Exposure to ambient air toxicants and the risk of amyotrophic lateral sclerosis (ALS): A matched case control study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with few risk factors identified and no known cure. Gene-environment interaction is hypothesized especially for sporadic ALS cases (90-95%) which are of unknown etiology. We aimed to investigate risk factors for ALS including exposure to ambient air toxics. METHODS: This population-based case-control study included 267 ALS cases (from the United States [U.S.] Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry National ALS Registry and Biorepository) and 267 age, sex, and county-matched controls identified via a commercial database. Exposure assessment for 34 ambient air toxicants was performed by assigning census tract-level U.S. Environmental Protection Agency (EPA) 2011 National Air Toxics Assessment (NATA) data to participants' residential ZIP codes. Conditional logistic regression was used to compute adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for individual compounds, chemical classes, and overall exposure. Sensitivity analyses using both conditional logistic regression and Bayesian grouped weighted quartile sum (GWQS) models were performed to assess the integrity of findings. RESULTS: Using the 2011 NATA, the highest exposure quartile (Q4) compared to the lowest (Q1) of vinyl chloride (aOR = 6.00, 95% CI: 1.87-19.25), 2,4-dinitrotoluene (aOR = 5.45, 95% CI: 1.53-19.36), cyanide (aOR = 4.34, 95% CI: 1.52-12.43), cadmium (aOR = 3.30, 95% CI: 1.11-9.77), and carbon disulfide (aOR = 2.98, 95% CI: 1.00-8.91) was associated with increased odds of ALS. Residential air selenium showed an inverse association with ALS (second quartile [Q2] vs. Q1: aOR = 0.38, 95% CI: 0.18-0.79). Additionally, residential exposure to organic/chlorinated solvents (Q4 vs Q1: aOR = 2.62, 95% CI: 1.003-6.85) was associated with ALS. CONCLUSIONS: Our findings using the 2011 NATA linked by census tract to residential area provide evidence of increased ALS risk in cases compared to controls for 2,4-dinitrotoluene, vinyl chloride, cyanide, and the organic/chlorinated solvents class. This underscores the importance of ongoing surveillance of potential exposures for at-risk populations.

Use of Immunosuppression and the Risk of Subsequent Overall or Cancer Mortality.

PURPOSE: To determine the incidence of all-cause and cancer mortality (CM) in association with immunosuppression. DESIGN: Retrospective cohort study at ocular inflammatory disease (OID) subspecialty centers. We harvested exposure and covariate data retrospectively from clinic inception (earliest in 1979) through 2010 inclusive. Then we ascertained overall and cancer-specific mortalities by National Death Index linkage. We constructed separate Cox models to evaluate overall and CM for each class of immunosuppressant and for each individual immunosuppressant compared with person-time unexposed to any immunosuppression. PARTICIPANTS: Patients with noninfectious OID, excluding those with human immunodeficiency infection or preexisting cancer. METHODS: Tumor necrosis factor (TNF) inhibitors (mostly infliximab, adalimumab, and etanercept); antimetabolites (methotrexate, mycophenolate mofetil, azathioprine); calcineurin inhibitors (cyclosporine); and alkylating agents (cyclophosphamide) were given when clinically indicated in this noninterventional cohort study. MAIN OUTCOME MEASURES: Overall mortality and CM. RESULTS: Over 187 151 person-years (median follow-up 10.0 years), during which 15 938 patients were at risk for mortality, we observed 1970 deaths, 435 due to cancer. Both patients unexposed to immunosuppressants (standardized mortality ratio [SMR] = 0.95, 95% confidence interval [CI], 0.90-1.01) and those exposed to immunosuppressants but free of systemic inflammatory diseases (SIDs) (SMR = 1.04, 95% CI, 0.95-1.14) had similar mortality risk to the US population. Comparing patients exposed to TNF inhibitors, antimetabolites, calcineurin inhibitors, and alkylating agents with patients not exposed to any of these, we found that overall mortality (adjusted hazard ratio [aHR] = 0.88, 0.89, 0.90, 1.11) and CM (aHR = 1.25, 0.89, 0.86, 1.23) were not significantly increased. These results were stable in sensitivity analyses whether excluding or including patients with SID, across 0-, 3-, or 5-year lags and across quartiles of immunosuppressant dose and duration. CONCLUSIONS: Our results, in a cohort where the indication for treatment was proven unassociated with mortality risk, found that commonly used immunosuppressants-especially the antimetabolites methotrexate, mycophenolate mofetil, and azathioprine; the TNF inhibitors adalimumab and infliximab, and cyclosporine-were not associated with increased overall and CM over a median cohort follow-up of 10.0 years. These results suggest the safety of these agents with respect to overall and CM for patients treated with immunosuppression for a wide range of inflammatory diseases. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Risk of longer-term neurological conditions in the Deepwater Horizon Oil Spill Coast Guard Cohort Study - Five years of follow-up.

