Projecting the Suicide Burden of Climate Change in the United States.

We quantify and monetize changes in suicide incidence across the conterminous United States (U.S.) in response to increasing levels of warming. We develop an integrated health impact assessment model using binned and linear specifications of temperature-suicide relationship estimates from Mullins and White (2019), in combination with monthly age- and sex-specific baseline suicide incidence rates, projections of six climate models, and population projections at the conterminous U.S. county scale. We evaluate the difference in the annual number of suicides in the U.S. corresponding to 1-6°C of warming compared to 1986-2005 average temperatures (mean U.S. temperatures) and compute 2015 population attributable fractions (PAFs). We use the U.S. Environmental Protection Agency's Value of a Statistical Life to estimate the economic value of avoiding these mortality impacts. Assuming the 2015 population size, warming of 1-6°C could result in an annual increase of 283-1,660 additional suicide cases, corresponding to a PAF of 0.7%-4.1%. The annual economic value of avoiding these impacts is $2 billion-$3 billion (2015 U.S. dollars, 3% discount rate, and 2015 income level). Estimates based on linear temperature-suicide relationship specifications are 7% larger than those based on binned temperature specifications. Accounting for displacement decreases estimates by 17%, while accounting for precipitation decreases estimates by 7%. Population growth between 2015 and the future warming degree arrival year increases estimates by 15%-38%. Further research is needed to quantify and monetize other climate-related mental health outcomes (e.g., anxiety and depression) and to characterize these risks in socially vulnerable populations.

Developing a Health Impact Model for Adult Lead Exposure and Cardiovascular Disease Mortality.

BACKGROUND: Lead (Pb) is a highly toxic pollutant. Evidence suggests it is associated with cardiovascular disease (CVD)-related mortality. OBJECTIVES: We present a rigorous approach for identifying concentration-response functions that relate adult Pb exposures to CVD mortality to inform a health impact model (HIM). We then use the model in a proof-of-concept example. METHODS: Building on previously conducted government literature reviews and a de novo supplemental literature review, we compiled and evaluated the available data on Pb and CVD mortality in humans. We applied a set of predefined selection criteria to identify studies that would be most useful in understanding the impact of Pb exposure on CVD mortality risk in adults. Once we identified the studies, we derived a HIM and used each study's concentration-response function in a proof-of-concept example. RESULTS: Our literature search identified 15 studies for full-text review. Of those 15 studies, 4 fit our criteria for use in the HIM. Using population and CVD mortality rates for 40- to 80-y-olds in 2014, we estimated that 34,000-99,000 deaths have been avoided due to the lowering of blood Pb levels from 1999 to 2014. Based on these values we estimated that approximately 16%-46% of the decreased CVD-related death rate from 1999 to 2014 may be attributable to decreased blood Pb levels. CONCLUSION: Our results demonstrate that decreases in Pb exposure can result in large benefits for the adult population. We have provided a HIM that can be used in a variety of applications from burden-of-disease estimates to regulatory impact assessments and have demonstrated its sensitivity to the choice of concentration-response function. https://doi.org/10.1289/EHP6552.

Estimating Lifetime Cost of Illness. An Application to Asthma.

Rationale: Approximately 8% of the U.S. population suffers from asthma, a chronic condition. It poses a substantial economic burden to society in the form of lost productivity and healthcare costs.Objectives: We use the Medical Expenditure Panel Survey 2002-2010 to quantify the lifetime costs of asthma at each age, the impact of adult asthma on earnings and choice of occupation, and the impact of childhood asthma on parental income.Methods: We developed a framework to estimate the present discounted value of the cumulative lifetime asthma-related healthcare costs and lost productivity experienced by an individual after onset. This approach allows for age- and asthma duration-related variability in annual costs as well as for the intermittent nature of asthma symptoms.Results: Estimated asthma-related annual healthcare expenditures across all life stages are $700-$2,200 (2010 U.S. dollars). Lost annual earnings among individuals aged 30-49 are over $4,000 (2010 U.S. dollars). The present discounted value of the cumulative lifetime healthcare costs and lost productivity for a new case of asthma is estimated at $36,500 using the 3% discount rate (2010 U.S. dollars).Conclusions: The economic burden of asthma is substantial and larger than previously estimated, reflecting expenditures on treatment and lost earnings.

