Environmental exposures are important risk factors for advanced liver fibrosis in African American adults.

Background & Aims: The prevalence and aetiology of liver fibrosis vary over time and impact racial/ethnic groups unevenly. This study measured time trends and identified factors associated with advanced liver fibrosis in the United States. Methods: Standardised methods were used to analyse data on 47,422 participants (≥20 years old) in the National Health and Nutrition Examination Survey (1999-2018). Advanced liver fibrosis was defined as Fibrosis-4 ≥2.67 and/or Forns index ≥6.9 and elevated alanine aminotransferase. Results: The estimated number of people with advanced liver fibrosis increased from 1.3 million (95% CI 0.8-1.9) to 3.5 million (95% CI 2.8-4.2), a nearly threefold increase. Prevalence was higher in non-Hispanic Black and Mexican American persons than in non-Hispanic White persons. In multivariable logistic regression analysis, cadmium was an independent risk factor in all racial/ethnic groups. Smoking and current excessive alcohol use were risk factors in most. Importantly, compared with non-Hispanic White persons, non-Hispanic Black persons had a distinctive set of risk factors that included poverty (odds ratio [OR] 2.09; 95% CI 1.44-3.03) and susceptibility to lead exposure (OR 3.25; 95% CI 1.95-5.43) but did not include diabetes (OR 0.88; 95% CI 0.61-1.27; p =0.52). Non-Hispanic Black persons were more likely to have high exposure to lead, cadmium, polychlorinated biphenyls, and poverty than non-Hispanic White persons. Conclusions: The number of people with advanced liver fibrosis has increased, creating a need to expand the liver care workforce. The risk factors for advanced fibrosis vary by race/ethnicity. These differences provide useful information for designing screening programmes. Poverty and toxic exposures were associated with the high prevalence of advanced liver fibrosis in non-Hispanic Black persons and need to be addressed. Impact and Implications: Because liver disease often produces few warning signs, simple and inexpensive screening tests that can be performed by non-specialists are needed to allow timely diagnosis and linkage to care. This study shows that non-Hispanic Black persons have a distinctive set of risk factors that need to be taken into account when designing liver disease screening programs. Exposure to exogenous toxins may be especially important risk factors for advanced liver fibrosis in non-Hispanic Black persons.

Dose-response relationship between World Trade Center dust exposure and hepatic steatosis.

BACKGROUND: The World Trade Center (WTC) attack exposed thousands of workers to toxic chemicals that have been linked to liver diseases and cancers. This study examined the relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis in the WTC General Responders Cohort (GRC). METHODS: All low-dose computed tomography (CT) scans of the chest performed on the WTC GRC between September 11, 2001 and December 31, 2018, collected as part of the World Trade Center Health Program, were reviewed. WTC dust exposure was categorized into five groups based on WTC arrival time. CT liver density was estimated using an automated algorithm, statistics-based liver density estimation from imaging. The relationship between the intensity of WTC dust exposure and the risk of hepatic steatosis was examined using univariate and multivariable regression analyses. RESULTS: Of the 1788 WTC responders, 258 (14.4%) had liver attenuation less than 40 Hounsfield units (HU < 40) on their earliest CT. Median time after September 11, 2001 and the earliest available CT was 11.3 years (interquartile range: 8.0-14.9 years). Prevalence of liver attenuation less than 40 HU was 17.0% for arrivals on September 11, 2001, 16.0% for arrivals on (September 12, 2001 or September 13, 2001), 10.9% for arrivals on September 14-30, 2001, and 9.0% for arrivals on January 10, 2001 or later (p = 0.0015). A statistically significant trend of increasing liver steatosis was observed with earlier arrival times (p < 0.0001). WTC arrival time remained a significant independent factor for decreased liver attenuation after controlling for other covariates. CONCLUSIONS: Early arrival at the WTC site was significantly associated with increasing hepatic steatosis.

Development and Validation of a Clinical Frailty Index for the World Trade Center General Responder Cohort.

