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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.

Supplementary Table 2. Mutational signature profiles for 5 environmental agents detected in the WTC debris (Kucab et al, Cell 2019).

Supplementary Table 1. Baseline patient and disease characteristics with response details in male first responders and recovery workers followed at MSKCC.

Background World Trade Center (WTC) rescue and recovery workers have a high burden of asthma, comorbid posttraumatic stress disorder (PTSD), and major depressive disorder (MDD). PTSD is associated with worse asthma outcomes. Objective In this study, we evaluated whether the relationship between PTSD and asthma morbidity is modified by the presence of MDD. Methods We used data from a cohort of WTC workers with asthma. Asthma control (asthma control questionnaire), resource utilization, and quality of life (asthma quality of life questionnaire) were evaluated. We used regression analyses to evaluate the adjusted association of PTSD and MDD with asthma control, resource utilization, and quality of life. Results Of the study cohort of 293 WTC workers with asthma, 19% had PTSD alone, 2% had MDD alone, and 12% had PTSD and MDD. Adjusted mean differences (95% confidence interval) in asthma control questionnaire scores were 1.32 (0.85-1.80) for WTC workers with PTSD and MDD, 0.44 (0.03-0.84) for those with PTSD alone, and 0.50 (−0.38 to 1.38) for workers with MDD alone compared with those without MDD or PTSD. WTC workers with PTSD and MDD, PTSD alone, and MDD alone had mean (95% confidence interval) adjusted differences in asthma quality of life questionnaire scores of −1.67 (−2.22 to −1.12), −0.56 (−2.23 to −1.12), and −1.21 (−2.23 to −0.18), respectively, compared with workers without MDD or PTSD. Similar patterns were observed for acute resource utilization. Conclusion PTSD and MDD seem to have a synergistic effect that worsens asthma control and quality of life. Efforts to improve asthma outcomes in this population should address the negative impacts of these common mental health conditions.

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.

The recent advent of single-cell RNA-sequencing technology has provided new fundamental insights into the heterogeneity of the prostate epithelium. Several independent studies have described extensive heterogeneity of the luminal epithelial compartment, including a major division between a novel population of luminal cells located in the proximal region of the prostate ducts versus luminal cells located more distally. Proximal luminal cells as well as novel periurethral cells display increased progenitor potential in organoid culture and tissue reconstitution assays, but not in lineage-tracing analyses during prostate homeostasis, suggesting context-dependent plasticity of these populations. Here we describe and synthesize recent findings regarding the epithelial cell populations in the mouse prostate, draw comparisons to the human prostate, and address the relevance of these findings to prostate diseases and cancer.

Background Comorbid posttraumatic stress disorder (PTSD) is highly prevalent and associated with increased morbidity among World Trade Center (WTC) rescue and recovery workers with asthma. However, the potential behavioral pathways underlying this relationship remain unclear. Objective To evaluate whether PTSD is associated with lower adherence to asthma self-management behaviors among WTC workers with asthma. Methods We used data from a prospective cohort of WTC workers with a physician diagnosis of asthma who were prescribed controller medications. Presence of comorbid PTSD was determined based on structured clinical interviews. Asthma self-management behaviors included medication adherence, inhaler technique, use of action plans, and trigger avoidance. We conducted unadjusted and multiple regression analyses to evaluate the association of PTSD with asthma self-management. Results Overall, 30% of 276 WTC workers with asthma had comorbid PTSD. Posttraumatic stress disorder was associated with worse asthma control and poorer quality of life. However, PTSD was not significantly associated with medication adherence (odds ratio [OR] –0.15; 95% confidence interval [CI] –0.5 to 0.2), inhaler technique (OR –0.12; 95% CI –0.7 to 0.5), use of action plans (OR 0.8; 95% CI 0.4 to 1.8), or trigger avoidance (OR 0.9; 95% CI 0.4 to 1.8). Conclusions We did not find significant differences in key asthma self-management behaviors between WTC workers with and without PTSD. These results suggest that other mechanisms, such as differences in symptom perception or inflammatory pathways, may explain the association between PTSD and increased asthma morbidity.