Estimated burden of disease from arsenic in drinking water supplied by domestic wells in the United States.

Well water around the world can be contaminated with arsenic, a naturally occurring geological element that has been associated with myriad adverse health effects. Persons obtaining their drinking water from private wells are often responsible for well testing and water treatment. High levels of arsenic have been reported in well water-supplied areas of the United States. We quantified - in cases and dollars - the potential burden of disease associated with the ingestion of arsenic through private well drinking water supplies in the United States. To estimate cancer and cardiovascular disease burden, we developed a Monte Carlo model integrating three input streams: (1) regional concentrations of arsenic in drinking water wells across the United States; (2) dose-response relationships in the form of cancer slope factors and hazard ratios; and (3) economic cost estimates developed for morbidity endpoints using 'cost-of-illness' methods and for mortality using 'value per statistical life' estimates. Exposure to arsenic in drinking water from U.S. domestic wells is modeled to contribute 500 annual premature deaths from ischemic heart disease and 1,000 annual cancer cases (half of them fatal), monetized at $10.9 billion (2017 USD) annually. These considerable public health burden estimates can be compared with the burdens of other priority public health issues to assist in decision-making.

Switching from branded to generic glatiramer acetate: 15-month GATE trial extension results.

BACKGROUND: Open-label 15-month follow-up of the double-blind, placebo-controlled Glatiramer Acetate clinical Trial to assess Equivalence with Copaxone® (GATE) trial. OBJECTIVE: To evaluate efficacy, safety, and tolerability of prolonged generic glatiramer acetate (GTR) treatment and to evaluate efficacy, safety, and tolerability of switching from brand glatiramer acetate (GA) to GTR treatment. METHODS: A total of 729 patients received GTR 20 mg/mL daily. Safety was assessed at months 12, 15, 18, 21, and 24 and Expanded Disability Status Scale and magnetic resonance imaging (MRI) scans at months 12, 18, and 24. The presence of glatiramer anti-drug antibodies (ADAs) was tested at baseline and months 1, 3, 6, 9, 12, 18, and 24. RESULTS: The mean number of gadolinium-enhancing lesions in the GTR/GTR and GA/GTR groups was similar at months 12, 18, and 24. The change in other MRI parameters was also similar in the GTR/GTR and GA/GTR groups. The annualized relapse rate (ARR) did not differ between the GTR/GTR and GA/GTR groups, 0.21 and 0.24, respectively. The incidence, spectrum, and severity of reported adverse events did not differ between the GTR/GTR and GA/GTR groups. Glatiramer ADA titers were similar in the GTR/GTR and GA/GTR groups. CONCLUSION: Efficacy and safety of GTR is maintained over 2 years. Additionally, switching from GA to GTR is safe and well tolerated.

Efficacy and safety of abobotulinumtoxinA liquid formulation in cervical dystonia: A randomized-controlled trial.