Objectives: To develop and validate a clinical frailty index to characterize aging among responders to the 9/11 World Trade Center (WTC) attacks. Methods: This study was conducted on health monitoring data on a sample of 6197 responders. A clinical frailty index, WTC FI-Clinical, was developed according to the cumulative deficit model of frailty. The validity of the resulting index was assessed using all-cause mortality as an endpoint. Its association with various cohort characteristics was evaluated. Results: The sample's median age was 51 years. Thirty items were selected for inclusion in the index. It showed a strong correlation with age, as well as significant adjusted associations with mortality, 9/11 exposure severity, sex, race, pre-9/11 occupation, education, and smoking status. Discussion: The WTC FI-Clinical highlights effects of certain risk factors on aging within the 9/11 responder cohort. It will serve as a useful instrument for monitoring and tracking frailty within this cohort.

Initial Whole-Genome Sequencing of Plasma Cell Neoplasms in First Responders and Recovery Workers Exposed to the World Trade Center Attack of September 11, 2001.

PURPOSE: The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. High incidence of multiple myeloma and precursor conditions has been reported among first responders to the WTC disaster. To expand on our prior screening studies, and to characterize the genomic impact of the exposure to known and potential carcinogens in the WTC debris, we were motivated to perform whole-genome sequencing (WGS) of WTC first responders and recovery workers who developed a plasma cell disorder after the attack. EXPERIMENTAL DESIGN: We performed WGS of nine CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after the WTC disaster. RESULTS: No significant differences were observed in comparing the post-WTC driver and mutational signature landscapes with 110 previously published WGSs from 56 patients with multiple myeloma and the CoMMpass WGS cohort (n = 752). Leveraging constant activity of the single-base substitution mutational signatures 1 and 5 over time, we estimated that tumor-initiating chromosomal gains were windowed to both pre- and post-WTC exposure. CONCLUSIONS: Although limitations in sample size preclude any definitive conclusions, our findings suggest that the observed increased incidence of plasma cell neoplasms in this population is due to complex and heterogeneous effects of the WTC exposure that may have initiated or contributed to progression of malignancy.

Retrospective Assessment of Risk Factors for Head and Neck Cancer Among World Trade Center General Responders.

Objective: To assess the reliability of a questionnaire designed to reconstruct risk factors for head and neck cancer relative to the 9/11 World Trade Center (WTC) response and over the lifetime. Methods: As part of a nested case-control study, 200 WTC Health Program (WTCHP) General Responder Cohort (GRC) members completed a newly-developed study questionnaire via telephone (with a trained interviewer) or online (self-administered). We assessed agreement between measures of tobacco and alcohol use in our questionnaire results and data collected previously during WTCHP-GRC monitoring visits using Cohens Kappa (κ) and intraclass correlation coefficient (ICC) for categorical and continuous measures, respectively. We compared agreement by disease status, survey mode, and year of WTCHP enrollment. Results: We observed high agreement between measures of lifetime, pre-WTC, and post-WTC smoking prevalence (all κ > 0.85) and smoking duration (all ICC > 0.84). There was moderate agreement between measures of smoking frequency (ICC: 0.61-0.73). Agreement between measures of smoking frequency, but not duration, differed by disease status, and agreement between smoking measures was higher for participants who completed our survey by phone than by web. Among cases, there were no differences based on enrollment in the WTCHP before or after diagnosis. Conclusion: Agreement between measures was generally high, although potential reporting bias and a mode effect that should be considered when interpreting analyses of self-reported data in this population; however differential misclassification appears to be minimal. Our questionnaire may be useful for future studies examining similar behavioral risk factors among disaster-exposed populations.

Cancer in General Responders Participating in World Trade Center Health Programs, 2003-2013.

