Recruitment of population-based controls for ALS cases from the National ALS Registry.

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.

Follow-Up of the Libby, Montana Screening Cohort: A 17-Year Mortality Study.

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 follow-up of this cohort also shows elevated mortality for some asbestos-related causes in non-occupational exposure groups.

Geographic Co-Occurrence of Mesothelioma and Ovarian Cancer Incidence.

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.

Intraprocedural predictors of post-stent retriever thrombectomy subarachnoid hemorrhage in middle cerebral artery stroke.

BACKGROUND: Stent retriever thrombectomy (SRT) in acute thromboembolic stroke can result in post-thrombectomy subarachnoid hemorrhage (PTSAH). Intraprocedural findings associated with PTSAH are not well defined. OBJECTIVE: To identify angiographic findings and procedural factors during SRT that are associated with PTSAH. MATERIALS AND METHODS: This was a retrospective, observational cohort study of consecutive patients with middle cerebral artery (MCA) acute ischemic stroke treated with SRT. Inclusion criteria were: (1) age ≥18 years; (2) thromboembolic occlusion of the MCA; (3) at least one stent retriever pass beginning in an M2 branch; (4) postprocedural CT or MRI scan within 24 hours; (5) non-enhanced CT Alberta Stroke Program Early CT Score >5. Exclusion criteria included multi-territory stroke before SRT. RESULTS: Eighty-five patients were enrolled; eight patients had PTSAH (group 1) and 77 did not (group 2). Baseline demographic and clinical characteristics were comparable between the two groups. In group 1, a significantly greater proportion of patients had more than two stent retriever passes (62.5% vs 18.2%, P=0.01), a stent retriever positioned ≥2 cm along an M2 branch (100% vs 30.2%, P=0.002), and the presence of severe iatrogenic vasospasm before SRT pass (37.5% vs 5.2%, P=0.02). One patient with PTSAH and associated mass effect deteriorated clinically. CONCLUSIONS: An increased number of stent retriever passes, distal device positioning, and presence of severe vasospasm were associated with PTSAH. Neurological deterioration with PTSAH can occur.

Current Research and Opportunities to Address Environmental Asbestos Exposures.

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).

Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study.

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.

Evaluation of mortality among marines and navy personnel exposed to contaminated drinking water at USMC base Camp Lejeune: a retrospective cohort study.

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 ß = 0.06, 95% CI: -0.05, 0.17), Hodgkin lymphoma and trichloroethylene (HR, high cumulative exposure = 1.97, 95% CI: 0.55, 7.03; ß = 0.00005, 95% CI: -0.00003, 0.00013) and benzene (HR, high cumulative exposure = 1.94, 95% CI: 0.54, 6.95; ß = 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 (ß = 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.

Mesothelioma incidence in 50 states and the District of Columbia, United States, 2003-2008.

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.

Associations between radiographic findings and spirometry in a community exposed to Libby amphibole.

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.

Association between cumulative fiber exposure and respiratory outcomes among Libby vermiculite workers.

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.

Libby vermiculite exposure and risk of developing asbestos-related lung and pleural diseases.

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.

Vermiculite worker mortality: estimated effects of occupational exposure to Libby amphibole.

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 > or =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.

Exposure to asbestos-containing vermiculite ore and respiratory symptoms among individuals who were children while the mine was active in Libby, Montana.

BACKGROUND: Libby, Montana, was home to the largest vermiculite ore mine in the United States. The processing, use, and transport of the ore, which was contaminated with amphibole asbestos, led to generalized contamination of the community. The mine closed in 1990. OBJECTIVES: We examined the prevalence of respiratory symptoms in 2000-2001 and their association with history of vermiculite exposure among people who were < or = 18 years of age when the mine closed. METHODS: Information on respiratory symptoms and exposure history was collected by questionnaire in 2000-2001, at which time participants were 10-29 years old. Logistic regression was used to model the associations between exposures and outcomes adjusted for age, sex, and tobacco smoke exposure. RESULTS: Of the 1,003 individuals included in the study, 10.8% reported usually having a cough, 14.5% reported experiencing shortness of breath when walking up a slight hill or hurrying on level ground, and 5.9% reported having coughed up bloody phlegm in the past year. These respiratory symptoms were positively associated with frequently handling vermiculite insulation compared with never handling vermiculite insulation. We found no association between vermiculite insulation in the house and respiratory symptoms. Respiratory symptoms were associated with other vermiculite exposures as well, and the number and frequency of these activities showed a positive trend with usually having a cough. We found no association between any of the activities and abnormal spirometry. CONCLUSIONS: These data suggest that residents of Libby, Montana, who were children when the mine closed experienced some respiratory symptoms associated with asbestos-contaminated vermiculite exposure.

Nested case-control study of autoimmune disease in an asbestos-exposed population.

OBJECTIVE: To explore the potential association between asbestos exposure and risk of autoimmune disease, we conducted a case-control study among a cohort of 7,307 current and former residents of Libby, Montana, a community with historical occupational and environmental exposure to asbestos-contaminated vermiculite. METHODS: Cases were defined as those who reported having one of three systemic autoimmune diseases (SAIDs): systemic lupus erythematosus, scleroderma, or rheumatoid arthritis (RA). Controls were randomly selected at a 3:1 ratio from among the remaining 6,813 screening participants using frequency-matched age and sex groupings. RESULTS: The odds ratios (ORs) and 95% confidence intervals (CIs) for SAIDs among those >or=65 years of age who had worked for the vermiculite mining company were 2.14 (95% CI, 0.90-5.10) for all SAIDs and 3.23 (95% CI, 1.31-7.96) for RA. In this age group, exposure to asbestos while in the military was also an independent risk factor, resulting in a tripling in risk. Other measures of occupational exposure to vermiculite indicated 54% and 65% increased risk for SAIDs and RA, respectively. Those who had reported frequent contact with vermiculite through various exposure pathways also demonstrated elevated risk for SAIDs and RA. We found increasing risk estimates for SAIDs with increasing numbers of reported vermiculite exposure pathways (p<0.001). CONCLUSION: These preliminary findings support the hypothesis that asbestos exposure is associated with autoimmune disease. Refined measurements of asbestos exposure and SAID status among this cohort will help to further clarify the relationship between these variables.

Vertebroplasty in focal Paget disease of the spine. Case report.

Paget disease is an idiopathic metabolic disease of bone that may involve the axial and appendicular skeleton. In up to one third of patients there may be pagetoid involvement of the spine, which can cause back pain and vertebral collapse, with instability or myeloradiculopathy. Although medical therapy is the mainstay of treatment, decompressive surgery or stabilization may be required. The authors report on a case of localized Paget disease of the spine treated successfully by performing percutaneous vertebroplasty. They propose this procedure as a useful intervention that can be undertaken safely in patients with spinal Paget disease, in whom acquisition of a transpedicular biopsy sample is required as part of diagnosis.