OBJECTIVE: To characterize the participant demographics in the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database compared with the web-portal National Amyotrophic Lateral Sclerosis (ALS) Registry (the Registry). METHODS: Demographics and ALS symptom information were compared between the self-reported registrant data in the Registry web portal (2010-2021) and the latest available PRO-ACT data (updated August 2022), which is a collection of clinical trials data. RESULTS: Greater percentages of younger (≤ 59 years old) but smaller percentages of older (60 + years old) participants were represented in PRO-ACT compared to Registry. Enrollment for minority race groups was greater in the Registry portal data, but race information was largely missing/unknown in PRO-ACT database. Median age at the time of diagnosis and age at the time of symptom onset were significantly higher for Registry enrollees compared to the participants of PRO-ACT. Symptom onset sites were similarly reported, but duration between self-noted symptom onset and diagnosis was slight, but significantly longer for the Registry enrollees (11 vs. 9 months). Hispanic were as likely as non-Hispanic to participate in research studies, based on the Registry data. CONCLUSION: There was a notable difference in the age distribution and minority representation of enrollees between the PRO-ACT and Registry study populations. Age distribution in the PRO-ACT database skewed to a younger and less diverse cohort. Despite the clinical heterogeneity and complex disease mechanism of ALS, identifying the underrepresented demographic niche in the PRO-ACT and Registry study populations can help improve patient participation and criteria for patient selection to enhance generalizability.

Objective: Amyotrophic lateral sclerosis (ALS) is an incurable, progressive neurodegenerative disease with a significant health burden and poorly understood etiology. This analysis assessed the narrative responses from 3,061 participants in the Centers for Disease Control and Prevention's National ALS Registry who answered the question, "What do you think caused your ALS?" Methods: Data analysis used qualitative methods and artificial intelligence (AI) using natural language processing (NLP), specifically, Bidirectional Encoder Representations from Transformers (BERT) to explore responses regarding participants' perceptions of the cause of their disease. Results: Both qualitative and AI analysis methods revealed several, often aligned themes, which pointed to perceived causes including genetic, environmental, and military exposures. However, the qualitative analysis revealed detailed themes and subthemes, providing a more comprehensive understanding of participants' perceptions. Although there were areas of alignment between AI and qualitative analysis, AI's broader categories did not capture the nuances discovered using the more traditional, qualitative approach. The qualitative analysis also revealed that the potential causes of ALS were described within narratives that sometimes indicate self-blame and other maladaptive coping mechanisms. Conclusions: This analysis highlights the diverse range of factors that individuals with ALS consider as perceived causes for their disease. Understanding these perceptions can help clinicians to better support people living with ALS (PLWALS). The analysis highlights the benefits of using traditional qualitative methods to supplement or improve upon AI-based approaches. This rapidly evolving area of data science has the potential to remove barriers to accessing the rich narratives of people with lived experience.

We thank Drs Miller, Loewen, Szeinuk, and Noonan for their comments and insights regarding the burden of asbestos-related disease (ARD) among current and former Libby residents, as well as on our publication.1 We agree with Dr Loewen’s observation that local physicians may not have noted ARD in this cohort of screening participants. This could have resulted in under-ascertainment of nonmalignant, ARD mortality. (Note that we reported results for asbestosis, a nonmalignant disease defined as interstitial pneumonitis and fibrosis caused by inhalation of asbestos.2) Still, the asbestosis SMRs we reported ranged from 82 (among workers categorized as “other asbestos occupation”) to 558 (among household contacts) in comparison with a national reference population. These SMRs clearly indicate a striking excess of nonmalignant ARD in the screening cohort.

