh transfers. Among donor egg pregnancies, rates of preeclampsia did not differ significantly between cryopreserved-warmed and fresh ET (10.78% vs. 12.13% for singletons and 28.0% vs. 25.15% for twins). Conclusion(s) Among ART pregnancies conceived using autologous eggs resulting in live births, those involving transfer of cryopreserved-warmed embryos, as compared with fresh ETs, had increased risk for preeclampsia with severe features and preeclampsia with preterm delivery.

Background Assisted Reproductive Technology (ART) includes fertility procedures where both egg and sperm are handled in the lab. ART use has increased considerably in recent years, accounting for 47 090 livebirths in the US in 2010. ART increases the probability of multiple gestation births, which are at higher risks than singletons for adverse outcomes. Additionally, ART is associated with a greater risk of complications during pregnancy, labour, and delivery, and increased risk of adverse perinatal outcomes in singleton births. Methods We merged Florida and Massachusetts birth records from 2004–06 with the National ART Surveillance System (NASS) and using NASS as the gold standard, calculated sensitivity, specificity, and positive predictive value (PPV) of ART reporting on the birth certificates by maternal, infant, and hospital characteristics. We fit random-effects logistic regression models to evaluate simultaneously the association of ART reporting with these predictors while accounting for correlation among births occurring in the same hospital. Results Sensitivity of ART reporting on the birth certificate was 28.9% in Florida and 41.4% in Massachusetts. Specificity was >99% in both states. PPV was 45.5% in Florida and 54.6% in Massachusetts. The odds of ART reporting varied by state and by several maternal and delivery characteristics including age, parity, history of fetal loss, plurality, race/Hispanic ethnicity, delivery payment source, pre-existing conditions, and complications during pregnancy or labour and delivery. Conclusions There was significant under-reporting of ART procedures on the birth certificates. Using data on ART births identified only from birth certificates yields a biased sample of the population of ART births.

Objectives and Study Design The aim of this study was two-fold: to investigate the association of Assisted Reproductive Technology (ART) and small newborn size, using standardized measures; and to examine within strata of fresh and cryopreserved embryos transfer, whether this association is influenced by parental infertility diagnoses. We used a population-based retrospective cohort from Michigan (2000–2009), Florida and Massachusetts (2000–2010). Our sample included 28,946 ART singletons conceived with non-donor oocytes and 4,263,846 non-ART singletons. Methods Regression models were used to examine the association of ART and newborn size, measured as small for gestational age (SGA) and birth-weight-z-score, among four mutually exclusive infertility groups: female infertility only, male infertility only, combined female and male infertility, and unexplained infertility, stratified by fresh and cryopreserved embryos transfer. Results We found increased SGA odds among ART singletons from fresh embryos transfer compared with non-ART singletons, with little difference by infertility source [adjusted odds-ratio for SGA among female infertility only: 1.18 (95% CI 1.10, 1.26), male infertility only: 1.20 (95% CI 1.10, 1.32), male and female infertility: 1.18 (95% CI 1.06, 1.31) and unexplained infertility: 1.24 (95% CI 1.10, 1.38)]. Conversely, ART singletons, born following cryopreserved embryos transfer, had lower SGA odds compared with non-ART singletons, with mild variation by infertility source [adjusted odds-ratio for SGA among female infertility only: 0.56 (95% CI 0.45, 0.71), male infertility only: 0.64 (95% CI 0.47, 0.86), male and female infertility: 0.52 (95% CI 0.36, 0.77) and unexplained infertility: 0.71 (95% CI 0.47, 1.06)]. Birth-weight-z-score was significantly lower for ART singletons born following fresh embryos transfer than non-ART singletons, regardless of infertility diagnoses.

Importance Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent. Objectives To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants. Design, Setting, and Participants Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015. Exposures Use of ART among all live births and use of certain ART procedures among ART births. Main Outcome and Measures Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth. Results Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity-adjustedPvalues for these associations were greater than .05. Conclusions and Relevance Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors.

To estimate smoking prevalence during the year before pregnancy and during pregnancy and adverse outcomes among women who delivered infants with and without assisted reproductive technology (ART) using linked birth certificates (BC) and National ART Surveillance System (NASS) data.Data were analyzed for 384,390 women and 392,248 infants born in Massachusetts and Michigan during 2008-2009. Maternal smoking prevalence was estimated using smoking indicated from BC by ART status. For ART users, to evaluate underreporting, prepregnancy smoking was estimated from BC, NASS, or both sources. Effect of prenatal smoking on preterm and mean birthweight (term only) for singleton infants were examined by ART status.Maternal smoking prevalence estimates were significantly lower for ART users than nonusers (prepregnancy = 3.2% vs. 16.7%; prenatal = 1.0% vs. 11.1%, p 0.05). When combining smoking information from BC and NASS, prepregnancy smoking prevalence estimates for ART users could be as high as 4.4% to 6.1%. Adverse effects of smoking on infant outcomes in ART pregnancies were consistent with the effects seen in non-ART pregnancies, specifically decline in infant birthweight and increase in preterm delivery, although association between smoking and preterm was not significant.A low, but substantial proportion of ART users smoked before and during pregnancy. As ART users are highly motivated to get pregnant, it should be clearly communicated that smoking can decrease fertility and adversely affect pregnancy outcomes. Continued efforts are needed to encourage smoking cessation and maintain tobacco abstinence among all women of reproductive age.