SummaryUnderstanding the cellular constituents of the prostate is essential for identifying the cell of origin for benign prostatic hyperplasia and prostate adenocarcinoma. Here we describe a comprehensive single-cell atlas of the adult mouse prostate epithelium, which demonstrates extensive heterogeneity. We observe distinct lobe-specific luminal epithelial populations (LumA, LumD, LumL, and LumV) in the distal region of the four prostate lobes, a proximally-enriched luminal population (LumP) that is not lobe-specific, as well as a periurethral population (PrU) that shares both basal and luminal features. Functional analyses suggest that LumP and PrU cells have multipotent progenitor activity in organoid formation and tissue reconstitution assays. Furthermore, we show that mouse distal and proximal luminal cells are most similar to human acinar and ductal populations, that a PrU-like population is conserved between species, and that the mouse lateral prostate is most similar to the human peripheral zone. Our findings elucidate new prostate epithelial progenitors, and help resolve long-standing questions about the anatomical relationships between the mouse and human prostate.

Asthma is a major source of morbidity among World Trade Center (WTC) rescue and recovery workers. While physical and mental health comorbidities have been associated with poor asthma control, the potential role and determinants of adherence to self-management behaviors (SMB) among WTC rescue and recovery workers is unknown.To identify modifiable determinants of adherence to asthma self-management behaviors in WTC rescue and recovery worker that could be potential targets for future interventions.We enrolled a cohort of 381 WTC rescue and recovery workers with asthma. Sociodemographic data and asthma history were collected during in-person interviews. Based on the framework of the Model of Self-regulation, we measured beliefs about asthma and controller medications. Outcomes included medication adherence, inhaler technique, use of action plans, and trigger avoidance.Medication adherence, adequate inhaler technique, use of action plans, and trigger avoidance were reported by 44%, 78%, 83%, and 47% of participants, respectively. Adjusted analyses showed that WTC rescue and recovery workers who believe that they had asthma all the time (odds ratio [OR]: 2.37; 95% confidence interval [CI]: 1.38-4.08), that WTC-related asthma is more severe (OR: 1.73; 95% CI: 1.02-2.93), that medications are important (OR: 12.76; 95% CI: 5.51-29.53), and that present health depends on medications (OR: 2.39; 95% CI: 1.39-4.13) were more likely to be adherent to their asthma medications. Illness beliefs were also associated with higher adherence to other SMB.Low adherence to SMB likely contributes to uncontrolled asthma in WTC rescue and recovery workers. Specific modifiable beliefs about asthma chronicity, the importance of controller medications, and the severity of WTC-related asthma are independent predictors of SMB in this population. Cognitive behavioral interventions targeting these beliefs may improve asthma self-management and outcomes in WTC rescue and recovery workers. Key message: This study identified modifiable beliefs associated with low adherence to self-management behaviors among World Trade Center rescue and recovery rescue and recovery workers with asthma which could be the target for future interventions.Improving World Trade Center-related asthma outcomes will require multifactorial approaches such as supporting adherence to controller medications and other self-management behaviors. This study identified several modifiable beliefs that may be the target of future efforts to support self-management in this patient population.

