Toxic chemical exposures among civilians in armed conflicts: the need for research equity, justice, and accountability.

OBJECTIVE: Armed conflicts result in the release of toxic chemicals into the surrounding environment and civilians are commonly exposed to these toxicants.This paper reviews the evidence on civilian exposure to toxic chemicals, including but not limited to inhaled toxic substances, in post-World War II armed conflicts, and proposes a framework for the implementation of long-term surveillance programs for these populations. MATERIALS AND METHODS: Four databases of peer-reviewed health articles were searched for all English-language articles with a primary focus on toxic chemical exposures among civilians in armed conflicts since World War II. The review was supplemented substantially by the gray literature. RESULTS: In the 66 articles that met the inclusion criteria, the authors categorized the chemical toxicants to which civilians have been exposed in modern armed conflicts as ubiquitous (e.g. smoke, dust, and munitions components present in all conflicts) or particular agents (e.g. specific chemical agents used in a few conflicts). While most studies focused on particular agents, the vast majority of civilians are in fact exposed to ubiquitous agents both in the acute conflict phase and through persistent environmental exposures after the cessation of hostilities. DISCUSSION/CONCLUSION: There is a dearth of research concerning civilian exposures to toxic chemicals during armed conflicts. In line with principles of equity, justice, and accountability, robust research and surveillance programs are urgently needed to document exposures and provide ongoing assessments and any necessary treatment for these long-ignored populations, most of whom live in the Global South.

Elastomeric half-mask respirator disinfection practices among healthcare personnel.

BACKGROUND: Disposable N95 respirator shortages during the COVID-19 and 2009 H1N1 influenza pandemics highlighted the need for reusable alternatives, such as elastomeric half-mask respirators (EHMRs). Two US medical organizations deployed reusable EHMRs during the COVID-19 response. In addition to wipe-based disinfection following patient care episodes expected per local policies at both organizations, postshift centralized cleaning and disinfection (C&D) was expected at one site (A), permitting shared-pool EHMR use, and optional at the other (Site B), where EHMRs were issued to individuals. Using a survey, we evaluated disinfection practices reported by EHMR users and predictors of disinfection behaviors and perceptions. METHODS: Surveys assessed EHMR disinfection practices, occupational characteristics, EHMR use frequency, training, and individual-issue versus shared-pool EHMR use. RESULTS: Of 1080 EHMR users completing the survey, 76% reported that they disinfect the EHMR after each patient encounter, which was the expected practice at both sites. Increasing EHMR use, recall of disinfection training, and work in intensive care or emergency settings significantly influenced higher reporting of this practice. 36% of respondents reported using centralized C&D, although reporting was higher at the site (A) where this was expected (53%). Confidence in cleanliness of the EHMR following centralized C&D was not influenced by individual versus shared-pool EHMR issue. CONCLUSIONS: Most EHMR users reported adherence with expected post-care individual-based disinfection of EHMRs but did not necessarily use standardized, centralized C&D. Future efforts to limit reliance on behavior related to respirator disinfection may improve EHMR implementation in healthcare to avert dependence on single-use, disposable N95 respirators.

Carcinogenic drug exposure among health-sector workers: the need for exposure assessment and surveillance.

Antineoplastic drugs (ANDs) used for chemotherapy can cause secondary cancers in treated patients and can pose carcinogenic risks to health-sector workers anywhere along these drugs' life cycle in a facility, from production to patient administration. Several PAHO/WHO Collaborating Centers (CCs) have experience addressing these hazards in the health sector. The objectives of this report are four-fold: 1) Provide an overview of longstanding research and prevention efforts, led by PAHO/WHO and its Occupational Health CCs, aimed at reducing the burden of occupational cancer in the Americas; 2) Discuss how robust AND exposure assessment and educational/outreach work by PAHO CCs can form the basis of exposure mitigation efforts among health-sector workers; 3) Through the presentation of original AND exposure assessment data from a pharmaceutical compounding facility in Chile, highlight relatively inexpensive methods by which such data can be generated; and 4) Discuss how effective, periodic environmental surveillance in healthcare facilities results in the identification of AND contamination in the work environment and enables the implementation of low-cost, high-impact interventions to reduce the risk of occupational cancer in health-sector workers, including in limited-resource settings. The risk of health-sector worker exposure to ANDs and other hazardous drugs is an important issue for inclusion within PAHO/WHO's broader efforts at reducing the impact of occupational cancer in the Americas. This report demonstrates that a wide range of accessible AND-exposure mitigation strategies are feasible at both a facility and a national policy level across the hemisphere.

