Autoimmune conditions in the World Trade Center general responder cohort: A nested case-control and standardized incidence ratio analysis.

BACKGROUND: The World Trade Center (WTC) general responder cohort (GRC) was exposed to environmental toxins possibly associated with increased risk of developing autoimmune conditions. OBJECTIVES: Two study designs were used to assess incidence and risks of autoimmune conditions in the GRC. METHODS: Three clinically trained professionals established the status of possible GRC cases of autoimmune disorders adhering to diagnostic criteria, supplemented, as needed, by specialists' review of consenting responders' medical records. Nested case-control analyses using conditional logistic regression estimated the risk associated with high WTC exposure (being in the 9/11/2001 dust cloud or ≥median days' response worked) compared with low WTC exposure (all other GRC members'). Four controls were matched to each case on age at case diagnosis (±2 years), sex, race/ethnicity, and year of program enrollment. Sex-specific and sensitivity analyses were performed. GRC age- and sex-adjusted standardized incidence ratios (SIRs) were compared with the Rochester Epidemiology Project (REP). Complete REP inpatient and outpatient medical records were reviewed by specialists. Conditions meeting standardized criteria on ≥2 visits were classified as REP confirmed cases. RESULTS: Six hundred and twenty-eight responders were diagnosed with autoimmune conditions between 2002 and 2017. In the nested case-control analyses, high WTC exposure was not associated with autoimmune domains and conditions (rheumatologic domain odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.77, 1.37; rheumatoid arthritis OR = 1.12, 95% CI = 0.70, 1.77). GRC members had lower SIR than REP. Women's risks were generally greater than men's. CONCLUSIONS: The study found no statistically significant increased risk of autoimmune conditions with WTC exposures.

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.

Cardiovascular disease in the World Trade Center Health Program General Responder Cohort.

BACKGROUND: Over 90,000 rescue and recovery responders to the September 2001 World Trade Center (WTC) attacks were exposed to toxic materials that can impair cardiac function and increase cardiovascular disease (CVD) risk. We examined WTC-related exposures association with annual and cumulative CVD incidence and risk over 17 years in the WTC Health Program (HP) General Responder Cohort (GRC). METHODS: Post 9/11 first occurrence of CVD was assessed in 37,725 responders from self-reported physician diagnosis of, or current treatment for, coronary artery disease, myocardial infarction, stroke and/or congestive heart failure from WTCHP GRC monitoring visits. Kaplan-Meier estimates of CVD incidence used the generalized Wilcoxon test statistic to account for censored data. Cox proportional hazards regression analyses estimated the CVD hazard ratio associated with 9/11/2001 arrival in responders with and without dust cloud exposure, compared with arrival on or after 9/12/2001. Additional analyses adjusted for comorbidities. RESULTS: To date, 6.3% reported new CVD. In covariate-adjusted analyses, men's CVD 9/11/2001 arrival risks were 1.40 (95% confidence interval [CI] = 1.26, 1.56) and 1.43 (95% CI = 1.29, 1.58) and women's were 2.16 (95% CI = 1.49, 3.11) and 1.59 (95% CI = 1.11, 2.27) with and without dust cloud exposure, respectively. Protective service employment on 9/11 had higher CVD risk. CONCLUSIONS: WTCHP GRC members with 9/11/2001 exposures had substantially higher CVD risk than those initiating work afterward, consistent with observations among WTC-exposed New York City firefighters. Women's risk was greater than that of men's. GRC-elevated CVD risk may also be occurring at a younger age than in the general population.

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.

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.

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.

Assessment of cumulative health risk in the World Trade Center general responder cohort.

BACKGROUND: Multiple comorbidities have been reported among rescue/recovery workers responding to the 9/11/2001 WTC disaster. In this study, we developed an index that quantifies the cumulative physiological burden of comorbidities and predicts life expectancy in this cohort. METHODS: A machine learning approach (gradient boosting) was used to model the relationship between mortality and several clinical parameters (laboratory test results, blood pressure, pulmonary function measures). This model was used to construct a risk index, which was validated by assessing its association with a number of health outcomes within the WTC general responder cohort. RESULTS: The risk index showed significant associations with mortality, self-assessed physical health, and onset of multiple chronic conditions, particularly COPD, hypertension, asthma, and sleep apnea. CONCLUSION: As an aggregate of several clinical parameters, this index serves as a cumulative measure of physiological dysregulation and could be utilized as a prognostic indicator of life expectancy and morbidity risk.