BACKGROUND: Following the September 11, 2001, attacks on the World Trade Center (WTC), thousands of workers were exposed to an array of toxins known to cause adverse health effects, including cancer. This study evaluates cancer incidence in the WTC Health Program General Responder Cohort occurring within 12 years post exposure. METHODS: The study population consisted of 28 729 members of the General Responder Cohort enrolled from cohort inception, July 2002 to December 31, 2013. Standardized incidence ratios (SIRs) were calculated with cancer case inclusion and follow-up starting post September 11, 2001 (unrestricted) and, alternatively, to account for selection bias, with case inclusion and follow-up starting 6 months after enrollment in the WTC Health Program (restricted). Case ascertainment was based on linkage with six state cancer registries. Under the restricted criterion, hazard ratios were estimated using multivariable Cox proportional hazards models for all cancer sites combined and for prostate cancer. RESULTS: Restricted analyses identified 1072 cancers in 999 responders, with elevations in cancer incidence for all cancer sites combined (SIR = 1.09, 95% confidence interval [CI] = 1.02 to 1.16), prostate cancer (SIR = 1.25, 95% CI = 1.11 to 1.40), thyroid cancer (SIR = 2.19, 95% CI = 1.71 to 2.75), and leukemia (SIR = 1.41, 95% CI = 1.01 to 1.92). Cancer incidence was not associated with any WTC exposure index (composite or individual) for all cancer sites combined or for prostate cancer. CONCLUSION: Our analyses show statistically significant elevations in cancer incidence for all cancer sites combined and for prostate and thyroid cancers and leukemia. Multivariable analyses show no association with magnitude or type of exposure.

Elevated prevalence of moderate-to-severe hepatic steatosis in World Trade Center General Responder Cohort in a program of CT lung screening.

BACKGROUND AND AIMS: To determine the prevalence of moderate-to-severe hepatic steatosis (HS) and associated risk factors in members of the World Trade Center (WTC) General Responder Cohort (GRC) who qualify for low-dose non-contrast computed tomography for lung cancer screening and compare them to non-WTC participants in the same screening program. METHODS: All participants gave written informed consent before participating in this IRB-approved study. Clinical variables and laboratory values were recorded. Hepatic attenuation measurement (Hounsfield unit; HU) was measured on low-dose computed tomography (LDCT) and a threshold attenuation value <40HU indicated moderate-to-severe HS. Bivariate and multivariable linear and logistic regression analyses were performed. Propensity scores (PS) were calculated and inverse probability weighting (IPW) was used to adjust for potential confounders when comparing the WTC with non-WTC participants. RESULTS: The prevalence of moderate-to-severe HS was 16.2% among 154 WTC participants compared to 5.3% among 170 non-WTC participants. In WTC members, moderate-to-severe HS was associated with higher BMI, higher laboratory liver function tests, and former smoking status. Using PS analysis and IPW to account for potential confounders, the odds ratio for moderate-to-severe HS was 3.4-fold higher (95% confidence interval: 1.7-6.7) in the WTC participants compared with non-WTC participants. Moderate-to-severe HS was also associated with higher BMI and former smoker status. CONCLUSION: Prevalence of moderate-to-severe HS was >3-fold higher in the WTC-GRC group than in other participants.

Automated measurement of liver attenuation to identify moderate-to-severe hepatic steatosis from chest CT scans.

PURPOSE: Develop and validate an automated method for measuring liver attenuation in non-contrast low-dose chest CT (LDCT) scans and compare it to the standard manual method for identifying moderate-to-severe hepatic steatosis (HS). METHOD: The automated method identifies a region below the right lung within the liver and uses statistical sampling techniques to exclude non-liver parenchyma. The method was used to assess moderate-to-severe HS on two IRB-approved cohorts: 1) 24 patients with liver disease examined between 1/2013-1/2017 with non-contrast chest CT and abdominal MRI scans obtained within three months of liver biopsy, and 2) 319 lung screening participants with baseline LDCT performed between 8/2011-1/2017. Agreement between the manual and automated CT methods, the manual MRI method, and pathology for determining moderate-to-severe HS was assessed using Cohen's Kappa by applying a 40 HU threshold to the CT method and 17.4% fat fraction to MRI. Agreement between the manual and automated CT methods was assessed using the intraclass correlation coefficient (ICC). Variability was assessed using Bland-Altman limits of agreement (LoA). RESULTS: In the first cohort, the manual and automated CT methods had almost perfect agreement (ICC = 0.97, κ = 1.00) with LoA of -7.6 to 4.7 HU. Both manual and automated CT methods had almost perfect agreement with MRI (κ = 0.90) and substantial agreement with pathology (κ = 0.77). In the second cohort, the manual and automated CT methods had almost perfect agreement (ICC = 0.94, κ = 0.87). LoA were -10.6 to 5.2 HU. CONCLUSION: Automated measurements of liver attenuation from LDCT scans can be used to identify moderate-to-severe HS on LDCT.