OBJECTIVE: To report multiple cause of death (MCOD) occurrence among patients in the United States with amyotrophic lateral sclerosis (ALS). METHODS: Using death certificate data for all ALS deaths from 50 U.S. states and the District of Columbia, 2011-2014, we tabulated MCOD, used association rules mining (ARM) to determine if MCOD occurred together, and calculated standardized mortality odds ratios (SMOR) for select causes, comparing ALS with other U.S. decedents. RESULTS: Among 24,328 death certificates, there were 25,704 MCOD, excluding ALS. ALS was listed as the sole cause of death in n = 11,263 (46%). The most frequent causes of death co-occurring with ALS were respiratory failure (n = 6503; 25.3%), cardiovascular disease (n = 6077; 12.6%), pneumonia (n = 1345; 5.2%), and pneumonitis (n = 856; 3.3%). The SMORs among ALS decedents compared with non-ALS decedents for falls and accidents were 3.4 (95% CI 2.6, 4.3) and 3.0 (95% CI 2.2, 4.2), respectively. From ARM analysis, falls and accidents were both associated with injuries. The most common causes identified were weakly to very strongly associated with being an ALS decedent compared with other U.S. deaths, with SMOR point estimates ranging from 1.3 to 51.1. INTERPRETATION: This study provides information about the natural history of ALS. With knowledge that some causes of death may be preventable, healthcare providers may be able to optimize patient care and possibly postpone mortality and reduce morbidity. Moreover, this study located gaps in data; medical certifiers completing death certificates for ALS decedents should ensure all MCOD data are recorded.

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disorder. The National ALS Registry launched surveillance projects to understand the distribution of ALS in targeted geographic cohorts. Objective: To describe the demographics, incidence, and survival of persons with ALS (PALS) identified in the Chicago and Detroit area population-based cohort. Methods: Neurologists in the catchment area provided case reports for eligible ALS cases diagnosed and/or cared for from 1 January 2009 through 31 December 2011. Crude incidence rates were calculated for 2009-2011 and stratified by race and ethnicity. Using data from the National Death Index through 2018, we modeled the effect of patient covariates on mortality using the Cox proportional hazard regression. Results: Of the 574 cases, 372 (64.8%) were diagnosed from 2009 to 2011. The combined crude incidence rates for 2009, 2010, and 2011 were 1.44, 1.53, and 1.73 cases per 100,000 person-years, respectively. Of the 486 subjects with complete survival data, 81% were deceased at the end of follow-up. Median survival time was 2.2 years, with 30% and 9% of subjects surviving past 5 and 10 years after diagnosis, respectively. Additionally, female PALS and PALS with longer time between symptom onset and diagnosis experienced longer survival. Nonwhites also experienced longer survival than Whites, except for those cases diagnosed in the younger age categories. Conclusion: Understanding the survival of ALS patients can aid in understanding variable prognostic factors, which can potentially extend survival and improve disease management.

Objective: In 2010, the United States Agency for Toxic Substances and Disease Registry (ATSDR) created the National ALS Registry (Registry) to examine the epidemiology of ALS and potential risk factors. We are currently recruiting population-based controls for an epidemiologic case-control study to examine ALS environmental risk factors using this Registry. To date, we have recruited 181 non-diseased, population-based controls for comparison to Registry cases (n = 280). Here we report our recruitment methods for controls and the associated response rates and costs. Methods: Eligible ALS cases had complete risk factor survey data, DNA analysis, and blood concentrations of persistent organic pollutants (POPs). Age, sex, and county-matched controls were identified from commercial/consumer databases using a targeted landline phone sample. Eligible controls were consented, surveyed, and mailed the POPs' blood analysis consent form. Once consented, phlebotomy was scheduled. Results: We mailed 3760 recruitment letters for 181 potential case-matches across 42 states between 9/2018 and 3/2020. After making phone contact and determining eligibility, 146 controls agreed to participate (response rate = 11.4%, cooperation rate = 22.8%). To date, 127 controls completed the survey and bloodwork. Though controls were matched to cases on age, sex, and county, unmatched characteristics (e.g. smoking) did not differ statistically. Interviewing and incentive costs are estimated at $211.85 per complete participation. Conclusions: Recruiting matched population-based controls for comparison to cases from the Registry for a study involving completion of a detailed survey and blood specimen provision is relatively feasible and cost effective. This recruitment method could be useful for case-control studies of other rare disorders.