BACKGROUND: Approved botulinum toxin A products require reconstitution. AbobotulinumtoxinA solution for injection is a ready-to-use liquid formulation of abobotulinumtoxinA. OBJECTIVES: The objective of this study was to demonstrate the superior efficacy of abobotulinumtoxinA solution for injection to placebo and to test the noninferior efficacy of abobotulinumtoxinA solution for injection versus abobotulinumtoxinA (dry formulation) in cervical dystonia. METHODS: This was a phase-3, multicenter, prospective, double-blind, randomized, active, and placebo-controlled study (N = 369). Patients with cervical dystonia were randomized (3:3:1) to abobotulinumtoxinA solution for injection 500 U, abobotulinumtoxinA 500 U, or placebo. Following the double-blind phase, patients received abobotulinumtoxinA solution for injection, open-label, for up to 4 cycles. The primary outcome was change from baseline at week 4 of the Toronto Western Spasmodic Torticollis Rating Scale total score. Secondary measures included change from baseline or cycle baseline in Toronto Western Spasmodic Torticollis Rating Scale scores. RESULTS: At week 4, both products were superior to placebo (Toronto Western Spasmodic Torticollis Rating Scale total score least square mean decrease from baseline, abobotulinumtoxinA solution for injection 500 U -12.5, abobotulinumtoxinA 500 U -14.0, placebo -3.9; P < .0001 vs placebo). The noninferiority limit of 3 points in the Toronto Western Spasmodic Torticollis Rating Scale total score at week 4 was not met for abobotulinumtoxinA solution for injection versus abobotulinumtoxinA. Toronto Western Spasmodic Torticollis Rating Scale total score reductions were maintained for up to 4 cycles of abobotulinumtoxinA solution for injection open-label follow-up treatment. Safety profiles of abobotulinumtoxinA solution for injection and abobotulinumtoxinA were similar, with dysphagia and injection-site pain the most frequent drug-related adverse events. CONCLUSIONS: Although the predefined noninferiority criterion was not met, abobotulinumtoxinA solution for injection was similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale total scores with a similar safety profile. AbobotulinumtoxinA solution for injection efficacy was maintained with chronic open-label treatment, and this novel formulation may add convenience as well as dosing accuracy to treatment with abobotulinumtoxinA. © 2016 International Parkinson and Movement Disorder Society.

Benefits of Decreased Mortality Risk from Reductions in Primary Mobile Source Fine Particulate Matter: A Limited Data Approach for Urban Areas Worldwide.

We developed an approach to estimate the public health benefits resulting from transportation projects or environmental actions that reduce mobile source fine particulate matter (PM2.5 ) in select urban areas worldwide when input data are limited or when a rapid order-of-magnitude assessment is needed. For a given reduction in direct PM2.5 emissions, we can use this approach to quantify (1) the subsequent reduction in ambient primary PM2.5 concentration in the urban area; (2) the public health benefits associated with mortality risk reductions, measured in terms of avoided premature deaths; and (3) the economic value of the reduced mortality risk. To illustrate our approach, we estimated the impact of a 100-metric-ton reduction in primary PM2.5 mobile source emissions in the year 2010 for 42 large, global cities. Our estimates of public health benefits and their economic value varied by city, as did the sensitivity to key assumptions and inputs. The estimated number of premature deaths avoided per 100-metric-ton reduction in PM2.5 emissions ranged from 12 to 202. City-level variability in these estimates was driven by the magnitude of the reduction in ambient PM2.5 concentration, the size of the urban population, and the baseline PM2.5 concentration. The economic value of mortality risk reductions per 100-metric-ton reduction in PM2.5 emissions ranged from $2 million to $328 million in 2010 U.S. dollars. Income per capita was the most important driver of the variability in the economic values across countries.

Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study.

The objective of this study was to assess the effect of secukinumab, a monoclonal antibody that inhibits interleukin (IL)-17A, on number of new active brain magnetic resonance imaging (MRI) lesions in subjects with relapsing-remitting multiple sclerosis (MS). Subjects (N = 73) were randomized 1:1 to secukinumab 10 mg/kg or placebo by intravenous infusion at weeks 0, 2, 4, 8, 12, 16, and 20. MRI scans were obtained within 30 days prior to randomization, on a monthly basis during the treatment period, and at study completion. The primary endpoint was the cumulative number of combined unique active lesions (CUAL) observed on brain MRI scans from week 4 to week 24. Compared with placebo, secukinumab non-significantly reduced the number of CUAL observed on 4-weekly MRI from week 4 to 24 (primary endpoint) by 49 % (95 % CI -10 to 77 %; P = 0.087) and significantly reduced the number of cumulative new gadolinium-enhancing T1 lesions by 67 % (31-84 %, P = 0.003). CUAL reductions were progressively greater from week 4 (1 %) to week 16 (49 %) and persisted until end-study (50 %). There were no serious adverse events; the adverse event rate was comparable to placebo (53 versus 49 %), although mild-to-moderate infection was somewhat more frequent (37 versus 23 %). This proof-of-concept study provides the first evidence that blocking IL-17A with an antibody may reduce MRI lesion activity in MS. Further studies are needed to confirm this finding and determine the magnitude of effect.