Los medicamentos antineoplásicos empleados en quimioterapia pueden causar distintos tipos de tumores secundarios en pacientes tratados y presentar riesgos cancerígenos para los trabajadores del sector de la salud en cualquier momento del ciclo de vida de estos medicamentos en las instalaciones, desde su producción hasta su administración al paciente. Varios centros colaboradores de la OPS/OMS tienen experiencia en cuanto a cómo abordar estos peligros en el sector de la salud. Este informe persigue cuatro objetivos: 1) ofrecer una visión general de la labor de investigación y prevención de larga data, liderada por la OPS/OMS y sus centros colaboradores de salud ocupacional, encaminada a reducir la carga del cáncer ocupacional en la Región de las Américas; 2) abordar cómo una evaluación sólida de la exposición a los medicamentos antineoplásicos y la labor educativa y divulgativa de los centros colaboradores de la OPS pueden sentar las bases de los esfuerzos de mitigación de la exposición en los trabajadores del sector de la salud; 3) mediante la presentación de datos originales sobre la evaluación de la exposición a los medicamentos antineoplásicos en una instalación de compuestos farmacéuticos en Chile, destacar métodos relativamente asequibles gracias a los cuales se pueden recopilar dichos datos; y 4) examinar cómo la vigilancia ambiental efectiva y periódica en los centros de salud permite detectar casos de contaminación de medicamentos antineoplásicos en el entorno de trabajo y facilita la ejecución de intervenciones de bajo costo y alto impacto para reducir el riesgo de cáncer ocupacional en los trabajadores del sector de la salud, incluso en entornos de recursos limitados.El riesgo de exposición de los trabajadores del sector de la salud a los medicamentos antineoplásicos y otros medicamentos peligrosos es una cuestión importante para su inclusión en los esfuerzos más amplios de la OPS/OMS para reducir los efectos del cáncer ocupacional en la Región de las Américas. En este informe se demuestra que una amplia gama de estrategias accesibles de mitigación de la exposición a los medicamentos antineoplásicos es factible tanto a nivel de las instalaciones como de las políticas nacionales en toda la Región.

Os medicamentos antineoplásicos usados para quimioterapia podem causar cânceres secundários em pacientes tratados e apresentar riscos carcinogênicos aos profissionais de saúde em qualquer momento do ciclo de vida desses fármacos dentro de um estabelecimento, desde sua produção até a administração ao paciente. Vários centros colaboradores da OPAS/OMS têm experiência em lidar com esses riscos no setor de saúde. Este relatório tem quatro objetivos: 1) fornecer uma visão geral dos esforços de longa data em pesquisa e prevenção liderados pela OPAS/OMS e por seus centros colaboradores de saúde ocupacional, cuja meta é reduzir a carga do câncer ocupacional nas Américas; 2) discutir como uma avaliação robusta da exposição aos antineoplásicos e o trabalho de extensão/educacional dos centros colaboradores da OPAS/OMS podem embasar os esforços de mitigação da exposição entre os profissionais de saúde; 3) por meio da apresentação de dados originais de avaliação da exposição a antineoplásicos obtidos de uma central de manipulação de medicamentos no Chile, destacar métodos relativamente econômicos para gerar esse tipo de dados; e 4) discutir como a vigilância ambiental eficaz e periódica em estabelecimentos de saúde resulta na identificação de contaminação por antineoplásicos no ambiente de trabalho e permite a implementação de intervenções de baixo custo e alto impacto para reduzir o risco de câncer ocupacional em profissionais de saúde, inclusive em contextos de recursos limitados.O risco de exposição dos profissionais de saúde aos medicamentos antineoplásicos e outros fármacos perigosos é uma questão importante a ser incluída nos esforços mais amplos da OPAS/OMS de reduzir o impacto do câncer ocupacional nas Américas. Este relatório demonstra a viabilidade de uma ampla gama de estratégias acessíveis de mitigação da exposição aos antineoplásicos, tanto no nível das instituições quanto no âmbito de políticas nacionais em todo o hemisfério.

The management of embedded metal fragment patients and the role of chelation Therapy: A workshop of the Department of Veterans Affairs-Walter Reed National Medical Center.