OBJECTIVE: To evaluate mortality patterns among participants in a community-based screening program for asbestos-related disease. METHODS: We calculated standardized mortality ratios (SMRs) and stratified results by exposure group (three occupational exposure groups, household contacts and residents without occupational asbestos exposure) and by radiographic abnormality presence. RESULTS: All-cause mortality (15.8%; 1,429/8,043) was statistically lower than expected. Asbestosis was statistically elevated in all exposure groups. Lung cancer was moderately associated with vermiculite miner/miller employment. Mesothelioma was elevated in that same exposure group and among residents. Systemic autoimmune disease mortality was also elevated. Radiographic parenchymal abnormalities were associated with lung cancer mortality. CONCLUSION: In addition to asbestos-related mortality in occupational exposure groups, this initial mortality follow-up of this cohort also shows elevated mortality for some asbestos-related causes in non-occupational exposure groups.

Background: Asbestos is an established cause of several cancers, including mesothelioma and ovarian cancer. Incidence of mesothelioma, the sentinel asbestos-associated cancer, varies by state, likely reflecting different levels of asbestos exposure. We hypothesized that states with high mesothelioma incidence may also have high ovarian cancer incidence. Materials and Methods: Using data from the Centers for Disease Control and Prevention National Program for Cancer Registries and the National Cancer Institute Surveillance, Epidemiology, and End Results Program, we examined the geographic co-occurrence of mesothelioma and ovarian cancer incidence rates by U.S. state for 2003-2015. Results: By state, mesothelioma incidence ranged from 0.5 to 1.3 cases per 100,000 persons and ovarian cancer incidence ranged from 9 to 12 cases per 100,000 females. When states were grouped by quartile of mesothelioma incidence, the average ovarian cancer incidence rate was 10% higher in states with the highest mesothelioma incidence than in states with the lowest mesothelioma incidence. Ovarian cancer incidence tended to be higher in states with high mesothelioma incidence (Pearson correlation r = 0.54; p < 0.0001). Conclusions: Data from state cancer registries show ovarian cancer incidence was positively correlated with mesothelioma incidence, suggesting asbestos may be a common exposure. The potential for asbestos exposure has declined since the 1970s because fewer products contain asbestos; however, some products, materials, and buildings may still release asbestos and thousands of workers may be exposed. Ensuring that people are protected from exposure to asbestos in their workplaces, homes, schools, and communities may reduce the risk of several cancers.

BACKGROUND: The International Classification of Disease, 10th Revision (ICD-10) did not include a code specific for Amyotrophic lateral sclerosis (ALS) until 2017. Instead, code G12.2 included both ALS and other motor neuron diseases (MND). Our objective was to determine US mortality rates for ALS exclusively by excluding other MND and progressive supranuclear palsy. METHODS: All mortality data coded as G12.2 under the pre-2017 rubric were obtained for 2011-2014. Deaths without ALS listed in one of the un-coded cause-of-death fields were excluded. ALS death rates per 100,000 persons were age-adjusted to the 2000 US standard population using the direct method. RESULTS: The proportion of excluded records coded G12.2 but not ALS was 0.21, resulting in 24,328 ALS deaths. The overall age-adjusted mortality rate was 1.70 (95% CI 1.68-1.72). The rate among males was 2.09 (95% CI 2.05-2.12) and females was 1.37 (95% CI 1.35-1.40). The overall rate among whites was 1.84, blacks 1.03, and other races 0.70. For both sexes and all races, the rate increased with age and peaked among 75-79 year-olds. Rates tended to be greater in states at higher latitudes. CONCLUSIONS: Previous reports of ALS mortality in the United States showed similar age, sex, and race distributions but with greater age-adjusted mortality rates due to the inclusion of other diseases in the case definition. When using ICD-10 data collected prior to 2017, additional review of multiple-cause of death data is required for the accurate estimation of ALS deaths.

OBJECTIVE: To analyze acute hazardous substance release surveillance data for events involving secondary contamination of hospital emergency departments (EDs). Secondary contamination of EDs may occur when a patient exposed to a hazardous chemical is not decontaminated before arrival at the ED and when ED staff are not wearing appropriate personal protective equipment. This can result in adverse health outcomes among department personnel, other patients, and visitors. Even events without actual secondary contamination risk can be real in their consequences and require the decontamination of the ED or its occupants, evacuation, or temporary shutdown of the ED. METHODS: Events involving secondary contamination were identified by using the Hazardous Substances Emergency Events Surveillance system and the National Toxic Substance Incidents Program from 2007 to 2013. RESULTS: Five incidents involving the threat of secondary contamination (0.02% of all events reported to the surveillance systems [n=33,001]) were detected and are described. Four incidents involved suspected secondary contamination in which the facility was evacuated or shut down. CONCLUSIONS: These results suggest that although rare, incidents involving secondary contamination continue to present a hazard for emergency departments. Suggested best practices to avoid secondary contamination have been described. Hospitals should be made aware of the risks associated with secondary contamination and the need to proactively train and equip staff to perform decontamination.

