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Background: Fatal and non-fatal events associated with drug misuse are skyrocketing in most United States jurisdictions, including Indiana. Historically, the role of the judiciary is to arrest, impose sanctions and protect society from harm. Adults arrested for drug abuse in Indiana can be sentenced to 1 of 17 correctional facilities. As an alternative, they may be eligible to participate in a problem-solving court (PSC) programme that refers individuals to treatment as a pretrial diversionary strategy. The aim of the study is to determine which interventions offered by PSCs and correctional facilities impact morbidity and mortality. The study began in 2019 and will end in 2023; therefore, the results in this manuscript are preliminary. Methods: The study cohort included two populations arrested for drug misuse: (1) adults sentenced to Indianan correctional facilities (1 January 2018 to 30 June 2021) and (2) adults participating in an Indiana PSC programme (1 January 2018 to 30 June 2021). The study used a mixed-methods design that integrated qualitative interviews of deputy wardens, PSC team members and service providers with the following quantitative datasets: sentencing information, emergency department visits, inpatient hospitalization admissions, prescription drug monitoring programme data and death records. The individuals will be followed at 2-week, 4-week, 6-month and 1-year intervals post-release. Difference-in-difference and time-toevent analyses will identify impactful interventions. A model will be created to show the effect of impactful interventions in Indiana counties that do not have PSCs. Results: Findings are preliminary. There is variability amongst correctional facilities regarding programme eligibility, provided services and provision of medication-assisted treatment. All correctional facilities were severely impacted by the COVID-19 pandemic. Conclusion: It is anticipated that the adoption of impactful interventions will lower opioid-related morbidity and mortality rates.

OBJECTIVE Women with type 1 diabetes (T1D) are thought to experience menopause earlier than women without diabetes, although not all studies agree. We assessed metabolic predictors of the age at which natural menopause occurs among women with T1D participating in the Epidemiology of Diabetes Complications study. METHODS Women with childhood-onset (

OBJECTIVES To update the U.S. portion of an historical cohort mortality study of workers with potential exposure to chloroprene (CD) and vinyl chloride (VC) with focus on lung and liver cancer. METHODS Subjects were 6864 workers from two sites with vital status determined through 2017 for 99% of subjects and cause of death for 97.2% of deaths. Historical exposures to CD and VC were estimated quantitatively. We performed external and internal mortality comparisons. RESULTS External comparisons revealed mostly deficits in deaths; internal comparisons revealed no consistent evidence of exposure-response relationships with CD or VC. CONCLUSIONS Our update continues to support the conclusion that the risk of death from lung or liver cancer is unrelated to exposure to CD or VC at levels experienced by workers in the two U.S. sites.

The ongoing substance misuse epidemic in the United States is complex and dynamic and should be approached as such in the development and evaluation of policy1. Drug overdose deaths (largely attributable to opioid misuse) in the United States have grown exponentially for almost four decades, but the mechanisms of this growth are poorly understood2. From analysis of 661,565 overdose deaths from 1999 to 2017, we show that the age-specific drug overdose mortality curve for each birth-year cohort rises and falls according to a Gaussian-shaped curve. The ascending portion of each successive birth-year cohort mortality curve is accelerated compared with that of all preceding birth-year cohorts. This acceleration can be attributed to either of two distinct processes: a stable peak age, with an increasing amplitude of mortality rate curves from one birth-year cohort to the next; or a youthward shift in the peak age of the mortality rate curves. The overdose epidemic emerged and increased in amplitude among the 1945–1964 cohort (Baby Boomers), shifted youthward among the 1965–1980 cohort (Generation X), and then resumed the pattern of increasing amplitude in the 1981–1990 Millennials. These shifting age and generational patterns are likely to be driven by socioeconomic factors and drug availability, the understanding of which is important for the development of effective overdose prevention measures. A new age–period–cohort analysis reveals distinct generational patterns in deaths from opioid overdose in the United States, suggesting increased risks for Baby Boomers and Millennials.

PURPOSE: To estimate the incidence of corneal endothelial transplantation and identify risk factors among patients with non-infectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with non-infectious ocular inflammation were identified from the Systemic Immunosuppressive Therapy for Eye Diseases Cohort Study. Time-to-event analysis was used to estimate the incidence of corneal endothelial transplantation (CET), including penetrating keratoplasty, Descemet stripping endothelial keratoplasty, or Descemet Membrane Endothelial Keratoplasty procedures. The incidence of CET was calculated; potential risk factors for CET were also evaluated using Cox regression, accounting for correlation between eyes of the same patient. RESULTS: Overall, 14,264 eyes met eligibility criteria for this analysis with a median follow-up 1.8 eye-years. The Kaplan-Meier estimated incidence of CET within 10 years was 1.10% (95% CI, 0.68%–1.53%). Risk factors for CET included age >60 years vs.