Exposure to retained metal fragments from war-related injuries can result in increased systemic metal concentrations, thereby posing potential health risks to target organs far from the site of injury. Given the large number of veterans who have retained fragments and the lack of clear guidance on how to medically manage these individuals, the Department of Veterans Affairs (VA) convened a meeting of chelation experts and clinicians who care for embedded fragment patients to discuss current practices and provide medical management guidance. Based on this group's clinical expertise and review of published literature, the evidence presented suggests that, at least in the case of lead fragments, short-term chelation therapy may be beneficial for embedded fragment patients experiencing acute symptoms associated with metal toxicity; however, in the absence of clinical symptoms or significantly elevated blood lead concentrations (greater than 80 µg/dL), chelation therapy may offer little to no benefit for individuals with retained fragments and pose greater risks due to remobilization of metals stored in bone and other soft tissues. The combination of periodic biomonitoring to assess metal body burden, longitudinal fragment imaging, and selective fragment removal when metal concentrations approach critical injury thresholds offers a more conservative management approach to caring for patients with embedded fragments.

Surveillance results and bone effects in the Gulf War depleted uranium-exposed cohort.

A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored in a clinical surveillance program since 1993. During the spring of 2017, 42 members of the cohort were evaluated with a protocol which includes exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes including measures of bone metabolism, and for participants >50 years, bone mineral density (BMD) determination. Elevated urine U concentrations were observed in cohort members with retained DU shrapnel fragments. Only the mean serum estradiol concentration, a marker of bone metabolism, was found to be significantly different for lower-vs- higher urine U (uU) cohort sub-groups. For the first time, a significant deficit in BMD was observed in the over age 50, high uU sub-group. After more than 25 years since first exposure to DU, an aging cohort of military veterans continues to exhibit few U-related adverse health effects in known target organs of U toxicity. The new finding of reduced BMD in older cohort members, while biologically plausible, was not suggested by other measures of bone metabolism in the full (all ages) cohort, as these were predominantly within normal limits over time. Only estradiol was recently found to display a difference as a function of uU grouping. As BMD is further impacted by aging and the U-burden from fragment absorption accrues in this cohort, a U effect may be clarified in future surveillance visits.

Impulse oscillometry measurement of distal airways obstruction in depleted uranium-exposed Gulf War veterans.

INTRODUCTION: A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium-related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens. METHODS: We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values. RESULTS: Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%). CONCLUSIONS: While oscillometry identified more veterans as obstructed, obstruction was not uranium-related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.

The U.S. Department of Veterans' Affairs depleted uranium exposed cohort at 25 Years: Longitudinal surveillance results.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly-fire incidents have been monitored for health changes in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: During the spring of 2015, an in-patient clinical surveillance protocol was performed on 36 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: On-going mobilization of U from embedded fragments is evidenced by elevated urine U concentrations. The DU isotopic signature is observed principally in participants possessing embedded fragments. Those with only an inhalation exposure have lower urine U concentration and a natural isotopic signature. CONCLUSIONS: At 25 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As U body burden continues to accrue from in-situ mobilization from metal fragment depots, and increases with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Occupational safety and health protections against Ebola virus disease.

Even as the Ebola epidemic is finally showing signs of remitting, controversy continues regarding the modes of disease transmission, the understanding of which necessarily dictates methods of prevention. The initial public health response to the epidemic was based on assumptions formed during previous outbreaks, and in the belief that transmission was restricted to direct "contact" with other infected patients. However, the current Ebola outbreak differed from previous experiences in its intensity of transmission, speed of spread, and fatality rate and was also particularly unforgiving on health workers occupationally infected. Even with these differences, however, other modes of transmission were not considered by public health authorities, thus denying both the hard-hit health worker populations and the wider public more protective guidance. International Labor Conventions require employers to provide a comprehensive safety program that anticipates work-related risks and specifies strategies for protection against them. Such a precautionary approach is recommended in future epidemic planning, especially where evidence regarding transmission is incomplete.

Biologic monitoring and surveillance results for the department of veterans affairs' depleted uranium cohort: Lessons learned from sustained exposure over two decades.

BACKGROUND: A small group of Gulf War I veterans wounded in depleted uranium (DU) friendly fire incidents have been monitored in a clinical surveillance program at the Veterans Affairs Medical Center, Baltimore since 1994. METHODS: An in-patient clinical surveillance protocol was performed on 35 members of the cohort, including exposure monitoring for total and isotopic uranium concentrations in urine and a comprehensive assessment of health outcomes. RESULTS: Although urine U concentrations continue to be elevated in this group, illustrating on-going in situ mobilization of U from embedded fragments, no consistent U-related health effects have been observed. CONCLUSIONS: Now more than 20 years since first exposure to DU, an aging cohort of military veterans continues to show no U-related health effects in known target organs of U toxicity. As tissue concentrations continue to accrue with exposure duration, critical tissue-specific U concentration thresholds may be reached, thus recommending on-going surveillance of this veteran cohort.