Asbestos-related diseases continue to result in approximately 120,000 deaths every year in the United States and worldwide. Although extensive research has been conducted on health effects of occupational exposures to asbestos, many issues related to environmental asbestos exposures remain unresolved. For example, environmental asbestos exposures associated with a former mine in Libby, Montana, have resulted in high rates of nonoccupational asbestos-related disease. Additionally, other areas with naturally occurring asbestos deposits near communities in the United States and overseas are undergoing investigations to assess exposures and potential health risks. Some of the latest public health, epidemiological, and basic research findings were presented at a workshop on asbestos at the 2014 annual meeting of the Society of Toxicology in Phoenix, Arizona. The following focus areas were discussed: a) mechanisms resulting in fibrosis and/or tumor development; b) relative toxicity of different forms of asbestos and other hazardous elongated mineral particles (EMPs); c) proper dose metrics (e.g., mass, fiber number, or surface area of fibers) when interpreting asbestos toxicity; d) asbestos exposure to susceptible populations; and e) using toxicological findings for risk assessment and remediation efforts. The workshop also featured asbestos research supported by the National Institute of Environmental Health Sciences, the Agency for Toxic Substances and Disease Registry, and the U.S. Environmental Protection Agency. Better protection of individuals from asbestos-related health effects will require stimulation of new multidisciplinary research to further our understanding of what constitutes hazardous exposures and risk factors associated with toxicity of asbestos and other hazardous EMPs (e.g., nanomaterials).

Public health registries can provide valuable information when health consequences of environmental exposures are uncertain or will likely take long to develop. They can also aid research on diseases that may have environmental causes that are not completely well defined. We discuss factors to consider when deciding whether to create an environmental health registry. Those factors include public health significance, purpose and outcomes, duration and scope of data collection and availability of alternative data sources, timeliness, availability of funding and administrative capabilities, and whether the establishment of a registry can adequately address specific health concerns. We also discuss difficulties, limitations, and benefits of exposure and disease registries, based on the experience of the Agency for Toxic Substances and Disease Registry.

BACKGROUND: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. METHODS: We conducted a retrospective cohort mortality study of 4,647 civilian, full-time workers employed at Camp Lejeune during 1973-1985 and potentially exposed to contaminated drinking water. We selected a comparison cohort of 4,690 Camp Pendleton workers employed during 1973-1985 and unexposed to contaminated drinking water. Mortality follow-up period was 1979-2008. Cause-specific standardized mortality ratios utilized U.S. age-, sex-, race-, and calendar period-specific mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune and Camp Pendleton workers and assess the effects of estimated cumulative contaminant exposures within the Camp Lejeune cohort. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels in drinking water serving workplaces at Camp Lejeune. The confidence interval (CI) indicated precision of effect estimates. RESULTS: Compared to Camp Pendleton, Camp Lejeune workers had mortality hazard ratios (HRs) >1.50 for kidney cancer (HR = 1.92, 95% CI: 0.58, 6.34), leukemias (HR = 1.59, 95% CI: 0.66, 3.84), multiple myeloma (HR = 1.84, 95% CI: 0.45, 7.58), rectal cancer (HR = 1.65, 95% CI: 0.36, 7.44), oral cavity cancers (HR = 1.93, 95% CI: 0.34, 10.81), and Parkinson's disease (HR = 3.13, 95% CI: 0.76, 12.81). Within the Camp Lejeune cohort, monotonic exposure-response relationships were observed for leukemia and vinyl chloride and PCE, with mortality HRs at the high exposure category of 1.72 (95% CI: 0.33, 8.83) and 1.82 (95% CI: 0.36, 9.32), respectively. Cumulative exposures were above the median for most deaths from cancers of the kidney, esophagus, rectum, prostate, and Parkinson's disease, but small numbers precluded evaluation of exposure-response relationships. CONCLUSION: The study found elevated HRs in the Camp Lejeune cohort for several causes of death including cancers of the kidney, rectum, oral cavity, leukemias, multiple myeloma, and Parkinson's disease. Only 14% of the Camp Lejeune cohort died by end of follow-up, producing small numbers of cause-specific deaths and wide CIs. Additional follow-up would be necessary to comprehensively assess drinking water exposure effects at the base.

