Trends in and Risk Factors for Recurrent Clostridioides difficile Infection, New Haven County, Connecticut, USA, 2015-2020.

Recurrent Clostridioides difficile infection (RCDI) causes an increased burden on the healthcare system. We calculated RCDI incidence and identified factors associated with RCDI cases in New Haven County, Connecticut, USA, during 2015-2020 by using data from population-based laboratory surveillance. A subset of C. difficile cases had complete chart reviews conducted for RCDI and potentially associated variables. RCDI was defined as a positive C. difficile specimen occurring 2-8 weeks after incident C. difficile infection. We compared cases with and without RCDI by using multiple regression. RCDI occurred in 12.0% of 4,301 chart-reviewed C. difficile cases, showing a U-shaped time trend with a sharp increase in 2020, mostly because of an increase in hospital-onset cases. Malignancy (odds ratio 1.51 [95% CI 1.11-2.07]) and antecedent nitrofurantoin use (odds ratio 2.37 [95% CI 1.23-4.58]) were medical risk factors for RCDI. The 2020 increase may reflect the impact of the COVID-19 pandemic.

Drug use and severe outcomes among adults hospitalized with influenza, 2016-2019.

BACKGROUND: Influenza is a persistent public health problem associated with severe morbidity and mortality. Drug use is related to myriad health complications, but the relationship between drug use and severe influenza outcomes is not well understood. The study objective was to evaluate the relationship between drug use and severe influenza-associated outcomes. METHODS: Data were collected by the Influenza Hospitalization Surveillance Network (FluSurv-NET) from the 2016-2017 through 2018-2019 influenza seasons. Among persons hospitalized with influenza, descriptive statistics and logistic regression models were used to analyze differences in demographic characteristics, risk and behavioral factors, and severe outcomes (intensive care unit [ICU] admission, mechanical ventilation, or death) between people who use drugs (PWUD), defined as having documented drug use within the past year, and non-PWUD. RESULTS: Among 48,430 eligible hospitalized influenza cases, 2019 were PWUD and 46,411 were non-PWUD. PWUD were younger than non-PWUD and more likely to be male, non-Hispanic Black or Hispanic/Latino, smoke tobacco, abuse alcohol, and have chronic conditions including asthma, chronic liver disease, chronic lung disease, or immunosuppressive conditions. PWUD had greater odds of ICU admission and mechanical ventilation, but not death compared with non-PWUD; however, these findings were not statistically significant after adjustment. Opioid use specifically was associated with increased risk of ICU admission and mechanical ventilation. CONCLUSION: These results support targeted initiatives to prevent influenza in this population, including influenza vaccination, which remains one of the most important tools to prevent influenza infection and associated severe outcomes.

Mortality among rescue and recovery workers and community members exposed to the September 11, 2001 World Trade Center terrorist attacks, 2003-2014.

BACKGROUND: Multiple chronic health conditions have been associated with exposure to the September 11, 2001 World Trade Center (WTC) terrorist attacks (9/11). We assessed whether excess deaths occurred during 2003-2014 among persons directly exposed to 9/11, and examined associations of 9/11-related exposures with mortality risk. MATERIALS AND METHODS: Deaths occurring in 2003-2014 among members of the World Trade Center Health Registry, a cohort of rescue/recovery workers and lower Manhattan community members who were exposed to 9/11, were identified via linkage to the National Death Index. Participants' overall levels of 9/11-related exposure were categorized as high, intermediate, or low. We calculated standardized mortality ratios (SMR) using New York City reference rates from 2003 to 2012. Proportional hazards were used to assess associations of 9/11-related exposures with mortality, accounting for age, sex, race/ethnicity and other potential confounders. RESULTS: We identified 877 deaths among 29,280 rescue/recovery workers (3.0%) and 1694 deaths among 39,643 community members (4.3%) during 308,340 and 416,448 person-years of observation, respectively. The SMR for all causes of death was 0.69 [95% confidence interval (CI) 0.65-0.74] for rescue/recovery workers and 0.86 (95% CI 0.82-0.90) for community members. SMRs for diseases of the cardiovascular and respiratory systems were significantly lower than expected in both groups. SMRs for several other causes of death were significantly elevated, including suicide among rescue recovery workers (SMR 1.82, 95% CI 1.35-2.39), and brain malignancies (SMR 2.25, 95% CI 1.48-3.28) and non-Hodgkin's lymphoma (SMR 1.79, 95% CI 1.24-2.50) among community members. Compared to low exposure, both intermediate [adjusted hazard ratio (AHR) 1.36, 95% CI 1.10-1.67] and high (AHR 1.41, 95% CI 1.06-1.88) levels of 9/11-related exposure were significantly associated with all-cause mortality among rescue/recovery workers (p-value for trend 0.01). For community members, intermediate (AHR 1.13, 95% CI 1.01-1.27), but not high (AHR 1.14, 95% CI 0.94-1.39) exposure was significantly associated with all-cause mortality (p-value for trend 0.03). AHRs for associations of overall 9/11-related exposure with heart disease- and cancer-related mortality were similar in magnitude to those for all-cause mortality, but with 95% CIs crossing the null value. CONCLUSIONS: Overall mortality was not elevated. Among specific causes of death that were significantly elevated, suicide among rescue/recovery workers is a plausible long-term consequence of 9/11 exposure, and is potentially preventable. Elevated mortality due to other causes, including non-Hodgkin's lymphoma and brain cancer, and small but statistically significant associations of 9/11-related exposures with all-cause mortality hazard warrant additional surveillance.