PURPOSE : The World Trade Center (WTC) attack of September 11, 2001 created an unprecedented environmental exposure to known and suspected carcinogens. A higher incidence of multiple myeloma (MM) and precursor disease has been reported among first responders to the WTC disaster compared to the unexposed population (Landgren, 2018). To expand on 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 were diagnosed with a plasma cell disorder after the attack. PATIENTS AND METHODS: We performed WGS of 9 CD138-positive bone marrow mononuclear samples from patients who were diagnosed with plasma cell disorders after exposure to the WTC disaster: 4 monoclonal gammopathy of undetermined significance (MGUS), 2 smoldering multiple myeloma (SMM), 2 MMs, and 1 patient with plasma cell leukemia (PCL). Eight patients (88%) were first responders and one was a recovery worker. Peripheral blood mononuclear cells were used as normal match. Median coverage for tumor and normal samples was 50.9X (range 47-76) and 37X (range 35-41), respectively. The landscape of genomic drivers and complex structural events was compared to 752 MM patients enrolled in the CoMMpass trial with available whole exome and low-coverage long-insert WGS data (IA15; NCT01454297). To characterize the mutational signature landscape we combined the WTC cohort with 110 whole genomes from 56 patients with multiple myeloma and myeloma precursor disease (Rustad et al. 2020; Landau et al. 2020) and we ran our three-step workflow: de novo extraction (i.e. sigprofiler), assignment, and fitting (i.e. mmsig). To exclude contribution of any environmental agents in the WTC debris with known mutational signatures (Kucab et al., 2019), we ran our fitting algorithm mmsig in each post-WTC case, including and forcing the extraction of these mutational signatures. RESULTS: No significant differences were observed in comparing the post-WTC driver and mutational signatures landscape with 110 previously published WGS from 56 patients with MM and the CoMMpass WGS cohort (n=752). Likewise, we did not observe any new or distinct mutational signatures among WTC-exposed patients. Following forced extraction of 5 mutational signatures associated with environmental agents detected in the WTC debris (e.g. PAHs), we did not find significant contributions from any of these described environmental mutational signatures. To reconstruct the temporal activity of each mutational process we divided all single nucleotide variants into subclonal and clonal. Clonal mutations were further subdivided into duplicated (acquired before a chromosomal gain) and unduplicated (Rustad et al. 2020). WTC-exposed patients had differing patterns in mutational signature timelines of AID and APOBEC activity. Overall, the mutational signature activity over time in post-WTC plasma cell dyscrasia reflects what has been previously observed in multiple myeloma without WTC-exposure (Rustad et al., 2020). Finally, leveraging constant activity of the clock-like single base substitution mutational signatures 1 and 5 over time and our molecular time workflow (Rustad et al., 2020), we estimated the age at which each evaluable patient acquired a tumor-initiating chromosomal gain and found that they were windowed to both pre- and post-WTC exposure across neoplasms (Figure 1). In some cases, clonal multi-chromosomal gain events were acquired decades before both the diagnosis and the WTC exposure. Specifically, of 6 patients with large clonal chromosomal gains, 1 MM case, 1 SMM, and 1 MGUS showed evidence of a pre-existing clone prior to WTC exposure, two MGUS showed evidence of multi-gain events following the exposure, and one MM case had a 1q gain in the same time window as the attack. CONCLUSIONS: Post-WTC plasma cell neoplasms had similar genomic landscapes to non-exposed cases. 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. The existence of pre-malignant clonal entities at time of WTC exposure may therefore be relevant for future WTC-related study. Figure 1 Disclosures Hultcrantz: Intellisphere LLC: Consultancy; Amgen: Research Funding; Daiichi Sankyo: Research Funding; GSK: Research Funding. Shah:Physicians Education Resource: Honoraria; Celgene/BMS: Research Funding. Iacobuzio-Donahue:BMS: Research Funding. Papaemmanuil:Isabl: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Illumina: Consultancy, Honoraria; Kyowa Hakko Kirin: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Prime Oncology: Consultancy, Honoraria; MSKCC: Patents & Royalties. Verma:BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; stelexis: Current equity holder in private company; Janssen: Research Funding; Medpacto: Research Funding. Dogan:National Cancer Institute: Research Funding; EUSA Pharma: Consultancy; Takeda: Consultancy; Seattle Genetics: Consultancy; Corvus Pharmaceuticals: Consultancy; Physicians Education Resource: Consultancy; Roche: Consultancy, Research Funding; AbbVie: Consultancy. Landgren:Celgene: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Cellectis: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Pfizer: Consultancy, Honoraria; Merck: Other; Karyopharma: Research Funding; Binding Site: Consultancy, Honoraria; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Seattle Genetics: Research Funding; Takeda: Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Janssen: Consultancy, Honoraria, Other: Independent Data Monitoring Committees for clinical trials, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Juno: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Adaptive: Consultancy, Honoraria; Cellectis: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding; Binding Site: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Glenmark: Consultancy, Honoraria, Research Funding.