BACKGROUND: Two drinking water systems at U.S. Marine Corps Base Camp Lejeune, North Carolina were contaminated with solvents during 1950s-1985. METHODS: We conducted a retrospective cohort mortality study of Marine and Naval personnel who began service during 1975-1985 and were stationed at Camp Lejeune or Camp Pendleton, California during this period. Camp Pendleton's drinking water was uncontaminated. Mortality follow-up was 1979-2008. Standardized Mortality Ratios were calculated using U.S. mortality rates as reference. We used survival analysis to compare mortality rates between Camp Lejeune (N = 154,932) and Camp Pendleton (N = 154,969) cohorts and assess effects of cumulative exposures to contaminants within the Camp Lejeune cohort. Models estimated monthly contaminant levels at residences. Confidence intervals (CIs) indicated precision of effect estimates. RESULTS: There were 8,964 and 9,365 deaths respectively, in the Camp Lejeune and Camp Pendleton cohorts. Compared to Camp Pendleton, Camp Lejeune had elevated mortality hazard ratios (HRs) for all cancers (HR = 1.10, 95% CI: 1.00, 1.20), kidney cancer (HR = 1.35, 95% CI: 0.84, 2.16), liver cancer (HR = 1.42, 95% CI: 0.92, 2.20), esophageal cancer (HR = 1.43 95% CI: 0.85, 2.38), cervical cancer (HR = 1.33, 95% CI: 0.24, 7.32), Hodgkin lymphoma (HR = 1.47, 95% CI: 0.71, 3.06), and multiple myeloma (HR = 1.68, 95% CI: 0.76, 3.72). Within the Camp Lejeune cohort, monotonic categorical cumulative exposure trends were observed for kidney cancer and total contaminants (HR, high cumulative exposure = 1.54, 95% CI: 0.63, 3.75; log10 beta = 0.06, 95% CI: -0.05, 0.17), Hodgkin lymphoma and trichloroethylene (HR, high cumulative exposure = 1.97, 95% CI: 0.55, 7.03; beta = 0.00005, 95% CI: -0.00003, 0.00013) and benzene (HR, high cumulative exposure = 1.94, 95% CI: 0.54, 6.95; beta = 0.00203, 95% CI: -0.00339, 0.00745). Amyotrophic Lateral Sclerosis (ALS) had HR = 2.21 (95% CI: 0.71, 6.86) at high cumulative vinyl chloride exposure but a non-monotonic exposure-response relationship (beta = 0.0011, 95% CI: 0.0002, 0.0020). CONCLUSION: The study found elevated HRs at Camp Lejeune for several causes of death including cancers of the kidney, liver, esophagus, cervix, multiple myeloma, Hodgkin lymphoma and ALS. CIs were wide for most HRs. Because <6% of the cohort had died, long-term follow-up would be necessary to comprehensively assess effects of drinking water exposures at the base.

RATIONALE AND OBJECTIVES: Subpleural fat can be difficult to distinguish from localized pleural thickening (LPT), a marker of asbestos exposure, on chest radiographs. The aims of this study were to examine the influence of body mass index (BMI) on the performance of radiograph readers when classifying LPT and to model the risk of false test results with varying BMI. MATERIALS AND METHODS: Subjects (n = 200) were patients being screened or treated for asbestos-related health outcomes. A film chest radiograph, a digital chest radiograph, and a high-resolution computed tomography (HRCT) chest scan were collected from each subject. All radiographs were independently read by seven B readers and scored using the International Labour Office system. HRCT scans, read by three experienced thoracic radiologists, served as the gold standard for the presence of LPT. We calculated measures of radiograph reader performance, including sensitivity and specificity, for each image modality. We also used logistic regression to estimate the probability of a false-positive and a false-negative result while controlling for covariates. RESULTS: The proportion of false-positive readings correlated with BMI. While controlling for covariates, regression modeling showed the probability of a false-positive result increased with increasing BMI category, younger age, not having pleural calcification, and among subjects not reporting occupational or household contact asbestos exposure. CONCLUSIONS: Clinicians should be cautious when evaluating radiographs of younger obese persons for the presence of asbestos-related pleural plaque, particularly in populations having an anticipated low or background prevalence of LPT.