Survey of Ambient Air Pollution Health Risk Assessment Tools.

Designing air quality policies that improve public health can benefit from information about air pollution health risks and impacts, which include respiratory and cardiovascular diseases and premature death. Several computer-based tools help automate air pollution health impact assessments and are being used for a variety of contexts. Expanding information gathered for a May 2014 World Health Organization expert meeting, we survey 12 multinational air pollution health impact assessment tools, categorize them according to key technical and operational characteristics, and identify limitations and challenges. Key characteristics include spatial resolution, pollutants and health effect outcomes evaluated, and method for characterizing population exposure, as well as tool format, accessibility, complexity, and degree of peer review and application in policy contexts. While many of the tools use common data sources for concentration-response associations, population, and baseline mortality rates, they vary in the exposure information source, format, and degree of technical complexity. We find that there is an important tradeoff between technical refinement and accessibility for a broad range of applications. Analysts should apply tools that provide the appropriate geographic scope, resolution, and maximum degree of technical rigor for the intended assessment, within resources constraints. A systematic intercomparison of the tools' inputs, assumptions, calculations, and results would be helpful to determine the appropriateness of each for different types of assessment. Future work would benefit from accounting for multiple uncertainty sources and integrating ambient air pollution health impact assessment tools with those addressing other related health risks (e.g., smoking, indoor pollution, climate change, vehicle accidents, physical activity).

Equivalence of Generic Glatiramer Acetate in Multiple Sclerosis: A Randomized Clinical Trial.

IMPORTANCE: The patents for the first approved treatments for relapsing-remitting multiple sclerosis are expiring, creating the opportunity to develop generic alternatives. OBJECTIVE: To evaluate in the Glatiramer Acetate Clinical Trial to Assess Equivalence With Copaxone (GATE) study whether generic glatiramer acetate (hereafter generic drug) is equivalent to the originator brand glatiramer acetate (hereafter brand drug) product, as measured by imaging and clinical end points, safety, and tolerability. DESIGN, SETTING, AND PARTICIPANTS: Randomized, multicenter, double-blind, active and placebo-controlled phase 3 trial. The setting included academic medical centers and clinical practices. Participants were patients with relapsing-remitting multiple sclerosis 18 to 55 years old with at least 1 relapse in the prior year and 1 to 15 gadolinium-enhancing brain magnetic resonance imaging lesions. They were randomized between December 7, 2011, and March 21, 2013. The last participant completed follow-up December 2, 2013. INTERVENTIONS: Participants were randomized 4.3:4.3:1 to receive generic glatiramer acetate (20 mg), brand glatiramer acetate (20 mg), or placebo by daily subcutaneous injection for 9 months. MAIN OUTCOMES AND MEASURES: The primary end point was the total number of gadolinium-enhancing lesions during months 7, 8, and 9. Additional end points included other magnetic resonance imaging parameters, annualized relapse rate, and Expanded Disability Status Scale score. Safety and tolerability were assessed by monitoring adverse events, injection site reactions, and laboratory test results. RESULTS: In total, 794 participants were randomized and treated with generic drug (n = 353), brand drug (n = 357), or placebo (n = 84). The estimated mean numbers of gadolinium-enhancing lesions with generic drug and brand drug were lower than with placebo (ratio, 0.488; 95% CI, 0.365-0.651; P < 001), confirming study sensitivity. For gadolinium-enhancing lesions, the estimated ratio of generic drug to brand drug was 1.095 (95% CI, 0.883-1.360), which was within the predefined equivalence margin of 0.727 to 1.375. The incidence, spectrum, and severity of reported adverse events, including injection site reactions, were similar in the generic drug and brand drug groups. CONCLUSIONS AND RELEVANCE: As treatment for relapsing-remitting multiple sclerosis, glatiramer acetate generic drug and brand drug had equivalent efficacy, safety, and tolerability. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01489254.

A method to screen U.S. environmental biomonitoring data for race/ethnicity and income-related disparity.