BACKGROUND: Long-term neurological health risks associated with oil spill cleanup exposures are largely unknown. We aimed to investigate risks of longer-term neurological conditions among U.S. Coast Guard (USCG) responders to the 2010 Deepwater Horizon (DWH) oil spill. METHODS: We used data from active duty members of the DWH Oil Spill Coast Guard Cohort Study (N=45224). Self-reported oil spill exposures were ascertained from post-deployment surveys. Incident neurological outcomes were classified using International Classification of Diseases, 9th Revision, codes from military health encounter records up to 5.5 years post-DWH. We used Cox Proportional Hazards regression to calculate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for various incident neurological diagnoses (2010-2015). Oil spill responder (n=5964) vs. non-responder (n= 39260) comparisons were adjusted for age, sex, and race, while within-responder comparisons were additionally adjusted for smoking. RESULTS: Compared to those not responding to the spill, spill responders had reduced risks for headache (aHR=0.84, 95% CI: 0.74-0.96), syncope and collapse (aHR=0.74, 95% CI: 0.56-0.97), and disturbance of skin sensation (aHR=0.81, 95% CI: 0.68-0.96). Responders reporting ever (n=1068) vs. never (n=2424) crude oil inhalation exposure were at increased risk for several individual and grouped outcomes related to headaches and migraines (aHR range: 1.39-1.83). Crude oil inhalation exposure was also associated with elevated risks for an inflammatory nerve condition, mononeuritis of upper limb and mononeuritis multiplex (aHR=1.71, 95% CI: 1.04-2.83), and tinnitus (aHR=1.91, 95% CI: 1.23-2.96), a condition defined by ringing in one or both ears. Risk estimates for those neurological conditions were higher in magnitude among responders reporting exposure to both crude oil and oil dispersants than among those reporting crude oil only. CONCLUSION: In this large study of active duty USCG responders to the DWH disaster, self-reported spill cleanup exposures were associated with elevated risks for longer-term neurological conditions.

Maternal Obesity, Birth Size, and Risk of Childhood Cancer Development.

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 <30% below expected size also increased the overall cancer risk (P for curvilinearity < 0.0001). Newborn size did not mediate the association between maternal obesity and childhood cancer. The results suggest a significant role of early-life exposure to maternal obesity- and fetal growth-related factors in childhood cancer development.

Mortality among United States aerospace materials manufacturing workers.

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.

Patterns and trends in accidental poisoning death rates in the US, 1979-2014.

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.

Non-random geographic distribution of patients with cutaneous T-cell lymphoma in the Greater Pittsburgh Area.