Background Cork University Hospital (CUH) is peripheral centre of paediatrics that provides a joint adult and paediatric emergency department service. Currently paediatric and emergency department staff use the 2009 BSPED Diabetic Keto-Acidosis (DKA) protocol. In light of upcoming new national DKA guidelines used by the Tertiary Paediatric centres, we aimed to see staff adherence to the current protocol in use. Objectives To evaluate paediatric & ED staff adherence to this protocol through documentation of management. Our secondary objectives included analysis of patient demographics, severity of DKA, complications and length of stay. Methods We retrospectively analysed all paediatric patients with T1DM presenting with DKA from January 2015 until July 2017. Patients were identified from Diabetes Nurse Specialist database. Data was recorded and comparison was made between initial treatment from emergency staff and subsequent review by paediatrics. Results The total number of patients on the DKA protocol during the time period was 53 and, following exclusion criteria, 37 (69%) charts were analysed. Notable exclusions were 6 patients (11%) commenced on protocol despite not meeting criteria for DKA diagnosis. The average age at presentation was 8.18 years, male to female ratio 2:3 and 81% (n=43) of presentations were new onset T1DM. A majority (56%) of presentations were of moderate severity. Within management from ED staff, 28% (n=10) had no protocol documentation. Only 8% (n=3) had the correct protocol documented and commenced. 31% (n=11) were seen by paediatric team directly. Paediatric staff incorrectly calculated protocol management plans in 65% (n=24) of cases. Despite 55% of presentations in severe acidosis meeting protocol requirement for ICU involvement they were not reviewed by the ICU team and ward managed. Conclusion Health care providers working in CUH adherence to BSPED 2009 guidelines protocol is poor. It is essential to implement the use of current DKA protocol in use for all DKA at presentation. Recognition of the definition is the starting point. We recommend thorough emergency & paediatric staff education and implementation of a mandatory proforma for DKA presentations.

A large number of World Trade Center (WTC) rescue and recovery workers are affected by asthma. While physical and mental health comorbidities have been associated with poor asthma control in this population, the potential role of allergen sensitization is unknown. This study examined the association of indoor sensitization and exposure as a risk factor for increased asthma morbidity in WTC workers. We used data from a prospective cohort of 331 WTC workers with asthma. Sensitization to indoor allergens was assessed by measurement of antigen-specific serum immunoglobulin E (IgE) levels. We used validated tools to evaluate the exposure to indoor allergens. Asthma morbidity outcomes included level of control (Asthma Control Questionnaire, ACQ), quality of life (Asthma Quality of Life Questionnaire, AQLQ) and acute resource utilization. The prevalence of sensitization to cat, dog, mouse, dust mite, cockroach, and mold allergens were 33%, 21%, 17%, 40%, 17%, and 17%, respectively. Unadjusted and regression analyses showed no significant relationship between sensitization and increased asthma morbidity (p &gt, 0.05 for all comparisons), except for sensitization to Aspergillus Fumigatus, cat and mouse epithelium, which were associated with decreased morbidity.