Infants and children are particularly vulnerable to in utero and early-life exposures. Thus, a mother’s exposures before and during pregnancy could have important consequences for her child’s health, including cancer development. We examined whether birth certificate–derived maternal anthropometric characteristics were associated with increased risk of subsequent childhood cancer development, accounting for established maternal and infant risk factors. Pennsylvania birth and cancer registry files were linked by the state Department of Health, yielding a virtual cohort of births and childhood cancers from 2003 through 2016. The analysis included 1,827,875 infants (13,785,309 person-years at risk), with 2,352 children diagnosed with any cancer and 747 with leukemia before age 14 years. Children born to mothers with a body mass index (weight (kg)/height (m)2) of ≥40 had a 57% (95% confidence interval: 12, 120) higher leukemia risk. Newborn size of ≥30% higher than expected was associated with 2.2-fold and 1.8-fold hazard ratios for total childhood cancer and leukemia, respectively, relative to those with expected size. Being

Background Skin intrinsic fluorescent (SIF) scores are indirect measures of advanced glycation end-products (AGEs). SIF scores are cross-sectionally associated with type 1 diabetes (T1D) complications such as increased albumin excretion rate (AER), coronary artery calcification (CAC) and neuropathy. We assessed predictors of SIF score change in those with T1D. Methods Data from the 30-year longitudinal Epidemiology of Diabetes Complications (EDC) study of childhood-onset T1D were used to assess AGEs measured with a SIF score produced by the SCOUT DS® device. SIF scores were assessed twice in 83 participants: between 2007-08 and again between 2010-14. Regression analyses were used to assess independent predictors of SIF score change Results At baseline, mean age was 47.9 ± 6.9 years, diabetes duration was 36.7 ± 6.4 years, and median glycosylated hemoglobin (HbA1c) was 7.1 (interquartile range: 6.5, 8.5). During a mean follow-up of 5.2 ± 0.9 years, mean change in SIF score was 2.9 ± 2.8 arbitrary units. In multivariable linear regression models, log HbA1c ( P < 0.001), log estimated glomerular filtration rate (eGFR) ( P < 0.001), overt nephropathy (defined as AER ≥ 200 µg/min, P = 0.06), and multiple daily insulin shots/pump use (MDI) exposure years ( P = 0.02) were independent predictors of SIF score change. Conclusions Increases in SIF score over 5 years were related to increased glycemic levels and decreased kidney function (eGFR). MDI and glomerular damage were related to a decreased SIF score. This is one of the first studies with repeated SIF assessments in T1D and provides unique, albeit preliminary, insight about these associations.

OBJECTIVE Evidence suggests that insulin deficiency and hyperglycemia may disrupt the female reproductive system's normal function, leading to delayed menarche and premature ovarian aging. We thus compared the length of the reproductive period of women with type 1 diabetes (T1D) to women without diabetes. METHODS Women with childhood-onset T1D (diagnosed in 1950-80) from the prospective Epidemiology of Diabetes Complications (EDC) study and nondiabetic women from the Pittsburgh site of the Study of Women's Health Across the Nation (SWAN) were studied. Exclusion criteria comprised not having reached natural menopause, hysterectomy/oophorectomy before menopause, and sex hormone therapy during the menopausal transition. Reproductive history was self-reported. The historical and Women's Ischemia Syndrome Evaluation hormonal algorithms were also used to assess menopause status. RESULTS Women in the T1D cohort (n = 105) were younger, more likely to be White, never smokers, with lower BMI and higher high-density lipoprotein cholesterol levels (all P values

Health system data incompletely capture the social risk factors for drug overdose. This study aimed to improve the accuracy of a machine-learning algorithm to predict opioid overdose risk by integrating human services and criminal justice data with health claims data to capture the social determinants of overdose risk. This prognostic study included Medicaid beneficiaries (n = 237,259) in Allegheny County, Pennsylvania enrolled between 2015 and 2018, randomly divided into training, testing, and validation samples. We measured 290 potential predictors (239 derived from Medicaid claims data) in 30-day periods, beginning with the first observed Medicaid enrollment date during the study period. Using a gradient boosting machine, we predicted a composite outcome (i.e., fatal or nonfatal opioid overdose constructed using medical examiner and claims data) in the subsequent month. We compared prediction performance between a Medicaid claims only model to one integrating human services and criminal justice data with Medicaid claims (i.e., integrated model) using several metrics (e.g., C-statistic, number needed to evaluate [NNE] to identify one overdose). Beneficiaries were stratified into risk-score decile subgroups. The samples (training = 79,087, testing = 79,086, validation = 79,086) had similar characteristics (age = 38±18 years, female = 56%, white = 48%, having at least one overdose = 1.7% during study period). Using the validation sample, the integrated model slightly improved on the Medicaid claims only model (C-statistic = 0.885; 95%CI = 0.877–0.892 vs. C-statistic = 0.871; 95%CI = 0.863–0.878), with small corresponding improvements in the NNE and positive predictive value. Nine of the top 30 most important predictors in the integrated model were human services and criminal justice variables. Using the integrated model, approximately 70% of individuals with overdoses were members of the top risk decile (overdose rates in the subsequent month = 47/10,000 beneficiaries). Few individuals in the bottom 9 deciles had overdose episodes (0-12/10,000). Machine-learning algorithms integrating claims and social service and criminal justice data modestly improved opioid overdose prediction among Medicaid beneficiaries for a large U.S. county heavily affected by the opioid crisis.

To update the U.S. portion of an historical cohort mortality study of workers with potential exposure to chloroprene (CD) and vinyl chloride (VC) with focus on lung and liver cancer.Subjects were 6864 workers from two sites with vital status determined through 2017 for 99% of subjects and cause of death for 97.2% of deaths. Historical exposures to CD and VC were estimated quantitatively. We performed external and internal mortality comparisons.External comparisons revealed mostly deficits in deaths; internal comparisons revealed no consistent evidence of exposure-response relationships with CD or VC.Our update continues to support the conclusion that the risk of death from lung or liver cancer is unrelated to exposure to CD or VC at levels experienced by workers in the two U.S. sites.