Declines in Human Papillomavirus (HPV)-Associated High-Grade Cervical Lesions After Introduction of HPV Vaccines in Connecticut, United States, 2008-2015.

BACKGROUND: Trends in human papillomavirus (HPV)-associated cervical lesions can provide an indication of vaccine impact. Our purpose was to measure trends in cervical lesions during 2008-2015 and to consider possible explanations including vaccination coverage, changes in screening for cervical cancer, and risk behaviors for acquiring HPV. METHODS: Connecticut (CT) implemented mandatory reporting of cervical intraepithelial neoplasia grades 2/3 and adenocarcinoma in situ (cervical intraepithelial neoplasia grade 2 or higher [CIN2+]) in 2008. Trends by age and birth cohort were modeled using negative binomial regression and change-point methods. To evaluate possible explanations for changes, these trends were compared to changes in HPV vaccination coverage, cervical cancer screening, an antecedent event to detection of a high-grade lesion, and changes in sexual behaviors and Chlamydia trachomatis, an infection with similar epidemiology to and shared risk factors for HPV. RESULTS: A significant decline in CIN2+ was first evident among women aged 21 years in 2010, followed by successive declines in women aged 22-26 years during 2011-2012. During 2008-2015, the rates of CIN2+ declined by 30%-74% among women aged 21-26 years, with greater declines observed in the younger women. Birth cohorts between 1985 and 1994 all experienced significant declines during the surveillance period, ranging from 25% to 82%. Ecological comparisons revealed substantial increases in HPV vaccination during this time period, and more modest reductions in cervical cancer screening and sexual risk behaviors. CONCLUSIONS: The age and cohort patterns in our data suggest that declines in CIN2+ during 2008-2015 are more likely driven by HPV vaccination, introduced in 2006, than by changes in screening or risk behavior.

Ten-year cancer incidence in rescue/recovery workers and civilians exposed to the September 11, 2001 terrorist attacks on the World Trade Center.

BACKGROUND: Cancer incidence in exposed rescue/recovery workers (RRWs) and civilians (non-RRWs) was previously reported through 2008. METHODS: We studied occurrence of first primary cancer among World Trade Center Health Registry enrollees through 2011 using adjusted standardized incidence ratios (SIRs), and the WTC-exposure-cancer association, using Cox proportional hazards models. RESULTS: All-cancer SIR was 1.11 (95% confidence interval (CI) 1.03-1.20) in RRWs, and 1.08 (95% CI 1.02-1.15) in non-RRWs. Prostate cancer and skin melanoma were significantly elevated in both populations. Thyroid cancer was significantly elevated only in RRWs while breast cancer and non-Hodgkin's lymphoma were significantly elevated only in non-RRWs. There was a significant exposure dose-response for bladder cancer among RRWs, and for skin melanoma among non-RRWs. CONCLUSIONS: We observed excesses of total and specific cancers in both populations, although the strength of the evidence for causal relationships to WTC exposures is somewhat limited. Continued monitoring of this population is indicated. Am. J. Ind. Med. 59:709-721, 2016. © 2016 Wiley Periodicals, Inc.

Is population structure sufficient to generate area-level inequalities in influenza rates? An examination using agent-based models.