BackgroundProstate cancer is the second leading cause of cancer-related death in men in the USA; death occurs when patients progress to metastatic castration-resistant prostate cancer (CRPC). Although immunotherapy with the Food and Drug Administration‐approved vaccine sipuleucel‐T, which targets prostatic acid phosphatase (PAP), extends survival for 2–4 months, the identification of new immunogenic tumor-associated antigens (TAAs) continues to be an unmet need.MethodsWe evaluated the differential expression profile of castration-resistant prostate epithelial cells that give rise to CRPC from mice following an androgen deprivation/repletion cycle. The expression levels of a set of androgen-responsive genes were further evaluated in prostate, brain, colon, liver, lung, skin, kidney, and salivary gland from murine and human databases. The expression of a novel prostate-restricted TAA was then validated by immunostaining of mouse tissues and analyzed in primary tumors across all human cancer types in The Cancer Genome Atlas. Finally, the immunogenicity of this TAA was evaluated in vitro and in vivo using autologous coculture assays with cells from healthy donors as well as by measuring antigen-specific antibodies in sera from patients with prostate cancer (PCa) from a neoadjuvant clinical trial.ResultsWe identified a set of androgen-responsive genes that could serve as potential TAAs for PCa. In particular, we found transglutaminase 4 (Tgm4) to be highly expressed in prostate tumors that originate from luminal epithelial cells and only expressed at low levels in most extraprostatic tissues evaluated. Furthermore, elevated levels ofTGM4expression in primary PCa tumors correlated with unfavorable prognosis in patients. In vitro and in vivo assays confirmed the immunogenicity of TGM4. We found that activated proinflammatory effector memory CD8 and CD4 T cells were expanded by monocyte-derived dendritic cell (moDCs) pulsed with TGM4 to a greater extent than moDCs pulsed with either PAP or prostate-specific antigen (PSA), and T cells primed with TGM4-pulsed moDCs produce functional cytokines following a prime/boost regiment or in vitro stimulation. An IgG antibody response to TGM4 was detected in 30% of vaccinated patients, while fewer than 8% of vaccinated patients developed antibody responses to PSA or prostate-specific membrane antigen (PSMA).ConclusionsThese results suggest that TGM4 is an immunogenic, prostate-restricted antigen with the potential for further development as an immunotherapy target.

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.

The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis.To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. Design/Setting/Intervention: The index patient was evaluated at an academic medical center. Whole-exome sequencing was performed on the proband and his parents. Genetic variants were validated by Sanger sequencing.We identified a novel de novo nonsense mutation, c.3265 CT (p.R1089X), in the retinoic acid-induced 1 (RAI1) gene in the proband. Mutations in the RAI1 gene are known to cause Smith-Magenis syndrome (SMS). On further evaluation, his clinical features were not typical of either SMS or ROHHAD syndrome.This study identifies a de novo RAI1 mutation in a child with morbid obesity and a clinical diagnosis of ROHHAD syndrome. Although extreme early-onset obesity, autonomic disturbances, and hypoventilation are present in ROHHAD, several of the clinical findings are consistent with SMS. This case highlights the challenges in the diagnosis of ROHHAD syndrome and its potential overlap with SMS. We also propose RAI1 as a candidate gene for children with morbid obesity.

Aim To examine the perspectives of children's nurses about parental presence during resuscitation. Methods Semi-structured interviews were used to collect data from nine children's nurses, working in the same emergency department, followed by thematic analysis to identify common themes. Findings Nurses thought that parents had a negative effect on the ability of professionals caring for the child. However, they also recognised the negative effect parental absence can have on the grieving process. During resuscitation nurses struggle personally and professionally to decide whether parents should be present. Conclusion There is a lack of guidance available about how to manage parental presence at the resuscitation of the child. Experienced children's nurses were having to 'gauge it every time'.

OBJECTIVE: Using data from a cohort of World Trade Center (WTC) rescue and recovery workers with asthma, we assessed whether meeting criteria for post-traumatic stress disorder (PTSD), sub-threshold PTSD, and for specific PTSD symptom dimensions are associated with increased asthma morbidity. METHODS: Participants underwent a Structured Clinical Interview for Diagnostic and Statistical Manual to assess the presence of PTSD following DSM-IV criteria during in-person interviews between December 2013 and April 2015. We defined sub-threshold PTSD as meeting criteria for two of three symptom dimensions: re-experiencing, avoidance, or hyper-arousal. Asthma control, acute asthma-related healthcare utilization, and asthma-related quality of life data were collected using validated scales. Unadjusted and multiple regression analyses were performed to assess the relationship between sub-threshold PTSD and PTSD symptom domains with asthma morbidity measures. RESULTS: Of the 181 WTC workers with asthma recruited into the study, 28% had PTSD and 25% had sub-threshold PTSD. Patients with PTSD showed worse asthma control, higher rates of inpatient healthcare utilization, and poorer asthma quality of life than those with sub-threshold or no PTSD. After adjusting for potential confounders, among patients not meeting the criteria for full PTSD, those presenting symptoms of re-experiencing exhibited poorer quality of life (p = 0.003). Avoidance was associated with increased acute healthcare use (p = 0.05). Sub-threshold PTSD was not associated with asthma morbidity (p > 0.05 for all comparisons). CONCLUSIONS: There may be benefit in assessing asthma control in patients with sub-threshold PTSD symptoms as well as those with full PTSD to more effectively identify ongoing asthma symptoms and target management strategies.