Risk factors for head and neck cancer in the World Trade Center Health Program General Responder Cohort: results from a nested case-control study.

OBJECTIVES: Head and neck cancers (HNCs) may be among the health consequences of involvement in the World Trade Center (WTC) response on and after 11 September 2001. We conducted a nested case-control study of WTC Health Program (WTCHP) general responders to examine the effects of WTC exposures and behavioural risk factors on HNC. METHODS: We enrolled 64 cases and 136 controls, matched on age, sex and race/ethnicity within risk sets. We assessed tobacco and alcohol use, sexual activity, and occupational exposures prior to, during and after WTC exposure until case diagnosis via questionnaire. We obtained WTC exposure information (duration (first to last day), total days and location of work) from the WTCHP General Responder Data Center. We assessed associations with HNC, and interaction among exposures, using conditional logistic regression. RESULTS: Responders in protective services versus other occupations had increased odds (OR: 2.51, 95% CI 1.09 to 5.82) of HNC. Among those in non-protective services occupations, arriving to the WTC effort on versus after 11 September 2001 was significantly associated with HNC (OR: 3.77, 95% CI 1.00 to 14.11). Duration of work was not significantly associated with HNC. Lifetime and post-WTC years of cigarette smoking and post-WTC number of sex partners were positively and significantly associated with HNC, while alcohol consumption was not. CONCLUSIONS: These findings suggest opportunities for HNC risk factor mitigation (eg, smoking cessation, human papillomavirus vaccination) and contribute to a risk factor profile which may assist WTCHP clinicians with identifying high-risk responders and improve detection and treatment outcomes in this population.

Increased Incidence of Thyroid Cancer among World Trade Center First Responders: A Descriptive Epidemiological Assessment.

An increased incidence of thyroid cancer among 9/11 rescue workers has been reported, the etiology of which remains unclear but which may, at least partly, be the result of the increased medical surveillance this group undergoes. This study aimed to investigate thyroid cancer in World Trade Center (WTC) responders by looking at the demographic data and questionnaire responses of thyroid cancer cases from the Mount Sinai WTC Health Program (WTCHP). WTCHP thyroid cancer tumors were of a similar size (p = 0.4), and were diagnosed at a similar age (p = 0.2) compared to a subset of thyroid cancer cases treated at Mount Sinai without WTC exposure. These results do not support the surveillance bias hypothesis, under which smaller tumors are expected to be diagnosed at earlier ages. WTCHP thyroid cancer cases also reported a past history of radiation exposure and a family history of thyroid conditions at lower rates than expected, with higher than expected rates of previous cancer diagnoses, family histories of other cancers, and high Body Mass Indexes (BMIs). Further research is needed to better understand the underlying risk factors that may play a role in the development of thyroid cancer in this group.

Excess HPV-related head and neck cancer in the world trade center health program general responder cohort.

The World Trade Center (WTC) attacks exposed rescue and recovery workers to a complex mix of toxicants, including carcinogens. our study compared site-specific cancer incidence of head and neck cancers (HNC) from 2003 through 2012 among 33,809 consented WTC General Responder Cohort (GRC) members to the New Jersey State Cancer Registry, using standardized incidence ratios (SIRs). HNC grouped using SEER ICD-O-3 codes into HPV-related (oropharyngeal) and non-related (other oral-nasal; laryngeal) tumors based on anatomical site. For the 73 GRC members identified with HNC, proportional hazard regression assessed the relationship between WTC exposure and other socio-demographic characteristics. An overall excess of HNC was not observed (SIR = 1.00, 95% CI: 0.78, 1.25) but excess cancer was seen in the latest observation period (2009-2012: SIR = 1.4; 95% CI: 1.01, 1.89). A similar temporal pattern was seen for HPV-related oropharyngeal cancer and laryngeal cancer, but not for non-HPV-related sites (oral-nasal cancer). HNC was significantly associated with increasing age (8% per year, 95% CI: 5%, 12%), non-Hispanic white ethnic group-ethnicity (hazard ratio (HR) = 3.51, 95 CI: 1.49, 8.27); there was a borderline association with the 9/11 occupation of military/protective services vs. others (HR = 1.83 95% CI: 0.99, 3.38; p = 0.0504). Caution is needed in interpreting these results given the small number of cases, potential for surveillance bias, and long latency for most cancers. Our findings highlight the need to examine the potentially carcinogenic effects of WTC exposure in the context of other strong risk factors, and the need for continued medical monitoring of WTC responders.