BACKGROUND: Environmental hazards may play a role in the etiology of cutaneous T-cell lymphoma (CTCL). Some studies have found an increased incidence of CTCL among workers in chemical science, transportation, and manufacturing industries, but other studies have not. This discrepancy may be attributable to population migration, complicating accurate assessment of lifetime exposures. The Pittsburgh population has very low migration rates and most CTCL patients seen at the University of Pittsburgh Medical Center (UPMC) Cutaneous Lymphoma Center are life-long local residents. The Greater Pittsburgh Area used to be an industrial hub. There are residential communities positioned within close proximity to inactive industrial sites that continue to contain pollutants. OBJECTIVE: To determine whether CTCL patients' residences cluster within specific Pittsburgh regions, in particular, those with high levels of environmental pollutants. METHODS: Our study included patients diagnosed with CTCL at the UPMC Cutaneous Lymphoma Center between 2000 and 2012. We mapped the longitudinal and latitudinal coordinates of patients' residences at diagnosis, superfund sites, toxic release inventory sites, particular matter levels, and dermatologists' offices using ArcMap 10.1. We then performed a SaTScan analysis using zip codes to assess for geographic clustering of patients' residences in the Pittsburgh metropolitan statistical area. We assessed for a correlation between case distribution and both environmental hazards sites and dermatologist density in the area. RESULTS: We identified 274 patients with CTCL in the Greater Pittsburgh area. We identified a statistically significant geographic cluster (p<.001) in zip code 15213, which is the most densely populated neighborhood in Pittsburgh and the site of the region's only CTCL clinic. We observed no relationship between the locations of superfund sites, toxic release inventory sites, or particular matter levels and CTCL case distribution. CONCLUSION: Our findings do not support an association between exposure to environmental toxins and CTCL. CTCL cases clustered in areas with the highest population density, which also happen to include a regional CTCL center. To evaluate a possibility of urban pollutants playing a role in etiology of CTCL, dermatologist density and access to care need to be addressed as potential confounders in the future studies.

Changes in six categories of alcohol-attributable mortality from before to during the early phases of the COVID-19 pandemic.

OBJECTIVE: The shelter-in-place mandates enacted early in the COVID-19 pandemic resulted in changes in alcohol use and consequent outcomes. We assessed changes in six categories of season-specific alcohol-attributable mortality from before to during the early phases of the COVID-19 pandemic in the U.S. METHODS: We used logistic regression models to assess alcohol-attributable mortality in the U.S. from 2017 through 2020 (n=11,632,725 decedents ages 18 and older). Outcomes included chronic fully alcohol-attributable deaths, poisonings, motor vehicle accidents, suicides, homicides, and falls. Exposure variables included year, season, the interaction between the year 2020 and season, rurality, the interaction between the year 2020 and rurality, decedent age, sex, race, ethnicity, marital status, and education. RESULTS: Compared to 2019, season-specific mortality age-adjusted rates of chronic fully alcohol-attributable deaths, homicides, poisonings, and falls increased during the COVID-19 pandemic. Suicide rates decreased in most 2020 seasons relative to the same seasons in 2019. Motor vehicle deaths decreased in the spring of 2020 vs. 2019. Relative to dying by any other cause, the odds of death by chronic fully alcohol-attributable causes and poisonings were higher across seasons in 2020 vs. 2019. The odds of death by suicide were higher among residents of rural counties in the spring of 2020 vs. 2019. CONCLUSIONS: There were distinct temporal changes in six types of alcohol-attributable deaths during the early phases of the COVID-19 pandemic.

Case-control study of environmental toxins and risk of amyotrophic lateral sclerosis involving the national ALS registry.

Objective: Neurotoxic chemicals are suggested in the etiology of amyotrophic lateral sclerosis (ALS). We examined the association of environmental and occupational risk factors including persistent organochlorine pesticides (OCPs) and ALS risk among cases from the Centers for Disease Control and Prevention National ALS Registry and age, sex, and county-matched controls. Methods: Participants completed a risk factor survey and provided a blood sample for OCP measurement. ALS cases were confirmed through the Registry. Conditional logistic regression assessed associations between ALS and risk factors including OCP levels. Results: 243 matched case-control pairs (61.7% male, mean [SD] age = 62.9 [10.1]) were included. Fifteen of the 29 OCPs examined had sufficient detectable levels for analysis. Modest correlations of self-reported years of exposure to residential pesticide mixtures and OCP serum levels were found (p<.001). Moreover, occupational exposure to lead including soldering and welding with lead/metal dust and use of lead paint/gasoline were significantly related to ALS risk (OR = 1.77, 95% CI: 1.11-2.83). Avocational gardening was a significant risk factor for ALS (OR = 1.57, 95% CI: 1.04-2.37). ALS risk increased for each 10 ng/g of α-Endosulfan (OR = 1.42, 95% CI: 1.14-1.77) and oxychlordane (OR = 1.24, 95% CI: 1.01-1.53). Heptachlor (detectable vs. nondetectable) was also associated with ALS risk (OR = 3.57, 95% CI: 1.50-8.52). Conclusion: This national case-control study revealed both survey and serum levels of OCPs as risk factors for ALS. Despite the United States banning many OCPs in the 1970s and 1980s, their use abroad and long half-lives continue to exert possible neurotoxic health effects.