PURPOSE: To determine the incidence of and predictive factors for cataract in intermediate uveitis. DESIGN: Retrospective cohort study METHODS: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study, in which medical records were reviewed to determine demographic and clinical data of every eye/patient at every visit at five participating United States tertiary care uveitis centers. The primary outcome was development of vision-compromising cataract as defined by a decrease in visual acuity to 20/40 or less, or requiring cataract surgery. Survival analysis assessed visually defined cataract to avoid bias due to timing of surgery vis-à-vis inflammatory status. RESULTS: Among 2,190 eyes of 1,302 patients with intermediate uveitis the cumulative incidence of cataract formation was 7.6% by one year (95% CI=6.2–9.1%), increasing to 36.6% by ten years (95% CI=31.2–41.6%). Increased cataract risk was observed in eyes with concurrent anterior uveitis causing posterior synechiae (HR=2.68, 95% CI=2.00–3.59, p

Aims We assessed the association of skin intrinsic fluorescence (SIF) scores, as a measure of advanced glycation end-products (AGE), with all-cause mortality in type 1 diabetes (T1D). Methods This is an observational retrospective study of a convenience sample from the Epidemiology of Diabetes Complications (EDC) study. AGEs were measured with a SIF score between 2007 and 2014; vital status was assessed in 2020. Results Among 245 participants, mean age was 48.6 ± 7.4 years, median diabetes duration was 39.5 years (IQR: 34.2, 44.9), and 53.5% were female. Compared to survivors, the deceased (n = 20) were older, with higher SIF scores, longer diabetes duration, lower body mass index (BMI), and an adverse risk factor profile (all p≤0.05). Univariate Cox regression showed a marginal association between SIF score and mortality (HR: 1.1, 95% CI 0.9–1.2, p = 0.06), which persisted after adjustment for multiple daily insulin shots/pump (MDI) use (HR: 1.1, 95% CI 1.0–1.2, p = 0.04). This association was attenuated after adjustment for T1D duration, A1c months, or estimated glomerular filtration rate (eGFR). Conclusions In individuals with long duration T1D, SIF scores adjusted for MDI predicted all-cause mortality, although this association was attenuated after adjustments. Given the nature of sampling and small number of events, our findings require replication.

Mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry. Exposure assessment for cobalt is presented.A historical database (1970 to 2012) of personal and area measurements of cobalt, tungsten, and nickel in the Swedish hardmetal industry was created. Log linear and exponential modeling of cobalt concentrations based on time period, job, and site was performed, and cumulative and mean exposures were calculated.Some 37% of the personal cobalt measurements exceeded 0.02 mg/m, mostly for powder production, pressing, and shaping. The log linear regression showed statistical differences (P 0.05) between sites, time periods, and jobs. Some 1.6% of the cobalt cumulative exposures for blue-collar workers exceeded 0.4 mg/m years.Low levels of cumulative and mean exposures were determined.

Objective The aim of this study was to investigate a cohort in German hardmetal industry, especially relationship between exposures to cobalt, with and without tungsten, and risks of total and cause-specific mortality. Methods The cohort comprises blue-collar workers at three German plants who were employed in hardmetal processing. Individual cumulative exposures and long-term average concentrations were estimated for cobalt, nickel, tungsten, respirable, and inhalable dust. Standardized mortality ratios (SMRs) were calculated for external comparisons. Time-dependent multivariable Cox models were performed for internal analyses. Results Elevated SMRs were found for all-cause, heart diseases, and nonmalignant respiratory diseases mortality, but not for lung cancer. Internal analyses did not show increased risks for any endpoints, and no exposure-response relationship was indicated. Conclusions This study does not provide evidence for elevated lung cancer risks. Methodologic limitations, incomplete ascertainment of death causes in particular, impede conclusions about exposure effects.

To evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer.Subjects were 7304 workers ever employed in one of eight US plants from 1952 to 2008. Vital status through 2012 was determined for 97% of subjects and cause of death for 98.3% of 1087 deaths. We computed standardized mortality ratios (SMRs) and evaluated exposure-response via relative risk regression analysis.We observed overall deficits in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer.We found no evidence that exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in the US hardmetal industry increases mortality risks from any other causes of death.

The ongoing substance misuse epidemic in the United States is complex and dynamic and should be approached as such in the development and evaluation of policy

Background: Transcatheter aortic valve replacement (TAVR) has increasingly become the treatment of choice for symptomatic, severe aortic stenosis in patients at high surgical risk. While women have better morbidity & mortality outcomes following TAVR, it is unclear if there is gender disparity in utilization. We investigated gender-based utilization trends of TAVR and assessed associations with income quartiles & comorbidities. Methods: The Nationwide Inpatient Sample (NIS) data was queried from January 2012 to December 2016 to identify patients undergoing TAVR using International Classification of Diseases (ICD) procedural codes. Statistical analyses included baseline comparisons by gender, analyzing associations between gender, TAVR utilization, income & co-morbidities, with use of Chi-square test for categorical variables and Wilcoxon rank sum test for age. The associations were also analyzed using a propensity score matched subset & a logistic regression model. Results: We identified 21,859 TAVR patients (46.9% women, n=10,259). Women were older than men (median, IQR: 83, 77-87 vs 82, 76-87) and had higher prevalence of hypertension, diastolic heart failure, and pulmonary hypertension (p Conclusion: These findings showed widening utilization gap of TAVR between men and women, despite knowledge of better long-term outcomes in women. Economic factors were not associated with the gender disparity in TAVR utilization. Therefore, further research into TAVR registries is needed to analyze factors impacting this disparity and measures to correct it.