Multiple Myeloma and Its Precursor Disease Among Firefighters Exposed to the World Trade Center Disaster.

Importance: The World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood. Objective: To characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS. Design, Setting, and Participants: Case series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781). Exposures: WTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002. Main Outcomes and Measures: Multiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS. Results: Sixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93). Conclusions and Relevance: Environmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

Development of a Physiological Frailty Index for the World Trade Center General Responder Cohort.

Responders to the 9/11/2001 WTC attacks were exposed to multiple toxic pollutants. Since 2002, the health of the responder cohort has been continuously tracked by the WTC Health Monitoring Program. However, no assessments have been made of frailty, an important health metric given the current average age of the WTC responder cohort (55 years). In this study, we use laboratory test results and other physiological parameters to construct a physiological frailty index (FI-Lab) for this cohort. The study sample comprised responders aged 40 years or older who completed a health monitoring visit at Mount Sinai Center within the past 5 years. For each subject, FI-Lab was computed as the proportion of 20 physiological parameters (lab tests, pulmonary function, and blood pressure) on which the subject had abnormal values. Using negative binomial regression models, we tested FI-Lab's association with the SF-12 wellbeing score and various demographic characteristics. FI-Lab showed strong associations with the physical and mental components of the SF-12 as well as age, race, and smoking status. Using a cutoff of 0.25 to define presence of physiological/preclinical frailty, we found frailty prevalence in the study sample to be approximately 12%. This study demonstrates the feasibility of assessing preclinical frailty in the WTC responder cohort.

Prostate cancer characteristics in the World Trade Center cohort, 2002-2013.

An increased incidence of prostate cancer was reported in three cohorts of World Trade Center (WTC) respondents. It is uncertain whether this increase is because of WTC-related exposures or enhanced surveillance. Prostate cancer cases (2002-2013) were obtained from the WTC Health Program. Age, race, and Gleason score distribution were compared with New York State Cancer Registry cases from the same time period. Multivariate models were adjusted for age and race. Analyses of clinical characteristics of prostate cancer cases within the cohort were also carried out, adjusting for age, race, and WTC exposure categories. WTC respondents had a prostate cancer age-standardized rate ratio of 1.65 [95% confidence interval (CI): 1.37-1.93] compared with New York State; age-specific ratios were highest for ages 30-49 (2.28; 95% CI: 1.51-3.43), 70-74 (2.05; 95% CI: 1.03-4.10), and 80-84 years (5.65; 95% CI: 1.41-22.58). High WTC exposure was associated with advanced clinical stage (5.58; 95% CI: 1.05-29.76; Ptrend=0.03). WTC respondents continue to have a higher prostate cancer rate compared with New York State as a whole. Respondents with a higher WTC exposure level may have had more advanced clinical stage of prostate cancer.

Mortality among World Trade Center rescue and recovery workers, 2002-2011.

BACKGROUND: Rescue and recovery workers responding to the 2001 collapse of the World Trade Center (WTC) sustained exposures to toxic chemicals and have elevated rates of multiple morbidities. METHODS: Using data from the World Trade Center Health Program and the National Death Index for 2002-2011, we examined standardized mortality ratios (SMR) and proportional cancer mortality ratios (PCMR) with indirect standardization for age, sex, race, and calendar year to the U.S. general population, as well as associations between WTC-related environmental exposures and all-cause mortality. RESULTS: We identified 330 deaths among 28,918 responders (SMR 0.43, 95%CI 0.39-0.48). No cause-specific SMRs were meaningfully elevated. PCMRs were elevated for neoplasms of lymphatic and hematopoietic tissue (PCMR 1.76, 95%CI 1.06-2.75). Mortality hazard ratios showed no linear trend with exposure. CONCLUSIONS: Consistent with a healthy worker effect, all-cause mortality among responders was not elevated. There was no clear association between intensity and duration of exposure and mortality. Surveillance is needed to monitor the proportionally higher cancer mortality attributed to lymphatic/hematopoietic neoplasms.