Summary Background More than 50 000 people participated in the rescue and recovery work that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC). Multiple health problems in these workers were reported in the early years after the disaster. We report incidence and prevalence rates of physical and mental health disorders during the 9 years since the attacks, examine their associations with occupational exposures, and quantify physical and mental health comorbidities. Methods In this longitudinal study of a large cohort of WTC rescue and recovery workers, we gathered data from 27 449 participants in the WTC Screening, Monitoring, and Treatment Program. The study population included police officers, firefighters, construction workers, and municipal workers. We used the Kaplan-Meier procedure to estimate cumulative and annual incidence of physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease), mental health disorders (depression, post-traumatic stress disorder [PTSD], and panic disorder), and spirometric abnormalities. Incidence rates were assessed also by level of exposure (days worked at the WTC site and exposure to the dust cloud). Findings 9-year cumulative incidence of asthma was 27·6% (number at risk: 7027), sinusitis 42·3% (5870), and gastro-oesophageal reflux disease 39·3% (5650). In police officers, cumulative incidence of depression was 7·0% (number at risk: 3648), PTSD 9·3% (3761), and panic disorder 8·4% (3780). In other rescue and recovery workers, cumulative incidence of depression was 27·5% (number at risk: 4200), PTSD 31·9% (4342), and panic disorder 21·2% (4953). 9-year cumulative incidence for spirometric abnormalities was 41·8% (number at risk: 5769); three-quarters of these abnormalities were low forced vital capacity. Incidence of most disorders was highest in workers with greatest WTC exposure. Extensive comorbidity was reported within and between physical and mental health disorders. Interpretation 9 years after the 9/11 WTC attacks, rescue and recovery workers continue to have a substantial burden of physical and mental health problems. These findings emphasise the need for continued monitoring and treatment of the WTC rescue and recovery population. Funding Centers for Disease Control and Prevention and National Institute for Occupational Safety and Health.

Background Multiple studies have demonstrated an initial high prevalence of spirometric abnormalities following World Trade Center (WTC) disaster exposure. We assessed prevalence of spirometric abnormalities and changes in spirometry between baseline and first follow-up evaluation in participants in the WTC Worker and Volunteer Medical Monitoring Program. We also determined the predictors of spirometric change between the two examinations. Methods Prebronchodilator and postbronchodilator spirometry, demographics, occupational history, smoking status, and respiratory symptoms and exposure onset were obtained at both examinations (about 3 years apart). Results At the second examination, 24.1% of individuals had abnormal spirometry findings. The predominant defect was a low FVC without obstruction (16.1%). Between examinations, the majority of individuals did not have a greater-than-expected decline in lung function. The mean declines in prebronchodilator FEV 1 and FVC were 13 mL/yr and 2 mL/yr, respectively (postbronchodilator results were similar and not reported). Significant predictors of greater average decline between examinations were bronchodilator responsiveness at examination 1 and weight gain. Conclusions Elevated rates of spirometric abnormalities were present at both examinations, with reduced FVC most common. Although the majority had a normal decline in lung function, initial bronchodilator response and weight gain were significantly associated with greater-than-normal lung function declines. Due to the presence of spirometric abnormalities > 5 years after the disaster in many exposed individuals, longer-term monitoring of WTC responders is essential.

To examine the perspectives of children's nurses about parental presence during resuscitation.Semi-structured interviews were used to collect data from nine children's nurses, working in the same emergency department, followed by thematic analysis to identify common themes.Nurses thought that parents had a negative effect on the ability of professionals caring for the child. However, they also recognised the negative effect parental absence can have on the grieving process. During resuscitation nurses struggle personally and professionally to decide whether parents should be present.There is a lack of guidance available about how to manage parental presence at the resuscitation of the child. Experienced children's nurses were having to 'gauge it every time'.