Background Opioid overdose survivors have an increased risk for death. Whether use of medications for opioid use disorder (MOUD) after overdose is associated with mortality is not known. Objective To identify MOUD use after opioid overdose and its association with all-cause and opioid-related mortality. Design Retrospective cohort study. Setting 7 individually linked data sets from Massachusetts government agencies. Participants 17 568 Massachusetts adults without cancer who survived an opioid overdose between 2012 and 2014. Measurements Three types of MOUD were examined: methadone maintenance treatment (MMT), buprenorphine, and naltrexone. Exposure to MOUD was identified at monthly intervals, and persons were considered exposed through the month after last receipt. A multivariable Cox proportional hazards model was used to examine MOUD as a monthly time-varying exposure variable to predict time to all-cause and opioid-related mortality. Results In the 12 months after a nonfatal overdose, 2040 persons (11%) enrolled in MMT for a median of 5 months (interquartile range, 2 to 9 months), 3022 persons (17%) received buprenorphine for a median of 4 months (interquartile range, 2 to 8 months), and 1099 persons (6%) received naltrexone for a median of 1 month (interquartile range, 1 to 2 months). Among the entire cohort, all-cause mortality was 4.7 deaths (95% CI, 4.4 to 5.0 deaths) per 100 person-years and opioid-related mortality was 2.1 deaths (CI, 1.9 to 2.4 deaths) per 100 person-years. Compared with no MOUD, MMT was associated with decreased all-cause mortality (adjusted hazard ratio [AHR], 0.47 [CI, 0.32 to 0.71]) and opioid-related mortality (AHR, 0.41 [CI, 0.24 to 0.70]). Buprenorphine was associated with decreased all-cause mortality (AHR, 0.63 [CI, 0.46 to 0.87]) and opioid-related mortality (AHR, 0.62 [CI, 0.41 to 0.92]). No associations between naltrexone and all-cause mortality (AHR, 1.44 [CI, 0.84 to 2.46]) or opioid-related mortality (AHR, 1.42 [CI, 0.73 to 2.79]) were identified. Limitation Few events among naltrexone recipients preclude confident conclusions. Conclusion A minority of opioid overdose survivors received MOUD. Buprenorphine and MMT were associated with reduced all-cause and opioid-related mortality. Primary funding source National Center for Advancing Translational Sciences of the National Institutes of Health.

Knowledge of state-specific infertility is limited. The objectives of this study were to explore state-specific estimates of lifetime prevalence of having ever experienced infertility, sought treatment for infertility, types of treatments sought, and treatment outcomes.Male and female adult residents aged 18-50 years from three states involved in the States Monitoring Assisted Reproductive Technology Collaborative (Florida, Massachusetts, and Michigan) were asked state-added infertility questions as part of the 2012 Behavioral Risk Factor Surveillance System, a state-based, health-related telephone survey. Analysis involved estimation of lifetime prevalence of infertility.The estimated lifetime prevalence of infertility among 1,285 adults in Florida, 1,302 in Massachusetts, and 3,360 in Michigan was 9.7%, 6.0%, and 4.2%, respectively. Among 736 adults in Florida, 1,246 in Massachusetts, and 2,742 in Michigan that have ever tried to get pregnant, the lifetime infertility prevalence was 25.3% in Florida, 9.9% in Massachusetts, and 5.8% in Michigan. Among those with a history of infertility, over half sought treatment (60.7% in Florida, 70.6% in Massachusetts, and 51.6% in Michigan), the most common being non-assisted reproductive technology fertility treatments (61.3% in Florida, 66.0% in Massachusetts, and 75.9% in Michigan).State-specific estimates of lifetime infertility prevalence in Florida, Massachusetts, and Michigan varied. Variations across states are difficult to interpret, as they likely reflect both true differences in prevalence and differences in data collection questionnaires. State-specific estimates are needed for the prevention, detection, and management of infertility, but estimates should be based on a common set of questions appropriate for these goals.

Objective To investigate the risk of preterm birth among liveborn singletons to primiparas who conceived with assisted reproductive technology (ART) using four mutually exclusive categories of infertility (female infertility only, male infertility only, female and male infertility, and unexplained infertility) and to examine preterm birth risk along the gestational age continuum. Design Retrospective cohort study. Setting Not applicable. Patient(s) Singletons born to primiparas who conceived with or without ART. Intervention(s) None. Main Outcome Measure(s) Preterm ( Result(s) For the male infertility only, female infertility only, combined male and female infertility, and unexplained infertility groups, ART-conceived singletons were significantly more likely than non-ART singletons to be born preterm: adjusted odds ratio (aOR) 1.24 (95% CI, 1.13, 1.37), aOR 1.60 (95% CI, 1.50, 1.70), aOR 1.49 (95% CI, 1.35, 1.64), and aOR 1.26 (1.12, 1.43) respectively. Among infants whose mothers were diagnosed with infertility, the odds of preterm birth were highest between 28–30 weeks [female infertility only, aOR 1.95 (95% CI, 1.59, 2.39); male and female infertility: 2.21 (95% CI, 1.62, 3.00)] compared with infants in the general population. Within the ART population, singletons of couples with female infertility only were more likely to be born preterm than singletons born to couples with other infertility diagnoses. Conclusion(s) Among singleton births to primiparas, those conceived with ART had an increased risk for preterm birth, even when only the male partner had been diagnosed with infertility. The risk of preterm birth for ART-conceived infants whose mothers were diagnosed with infertility included the earliest deliveries.