Posttraumatic stress symptoms and smoking among World Trade Center disaster responders: A longitudinal investigation.

PURPOSE: The current longitudinal study examined posttraumatic stress disorder (PTSD) symptom severity in relation to smoking abstinence and reduction over time among responders to the World Trade Center (WTC) disaster. METHOD: Participants were 763 police and 1881 non-traditional (e.g., construction workers) WTC responders who reported being smokers at an initial examination obtained between July 2002 and July 2011 at the WTC Health Program (WTC-HP). WTC responders were reassessed, on average, 2.5 years later. RESULTS: For police WTC responders, higher levels of WTC-related PTSD symptoms at the initial visit were associated with a decreased likelihood of smoking abstinence (OR=0.98, p=.002) and with decreased smoking reduction (ß=-.06, p=.012) at the follow-up visit. WTC-related PTSD symptom severity was not related to likelihood of smoking abstinence or change in number of cigarettes smoked among non-traditional responders. Post hoc analyses suggested that for police, hyperarousal PTSD symptoms were predictive of decreased abstinence likelihood at the follow-up visit (OR=0.56, p=.006). DISCUSSION: The present findings suggest that PTSD symptoms may be differentially related to smoking behavior among police and non-traditional WTC responders in a naturalistic, longitudinal investigation. Future work may benefit from exploring further which aspects of PTSD (as compared to each other and to common variance) explain smoking maintenance.

Discordance in thyroglobulin measurements by radioimmunoassay and immunometric assay: a useful means of identifying thyroglobulin assay interference.

BACKGROUND: Serum thyroglobulin (Tg) is useful for monitoring patients with differentiated thyroid cancer (DTC) but is limited by interference from anti-Tg antibodies (TgAb). We determined Tg assay discordance between a radioimmunoassay (RIA) and one of two immunometric assays (IMA) in DTC patients over a 9-year period to gauge assay performance against evidence of recurrent/progressive DTC. METHODS: Patients with DTC monitored for >1 year attending local clinics between September 2000 and January 2010 were included. All samples were analysed for Tg using both RIA and IMA. TgAb were measured on all Tg requests made after May 2006. Bias plots comparing RIA against IMA were established to calculate a 2-SD outlier limit. Clinical records were viewed to compare discordant Tg results against clinical evidence of recurrent/progressive DTC. RESULTS: Discordant Tg results were observed in 53/433 patients (12.2%). Four were discordant owing to a higher IMA result, one of which demonstrated recurrence. The remaining 49 patients demonstrated a disproportionately higher RIA result, of which four had recurrent/persistent disease. Twelve patients with a higher RIA result but no evidence of recurrence underwent thyrogen stimulation testing, which was negative in all 12. In many cases, assay discordance appeared more sensitive at indicating interference than direct measurement of TgAb. CONCLUSIONS: Interference was evident with both Tg assays, such that neither could be solely relied upon to provide the correct result in the presence of TgAb. The concomitant measurement of Tg by RIA and IMA methods should be considered as an alternative to monitoring TgAb status.

Cancer incidence in world trade center rescue and recovery workers, 2001-2008.