OBJECTIVE: Vascular damage is thought to have a role in premature ovarian aging. We thus assessed the association between the presence, and age at onset of, vascular diabetes complications and age at natural menopause in women with type 1 diabetes. METHODS: Female participants of the Epidemiology of Diabetes Complications study with type 1 diabetes who experienced natural menopause and who never received hormone therapy during their menopausal transition were included in the analysis (n=105). Microalbuminuria (MA), overt nephropathy, proliferative retinopathy, confirmed distal symmetric polyneuropathy, and coronary artery disease, were assessed during biennial clinical exanimations for the first 10 years of follow-up and at year 18, 25 and 30. Menopausal status was determined via self-report and sex hormone data. For each complication, separate linear regression models were used to assess whether, compared with women without the complication of interest, an earlier age at complication development (i.e.

OBJECTIVES: The purpose of this study was to examine US accidental poisoning death rates by demographic and geographic factors from 1979 to 2014, including High Intensity Drug Trafficking Areas. METHODS: Crude and age-adjusted death rates were formed for age group, race, sex, and county for accidental poisonings (ICD 9th revision: E850-E869; ICD 10th revision: X40-X49) from 1979 to 2014 using the Mortality and Population Data System housed at the University of Pittsburgh. Rate ratios were calculated comparing rates from 2014 to 1979, overall, by sex, age group, race, and county. Joinpoint regression detected changes in trends and calculated the average annual percentage change (AAPC) as a summary measure of trend. RESULTS: Drug poisoning mortality rates have risen an average of 6% per year since 1979. Increases are occurring in all ages 15+, and in all race-sex groups. HIDTA counties with the highest mortality rates were in Appalachia and New Mexico. Many of the HIDTA border counties had lower rates of mortality. CONCLUSIONS: The drug poisoning mortality epidemic is continuing to grow. While HIDTA resources are appropriately targeted at many areas in the US most affected, rates are also rapidly rising in some non-HIDTA areas.Copyright © 2015. Published by Elsevier Inc. Language: en

Unconventional natural gas development (UNGD) has been rapidly expanding in Pennsylvania since the mid-2000s. The objective was to analyze associations between UNGD exposure during pregnancy and subsequent development of childhood cancer using Pennsylvania birth and cancer registry data. Birth records and childhood cancer registry records that were linked to birth records were obtained through an IRB-approved application process with the Pennsylvania Department of Health. The present analysis included infants born from 2007 to 2015, a period of rapid UNGD expansion in the state. We excluded mothers and their infants living in the most urban areas (i.e., Pittsburgh and Philadelphia), where exposure to many competing pollution sources may confound the analysis. For each mother, an inverse distance weighted (IDW) well count was calculated based on all active wells drilled within a 10-mile radius of the mother’s residence during the one-year period up to the date of birth. Person-years were accumulated for each child from the birth date until either the date of first childhood cancer diagnosis or, for noncases, the end of the study period (December 31, 2016). Cox proportional hazards models were used to investigate associations between IDW well count and hazard ratio (HR) of cancer development among children. There were 812,143 infants born during the study period with complete outcome and covariate data. Of these, there were 859 and 259 children diagnosed with any type of cancer and the most common type, leukemia, respectively. Models were adjusted for infant sex, congenital anomalies, proximity to major roadways, and maternal factors. After adjustment, the hazard ratio of developing any cancer for children born to mothers living in the highest quartile of UNGD exposure was 1.3 (95% confidence interval: 1.0-1.8) compared to the lowest quartile. Childhood leukemia risk was also 1.3 times higher for children born to the most versus least exposed mothers, although the 95% confidence interval was wider (0.8-2.2). In conclusion, children born to mothers living close to UNGD may be at a slightly increased risk for childhood cancer, although the risk is smaller compared to other established risk factors like the presence of a birth defect or older maternal age. As most of the epidemiologic health studies to date have used well density as a surrogate for UNGD exposure, future studies should consider incorporating environmental sampling or personalized monitoring into their exposure assessments. Citation Format: Shaina L. Stacy, Jeanine M. Buchanich, James P. Fabisiak, Linda Robertson, Ravi K. Sharma, Evelyn O. Talbott, Jian-Min Yuan. Unconventional natural gas operations and childhood cancer development in a Pennsylvania birth cohort [abstract]. In: Proceedings of the AACR Special Conference on Environmental Carcinogenesis: Potential Pathway to Cancer Prevention; 2019 Jun 22-24; Charlotte, NC. Philadelphia (PA): AACR; Can Prev Res 2020;13(7 Suppl): Abstract nr A22.

Objectives To evaluate long-term mortality rates among aerospace material manufacturing workers as follow-up to an earlier observed excess of nephritis/nephrosis. Methods Subjects were 2020 workers ever employed in the facility during 1963-2014. Vital status through 2014 was determined for all subjects and cause of death for 99.2% of 492 deaths. We computed standard mortality ratios (SMR) and internal relative risks. Results SMRs for nephritis/nephrosis were unremarkable. We observed statistically significant elevated SMRs for kidney cancer among all workers and for the category "other lymphatic hematopoietic tissue cancer" (4/5 deaths from multiple myeloma) among long-term workers with potential plant exposure. Conclusions We found no evidence of elevated mortality rates for nephritis/nephrosis. Study limitations precluded robust evaluation of whether the elevated rates for kidney cancer and other lymphatic hematopoietic tissue cancer were related to occupational factors at the study site. Our findings for these two cancers warrant continued mortality follow-up.

