Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-19 (of 19 Records) |
Query Trace: Bove F[original query] |
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Serological and metagenomic interrogation of cerebrospinal fluid implicates enteroviruses in pediatric acute flaccid myelitis (preprint)
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . bioRxiv 2019 666230 Background Since 2014, the United States has experienced a biennial spike in pediatric acute flaccid myelitis (AFM). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF) and only inconsistently identified from the respiratory tract, serum, or stool.Methods We interrogated CSF from children with AFM (n=42) and pediatric controls with other neurologic diseases (OND) (n=58). Samples were incubated with T7 bacteriophage expressing 481,966 sixty-two amino acid peptides with a fourteen amino acid overlap tiled across all known vertebrate virus and arbovirus genomes, an adaption of the VirScan method. Antibody-bound phage were deep sequenced to quantify enriched peptides with normalized counts expressed as reads per hundred thousand (rpK). EV antibody findings were confirmed with ELISA using whole viral protein 1 (VP1) from contemporary enterovirus (EV) A71 and D68 strains. Separately, metagenomic next-generation sequencing (mNGS) of CSF RNA, both unbiased and with targeted enrichment for EVs, was performed.Results The most significantly enriched viral family by VirScan of CSF in AFM versus OND controls was Picornaviridae (mean rpK 11,266 versus mean rpK 950, p-adjusted < 0.001, Wilcoxon signed-rank test with Bonferroni adjustment). Enriched Picornaviridae peptides belonged almost entirely to the genus Enterovirus. The mean EV VP1 ELISA signal in AFM (mean OD 0.51) was significantly higher than OND controls (mean OD 0.08, p-value < 0.001, Mann-Whitney test). mNGS did not detect additional enterovirus RNA in CSF.Conclusion Despite the rare detection of EV RNA in the CNS of patients with AFM, a pan-viral serologic assay identified high levels of CSF EV antibodies in AFM CSF compared to CSF from OND controls. These results provide further evidence for a causal role of non-polio enteroviruses in AFM. |
Causes of death among United States decedents with ALS: An eye toward delaying mortality
Larson TC , Goutman SA , Davis B , Bove FJ , Thakur N , Mehta P . Ann Clin Transl Neurol 2023 10 (5) 757-764 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. |
Evaluating the effectiveness of state-level policies on childhood blood lead testing rates
Ruckart PZ , Bove FJ , Dallas C . J Public Health Manag Pract 2022 29 (2) 241-249 CONTEXT: Lead exposure can harm nearly every organ in the human body. Millions of US children are exposed to lead hazards. Identifying lead-exposed children using blood lead testing is essential for connecting them to appropriate follow-up services. However, blood lead testing is not consistently conducted for at-risk children. Thus, determining which policies help improve blood lead testing rates is essential. OBJECTIVE: This analysis provides critical evidence to better understand which state-level policies are more effective at increasing childhood blood lead testing rates. These include metrics, incentives, other managed care organization guidance, provider guidelines, mandatory reporting of results to state health departments, data sharing between Medicaid and other state agencies, and proof of testing for school enrollment. DESIGN: This analysis included 33 states with complete data on the number of children tested for blood lead in 2017-2018 as reported to the Centers for Disease Control and Prevention. Linear regression modeling was conducted to examine associations between testing rates and the aforementioned policies. Fully adjusted models included percentages of the population living in pre-1980 housing, younger than 6 years with Medicaid coverage, and foreign-born. RESULTS: Strongest unadjusted and adjusted regression coefficients were observed for requiring proof of testing for school enrollment (β = .12, P = .03) and metrics (β = .06, P = .01), respectively. CONCLUSION: Policies associated with higher childhood blood lead testing rates can be used by policy makers; local, state, and federal public health agencies; professional organizations; nonprofit organizations; and others to inform development and implementation of additional policies to increase childhood blood lead testing. |
Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance in Anopheles gambiae provides a real-time molecular diagnostic for anti-malarial intervention deployment.