Introduction: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder with a prevalence of 15 - 20% in the general population. OSA is related to numerous disorders and increases risk of cardiovascular disease (CVD) and CV events including myocardial infarction and cerebrovascular accidents. Behavioral modification is a quintessential component of treatment for OSA. Hypothesis: We sought to evaluate and quantify the impact of Law Enforcement Cardiac Screening (LECS) program on change in OSA risk. Methods: Patients seen in World Trade Center (WTC) LECS from 2008 - 2010 were reevaluated in WTC CHEST from 2012 - 2014. We analyzed 959 patients’ anthropometric measurements and CV risk factors against status of high risk for OSA (OSA+) defined as never met, only met criteria in LECS, only met criteria in CHEST and met criteria in both LECS and CHEST. OSA+ was defined as 2 or more positive categories on the Berlin Questionnaire (BQ). Independent t-test, ANOVA, and multivariate regression analyses were used to assess the impact of WTC LECS on OSA+ as it relates to body mass index (BMI), waist circumference, and high sensitivity CRP (hsCRP) Results: We found that those who only met high risk for OSA criteria in 2008 - 2010 (LECS only) had a significant decrease in BMI when reevaluated in 2012 - 2014 (CHEST) (41.5 kg/m2 vs. 38.4 kg/m2 respectively; p < 0.001). Patients only diagnosed in 2008 - 2010 had a significant decrease in hsCRP compared to those diagnosed in 2012 - 2014 (-1.44 vs -0.37 respectively, p = 0.040). Conclusions: Using the BQ as screening tool for OSA in a large population of asymptomatic middle aged participants allowed identification approximately 40% of the initial screening population to be at OSA+. Identifying these participants allowed us to counsel and advise patients of pertinent behavioral modifications known to improve risks for OSA. These efforts resulted in significant reduction in anthropometric measurements and improved CVD 10 year risk.

Background: The prevalence of hypovitaminosis D has greatly increased in the American population, and is now estimated at 45%. There is increasing evidence that vitamin D is not only important for bone health but vitamin D deficiency is linked to chronic disease such as cardiovascular disease (CVD), diabetes, and cancers. The American obesity epidemic has increased the prevalence of Obstructive Sleep Apnea (OSA) in the American population. Patients with OSA are not just at risk for increased fatigue and daytime drowsiness but when untreated, OSA can increase the risk for a broad range of cardiovascular morbidities, such as hypertension, coronary artery, disease, and heart failure. Since vitamin D deficiency and OSA have independently been associated with CVD it is crucial to assess their relationship to each other. Few studies to date have examined the relationship between low levels of serum 25 hydroxyvitamin D (Vit-D) and risk for OSA. We aim to show a relationship between hypovitaminosis D and OSA in a large population. Methodology: We evaluated 813 participants in the World Trade Center-CHEST Program from January 2011 to September 2013. After excluding those taking vitamin D supplementation, analysis was performed on 624. Blood samples were analyzed for various laboratory parameters including Vit-D and hs-CRP. Vit-D insufficiency was defined as Vit-D < 30 ng/ml. Using the Berlin Questionnaire, a validated questionnaire to evaluate OSA risk, subjects were classified as low risk or high risk. In addition, those with self-reported physician diagnosis of OSA were classified separately. Independent t-test, ANOVA, and chi-squared analyses were performed. Results: Insufficient Vit D was noted in 74.5% (468) of the participants. Subjects who screened positive for high risk of having OSA had lower mean Vit-D levels compared with those with low risk for OSA. Those with the lowest mean Vit-D level were most likely to have a verified diagnosis fsleep apnea (p=0.015). Conclusion: A significant association was found between hypovitaminosis D and OSA in this study population. Those with high risk for OSA and diagnosed OSA have significantly decreased Vit D levels. It is imperative to evaluate Vitamin D levels and OSA risk in order to achieve optimal management of CVD.