BACKGROUND: World Trade Center (WTC) rescue and recovery workers were exposed to a complex mix of pollutants and carcinogens. OBJECTIVE: The purpose of this investigation was to evaluate cancer incidence in responders during the first 7 years after 11 September 2001. METHODS: Cancers among 20,984 consented participants in the WTC Health Program were identified through linkage to state tumor registries in New York, New Jersey, Connecticut, and Pennsylvania. Standardized incidence ratios (SIRs) were calculated to compare cancers diagnosed in responders to predicted numbers for the general population. Multivariate regression models were used to estimate associations with degree of exposure. RESULTS: A total of 575 cancers were diagnosed in 552 individuals. Increases above registry-based expectations were noted for all cancer sites combined (SIR = 1.15; 95% CI: 1.06, 1.25), thyroid cancer (SIR = 2.39; 95% CI: 1.70, 3.27), prostate cancer (SIR = 1.21; 95% CI: 1.01, 1.44), combined hematopoietic and lymphoid cancers (SIR = 1.36; 95% CI: 1.07, 1.71), and soft tissue cancers (SIR = 2.26; 95% CI: 1.13, 4.05). When restricted to 302 cancers diagnosed ≥ 6 months after enrollment, the SIR for all cancers decreased to 1.06 (95% CI: 0.94, 1.18), but thyroid and prostate cancer diagnoses remained greater than expected. All cancers combined were increased in very highly exposed responders and among those exposed to significant amounts of dust, compared with responders who reported lower levels of exposure. CONCLUSION: Estimates should be interpreted with caution given the short follow-up and long latency period for most cancers, the intensive medical surveillance of this cohort, and the small numbers of cancers at specific sites. However, our findings highlight the need for continued follow-up and surveillance of WTC responders.

Prevalence and predictors of posttraumatic stress symptoms in utility workers deployed to the World Trade Center following the attacks of September 11, 2001.

BACKGROUND: Recent attention has begun to be focused on the effects of disaster recovery work on nonrescue workers. The goal of this study was to assess the prevalence and predictors of posttraumatic stress disorder (PTSD) and related symptoms in a population of utility workers deployed to the World Trade Center (WTC) site in the aftermath of 9/11. METHODS: Utility workers deployed to the WTC site were screened at their place of employment between 10 and 34 months following the WTC attacks, utilizing both structured interviews and self-report measures. PTSD symptoms were assessed by the CAPS and the PCL; co-morbid disorders were also assessed. 2,960 individuals with complete CAPS and PCL data were included in the analyses. RESULTS: Eight percent of participants had symptoms consistent with full PTSD, 9.3% with subthreshold PTSD, 6% with MDD, 3.5% with GAD, and 2.5% with panic disorder. Although risk factors included psychiatric and trauma history, 51% of individuals with probable PTSD had neither; subjective perception of threat to one's life was the best predictor of probable PTSD. Extent of exposure predicted 89% of PTSD cases in those without a psychiatric or trauma history, but only 67% of cases among those with both. CONCLUSIONS: Nonrescue workers deployed to a disaster site are at risk for PTSD and depression. Extent of exposure affected the most vulnerable workers differently than the least vulnerable ones. These results suggest that the relationship among predictors of PTSD may be different for different vulnerability groups, and underscore the importance of screening, education, and prevention programs for disaster workers.

Reliability of the proposed international classification of high-resolution computed tomography for occupational and environmental respiratory diseases.

PURPOSE: We have developed a classification of high-resolution computed tomography (HRCT) images for screening, surveillance and epidemiological studies of respiratory diseases caused by occupational and environmental factors. The proposed classification consists of three parts: a guideline explaining the elements of the classification scheme, a reading sheet, and reference films to aid in assessing thin-section CT films. We assessed the reliability of the proposed classification system by blinded, independent trial reading. MATERIALS AND METHODS: Seven independent radiologists and pulmonologists performed a trial reading to measure the reliability of the classification system using HRCT films from 27 pneumoconiosis patients and 7 normal controls. RESULTS: The agreement was moderate to good for rounded opacities (weighted kappa=0.68 and 0.64), irregular opacities (0.59, 0.48), honeycombing (0.65, 0.47), emphysema (0.76, 0.62) and large opacities (0.48, 0.52). Ground glass opacities (0.16, 0.20) showed poor to fair agreement. Intra-reader agreement of each of the seven readers was moderate to good (mean: weighted kappa=0.52-0.80) for parenchymal findings, but the agreement was relatively low (mean weighted kappa=0.52) for ground glass opacities. CONCLUSION: The proposed classification is able to describe early dust-related fibrotic changes and provide a semi-quantitative description of the HRCT features of major fibrotic changes in the parenchyma and pleura. Reliability, as measured by inter-reader agreement, was satisfactory.