BACKGROUND: Environmental biomonitoring data provide one way to examine race/ethnicity and income-related exposure disparity and identify potential environmental justice concerns. METHODS: We screened U.S. National Health and Nutrition Examination Survey (NHANES) 2001-2008 biomonitoring data for 228 chemicals for race/ethnicity and income-related disparity. We defined six subgroups by race/ethnicity-Mexican American, non-Hispanic black, non-Hispanic white-and income-Low Income: poverty income ratio (PIR) <2, High Income: PIR ≥ 2. We assessed disparity by comparing the central tendency (geometric mean [GM]) of the biomonitoring concentrations of each subgroup to that of the reference subgroup (non-Hispanic white/High Income), adjusting for multiple comparisons using the Holm-Bonferroni procedure. RESULTS: There were sufficient data to estimate at least one geometric mean ratio (GMR) for 108 chemicals; 37 had at least one GMR statistically different from one. There was evidence of potential environmental justice concern (GMR significantly >1) for 12 chemicals: cotinine; antimony; lead; thallium; 2,4- and 2,5-dichlorophenol; p,p'-dichlorodiphenyldichloroethylene; methyl and propyl paraben; and mono-ethyl, mono-isobutyl, and mono-n-butyl phthalate. There was also evidence of GMR significantly <1 for 25 chemicals (of which 17 were polychlorinated biphenyls). CONCLUSIONS: Although many of our results were consistent with the U.S. literature, findings relevant to environmental justice were novel for dichlorophenols and some metals.

Urinary cadmium in the 1999-2008 U.S. National Health and Nutrition Examination Survey (NHANES).

Chronic low-level cadmium (Cd) exposure is linked to kidney and cardiovascular disease, fractures, and cancer. Diet and smoking are primary sources of exposure in the general population. We analyzed urinary Cd in NHANES 1999-2008 to determine whether levels declined significantly over the decade for U.S. children, teens, and adults (nonsmokers and smokers) and, if so, factors influencing the decline(s). For each subpopulation, we modeled log urinary Cd using variable-threshold censored multiple regression. Models included individual-level covariates (age, gender, BMI, income, race/ethnicity/country of origin, education, survey period), smoking, housing (home age, water source, filter use), and diet (supplement use; 24-h calorie, fat, protein, micronutrient, and Cd-containing food intakes), creatinine, and survey year variables. Geometric mean urinary Cd (ng/mL) declined 20-25% in these subpopulations, and the regressions showed statistically significant declines in later years for teens and adults. While certain covariates were significantly associated with Cd by subpopulation (creatinine; age; BMI; race/ethnicity/origin; education; smokers in the home; serum cotinine; 24-h fat, Mg, Fe intakes; use of dietary supplements), they did not help explain the declines. Instead, unidentified time-related factors appeared responsible. Despite the declines, millions of Americans remain potentially at risk of adverse outcomes associated with low-level Cd exposure.

Distributional benefit analysis of a national air quality rule.

Under Executive Order 12898, the U.S. Environmental Protection Agency (EPA) must perform environmental justice (EJ) reviews of its rules and regulations. EJ analyses address the hypothesis that environmental disamenities are experienced disproportionately by poor and/or minority subgroups. Such analyses typically use communities as the unit of analysis. While community-based approaches make sense when considering where polluting sources locate, they are less appropriate for national air quality rules affecting many sources and pollutants that can travel thousands of miles. We compare exposures and health risks of EJ-identified individuals rather than communities to analyze EPA's Heavy Duty Diesel (HDD) rule as an example national air quality rule. Air pollutant exposures are estimated within grid cells by air quality models; all individuals in the same grid cell are assigned the same exposure. Using an inequality index, we find that inequality within racial/ethnic subgroups far outweighs inequality between them. We find, moreover, that the HDD rule leaves between-subgroup inequality essentially unchanged. Changes in health risks depend also on subgroups' baseline incidence rates, which differ across subgroups. Thus, health risk reductions may not follow the same pattern as reductions in exposure. These results are likely representative of other national air quality rules as well.