Njoroge H , Van't Hof A , Oruni A , Pipini D , Nagi SC , Lynd A , Lucas ER , Tomlinson S , Grau-Bove X , McDermott D , Wat'senga FT , Manzambi EZ , Agossa FR , Mokuba A , Irish S , Kabula B , Mbogo C , Bargul J , Paine MJI , Weetman D , Donnelly MJ . Mol Ecol 2022 31 (16) 4307-4318 Studies of insecticide resistance provide insights into the capacity of populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on pyrethroid insecticides, primarily in long lasting insecticidal nets (LLINs). Resistance in the major malaria vectors has increased in concert with the expansion of LLIN distributions. Identifying genetic mechanisms underlying high-level resistance is crucial for the development and deployment of resistance-breaking tools. Using the Anopheles gambiae 1000 genomes (Ag1000g) data we identified a very recent selective sweep in mosquitoes from Uganda which localized to a cluster of cytochrome P450 genes. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in Cyp6p4 (I236M), an upstream insertion of a partial Zanzibar-like transposable element (TE) and a duplication of the Cyp6aa1 gene. The mutations appear to have originated recently in An. gambiae from the Kenya-Uganda border, with stepwise replacement of the double-mutant (Zanzibar-like TE and Cyp6p4-236M) with the triple-mutant haplotype (including Cyp6aa1 duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple-mutant haplotype is strongly associated with increased expression of genes able to metabolise pyrethroids and is strongly predictive of resistance to pyrethroids most notably deltamethrin. Importantly, there was increased mortality in mosquitoes carrying the triple-mutation when exposed to nets co-treated with the synergist piperonyl butoxide (PBO). Frequencies of the triple-mutant haplotype remain spatially variable within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO-pyrethroid co-treated LLINs across African countries. |
Incidence of amyotrophic lateral sclerosis in the United States, 2014-2016
Mehta P , Raymond J , Punjani R , Larson T , Han M , Bove F , Horton DK . Amyotroph Lateral Scler Frontotemporal Degener 2022 23 1-5 Objective: To estimate the incidence of amyotrophic lateral sclerosis (ALS) in the United States for calendar years 2014-2016 using data from the National ALS Registry (Registry). The Registry collects data on ALS patients in the United States to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with the disease. Methods: To identify adult incident cases of ALS, the Registry compiles data from three national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). For cases that are not included in these databases, the Registry includes data collected from patients who voluntarily enroll via a secure web portal. Results: The Registry identified 5695 ALS cases in 2014; 6045 cases in 2015; and 4861 cases in 2016 for age-adjusted incidence rates of 1.7 (2014), 1.5 (2015), and 1.5 (2016) per 100,000 U.S. population, respectively. ALS was more common among whites, males, and persons aged 60-79 years. Conclusions: This is the first time administrative and self-reported databases have been used to describe the incidence of ALS for the United States resulting in a better estimate of disease demographics. |
Per- and Polyfluoroalkyl Substances Multi-Site Study
Uzochukwu C , Weems M , Pavuk M , Bove F , Reh C , Breysse P . J Environ Health 2021 84 (3) 34-37 The article provides information on the health effects of drinking water exposed to per- and polyfluoroalkyl substances (PFAS). Topics include the Multi-Site Study (MSS) of the Health Implications of Exposure to PFAS-Contaminated Drinking Water, the establishment of pharmacokinetic modeling and historical reconstruction work groups, and the community engagement efforts to provide answers regarding the potential effects of elevated PFAS level on public health. |
Prevalence of amyotrophic lateral sclerosis (ALS), United States, 2016
Mehta P , Raymond J , Punjani R , Larson T , Bove F , Kaye W , Nelson LM , Topol B , Han M , Muravov O , Genson C , Davis B , Hicks T , Horton K . Amyotroph Lateral Scler Frontotemporal Degener 2021 23 1-6 Objective: To estimate the prevalence of amyotrophic lateral sclerosis (ALS) in the United States for 2016 using data from the National ALS Registry (Registry). Established in 2009, the Registry collects data on ALS patients in the U.S. to better describe the epidemiology of ALS, examine risk factors such as environmental and occupational exposures, and characterize the demographics of those living with the disease. Methods: To identify adult prevalent cases of ALS, the Registry compiles data from three national administrative databases (maintained by the Centers for Medicare and Medicaid Services, the Veterans Health Administration, and the Veterans Benefits Administration). To ascertain cases not necessarily included in these databases and to better understand risk-factors associated with ALS and disease progression, the Registry also includes data collected from patients who voluntarily enroll via a web portal to complete online surveys. Results: In 2016, the Registry conservatively identified 16,424 adult persons who met the Registry definition of ALS for an age-adjusted prevalence rate of 5.2 per 100,000 U.S. population. The pattern of patient characteristics (e.g., age, sex, and race/ethnicity) has not changed from previous Registry reports. Overall, ALS was more common among whites, males, and persons aged 60-69 years. The age groups with the lowest number of ALS cases were persons aged 18-39 years. Males had a higher prevalence rate of ALS than females overall and across all data sources. Conclusions: Data collected by the National ALS Registry are being used to better describe the epidemiology and demographics of ALS in the U.S. |
Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Schubert RD , Hawes IA , Ramachandran PS , Ramesh A , Crawford ED , Pak JE , Wu W , Cheung CK , O'Donovan BD , Tato CM , Lyden A , Tan M , Sit R , Sowa GA , Sample HA , Zorn KC , Banerji D , Khan LM , Bove R , Hauser SL , Gelfand AA , Johnson-Kerner BL , Nash K , Krishnamoorthy KS , Chitnis T , Ding JZ , McMillan HJ , Chiu CY , Briggs B , Glaser CA , Yen C , Chu V , Wadford DA , Dominguez SR , Ng TFF , Marine RL , Lopez AS , Nix WA , Soldatos A , Gorman MP , Benson L , Messacar K , Konopka-Anstadt JL , Oberste MS , DeRisi JL , Wilson MR . Nat Med 2019 25 (11) 1748-1752 Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)(1-6). Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)(2). CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM. |
Reconstructing historical VOC concentrations in drinking water for epidemiological studies at a U.S. military base: Summary of results
Maslia Morris L , Aral Mustafa M , Ruckart Perri Z , Bove Frank J . Water (Basel) 2016 8 (10) 449 A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds (VOC) at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water-at monthly intervals-delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s-1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (g/L) compared to a one-time maximum measured value of 215 g/L and exceeded the U.S. Environmental Protection Agency's current maximum contaminant level (MCL) of 5 g/L during the period November 1957-February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 g/L compared to a one-time maximum measured value of 1400 g/L during the period August 1953-December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 g/L) and intermittently during the period June 1972-February 1985 (maximum reconstructed TCE concentration of 66 g/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach. |
Evaluation of contaminated drinking water and male breast cancer at Marine Corps Base Camp Lejeune, North Carolina: a case control study
Ruckart PZ , Bove FJ , Shanley E 3rd , Maslia M . Environ Health 2015 14 (1) 74 BACKGROUND: Solvents contaminated drinking water supplies at Marine Corps Base Camp Lejeune during 1950s-1985. METHODS: We conducted a case-control study among Marines to evaluate associations between residential exposure to contaminated drinking water at Camp Lejeune and male breast cancer risk. The study included 71 male breast cancer cases and 373 controls identified from the Department of Veteran's Affairs (VA) cancer registry whose military personnel records were available. Controls were selected from cancers not known to be associated with solvent exposure and included 270 skin cancers, 71 mesotheliomas, and 32 bone cancers. Base assignment and risk factor information came from military personnel and VA records. Groundwater contaminant fate/transport and distribution system models provided monthly estimated residential contaminant levels. We conducted exact logistic regression using the 50(th) percentile level among exposed controls to create low and high exposure categories. We calculated 95 % confidence intervals (CIs) to indicate precision of effect estimates. Exploratory analyses used proportional hazards methods to evaluate associations between exposures and age at diagnosis. RESULTS: After adjusting for age at diagnosis, race, and service in Vietnam, the odds ratio (OR) for ever stationed at Camp Lejeune was 1.14 (95 % CI: 0.65, 1.97). Adjusted ORs for high residential cumulative exposures to tetrachloroethylene (PCE), t-1,2 dichloroethylene (DCE), and vinyl chloride were 1.20 [95 % CI: 0.16-5.89], 1.50 [95 % CI: 0.30-6.11], 1.19 [95 % CI: 0.16-5.89], respectively, with a monotonic exposure response relationship for PCE only. However these results were based on two or three cases in the high cumulative exposure categories. Ever stationed at Camp Lejeune and high cumulative exposures to trichloroethylene (TCE), PCE, DCE and vinyl chloride were associated with earlier age at onset for male breast cancer; hazard ratios ranged from 1.4-2.7 with wide confidence intervals for cumulative exposure variables. CONCLUSION: Findings suggested possible associations between male breast cancer and being stationed at Camp Lejeune and cumulative exposure to PCE, DCE, and vinyl chloride. TCE, PCE, DCE and vinyl chloride cumulative exposures showed possible associations with earlier age at onset of male breast cancer. However, this study was limited by small numbers of cases in high exposure categories. |
Evaluation of contaminated drinking water and preterm birth, small for gestational age, and birth weight at Marine Corps Base Camp Lejeune, North Carolina: a cross-sectional study