BACKGROUND: The decline in asbestos use in the United States may impact mesothelioma incidence. OBJECTIVE: This report provides national and state-specific estimates of mesothelioma incidence in the United States using cancer surveillance data for the entire US population. METHODS: Data from the National Program for Cancer Registries and the Surveillance, Epidemiology, and End Results program were used to calculate incidence rates and annual percent change. RESULTS: During 2003-2008, an average of 1.05 mesothelioma cases per 100,000 persons were diagnosed annually in the United States; the number of cases diagnosed each year remained level, whereas rates decreased among men and were stable among women. CONCLUSION: US population-based cancer registry data can be used to determine the burden of mesothelioma and track its decline. Even 30 years after peak asbestos use in the United States, 3200 mesothelioma cases are diagnosed annually, showing that the US population is still at risk.

BACKGROUND: Among asbestos-exposed individuals, abnormal spirometry is usually associated with parenchymal abnormalities or diffuse pleural thickening. Localised pleural thickening (LPT), the most common abnormality associated with asbestos exposure, is typically thought to be a marker of exposure with little clinical consequence. Our objective was to determine if abnormal spirometry is associated with LPT independent of other abnormalities, using data from community-based screening conducted in Libby, Montana. METHODS: Subjects were a subset of screening participants comprising persons with interpretable spirometry and chest radiograph results (n=6475). Chest radiographs were independently evaluated by two or three B readers, and participants were classified by mutually exclusive categories of spirometry outcome: normal, restriction, obstruction or mixed defect. RESULTS: Restrictive spirometry was strongly associated with parenchymal abnormalities (OR 2.9; 95% CI 1.4 to 6.0) and diffuse pleural thickening (OR 4.1; 95% CI 2.1 to 7.8). Controlling for the presence of these abnormalities as well as age, smoking status and other covariates, restrictive spirometry was also associated with LPT (OR 1.4; 95% CI 1.1 to 1.8). The risk of restrictive spirometric findings correlated with the severity of LPT. CONCLUSIONS: In this large community-based screening cohort, restrictive spirometry is significantly associated with LPT, indicating that this abnormality may result in lung function impairment. Physicians treating patients exposed to Libby amphibole should be aware that LPT may have functional consequences.

OBJECTIVE: To examine the association between cumulative fiber exposure and health outcomes in workers (n = 336) with Libby amphibole exposure. METHODS: Exposure-response relationships were explored by the use of logistic regression, with cumulative fiber exposure modeled in categories and as a continuous variable. RESULTS: The use of spline functions with lifetime cumulative fiber exposure as a continuous variable showed that the odds of localized pleural thickening were significantly elevated at less than 1 f/cc-y. Odds of parenchymal abnormalities, restrictive spirometry, and chronic bronchitis were also significantly elevated at 108, 166, and 24 f/cc-y, respectively. CONCLUSIONS: The odds of several pulmonary health outcomes are correlated with cumulative exposure to Libby amphibole. That relatively low-lifetime cumulative exposures are associated with localized pleural thickening has implications for the non-cancer-risk assessment for Libby amphibole.

PURPOSE OF REVIEW: The vermiculite ore formerly mined in Libby, Montana, contains asbestiform amphibole fibers of winchite, richterite, and tremolite asbestos. Because of the public health impact of widespread occupational and nonoccupational exposure to amphiboles in Libby vermiculite, numerous related studies have been published in recent years. Here we review current research related to this issue. RECENT FINDINGS: Excess morbidity and mortality classically associated with asbestos exposure have been well documented among persons exposed to Libby vermiculite. Excess morbidity and mortality have likewise been documented among persons with only nonoccupational exposure. A strong exposure-response relationship exists for many malignant and nonmalignant outcomes and the most common outcome, pleural plaques, may occur at low lifetime cumulative exposures. SUMMARY: The public health situation related to Libby, Montana, has led to huge investments in public health actions and research. The resulting studies have added much to the body of knowledge concerning health effects of exposures to Libby amphibole fibers specifically and asbestos exposure in general.