Chapter 4 embedded metal fragments.

The continued evolution of military munitions and armor on the battlefield, as well as the insurgent use of improvised explosive devices, has led to embedded fragment wounds containing metal and metal mixtures whose long-term toxicologic and carcinogenic properties are not as yet known. Advances in medical care have greatly increased the survival from these types of injuries. Standard surgical guidelines suggest leaving embedded fragments in place, thus individuals may carry these retained metal fragments for the rest of their lives. Nursing professionals will be at the forefront in caring for these wounded individuals, both immediately after the trauma and during the healing and rehabilitation process. Therefore, an understanding of the potential health effects of embedded metal fragment wounds is essential. This review will explore the history of embedded fragment wounds, current research in the field, and Department of Defense and Department of Veterans Affairs guidelines for the identification and long-term monitoring of individuals with embedded fragments.

Performance of Impulse Oscillometry in Identifying Restrictive Lung Defects in a Veteran Cohort.

Background: Impulse oscillometry (IOs) is a technique used to evaluate lung function that uses sound waves imposed over tidal breathing to characterize the airways and lung parenchyma. IOs has been particularly useful in the identification of obstructive lung defects. The present analysis seeks to explore the use of IOs in the identification of restrictive lung physiology among a group of Gulf War I veterans exposed to depleted uranium (DU). Methods: A total of 36 out of a dynamic 85-veteran cohort attended in-person surveillance visits in 2019 and completed both IOs and PFTs. Performance on IOs was evaluated in a cross-sectional analysis of the group overall and in those identified as having restrictive lung defects defined by either spirometry (FEV1/FVC ≥ LLN and FVC < LLN) or lung volumes (TLC < LLN). Results: A total of 6 individuals were identified as having restriction (4 based on spirometry alone and an additional 2 by lung volumes). When restriction was present, IOs values of both resistance and reactance were significantly more abnormal. Conclusion: In the assessment of lung function, IOs may be advantageous over PFTs because it is faster to perform and effort-independent. Although little is known about the utility of IOs in identifying restrictive lung physiology, our results support its use.

Respiratory Health Associated with Systemic Metal Exposure in Post 9/11 Veterans in the Department of Veterans Affairs Toxic Embedded Fragment Registry.

OBJECTIVE: Adverse respiratory outcomes in post-9/11 Veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, pulmonary physiology tests (pulmonary function and oscillometry) and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses and physiology measures were compared in Veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to Veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post 9/11 Veterans are not associated with adverse respiratory health outcomes.

Long-term exposure to depleted uranium in Gulf-War veterans does not induce chromosome aberrations in peripheral blood lymphocytes.

Depleted uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic, and long-term exposure may cause adverse health effects. This study evaluates genotoxic effects of exposure to DU by measuring chromosome damage in peripheral blood lymphocytes with fluorescence in situ hybridization whole-chromosome painting. Study participants are Gulf War-I Veterans with embedded DU fragments and/or inhalation exposure due to involvement in friendly-fire incidents; they are enrolled in a long-term health surveillance program at the Baltimore Veterans Administration Medical Center. Blood was drawn from 35 exposed male veterans aged 39 to 62 years. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use, against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. Translocation frequencies in these Veterans were all well within the normal range of published values for healthy control subjects from around the world. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans.

Succimer chelation does not produce lasting reductions of blood lead levels in a rodent model of retained lead fragments.

Retained lead fragments from nonfatal firearm injuries pose a risk of lead poisoning. While chelation is well-established as a lead poisoning treatment, it remains unclear whether chelation mobilizes lead from embedded lead fragments. Here, we tested whether 1) DMSA/succimer or CaNa2EDTA increases mobilization of lead from fragments in vitro, and 2) succimer is efficacious in chelating fragment lead in vivo, using stable lead isotope tracer methods in a rodent model of embedded fragments. DMSA was > 10-times more effective than CaNa2EDTA in mobilizing fragment lead in vitro. In the rodent model, succimer chelation on day 1 produced the greatest blood lead reductions, and fragment lead was not mobilized into blood. However, with continued chelation and over 3-weeks post-chelation, blood lead levels rebounded with mobilization of lead from the fragments. These findings suggest prolonged chelation will increase fragment lead mobilization post-chelation, supporting the need for long-term surveillance in patients with retained fragments.