Long-term visual acuity outcomes following cataract surgery in eyes with ocular inflammatory disease.

PURPOSE: To evaluate the long-term visual acuity (VA) outcome of cataract surgery in inflammatory eye disease. SETTING: Tertiary care academic centres. DESIGN: Multicentre retrospective cohort study. METHODS: A total of 1741 patients with non-infectious inflammatory eye disease (2382 eyes) who underwent cataract surgery while under tertiary uveitis management were included. Standardised chart review was used to gather clinical data. Multivariable logistic regression models with adjustment for intereye correlations were performed to evaluate the prognostic factors for VA outcomes. Main outcome measure was VA after cataract surgery. RESULTS: Uveitic eyes independent of anatomical location showed improved VA from baseline (mean 20/200) to within 3 months (mean 20/63) of cataract surgery and maintained through at least 5 years of follow-up (mean 20/63). Eyes that achieved 20/40 or better VA at 1 year were more likely to have scleritis (OR=1.34, p<0.0001) or anterior uveitis (OR=2.2, p<0.0001), VA 20/50 to 20/80 (OR 4.76 as compared with worse than 20/200, p<0.0001) preoperatively, inactive uveitis (OR=1.49, p=0.03), have undergone phacoemulsification (OR=1.45 as compared with extracapsular cataract extraction, p=0.04) or have had intraocular lens placement (OR=2.13, p=0.01). Adults had better VA immediately after surgery, with only 39% (57/146) paediatric eyes at 20/40 or better at 1 year. CONCLUSIONS: Our results suggest that adult and paediatric eyes with uveitis typically have improved VA following cataract surgery and remain stable thereafter for at least 5 years.

Incidence and remission of post-surgical cystoid macular edema following cataract surgery in eyes with intraocular inflammation.

PURPOSE: To evaluate the incidence, remission and relapse of post-surgical cystoid macular edema (PCME) following cataract surgery in inflammatory eye disease. METHODS: A total of 1859 eyes that had no visually significant macular edema prior to cataract surgery while under tertiary uveitis management were included. Standardized retrospective chart review was used to gather clinical data. Univariable and multivariable logistic regression models with adjustment for inter-eye correlations were performed. RESULTS: PCME causing VA 20/50 or worse was reported in 286 eyes (15%) within 6 months of surgery. Adults age 18-64 years as compared to children (adjusted Odds ratio (aOR) 2.42, for ages 18-44 and aOR 1.93 for ages 45-64, overall p = 0.02); concurrent use of systemic immunosuppression (conventional aOR 1.53 and biologics aOR 2.68, overall p =0.0095); pre-operative VA 20/50 or worse (overall p <0.0001); cataract surgery performed before 2000 (overall p=0.03) and PMCE in fellow eye (aOR 3.04, p=0.0004) were associated with development of PCME within 6 months of cataract surgery. PCME resolution was seen in 81% of eyes at 12 months and 91% of eyes at 24 months. CME relapse was seen in 12% eyes at 12 months and 19% eyes at 24 months. CONCLUSIONS: PCME occurs frequently in uveitic eyes undergoing cataract surgery, however, most resolve within a year. CME recurrences likely are due to the underlying disease process and not relapses of PCME.

Posterior capsular opacification and YAG laser capsulotomy in uveitis patients following cataract surgery.