BACKGROUND: In New Haven County, CT (NHC), influenza hospitalization rates have been shown to increase with census tract poverty in multiple influenza seasons. Though multiple factors have been hypothesized to cause these inequalities, including population structure, differential vaccine uptake, and differential access to healthcare, the impact of each in generating observed inequalities remains unknown. We can design interventions targeting factors with the greatest explanatory power if we quantify the proportion of observed inequalities that hypothesized factors are able to generate. Here, we ask if population structure is sufficient to generate the observed area-level inequalities in NHC. To our knowledge, this is the first use of simulation models to examine the causes of differential poverty-related influenza rates. METHODS: Using agent-based models with a census-informed, realistic representation of household size, age-structure, population density in NHC census tracts, and contact rates in workplaces, schools, households, and neighborhoods, we measured poverty-related differential influenza attack rates over the course of an epidemic with a 23 % overall clinical attack rate. We examined the role of asthma prevalence rates as well as individual contact rates and infection susceptibility in generating observed area-level influenza inequalities. RESULTS: Simulated attack rates (AR) among adults increased with census tract poverty level (F = 30.5; P < 0.001) in an epidemic caused by a virus similar to A (H1N1) pdm09. We detected a steeper, earlier influenza rate increase in high-poverty census tracts-a finding that we corroborate with a temporal analysis of NHC surveillance data during the 2009 H1N1 pandemic. The ratio of the simulated adult AR in the highest- to lowest-poverty tracts was 33 % of the ratio observed in surveillance data. Increasing individual contact rates in the neighborhood did not increase simulated area-level inequalities. When we modified individual susceptibility such that it was inversely proportional to household income, inequalities in AR between high- and low-poverty census tracts were comparable to those observed in reality. DISCUSSION: To our knowledge, this is the first study to use simulations to probe the causes of observed inequalities in influenza disease patterns. Knowledge of the causes and their relative explanatory power will allow us to design interventions that have the greatest impact on reducing inequalities. CONCLUSION: Differential exposure due to population structure in our realistic simulation model explains a third of the observed inequality. Differential susceptibility to disease due to prevailing chronic conditions, vaccine uptake, and smoking should be considered in future models in order to quantify the role of additional factors in generating influenza inequalities.

Monitoring Effect of Human Papillomavirus Vaccines in US Population, Emerging Infections Program, 2008-2012.

In 2007, five Emerging Infections Program (EIP) sites were funded to determine the feasibility of establishing a population-based surveillance system for monitoring the effect of human papillomavirus (HPV) vaccine on pre-invasive cervical lesions. The project involved active population-based surveillance of cervical intraepithelial neoplasia grades 2 and 3 and adenocarcinoma in situ as well as associated HPV types in women >18 years of age residing in defined catchment areas; collecting relevant clinical information and detailed HPV vaccination histories for women 18-39 years of age; and estimating the annual rate of cervical cancer screening among the catchment area population. The first few years of the project provided key information, including data on HPV type distribution, before expected effect of vaccine introduction. The project's success exemplifies the flexibility of EIP's network to expand core activities to include emerging surveillance needs beyond acute infectious diseases. Project results contribute key information regarding the impact of HPV vaccination in the United States.

The prevalence of HPV associated cervical intraepithelial neoplasia in women under age 21: who will be missed under the new cervical cancer screening guidelines?

STUDY OBJECTIVE: To quantify the number of adolescent females < age 21 years with pre-cancerous cervical lesions (cervical intraepithelial neoplasia grade 2 or higher (CIN 2+) or adenocarcinoma in situ (AIS)) in Connecticut in the time period before new cervical screening recommendations went into effect and identify any demographic associations with a diagnosis of CIN 3. DESIGN: Descriptive analysis, surveillance. SETTING: CIN 2+/AIS precancerous cervical lesions have been reportable conditions in Connecticut since 2008 for the purpose of public health surveillance. PARTICIPANTS: All women < 21 years old with pre-cancerous cervical lesions diagnosed between 2008 and 2010 (N = 681). RESULTS: Of the 681 reports, 478 (70.2%) women had CIN 2, 92 had CIN 2/3 (13.5%), and 110 (16.2%) had CIN 3. CIN 3 occurred at an average rate statewide of 19/100,000 per year for women ages 13-20. The majority of adolescents with pre-cancerous cervical lesions CIN 2+/AIS (70%) were 19 and 20 years of age. CIN 3 vs CIN 2 is not found to be associated with age, insurance status, specimen collection year, or living in a non-urban vs urban county. CONCLUSION: The majority of cases of pre-cancerous cervical lesions in adolescents diagnosed before new screening recommendations were in effect are CIN 2 and therefore, likely to regress. CIN 3 has been infrequently found in adolescent females under age 19 years; however, under the new screening guidelines, 110 cases of CIN 3 including 77 in women 19-20 years could have been missed in the adolescent female in Connecticut from 2008-2010 (54.4 per 100,000 per year for 19-20 year olds). Based upon these findings, it is necessary that clinicians educate adolescents and parents about the new screening guidelines and the importance of establishing regular cervical cancer screening beginning at age 21.