INTRODUCTION The epidemic of substance use disorders and drug overdose deaths is a growing public health crisis in the United States. Every day, 174 people die from drug overdoses. Currently, opioids (including prescription opioids, heroin, and synthetic opioids such as fentanyl and its chemical analogs) are the leading cause of overdose deaths. The overdose mortality data can reveal the complex and evolving dynamics of drug use in the United States. RATIONALE Reports on the U.S. drug overdose epidemic tend to focus on changes in yearly statistics. Improved understanding of the long-term dynamics of the overdose epidemic may aid in the development of more effective epidemic prevention and control strategies. At present, there are no reliable methods to forecast the likely future course of the epidemic. We focused on deaths from overdoses as a relatively reliable metric of the epidemic because all deaths are required to be reported in all U.S. states and territories using the standardized International Classification of Diseases. In an effort to understand the epidemic dynamics and perhaps predict its future course, we analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System where unintentional drug poisoning was identified as the main cause of death. We examined the time course of the overall number of deaths; the contributions of individual drugs (prescription opioids, heroin, synthetic opioids like fentanyl, methadone, cocaine, methamphetamine) to the overall curve; changes in the populations most affected by each drug as measured by demographic factors of age, sex, race, and urbanicity; and changes in the geographic distribution of deaths due to each drug as measured by the county of residence of each decedent. RESULTS The overall mortality rate for unintentional drug poisonings in the United States grew exponentially from 1979 through 2016. This exponentially increasing mortality rate has tracked along a remarkably smooth trajectory (log linear R 2 = 0.99) for at least 38 years (left panel). By contrast, the trajectories of mortality rates from individual drugs have not tracked along exponential trajectories. Cocaine was a leading cause in 2005–2006, which was overtaken successively by prescription opioids, then heroin, and then synthetic opioids such as fentanyl. The demographic patterns of deaths due to each drug have also shown substantial variability over time. Until 2010, most deaths were in 40- to 50-year-old persons, from cocaine and increasingly from prescription drugs. Deaths from heroin and then fentanyl have subsequently predominated, affecting younger persons, ages 20 to 40 (middle panel). Mortality rates for males have exceeded those for females for all drugs. Rates for whites exceeded those for blacks for all opioids, but rates were much greater among blacks for cocaine. Death rates for prescription drugs were greater for rural than urban populations. The geographic patterns of deaths also vary by drug. Prescription opioid deaths are widespread across the United States (right panel), whereas heroin and fentanyl deaths are predominantly located in the northeastern United States and methamphetamine deaths in the southwestern United States. Cocaine deaths tend to be associated with urban centers. The online manuscript provides many details of the patterns of mortality in these data. CONCLUSION The U.S. drug overdose epidemic has been inexorably tracking along an exponential growth curve since at least 1979. Although there have been transient periods of minor acceleration or deceleration, the overall drug overdose mortality rate has regularly returned to the exponential growth curve. This historical pattern of predictable growth for at least 38 years suggests that the current opioid epidemic may be a more recent manifestation of an ongoing longer-term process. This process may continue along this path for several more years into the future. Paradoxically, there has been substantial variability with which specific drugs have become dominant in varying populations and geographic locales. This variability all but negates the possibility of confident predictions about the future role of specific drugs. Indeed, it is possible that a future overdose epidemic may be driven by a new or obscure drug that is not among the leading causes of drug overdose death today. Understanding the forces that are holding multiple subepidemics together onto a smooth exponential trajectory may be important in revealing, and effectively dealing with, the root causes of the epidemic.

Objectives:A complete and accurate count of the number of opioid-related overdose deaths is essential to properly allocate resources. We determined the rate of unintentional overdose deaths (non–opioid-related, opioid-related, or unspecified) in the United States and by state from 1999 to 2015 and the possible effects of underreporting on national estimates of opioid abuse.Methods:We abstracted unintentional drug overdose deaths ( International Classification of Diseases, 10th Revision, codes X40-X44) with contributory drug-specific T codes (T36.0-T50.9) from the Mortality Multiple Cause Micro-Data Files. We assumed that the proportion of unspecified overdose deaths that might be attributed to opioids would be the same as the proportion of opioid-related overdose deaths among all overdose deaths and calculated the number of deaths that could be reallocated as opioid-related for each state and year. We then added these reallocated deaths to the reported deaths to determine their potential effect on total opioid-related deaths.Results:From 1999 to 2015, a total of 438 607 people died from unintentional drug overdoses. Opioid-related overdose deaths rose 401% (from 5868 to 29 383), non–opioid-related overdose deaths rose 150% (from 3005 to 7505), and unspecified overdose deaths rose 220% (from 2255 to 29 383). In 5 states (Alabama, Indiana, Louisiana, Mississippi, and Pennsylvania), more than 35% of unintentional overdose deaths were coded as unspecified. Our reallocation resulted in classifying more than 70 000 unspecified overdose deaths as potential additional opioid-related overdose deaths.Conclusions:States may be greatly underestimating the effect of opioid-related overdose deaths because of incomplete cause-of-death reporting, indicating that the current opioid overdose epidemic may be worse than it appears.