OBJECTIVE: To evaluate the incidence of visually significant posterior capsule opacification (PCO with visual acuity ≤20/50) and the incidence of Nd:YAG laser capsulotomy in the year following cataract surgery for uveitic eyes. METHOD: Patients were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) Cohort Study using a standardized chart review process. RESULTS: Among 1,855 uveitic eyes of 1,370 patients who had undergone cataract surgery, visually significant PCO occurred in 297 eyes (16%), and YAG laser capsulotomy was done in 407 eyes (22%) within the first year following surgery. Higher odds of developing 20/50 visual acuity attributed to PCO were noted in children and young adults compared with adults older than 65 years of age (overall p = 0.03). Poorer preoperative visual acuity (overall p = 0.0069) and postoperative inflammation (odds ratio [OR] = 1.83; 95% CI, 1.37-2.45; p < 0.0001) were associated with PCO incidence. In multivariable analysis, risk factors for YAG laser capsulotomy were younger age groups compared with those older than 65 years of age at the time of surgery (adjusted OR [aOR] = 1.90-2.24; 95% CI, 1.90-2.24; overall p = 0.0007), female sex (aOR = 1.37; 95% CI, 1.03-1.82; p = 0.03), postoperative active inflammation (aOR = 165; 95% CI, 1.27-2.16; overall p < 0.0001), extracapsular cataract extraction compared with phacoemulsification (aOR = 1.70; 95% CI, 1.17-2.47; overall p < 0.0001), and insertion of an intraocular lens (aOR = 4.60; 95% CI, -2.29-9.25; p < 0.0001). Black race was associated with lower YAG laser capsulotomy incidence than Whites (aOR = 0.36; 95% CI, 0.24-0.52; overall p < 0.0001). CONCLUSIONS: Vision-reducing (≤20/50) PCO is common, occurring in about one sixth of uveitic eyes within 1 year of cataract surgery; a higher number (22%) of eyes underwent YAG laser capsulotomy within the first year. Age and postoperative inflammation following cataract surgery are the variables most associated with the incidence of visually significant PCO and YAG laser capsulotomy.

Development and validation of an overdose risk prediction tool using prescription drug monitoring program data.

OBJECTIVES: To develop and validate a machine-learning algorithm to predict fatal overdose using Pennsylvania Prescription Drug Monitoring Program (PDMP) data. METHODS: The training/testing (n = 3020,748) and validation (n = 2237,701) cohorts included Pennsylvania residents with a prescription dispensing from February 2018-September 2021. Potential predictors (n = 222) were measured in the 6 months prior to a random index date. Using a gradient boosting machine, we developed a 20-variable model to predict risk of fatal drug overdose in the 6 months after the index date. RESULTS: Beneficiaries in the training (n = 1,812,448), testing (n = 1,208,300), and validation (n = 2,237,701) samples had similar age, with low rates of fatal overdose during 6-month follow up (0.12%, 0.12%, 0.04%, respectively). The validation c-statistic was 0.86 for predicting fatal overdose using 20 PDMP variables. When ranking individuals based on risk score, the prediction model more accurately identified fatal overdose at 6 months compared to using opioid dosage or opioid/benzodiazepine overlap, although the percentage of individuals in the highest risk percentile who died at 6 months was less than 1%. CONCLUSIONS AND POLICY IMPLICATIONS: A gradient boosting machine algorithm predicting fatal overdose derived from twenty variables performed well in discriminating risk across testing and validation samples, improving on single factor risk measures like opioid dosage.

Reductions in Childhood Pneumonia Mortality After Vaccination in the United States.

BACKGROUND: We aim to estimate the magnitude of the reduction in pneumococcal pneumonia and meningitis mortality after the mass introduction of pneumococcal conjugate vaccine (PCV)7 and PCV13 in children in the United States. METHODS: We assessed the trends in mortality rates from pneumococcal pneumonia and meningitis, in the United States between 1994 and 2017. We fitted an interrupted time-series negative binomial regression model (adjusted by trend, seasonality, PCV7/PCV13 coverage, and H. influenzae type b vaccine coverage) to estimate the counterfactual rates without vaccination. We reported a percent reduction in mortality estimates relative to the projected no-vaccination scenario, using the formula 1 minus the incidence risk ratio, with 95% confidence intervals (CIs). RESULTS: Between 1994 and 1999 (the prevaccination period), the all-cause pneumonia mortality rate for 0-1-month-old children was 2.55 per 100,00 pop., whereas for 2-11 months-old children, this rate was 0.82 deaths per 100,000 pop. During the PCV7-period in 0-59-month-old children in the United States, the adjusted reduction of all-cause pneumonia was 13% (95% CI: 4-21) and 19% (95% CI: 0-33) of all-cause meningitis For PCV13, the reductions in this age group were 21% (95% CI: 4-35) for all-cause pneumonia mortality and 22% (95% CI: -19 to 48) for all-cause meningitis mortality. PCV13 had greater reductions of all-cause pneumonia than PCV13 in 6-11-month-old infants. CONCLUSIONS: The universal introduction of PCV7, and later PCV13, for children 0-59 months old in the United States was associated with decreases in mortality due to all-cause pneumonia.