Individual and geographic disparities in human papillomavirus types 16/18 in high-grade cervical lesions: Associations with race, ethnicity, and poverty.

BACKGROUND: Current vaccines protect against 2 human papillomavirus (HPV) types, HPV 16 and 18, which are associated with 70% of cervical cancers and 50% of high-grade cervical lesions. HPV type distribution was examined among women with high-grade lesions by individual and area-based measures of race, ethnicity, and poverty. METHODS: This analysis included 832 women aged 18 to 39 years reported to a surveillance registry in Connecticut during 2008 to 2010. Diagnostic specimens were obtained for HPV DNA testing. Individual measures were obtained from surveillance reports, medical records, and patient interviews. Cases were geocoded to census tracts and linked to area-based measures of race, ethnicity, and poverty. Statistical analysis included use of generalized estimating equations. RESULTS: Overall, 44.8% of women had HPV 16/18. In a multivariate model controlled for confounding by age and diagnosis grade, black race (adjusted prevalence ratio [aPR] = 0.54, 95% confidence interval [CI] = 0.34-0.88), Hispanic ethnicity (aPR = 0.59, 95% CI = 0.40-0.88), and higher area-based poverty (aPR = 0.59, 95% CI = 0.40-0.87) were associated with a lower likelihood of HPV 16/18 positivity. Black and Hispanic women were less likely to have HPV 16/18 than white women across all levels of area-based measures. CONCLUSIONS: Black race, Hispanic ethnicity, and higher area-based poverty are salient predictors of lower HPV 16/18 positivity among women with high-grade cervical lesions. These data suggest that HPV vaccines might have lower impact among black and Hispanic women and those living in high poverty areas. These findings have implications for vaccine impact monitoring, vaccination programs, and new vaccine development.

Declining rates of high-grade cervical lesions in young women in Connecticut, 2008-2011.

Vaccines that prevent infection with human papillomavirus (HPV) types 16 and 18 that are known to cause cervical cancer have been available in the United States since 2006. High-grade cervical lesions are important for monitoring early vaccine impact because they are strong surrogates for cancer yet can develop within years after infection as opposed to decades. Trends in high-grade cervical lesions including cervical intraepithelial neoplasia grades 2, 2/3, and 3 and adenocarcinoma in situ among women ages 21 to 39 years old were examined using a statewide surveillance registry in Connecticut from 2008 to 2011. During this time period, HPV vaccine initiation increased among adolescent females from 45% to 61%. Analyses were stratified by age, according to census tract measures of proportion of population Black, Hispanic, living in poverty, and by urban/nonurban counties. The annual rate per 100,000 females ages 21 to 24 years declined from 834 in 2008 to 688 in 2011 (P(trend) < 0.001). No significant declines were observed among women ages 25 to 39 years. Significant declining trends also occurred in census tracts with lower proportions of the population being Black, Hispanic, or living below the federal poverty level. Declines in high-grade cervical lesions have occurred among young women during 2008 to 2011. This is the first report of declines in cervical neoplasia in the United States since HPV vaccines became available. Continued surveillance is needed to measure vaccine impact and monitor health disparities.

Geographic poverty and racial/ethnic disparities in cervical cancer precursor rates in Connecticut, 2008-2009.

OBJECTIVES: We examined associations of geographic measures of poverty, race, ethnicity, and city status with rates of cervical intraepithelial neoplasia grade 2 or higher and adenocarcinoma in situ (CIN2+/AIS), known precursors to cervical cancer. METHODS: We identified 3937 cases of CIN2+/AIS among women aged 20 to 39 years in statewide surveillance data from Connecticut for 2008 to 2009. We geocoded cases to census tracts and used census data to calculate overall and age-specific rates. Poisson regression determined whether rates differed by geographic measures. RESULTS: The average annual rate of CIN2+/AIS was 417.6 per 100,000 women. Overall, higher rates of CIN2+/AIS were associated with higher levels of poverty and higher proportions of Black residents. Poverty was the strongest and most consistently associated measure. However, among women aged 20 to 24 years, we observed inverse associations between poverty and CIN2+/AIS rates. CONCLUSIONS: Disparities in cervical cancer precursors exist for poverty and race, but these effects are age dependent. This information is necessary to monitor human papillomavirus vaccine impact and target vaccination strategies.