Among the many challenges for public officials in controlling the opioid epidemic, one major problem is how to accurately measure, track, and forecast the epidemic’s course, and how to reliably assess the effectiveness—and cost-­effectiveness—of epidemic control measures. In this review we summarize available epidemiological data on substance use disorders and their complications that can be useful to measure and track the epidemic in Pennsylvania. We examine the data through the lens of a systems approach, with the goal of using epidemiological data to create and parameterize dynamic models of the epidemic. We suggest that by integrating a variety of datasets into systems models, it should be possible to forecast and predict the future trajectory of the epidemic and make appropriate decisions on how to mitigate the epidemic. In addition, we identify several potentially valuable data sources that are currently underused for public health decision making.

Opioid overdose deaths in the United States quadrupled from 1999 (n = 8050 deaths) to 2015 (n = 33 091 deaths), and the number of deaths associated with synthetic opioids, such as fentanyl, increased from 3105 deaths in 2013 to nearly 20 000 deaths in 2016. Given this rapid increase, timely surveillance for drugs in circulation is crucial. However, current surveillance systems used to track drug overdoses do not detect new drugs in circulation quickly. We studied the change in the presence of fentanyl in “stamp bag” drug evidence in Allegheny County, Pennsylvania, from 2010 through 2016. Stamp bags are small wax packets with individual stamps that contain mixtures of drugs, most commonly heroin, that law enforcement officers seize and retain as legal evidence. The proportion of stamp bags determined to contain fentanyl or a fentanyl analog was 2.1% in 2014 and rose sharply to 17.1% in 2016. Monitoring the chemical makeup of drug evidence items could help public health authorities identify drug use trends in their jurisdictions.

OBJECTIVE Exposures associated with coal mining activities, including diesel fuel exhaust, products used in coal processing, and heavy metals and other forms of particulate matter, may impact the health of nearby residents. We investigated the relationships between county-level circulatory hospitalization rates (CHRs) in coal and non-coal-mining communities of West Virginia, coal production, coal employment, and sociodemographic factors. METHODS Direct age-adjusted CHRs were calculated using West Virginia hospitalizations from 2005 to 2009. Spatial regressions were conducted to explore associations between CHR and total, underground, and surface coal production. RESULTS After adjustment, neither total, nor surface, nor underground coal production was significantly related to rate of hospitalization for circulatory disease. CONCLUSIONS Our findings underscore the significant role sociodemographic and behavioral factors play in the health and well-being of coal mining communities.

Objective To examine changes in cause-specific Years of Life Lost (YLL) by age, race, and sex group in the USA from 1990 to 2014. Methods 60 million death reports from the National Center for Health Statistics (NCHS) were categorized by age group, sex, race, and cause of death. YLL were calculated using age-specific life expectancies. Age groups were: infants

Objective To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry. Methods Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements. Results Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures. Conclusions The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.

Objective The aim of this study was to characterize the mortality at two hardmetal production factories in the United Kingdom as part of an international study. Methods Standardized mortality ratios (SMRs) were calculated on the basis of mortality rates for England and Wales, and local rates. A nested case-control study of lung cancer was undertaken. Results The cohort comprised 1538 workers, with tracing complete for 94.4%. All-cause mortality was statistically significantly low for all cancers and nonmalignant respiratory disease, and for lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance workers was elevated, based on only six deaths. The odds ratio for lung cancer per year of exposure to hardmetal was 0.93 (0.76 to 1.13). Conclusions In this small study, there is no evidence to support that working in the UK hardmetal manufacturing industry increased mortality from any cause including lung cancer.

OBJECTIVE This study retrospectively investigates causes of death among workers of a hardmetal plant in Austria. METHODS A retrospective cohort was formed of 1965 workers still employed in or after 1970. Follow-up was until end of 2014 based on national databases. Cobalt exposure was assessed through industrial hygiene data and urine analyses. Cox proportional hazards models were calculated for selected causes of death. RESULTS During 45,598 years of observation in total 177 deaths were observed. Forty-nine workers died from any cancer, 10 from lung cancer, and three from chronic obstructive pulmonary disease. Only the latter showed a significant association with cumulative exposure. CONCLUSIONS Although this is a young study population with little power to detect subtle effects, at least it does not indicate a pronounced cancer risk among tungsten carbide workers due to cobalt.

Accidental poisoning cases were abstracted from death record reports provided by the US National Center for Health Statistics for the period 1979 to 2015. A graph of the resultant death counts by year generated a tight exponential curve (R2 = 0.99) with growth rate of 9% per year and a doubling time of approximately 8 years. The mechanisms that have driven five continuous epidemic doublings of overdose deaths over a 37 year period, despite considerable variability in drug usage and drug control activities, are unclear. That this continuous exponential growth pattern began well before the onset of the current opioid epidemic suggests that deep sociological, economic, and technological factors may be operative. Regardless of underlying mechanisms, simple extrapolation of the fitted curve forecasts approximately 300,000 new deaths in the next five years.

BACKGROUND Exposures associated with coal mining have long been linked to occupational disease. More recently, investigators have suggested that this industry may affect community health. METHODS We explored associations between age-adjusted, county-level respiratory disease hospitalization rates (RHRs) in West Virginia and total, surface, and underground coal production, taking into account relevant sociodemographic and behavioral covariates. RHRs were calculated for 2005 to 2009, and analyses were performed to assess the effect of coal production after adjusting for sociodemographic factors. RESULTS After controlling for percent below poverty, percent urban, and smoking, neither total nor underground tonnage was associated with RHR. Surface coal production, however, was significantly related with RHR (P < 0.05). CONCLUSIONS Surface coal production makes a small but significant contribution to RHR in West Virginia after accounting for other important sociodemographic and behavioral determinants of health.