RATIONALE AND OBJECTIVES: Analog film radiographs are typically used to classify pneumoconiosis to allow comparison with standard film radiographs. The aim of this study was to determine if digital radiography is comparable to film for the purpose of classifying pneumoconiotic pleural abnormalities. MATERIALS AND METHODS: Subjects were 200 asbestos-exposed patients, from whom digital and film chest radiographs were obtained along with chest high-resolution computed tomographic scans. Using a crossover design, radiographs were independently read on two occasions by seven readers, using conventional International Labour Organization standards for film and digitized standards for digital. High-resolution computed tomographic scans were read independently by three readers. Areas under the receiver-operating characteristic curves were calculated using high-resolution computed tomographic ratings as the gold standard for disease status. Mixed linear models were fit to estimate the effects of order of presentation, occasion, and modality, treating the seven readers as a random effect. Comparing digital and film radiography for each reader and occasion, crude agreement and agreement beyond chance (kappa) were also calculated. RESULTS: The linear models showed no statistically significant sequence effect for order of presentation (P = .73) or occasion (P = .28). Most important, the difference between modalities was not statistically significant (digital vs film, P = .54). The mean area under the curve for film was 0.736 and increased slightly to 0.741 for digital. Mean crude agreement for the presence of pleural abnormalities consistent with pneumoconiosis across all readers and occasions was 78.3%, while the mean kappa value was 0.49. CONCLUSIONS: These results indicate that digital radiography is not statistically different from analog film for the purpose of classifying pneumoconiotic pleural abnormalities, when appropriate standards are used.

PURPOSE: To assess how early pleural and/or parenchymal abnormalities consistent with asbestos exposure could be ascertained and to identify factors associated with progression. MATERIALS AND METHODS: Informed consent was obtained under an institutional review board-approved protocol. Multiple sequential chest radiographs obtained between 1955 and 2004 in 84 workers exposed to amphiboles associated with vermiculite in the town of Libby, Montana, were studied. A panel of three NIOSH B readers reviewed each worker's longitudinal chest radiograph series in reverse chronologic order and achieved a consensus reading for each radiograph. Measures of exposure were compared between workers with and those without progression of parenchymal and pleural abnormalities. RESULTS: Because of the way the study was designed, all subjects had pleural (n = 84) and/or parenchymal (n = 26) abnormalities on the most recent chest radiograph. Compared with other investigations that used different methods, this investigation revealed shorter latency periods (defined as the interval between date of hire and date of earliest radiographic detection) for circumscribed pleural plaque (median latency, 8.6 years) and pleural calcification (median latency, 17.5 years). Pleural abnormalities progressed in 64 workers, while parenchymal abnormalities progressed in 14. No significant differences were found with regard to measures of exposure between workers with and those without progression. CONCLUSION: The latency period for the development of pleural plaques may be shorter than previously reported. Early plaques are subtle and may not be detectable except at retrospective review. (c) RSNA, 2010.

OBJECTIVE: To examine the relationship between cumulative fiber exposure (CFE) and mortality in a retrospective cohort study of vermiculite workers exposed to Libby amphibole (n = 1862). METHODS: Extended Cox regression was used to estimate the hazards associated with CFE as a time-dependent covariate of multiple-cause mortality. RESULTS: The Cox models for mesothelioma, asbestosis, lung cancer, and non-malignant respiratory disease were significant with rate ratios that increased monotonically with CFE. The model for deaths due to cardiovascular disease was also significant (rate ratio for CFE ≥44.0 f/cc-y vs <1.4 f/cc-y was 1.5; 95% confidence interval = 1.1 to 2.0). CONCLUSIONS: By using a within-cohort comparison, the results demonstrate a clear exposure-response relationship between CFE and mortality from asbestos-related causes. The finding of an association between CFE and cardiovascular mortality suggests persons exposed to Libby amphibole should be monitored for this outcome.