Sex differences in asthma and gastroesophageal reflux disease incidence among the World Trade Center Health Program General Responder Cohort.

BACKGROUND: Asthma and gastroesophageal reflux disease (GERD) are two common conditions among the responders to the WTC attacks. This study examined whether the cumulative incidence rates of asthma and GERD differed by sex among 24,022 and 23,557 WTC responders, respectively. METHODS: Cox proportional hazards regression was used to examine the sex difference in the rate of onset of physician-diagnosed asthma or GERD, from 9/12/2001 through 12/31/2015. RESULTS: The cumulative incidence of asthma reached 23% for women and 17% for men by the end of 2015, and the cumulative incidence of GERD reached 45% for women and 38% for men. Comparing women to men, the hazard ratio was 1.48 (95% confidence interval (CI): 1.27, 1.74) for asthma, and 1.25 (95% CI: 1.13, 1.38) for GERD. CONCLUSIONS: WTC general responders have a substantial burden of asthma and GERD, with higher incidence in women. Am. J. Ind. Med. 59:815-822, 2016. © 2016 Wiley Periodicals, Inc.

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.

The response to September 11: a disaster case study.

BACKGROUND: The response to 9/11 continues into its 14th year. The World Trade Center Health Program (WTCHP), a long-term monitoring and treatment program now funded by the Zadroga Act of 2010, includes >60,000 World Trade Center (WTC) disaster responders and community members ("survivors"). The aim of this review is to identify several elements that have had a critical impact on the evolution of the WTC response and, directly or indirectly, the health of the WTC-exposed population. It further explores post-disaster monitoring efforts, recent scientific findings from the WTCHP, and some implications of this experience for ongoing and future environmental disaster response. FINDINGS: Transparency and responsiveness, site safety and worker training, assessment of acute and chronic exposure, and development of clinical expertise are interconnected elements determining efficacy of disaster response. CONCLUSION: Even in a relatively well-resourced environment, challenges regarding allocation of appropriate attention to vulnerable populations and integration of treatment response to significant medical and mental health comorbidities remain areas of ongoing programmatic development.

Implications of the World Trade Center Health Program (WTCHP) for the public health response to the Great East Japan Earthquake.

The attacks on the World Trade Center (WTC) on September 11, 2001 resulted in a serious burden of physical and mental illness for the 50,000 rescue workers that responded to 9/11 as well as the 400,000 residents and workers in the surrounding areas of New York City. The Zadroga Act of 2010 established the WTC Health Program (WTCHP) to provide monitoring and treatment of WTC exposure-related conditions and health surveillance for the responder and survivor populations. Several reports have highlighted the applicability of insights gained from the WTCHP to the public health response to the Great East Japan Earthquake. Optimal exposure monitoring processes and attention to the welfare of vulnerable exposed sub-groups are critical aspects of the response to both incidents. The ongoing mental health care concerns of 9/11 patients accentuate the need for accessible and appropriately skilled mental health care in Fukushima. Active efforts to demonstrate transparency and to promote community involvement in the public health response will be highly important in establishing successful long-term monitoring and treatment programs for the exposed populations in Fukushima.

A randomized triple blind trial to assess the effect of an anthelmintic programme for working equids in Morocco.

BACKGROUND: Gastro-intestinal parasitism has been identified as a significant cause of disease in working equids in many countries. This randomized triple-blind trial was designed to assess the impact of an anthelmintic treatment programme (using oral ivermectin and fenbendazole) comparing treated and placebo control populations of working donkeys, mules and horses in field conditions in Morocco. In particular, we assessed animal body weight and condition score, together with a questionnaire-based owner evaluation of number of subjective animal health parameters. Faecal worm egg count was also measured. RESULTS: 239 animals completed the full study, 130 in the treatment group and 109 in the control group. Although the average animal weight increased during the study, this change was not significantly different between the two groups. Animals in the treatment group had a significantly lower strongyle worm egg count and increased in body condition score compared to animals in the control group at each examination during the study period. Owners of animals in the treatment group reported improvement in health and work ability and a beneficial effect on pruritus during the early period of the study. These differences in owner perception between treatment groups had disappeared in the latter stages of the study. CONCLUSION: This study demonstrated that a routine anthelmintic treatment programme of three treatments annually can have a significant effect on faecal worm egg count. There may be beneficial consequences for the animal health and productivity. Further research on other populations of working equids in different environments would facilitate the objective planning of effective parasite control strategies for specific situations and provide better understanding of the likely clinical benefits of such programmes.