Cardiac amyloidosis (CA) is an underdiagnosed cause of cardiomyopathy and is highly fatal if untreated. Recent trends of CA and related healthcare utilization in the US are unknown. To address this gap, we examined changes in hospitalization rates, inpatient mortality and financial outcomes of CA

OBJECTIVE To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with specific chemical or physical exposures. METHODS Subjects were 210,784 workers employed from 1952 to 2001. We conducted a cohort incidence study and two nested case-control studies with focus on the North Haven facility where we previously observed a not statistically significant overall elevation in GB rates. We estimated individual-level exposure metrics for 11 agents. RESULTS In the total cohort, none of the agent metrics considered was associated with increased GB risk. The GB incidence rates in North Haven were also not related to workplace exposures, including the "blue haze" exposure unique to North Haven. CONCLUSIONS If not due to chance alone, GB rates in North Haven may reflect external occupational factors, nonoccupational factors, or workplace factors unique to North Haven unmeasured in the current evaluation.

OBJECTIVE To evaluate mortality rates among a cohort of jet engine manufacturing workers. METHODS Subjects were 222,123 workers employed from 1952 to 2001. Vital status was determined through 2004 for 99% of subjects and cause of death for 95% of 68,317 deaths. We computed standardized mortality ratios and modeled internal cohort rates. RESULTS Mortality excesses reported initially no longer met the criteria for further investigation. We found two chronic obstructive pulmonary disease-related mortality excesses that met the criteria in two of eight study plants. CONCLUSIONS At the total cohort level, chronic obstructive pulmonary disease-related categories were not related to any factors or occupational exposures considered. A full evaluation of these excesses was limited by lack of data on smoking history. Occupational exposures received outside of work or uncontrolled positive confounding by smoking cannot be ruled out as reasons for these excesses.

OBJECTIVE To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed. METHODS Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases. RESULTS In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk. CONCLUSIONS If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.

Objective To reconstruct agent-specific occupational exposures for a cohort of jet engine manufacturing workers for use in an epidemiological mortality study. Methods Potential chemical and physical exposures at eight jet engine manufacturing and overhaul/repair plants were evaluated for the period 1952 to 2001. Eleven agents were selected for detailed examination, and a job-exposure matrix was constructed. Results Quantitative exposure estimates were generated for metalworking fluids, nickel, cobalt, chromium, solvents, and incomplete combustion aerosol from metalworking fluids. Qualitative exposure estimates were assigned for ionizing radiation, electromagnetic fields, polychlorinated biphenyls, and lead-cadmium. All exposures showed decreasing trends over the study period. Conclusions The quantitative exposure levels generated in this study were lower than early contemporaneous professional practice recommendations and were similar to or lower than published data from other industries.

INTRODUCTION: The purpose of this study was to examine county and state-level accidental poisoning mortality trends in Pennsylvania from 1979 to 2014. METHODS: Crude and age-adjusted death rates were formed for age group, race, sex, and county for accidental poisonings (ICD 10 codes X40-X49) from 1979 to 2014 for ages 15+ using the Mortality and Population Data System housed at the University of Pittsburgh. Rate ratios were calculated comparing rates from 1979 to 2014, overall and by sex, age group, and race. Joinpoint regression was used to detect statistically significant changes in trends of age-adjusted mortality rates. RESULTS: Rate ratios for accidental poisoning mortality in Pennsylvania increased more than 14-fold from 1979 to 2014. The largest rate ratios were among 35-44 year olds, females, and White adults. The highest accidental poisoning mortality rates were found in the counties of Southwestern Pennsylvania, those surrounding Philadelphia, and those in Northeast Pennsylvania near Scranton. CONCLUSIONS: The patterns and locations of accidental poisoning mortality by race, sex, and age group provide direction for interventions and policy makers. In particular, this study found the highest rate ratios in PA among females, whites, and the age group 35-44. Language: en

Arterial stiffness decreases with weight loss in overweight/obese young adults. We aimed to determine the mechanisms by which this occurs.We evaluated carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) in 344 young adults (23% male, BMI 25-40 kg/m(2)) at baseline, 6, and 12 months in a behavioral weight loss intervention. Linear mixed models were used to evaluate associations between weight loss and arterial stiffness and to examine whether improvements in obesity-related factors explained these associations.At 6 months (7% mean weight loss), there was a significant median decrease of 47.5 cm/s in cfPWV (p 0.0001) and a mean decrease of 11.7 cm/s in baPWV (p = 0.049). At 12 months (6% mean weight loss), only cfPWV remained reduced. In models adjusting for changes in mean arterial pressure and obesity-related factors, changes in BMI (p = 0.01) and common carotid artery diameter (p = 0.003) were positively associated with change in cfPWV. Reductions in heart rate (p 0.0001) and C-reactive protein (p = 0.02) were associated with reduced baPWV and accounted for the association between weight loss and reduced baPWV.Weight loss is associated with reduced cfPWV independently of changes in established hemodynamic and cardiometabolic risk factors, but its association with reduced baPWV is explained by concurrent reductions in heart rate and inflammation.