Ruckart PZ , Bove FJ , Maslia M . Environ Health 2014 13 99 BACKGROUND: Births during 1968-1985 at Camp Lejeune were exposed to drinking water contaminated with trichloroethylene (TCE), tetrachloroethylene (PCE), and benzene. METHODS: We conducted a cross-sectional study to evaluate associations between residential prenatal exposure to contaminated drinking water at Camp Lejeune during 1968-1985 and preterm birth, small for gestational age (SGA), term low birth weight (TLBW), and mean birth weight (MBW) deficit. Birth certificates identified mothers residing at Camp Lejeune at delivery. We analyzed exposure data for the entire pregnancy and individual trimesters. For each period examined, births were categorized as unexposed if mothers did not reside at Camp Lejeune or if their residence on base received uncontaminated drinking water. Ground water contaminant fate/transport and distribution system models provided monthly estimated contaminant levels at residences. For PCE and TCE, the exposed group was divided into four levels: < median value, ≥ median value, ≥75th percentile, and ≥90th percentile. For benzene, the exposed group was categorized as <1 part per billion (ppb) versus ≥1 ppb because of sparse data. Magnitude of effect estimates and exposure response relationships were used to assess associations. Confidence intervals (CIs) indicated precision of estimates. RESULTS: For the highest TCE exposure category during the entire pregnancy, odds ratios (ORs) were 1.5 (95% CI: 1.2, 1.9) and 1.3 (95% CI: 0.8, 2.2) for SGA and TLBW, respectively, and reduced MBW beta = -78.3 g (95% CI: -115.0, -41.7). The OR =1.3 (95% CI: 1.0, 1.6) for preterm birth and the highest PCE exposure category during the entire pregnancy. Monotonic exposure-response relationships were observed for benzene exposure during the entire pregnancy and TLBW (highest category OR =1.5, 85% CI: 0.9, 2.3). Although a monotonic association between benzene and adjusted MBW difference was also observed (highest category beta = -36.2 g, 95% CI: -72.3, -0.1), the association disappeared when TCE was also added to the model. We found no evidence suggesting any other associations between outcomes and exposures. CONCLUSION: Findings suggested associations between in utero exposures to TCE and SGA, TLBW and reduced MBW; benzene and TLBW; and PCE and preterm birth. |
Mortality study of civilian employees exposed to contaminated drinking water at USMC Base Camp Lejeune: a retrospective cohort study
Bove FJ , Ruckart PZ , Maslia M , Larson TC . Environ Health 2014 13 68 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
Bove FJ , Ruckart PZ , Maslia M , Larson TC . Environ Health 2014 13 (1) 10 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. |
Evaluation of exposure to contaminated drinking water and specific birth defects and childhood cancers at Marine Corps Base Camp Lejeune, North Carolina: a case-control study
Ruckart PZ , Bove FJ , Maslia M . Environ Health 2013 12 104 BACKGROUND: Drinking water supplies at Marine Corps Base Camp Lejeune were contaminated with trichloroethylene, tetrachloroethylene, benzene, vinyl chloride and trans-1,2-dichloroethylene during 1968 through 1985. METHODS: We conducted a case control study to determine if children born during 1968-1985 to mothers with residential exposure to contaminated drinking water at Camp Lejeune during pregnancy were more likely to have childhood hematopoietic cancers, neural tube defects (NTDs), or oral clefts. For cancers, exposures during the first year of life were also evaluated. Cases and controls were identified through a survey of parents residing on base during pregnancy and confirmed by medical records. Controls were randomly sampled from surveyed participants who had a live birth without a major birth defect or childhood cancer. Groundwater contaminant fate and transport and distribution system models provided estimates of monthly levels of drinking water contaminants at mothers' residences. Magnitude of odds ratios (ORs) was used to assess associations. Confidence intervals (CIs) were used to indicate precision of ORs. We evaluated parental characteristics and pregnancy history to assess potential confounding. RESULTS: Confounding was negligible so unadjusted results were presented. For NTDs and average 1st trimester exposures, ORs for any benzene exposure and for trichloroethylene above 5 parts per billion were 4.1 (95% CI: 1.4-12.0) and 2.4 (95% CI: 0.6-9.6), respectively. For trichloroethylene, a monotonic exposure response relationship was observed. For childhood cancers and average 1st trimester exposures, ORs for any tetrachloroethylene exposure and any vinyl chloride exposure were 1.6 (95% CI: 0.5-4.8), and 1.6 (95% CI: 0.5-4.7), respectively. The study found no evidence suggesting any other associations between outcomes and exposures. CONCLUSION: Although CIs were wide, ORs suggested associations between drinking water contaminants and NTDs. ORs suggested weaker associations with childhood hematopoietic cancers. |
Investigating suspected cancer clusters and responding to community concerns: guidelines from CDC and the Council of State and Territorial Epidemiologists