Background: Recent studies have found a high prevalence of obstructive sleep apnea (OSA) among responders of the World Trade Center (WTC) disaster. Exposure to particulate matter (PM) causing upper airway inflammation is considered a significant contributing factor in the pathogenesis of OSA. The Berlin Questionnaire (BQ) is a widely used questionnaire to screen for OSA with published sensitivity up to 86% and specificity of 87% for OSA risk. We aim to investigate whether a relationship exists between OSA risk using the BQ and exposure to PM using the Wisnevsky exposure score. Methodology: We evaluated 808 participants in the WTC-CHEST Program from January 2011 to September 2013. High risk for OSA was identified as 2 or more positive categories in the BQ. The subjects were categorized into four exposure groups: very high, high, intermediate and low (Wisnevsky exposure score). Chi-square and Binary Logistic Regression analyses were performed to determine if there was a significant relationship between OSA risk and PM exposure. Results: High risk for OSA is associated with PM exposure in the study population (p=0.002). Using a binary logistic regression adjusting for gender and age, high risk for OSA was still found to be significantly associated with PM exposure (p = 0.022). Conclusion: Prior investigations have demonstrated a link between PM exposure and pulmonary disease, digestive disorders and PTSD. These results provide strong evidence for the association of PM exposure and OSA. In fact, PM exposure in this cohort of WTC first responders is one of the most significant contributors to increased OSA risk. Assessment of both OSA risk and exposure to PM are important as both have been linked to an increase in cardiovascular risk.

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.

Objective: Determine if World Trade Center (WTC) disaster responders had lowerlungfunctionandhigherbronchodilatorresponsivenessthanthosewith respiratory symptoms and conditions. Methods: We evaluated cardinal respiratory symptoms (dyspnea, wheezing, dry cough, productive cough) and determinedthedifferenceinFEV1,FVC, andbronchodilatorresponsiveness. Results: All respiratory symptoms were associated with a lower FEV1 and FVC, and a larger bronchodilator response. Responders reporting chronic productive cough, starting during WTC work and persisting, had a mean FEV1 109 mL lower than those without chronic persistent cough; their odds of having abnormally low FEV1 was 1.40 times higher; and they were 1.65 times as likely to demonstrate bronchodilator responsiveness. Conclusions: Responders reporting chronic persistent cough, wheezing or dyspnea at first medical examination were more likely to have lower lung function and bronchodilator responsiveness.

Background More than 20,000 responders have been examined through the World Trade Center (WTC) Medical Monitoring and Treatment Program since September 11, 2001. Studies on WTC firefighters have shown elevated rates of sarcoidosis. The main objective of this study was to report the incidence of “sarcoid like” granulomatous pulmonary disease in other WTC responders. Methods Cases of sarcoid like granulomatous pulmonary disease were identified by: patient self-report, physician report and ICD-9 codes. Each case was evaluated by three pulmonologists using the ACCESS criteria and only “definite” cases are reported. Results Thirty-eight patients were classified as “definite” cases. Six-year incidence was 192/100,000. The peak annual incidence of 54 per 100,000 person-years occurred between 9/11/2003 and 9/11/2004. Incidence in black responders was nearly double that of white responders. Low FVC was the most common spirometric abnormality. Conclusions Sarcoid like granulomatous pulmonary disease is present among the WTC responders. While the incidence is lower than that reported among firefighters, it is higher than expected. Am. J. Ind. Med. 54:175–184, 2011. © 2010 Wiley-Liss, Inc.

We report on cases of multiple myeloma (MM) observed in World Trade Center (WTC) responders registered in the WTC Medical Program.Possible cases of MM diagnosed between September 11, 2001, and September 10, 2007, in responders were confirmed if they met the World Health Organization and Mayo Clinic diagnostic criteria.Among 28,252 responders of known sex and age, eight cases of MM were observed (6.8 expected). Four of these cases were observed in responders younger than 45 years at the time of diagnosis (1.2 expected). A slight deficit of MM cases was observed in responders older than 45 years (4 observed, 5.6 expected).In this case series, we observe an unusual number of MM cases in WTC responders under 45 years. This finding underscores the importance of maintaining surveillance for cancer and other emerging diseases in this highly exposed population.

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.