Objective To determine whether IARC’s 2001 decision to downgrade the classification of insulation glass wool from Group 2B to Group 3 remains valid in light of epidemiological evidence reported after 2001. Methods We performed a systematic review of epidemiological evidence regarding respiratory cancer risks in relation to man-made vitreous fiber (MMVF) exposure before and after the 2001 IARC re-evaluation with focus on glass wool exposure and respiratory system cancer. Results Since 2001, three new community-based, case-control studies, two detailed analyses of existing cohort studies and two reviews/meta-analyses were published. These studies revealed no consistent evidence of an increased respiratory system cancer risk in relation to glass wool exposure. Conclusions From our evaluation of the epidemiological evidence published since 2001, we conclude that IARC’s 2001 decision to downgrade insulation glass wool from Group 2B to Group 3 remains valid.

Purpose To compare ascertainment of central nervous system (CNS) neoplasms with the use of mortality and incidence data as part of an occupational epidemiology study. Methods Deaths were identified by matching the cohort of 223,894 jet engine manufacturing employees to the U.S. Social Security Administration death files and the National Death Index. Incident cancer cases were identified by matching the cohort to 19 state cancer registries. Results We identified 718 cases overall: 59% by the use of both mortality and cancer incidence tracing; 24% by the use of only mortality tracing, and 17% by the use of only cancer incidence tracing. Compared with state cancer registries, death certificates missed 38% of the malignant, more than six times the benign and nearly 1.5 times the unspecified CNS cases. The positive predictive value of death certificates, with cancer registry as gold standard, was 6% for unspecified, 35% for benign, and 86% for malignant histologies. Conclusions Death certificates seriously underascertained benign and unspecified CNS tumors; analyses determined with mortality data would not accurately capture the true extent of disease among the cohort. Most state cancer registries have only collected nonmalignant CNS tumor information since 2004, which currently limits the usefulness of state cancer registries as a source of nonmalignant CNS tumor identification. Underascertainment of CNS deaths could seriously affect interpretation of results, more so if examining nonmalignant CNS.

Objective To systematically compare midlife mortality patterns in the United States across racial and ethnic groups during 1999-2016, documenting causes of death and their relative contribution to excess deaths. Design Trend analysis of US vital statistics among racial and ethnic groups. Setting United States, 1999-2016. Population US adults aged 25-64 years (midlife). Main outcome measures Absolute changes in mortality measured as average year-to-year change during 1999-2016 and 2012-16; excess deaths attributable to increasing mortality; and relative changes in mortality measured as relative difference between mortality in 1999 versus 2016 and the nadir year versus 2016, and the slope of modeled mortality trends for 1999-2016 and for intervals between joinpoints. Results During 1999-2016, all cause mortality in midlife increased not only among non-Hispanic (NH) whites but also among NH American Indians and Alaskan Natives. Although all cause mortality initially decreased among NH blacks, Hispanics, and NH Asians and Pacific Islanders, this trend ended in 2009-11. Drug overdoses were the leading cause of increased mortality in midlife in each population, but mortality also increased for alcohol related conditions, suicides, and organ diseases involving multiple body systems. Although midlife mortality among NH whites increased across a multitude of conditions, a similar trend affected non-white populations. Absolute (year-to-year) increases in midlife mortality among non-white populationsoften matched or exceeded those of NH whites, especially in 2012-16, when the rate of increase intensified for many causes of death. During 1999-2016, NH American Indians and Alaskan Natives experienced large increases in midlife mortality from 12 causes, not only drug overdoses (411.4%) but also hypertensive diseases (269.3%), liver cancer (115.1%), viral hepatitis (112.1%), and diseases of the nervous system (99.8%). NH blacks experienced increased midlife mortality from 17 causes, including drug overdoses (149.6%), homicides (21.4%), hypertensive diseases (15.5%), obesity (120.7%), and liver cancer (49.5%). NH blacks also experienced retrogression: after a period of stable or declining midlife mortality early in 1999-2016, death rates increased for alcohol related liver disease, chronic lower respiratory tract disease, suicides, diabetes, and pancreatic cancer. Among Hispanics, midlife mortality increased across 12 causes, including drug overdoses (80.0%), hypertensive diseases (40.6%), liver cancer (41.8%), suicides (21.9%), obesity (106.6%), and metabolic disorders (60.0%). Retrogression also occurred in this population; after a period of declining mortality, death rates increased for alcohol related liver disease, mental and behavioral disorders involving psychoactive substances, and homicides. NH Asians and Pacific Islanders were least affected by this trend but also experienced increases in midlife mortality from drug overdoses (300.6%), alcohol related liver disease (62.9%), hypertensive diseases (28.3%), and brain cancer (56.6%). The suicide rate in this group increased by 29.7% after 2001. The relative increase in US midlife mortality differed by sex and geography. For example, the relative increase in fatal drug overdoses was greater among women than among men. Although the relative increase in midlife mortality was generally greater in non-metropolitan (ie, rural) areas, the relative increase in drug overdoses among NH whites and Hispanics was greatest in suburban fringe areas of large cities, and among NH blacks was greatest in small cities. Conclusions Mortality in midlife in the US has increased across racial-ethnic populations for a variety of conditions, especially in recent years, offsetting years of progress in lowering mortality rates. This reversal carries added consequences for racial groups with high baseline mortality rates, such as for NH blacks and NH American Indians and Alaskan Natives. That death rates are increasing throughout the US population for dozens of conditions signals a systemic cause and warrants prompt action by policy makers to tackle the factors responsible for declining health in the US.