Human papillomavirus vaccination history among women with precancerous cervical lesions: disparities and barriers.

OBJECTIVE: To estimate racial, ethnic, and socioeconomic differences in human papillomavirus (HPV) vaccination history among women aged 18-27 years with precancerous cervical lesions diagnosed, barriers to vaccination, and timing of vaccination in relation to the abnormal cytology result that preceded the diagnosis of the cervical lesion. METHODS: High-grade cervical lesions are reportable conditions in Connecticut for public health surveillance. Telephone interviews and medical record reviews were conducted during 2008-2010 for women (n=269) identified through the surveillance registry. RESULTS: Overall, 43% of women reported history of one or more doses of HPV vaccine. The mean age at vaccination was 22 years. Publicly insured (77%) and uninsured (85%) women were more likely than privately insured women (48%) to report no history of vaccination (P<.05). Among unvaccinated women, being unaware of HPV vaccine was reported significantly more often among Hispanics than non-Hispanics (31% compared with 13%, P=.02) and among those with public or no insurance compared with those with private insurance (26% and 36% compared with 6%, P<.05 for both). The most commonly reported barrier was lack of provider recommendation (25%). Not having talked to a provider about vaccine was reported significantly more often among those with public compared with private insurance (41% compared with 18%, P<.001). Approximately 35% of women received vaccine after an abnormal cytology result; this occurred more frequently among African American women compared with white women (80% compared with 30%, P<.01). CONCLUSION: Catch-up vaccination strategies should focus on provider efforts to increase timely coverage among low-income and minority women.

Association between World Trade Center exposure and excess cancer risk.

CONTEXT: The terrorist attacks of September 11, 2001, resulted in the release of known and suspected carcinogens into the environment. There is public concern that exposures may have resulted in increased cancers. OBJECTIVE: To evaluate cancer incidence among persons enrolled in the World Trade Center Health Registry. DESIGN, SETTING, AND PARTICIPANTS: Observational study of 55,778 New York State residents enrolled in the World Trade Center Health Registry in 2003-2004, including rescue/recovery workers (n = 21,850) and those not involved in rescue/recovery (n = 33,928), who were followed up from enrollment through December 31, 2008. Within-cohort comparisons using Cox proportional hazards models assessed the relationship between intensity of World Trade Center exposure and selected cancers. MAIN OUTCOME MEASURES: Cases were identified through linkage with 11 state cancer registries. Standardized incidence ratios (SIRs) adjusted for age, race/ethnicity, and sex were computed with 2003-2008 New York State rates as the reference, focusing on cancers diagnosed in 2007-2008 as being most likely to be related to exposure during September 11 and its aftermath. The total and site-specific incidence rate differences (RDs) per 100,000 person-years between the study population and the New York State population in 2007-2008 also were calculated. RESULTS: There were 1187 incident cancers diagnosed, with an accumulated 253,269 person-years (439 cancers among rescue/recovery workers and 748 among those not involved in rescue/recovery). The SIR for all cancer sites combined in 2007-2008 was not significantly elevated (SIR, 1.14 [95% CI, 0.99 to 1.30]; RD, 67 [95% CI, -6 to 126] per 100,000 person-years among rescue/recovery workers vs SIR, 0.92 [95% CI, 0.83 to 1.03]; RD, -45 [95% CI, -106 to 15] per 100,000 person-years among those not involved in rescue/recovery). Among rescue/recovery workers, the SIRs had significantly increased by 2007-2008 for 3 cancer sites and were 1.43 (95% CI, 1.11 to 1.82) for prostate cancer (n = 67; RD, 61 [95% CI, 20 to 91] per 100,000 person-years), 2.02 (95% CI, 1.07 to 3.45) for thyroid cancer (n = 13; RD, 16 [95% CI, 2 to 23] per 100,000 person-years), and 2.85 (95% CI, 1.15 to 5.88) for multiple myeloma (n = 7; RD, 11 [95% CI, 2 to 14] per 100,000 person-years). No increased incidence was observed in 2007-2008 among those not involved in rescue/recovery. Using within-cohort comparisons, the intensity of World Trade Center exposure was not significantly associated with cancer of the lung, prostate, thyroid, non-Hodgkin lymphoma, or hematological cancer in either group. CONCLUSIONS: Among persons enrolled in the World Trade Center Health Registry, there was an excess risk for prostate cancer, thyroid cancer, and myeloma in 2007-2008 compared with that for New York State residents; however, these findings were based on a small number of events and multiple comparisons. No significant associations were observed with intensity of World Trade Center exposures. Longer follow-up for typically long-latency cancers and attention to specific cancer sites are needed.