Abrams B , Anderson H , Blackmore C , Bove FJ , Condon SK , Eheman CR , Fagliano J , Haynes LB , Lewis LS , Major J , McGeehin MA , Simms E , Sircar K , Soler J , Stanbury M , Watkins SM , Wartenberg D . MMWR Recomm Rep 2013 62 1-24 This report augments guidelines published in 1990 for investigating clusters of health events (CDC. Guidelines for investigating clusters of health events. MMWR 1990;39[No. RR-11]). The 1990 Guidelines considered any noninfectious disease cluster, injuries, birth defects, and previously unrecognized syndromes or illnesses. These new guidelines focus on cancer clusters. State and local health departments can use these guidelines to develop a systematic approach to responding to community concerns regarding cancer clusters. The guidelines are intended to apply to situations in which a health department responds to an inquiry about a suspected cancer cluster in a residential or community setting only. Occupational or medical treatment-related clusters are not included in this report. Since 1990, many improvements have occurred in data resources, investigative techniques, and analytic/statistical methods, and much has been learned from both large- and small-scale cancer cluster investigations. These improvements and lessons have informed these updated guidelines. These guidelines utilize a four-step approach (initial response, assessment, major feasibility study, and etiologic investigation) as a tool for managing a reported cluster. Even if a cancer cluster is identified, there is no guarantee that a common cause or an environmental contaminant will be implicated. Identification of a common cause or an implicated contaminant might be an expected outcome for the concerned community. Therefore, during all parts of an inquiry, responders should be transparent, communicate clearly, and explain their decisions to the community. |
Association between cumulative fiber exposure and respiratory outcomes among Libby vermiculite workers
Larson TC , Antao VC , Bove FJ , Cusack C . J Occup Environ Med 2012 54 (1) 56-63 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. |
"Complexities in hindcasting models - when should we say enough is enough,"
Maslia ML , Aral MM , Faye RE , Grayman WM , Suarez-Soto RJ , Sautner JB , Anderson BA , Bove FJ , Ruckart PZ , Moore SM . Ground Water 2011 50 (1) 10-6; discussion 16-8 In a recent article, TP Clement (2010, hereafter referred to as TPC) discusses the complexities and limitations of "hindcasting" models and criticizes the use of complex models when undertaking investigations of subsurface reactive transport processes. TPC implies that complex numerical models that stimulate reactive transport processes in groundwater are likely if not always an inappropriate tool to apply to "hindcasting" investiagtions and that scientists and engineers who implement these investiagtions using such models are somehow not aware of teh technical and scientific complexities and limitations of such methods and approaches. To illustrate his point of view, TPC uses a case study of an ongoing health study of exposure to volatile organic compounds (VOCs) in drinking water at US Marine Corps Base Camp Lejeune, North Carolina (hereafter referred to as the case-control health study at Camp Lejeune). The article presents some thought-provoking points-of-view. However, we believe there is a lack of detail on several key issues that require specificity and clarification, particularly with respect to modleing approaches and methods, the physics of containment occurrence and reactive transport in teh subsurface, and agency policies for the review and dissemination of data and reports. |
Vermiculite worker mortality: estimated effects of occupational exposure to Libby amphibole
Larson TC , Antao VC , Bove FJ . J Occup Environ Med 2010 52 (5) 555-60 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. |
Reconstructing historical exposures to volatile organic compound-contaminated drinking water at a U.S. military base
Maslia ML , Aral MM , Faye RE , Suarez-Soto RJ , Sautner JB , Wang J , Jang W , Bove FJ , Ruckart PZ . Water Qual Expo Health 2009 1 (1) 49-68 Two of three water-distribution systems that have historically supplied drinking water to family housing at U.S. Marine Corps Base Camp Lejeune, North Carolina, were contaminated with volatile organic compounds (VOCs). Scientific data relating to the harmful effects of VOCs on a child or fetus are limited. Therefore, the U.S. Agency for Toxic Substances and Disease Registry (ATSDR) is conducting an epidemiological study to evaluate potential associations between in utero and infant (up to 1 year of age) exposures to VOCs in contaminated drinking water at Camp Lejeune and specific birth defects and childhood cancers. The study includes births that occurred during the period 1968-1985 to women who were pregnant while they resided in family housing at Camp Lejeune. To support the epidemiological study, water-modeling techniques are being used to reconstruct historical conditions of groundwater flow, contaminant fate and transport, and the distribution of drinking water contaminated with VOCs. Results for this phase of the study indicate that PCE concentrations in drinking water, delivered to the Tarawa Terrace housing area, exceeded the current maximum contaminant level for PCE of 5 micrograms per liter (µg/L) for 346 months-November 1957-February 1987; the maximum simulated PCE concentration in Tarawa Terrace drinking water was 183 µg/L during March 1984 compared to a measured concentration of 215 µg/L during February 1985. |
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