Corneal Endothelial Transplantation in Uveitis: Incidence and Risk Factors.

PURPOSE: To estimate the incidence of corneal endothelial transplantation (CET) and identify risk factors among patients with noninfectious ocular inflammation. DESIGN: Retrospective cohort study. METHODS: Adult patients attending United States tertiary uveitis care facilities diagnosed with noninfectious 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 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 of 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 <40 years (adjusted hazard ratio [aHR], 16.5; 95% CI, 4.70-57.9), anterior uveitis and scleritis vs other types (aHR, 2.97; 95% CI, 1.46-6.05; and aHR, 4.14; 95% CI,1.28-13.4, respectively), topical corticosteroid treatment (aHR, 2.84; 95% CI, 1.32-6.13), cataract surgery (aHR, 4.44; 95% CI, 1.73-11.4), tube shunt surgery (aHR, 11.9; 95% CI, 5.30-26.8), band keratopathy (aHR, 5.12; 95% CI, 2.34-11.2), and hypotony (aHR, 7.38; 95% CI, 3.14-17.4). Duration of uveitis, trabeculectomy, peripheral anterior synechia, and ocular hypertension had no significant association after multivariate adjustment. CONCLUSIONS: In patients with ocular inflammation, CET occurred infrequently. Tube shunt surgery, hypotony, band keratopathy, cataract surgery, and anterior segment inflammation were associated with increased risk of undergoing CET; these factors likely are associated with endothelial cell damage.

Fiber glass exposure and human respiratory system cancer risk: lack of evidence persists since 2001 IARC re-evaluation.

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.

Mortality Patterns Among Industrial Workers Exposed to Chloroprene and Other Substances: Extended Follow-Up.

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.

Association of age at diabetes complication diagnosis with age at natural menopause in women with type 1 diabetes: The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study.

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., <30 years of age) was associated with an earlier age at natural menopause. RESULTS: Although results from multivariable linear regression models suggested a similar age at menopause between women with normo-albuminuria and those diagnosed with MA after 30 years of age, menopause occurred 2.06 years earlier (ß±SE=-2.06±1.08) among women diagnosed with MA before age 30 (p=0.06). No significant association was observed for other complications. CONCLUSION: Among women with type 1 diabetes, menopause appears to occur earlier in those diagnosed with MA before age 30 compared to those with normo-albuminuria, suggesting that vascular dysfunction associated with early microvascular disease may affect ovarian aging.

Predictors of the age at which natural menopause occurs in women with type 1 diabetes: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study.

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 (<17 y) of T1D who underwent natural menopause without use of hormone therapy during their menopausal transition were included in the analysis (n = 105; mean baseline age, 29.5 and diabetes duration, 20.2 y). Self-reported reproductive history and the Women's Ischemia Syndrome Evaluation hormonal algorithms were used to determine menopause status. Linear regression was used to ascertain whether time-weighted metabolic factors (eg, BMI, lipids, HbA1c, insulin dose, albumin excretion rate [AER]) were associated with age at natural menopause. RESULTS: Univariately, only insulin dose (ß = -4.87, P = 0.04) and log (AER) (ß = -0.62, P = 0.02) were associated (negatively) with age at natural menopause. Adjusting for BMI, smoking status, lipids, HbA1c, number of pregnancies, and oral contraceptive use, each 0.1 unit increase in the daily dose of insulin per kilogram body weight was associated with 0.64 years younger age at natural menopause (P = 0.01), while for every 30% increase in AER, age at natural menopause decreased by 0.18 years (P = 0.03). CONCLUSION: Higher average levels of insulin dose and AER over time were significantly associated with a younger age at which natural menopause occurred among women with T1D. The biologic mechanisms underlying the observed associations between exogenous insulin dose and AER on reproductive health should be investigated among women with T1D.

Evaluating the effectiveness of problem-solving courts at preventing fatal and non-fatal opioid events: preliminary findings from Indiana.

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-to-event 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.