Racial/Ethnic and poverty disparities in human papillomavirus vaccination completion.

BACKGROUND: Two vaccines against human papillomavirus (HPV), a necessary cause of cervical cancer, are currently licensed and recommended for routine administration in the U.S. to girls in a three-dose series. PURPOSE: This study examined effects of race/ethnicity, poverty, and year on completion of the three-dose HPV vaccine series among those who initiated vaccination. METHODS: Data from the 2008-2009 National Immunization Survey-Teen for girls aged 13-17 years who received at least one dose of HPV vaccine (n=7606) were analyzed in 2010-2011 using logistic regression to adjust for covariates including measures of access to care. RESULTS: During this 2-year period, 55% of adolescent girls who initiated vaccination completed the three-dose series. Completion was significantly higher in 2009 (60%) compared to 2008 (48%; p<0.001). After controlling for covariates, adolescents who were black (AOR=0.48, 95% CI=0.40, 0.57) or Hispanic (AOR=0.75, 95% CI=0.64, 0.88) were significantly less likely to complete vaccination than whites. Adolescents living below the federal poverty level were significantly less likely to complete vaccination than adolescents with household incomes >$75,000 (AOR=0.76, 95% CI=0.63, 0.92). There was no significant interaction between race/ethnicity and year (p=0.92). Although poverty was associated with lower completion rates in 2008, this association was not observed in 2009 (p<0.05 for poverty-year interaction). CONCLUSIONS: HPV vaccination completion rates increased between 2008 and 2009. However, significant differences by race/ethnicity and poverty were observed, and the racial/ethnic differences persisted.

Mortality among survivors of the Sept 11, 2001, World Trade Center disaster: results from the World Trade Center Health Registry cohort.

BACKGROUND: The Sept 11, 2001 (9/11) World Trade Center (WTC) disaster has been associated with several subacute and chronic health effects, but whether excess mortality after 9/11 has occurred is unknown. We tested whether excess mortality has occurred in people exposed to the WTC disaster. METHODS: In this observational cohort study, deaths occurring in 2003-09 in WTC Health Registry participants residing in New York City were identified through linkage to New York City vital records and the National Death Index. Eligible participants were rescue and recovery workers and volunteers; lower Manhattan area residents, workers, school staff and students; and commuters and passers-by on 9/11. Study participants were categorised as rescue and recovery workers (including volunteers), or non-rescue and non-recovery participants. Standardised mortality ratios (SMR) were calculated with New York City rates from 2000-09 as the reference. Within the cohort, proportional hazards were used to examine the relation between a three-tiered WTC-related exposure level (high, intermediate, or low) and total mortality. FINDINGS: We identified 156 deaths in 13,337 rescue and recovery workers and 634 deaths in 28,593 non-rescue and non-recovery participants. All-cause SMRs were significantly lower than that expected for rescue and recovery participants (SMR 0·45, 95% CI 0·38-0·53) and non-rescue and non-recovery participants (0·61, 0·56-0·66). No significantly increased SMRs for diseases of the respiratory system or heart, or for haematological malignancies were found. In non-rescue and non-recovery participants, both intermediate and high levels of WTC-related exposure were significantly associated with mortality when compared with low exposure (adjusted hazard ratio 1·22, 95% CI 1·01-1·48, for intermediate exposure and 1·56, 1·15-2·12, for high exposure). High levels of exposure in non-rescue and non-recovery individuals, when compared with low exposed non-rescue and non-recovery individuals, were associated with heart-disease-related mortality (adjusted hazard ratio 2·06, 1·10-3·86). In rescue and recovery participants, level of WTC-related exposure was not significantly associated with all-cause mortality (adjusted hazard ratio 1·25, 95% CI 0·56-2·78, for high exposure and 1·03, 0·52-2·06, for intermediate exposure when compared with low exposure). INTERPRETATION: This exploratory study of mortality in a well defined cohort of 9/11 survivors provides a baseline for continued surveillance. Additional follow-up is needed to establish whether these associations persist and whether a similar association over time will occur in rescue and recovery participants. FUNDING: US Centers for Disease Control and Prevention (National Institute for Occupational Safety and Health, Agency for Toxic Substances and Disease Registry, and National Center for Environmental Health); New York City Department of Health and Mental Hygiene.