Laying the Foundation for a Mesothelioma Patient Registry: Development of Data Collection Tools.

Mesothelioma, a cancer of mesothelial cells that line the chest, lungs, heart, and abdomen, is a relatively rare disease. In the United States, approximately 3000 individuals are diagnosed with mesothelioma annually. The primary risk factor for mesothelioma is occupational asbestos exposure which can occur decades prior to disease development, though in approximately 20% of cases, known asbestos exposure is lacking. While several other countries have developed mesothelioma registries to collect key clinical and exposure data elements to allow better estimation of incidence, prevalence, and risk factors associated with disease development, no national mesothelioma registry exists in the U.S. Therefore, as part of a larger feasibility study, a patient exposure questionnaire and a clinical data collection tool were created using a series of key informant interviews. Findings suggest that risk factor and clinical data collection via an on-line questionnaire is feasible, but specific concerns related to confidentiality, in the context of employer responsibility for exposure in the unique U.S. legal environment, and timing of enrollment must be addressed. Lessons learned from piloting these tools will inform the design and implementation of a mesothelioma registry of national scope.

The Department of Veterans' Affairs Depleted Uranium Cohort in the Time of COVID-19: Translating a Traditional Surveillance Protocol to a Telehealth Platform.

OBJECTIVE: In 2021, 37 members of a cohort of depleted uranium-exposed Gulf War I veterans were evaluated using a protocol tailored to accommodate COVID-19 safety practices on a telehealth platform. METHODS: Individual elements of the legacy protocol were reviewed for urgency and feasibility of inclusion in a modified, telehealth platform. RESULTS: The redesigned protocol included a participant readiness for telehealth assessment, nurse and physician telehealth visits, collection of usual health questionnaires, and urine collections for exposure monitoring for uranium and other fragment-related metal measures. CONCLUSIONS: Despite some limitations in scope, the telehealth platform permitted a visual "visit" with surveillance participants who expressed a high comfort level with the format. The telehealth platform has apparent utility for occupational surveillance and should be explored as a standard approach for surveillance outside of public health emergencies.

Physiological Impacts of Surgical Mask Coverage of Elastomeric Half-mask Respirator Exhalation Valves in Healthcare Workers.

OBJECTIVES: Elastomeric half-mask respirator (EHMR) use in healthcare increased significantly during the COVID-19 pandemic. Concern for potential release of infectious aerosols from EHMR exhalation valves prompted recommendations to cover them with surgical masks (SMs), thereby improving source control. The physiological and subjective effects of wearing a SM over the exhalation valve of an EHMR, however, are unknown. METHODS: Twelve healthy healthcare worker volunteers completed a 30-min series of simulated healthcare-related tasks, including resting, talking, walking, and bending, proning and supinating a weighted manikin, and performing cardiopulmonary resuscitation. This series recurred three times with different mask configurations-SM only, EHMR only, or EHMR with SM covering the exhalation valve. A transcutaneous sensor continuously measured carbon dioxide (tcPCO2), oxygen saturation (SpO2), and heart rate (HR) from each subject. Subjects scored their rates of perceived exertion (RPE) and levels of discomfort after each round. Physiological parameters and subjective scores were analyzed using mixed linear models with a fixed effect for mask type, activity, age, body mass index (BMI), and gender. Analysis also tested for interaction between mask type and activity. RESULTS: Physiological parameters remained within normal ranges for all mask configurations but varied by task. Statistically significant but small decreases in mean tcPCO2 (37.17 versus 37.88 mmHg, P < 0.001) and SpO2 (97.74 versus 97.94%, P < 0.001) were associated with wearing EHMR with SM over the exhalation valve compared with EHMR alone. Mean HR did not differ between these mask configurations. Wearing SM only was associated with lower RPE and level of discomfort compared with EHMR, but these subjective scores did not differ when comparing EHMR with SM to EHMR only. Age, BMI, and gender had no significant effect on any outcomes. CONCLUSIONS: Wearing a SM over an EHMR did not produce clinically significant changes in tcPCO2, SpO2, or HR compared with uncovered EHMR during healthcare-related tasks. Covered EHMR use also did not affect perceived exertion or discomfort compared with uncovered EHMR use. Covering the exhalation valve of an EHMR with a SM for source control purposes can be done safely.