Selective inhibition of HDAC class IIA as therapeutic intervention for KMT2A-rearranged acute lymphoblastic leukemia.

KMT2A-rearranged acute lymphoblastic leukemia (ALL) is characterized by deregulation of the epigenome and shows susceptibility towards histone deacetylase (HDAC) inhibition. Most broad-spectrum HDAC inhibitors simultaneously target multiple human HDAC isoforms. Consequently, they often induce toxicity and especially in combination with other therapeutic agents. Therefore, more specifically targeting HDAC isoforms may represent a safer therapeutic strategy. Here we show that shRNA-mediated knock-down of the class IIA HDAC isoforms HDAC4, HDAC5, and HDAC7 results in apoptosis induction and cell cycle arrest in KMT2A-rearranged ALL cells. In concordance, the HDAC4/5 selective small molecule inhibitor LMK-235 effectively eradicates KMT2A-rearranged ALL cell lines as well as primary patient samples in vitro. However, using a xenograft mouse model of KMT2A-rearranged ALL we found that the maximum achievable dose of LMK-235 was insufficient to induce anti-leukemic effects in vivo. Similar results were obtained for the specific class IIA HDAC inhibitors MC1568 and TMP195. Finally, LMK-235 appeared to exert minimal anti-leukemic effects in vivo in combination with the BCL-2 inhibitor venetoclax, but not enough to prolong survival in treated mice. In conclusion, class IIA HDAC isoforms represent attractive therapeutic target in KMT2A-rearranged ALL, although clinical applications require the development of more stable and efficient specific HDAC inhibitors.

Socioeconomic status, smoking, and lung cancer: mediation and bias analysis in the SYNERGY study.

BACKGROUND: Increased lung-cancer risks for low socioeconomic status (SES) groups are only partially attributable to smoking habits. Little effort has been made to investigate the persistent risks related to low SES by quantification of potential biases. METHODS: Based on 12 case-control studies, including 18 centers of the international SYNERGY project (16,550 cases, 20,147 controls), we estimated controlled direct effects (CDE) of SES on lung cancer via multiple logistic regression, adjusted for age, study center, and smoking habits, and stratified by sex. We conducted mediation analysis by inverse odds ratio weighting to estimate natural direct effects (NDE) and natural indirect effects via smoking habits. We considered misclassification of smoking status, selection bias, and unmeasured mediator-outcome confounding by genetic risk, both separately as well as by multiple quantitative bias analysis, using bootstrap to create 95% simulation intervals (SI). RESULTS: Mediation analysis of lung-cancer risks for SES estimated mean proportions of 43% in men and 33% in women attributable to smoking. Bias analyses decreased direct effects of SES on lung cancer, with selection bias showing the strongest reduction in lung-cancer risk in the multiple bias analysis. Lung-cancer risks remained increased for lower SES groups, with higher risks in men [4th versus 1st (highest) SES quartile: CDE 1.50 (SI 1.32-1.69)] than women [CDE 1.20 (SI 1.01-1.45)]. NDE were similar to CDE, particularly in men. CONCLUSIONS: Bias adjustment lowered direct lung-cancer risk estimates of lower SES groups. However, risks for low SES remained elevated, likely attributable to occupational hazards or other environmental exposures.

Applying a 'presumably plausible' principle in a new one-time financial compensation system for occupational diseases in the Netherlands.

OBJECTIVES: In the Netherlands, a new regulation has been adopted for recognition and compensation of serious substance-related occupational diseases. A national advisory committee has a key task of providing advice on the protocols for operationalisation of individual causality assessment in this new context. METHODS: Protocol development involves gathering the best available population-level evidence on causality and using this evidence to determine individual causality. Here, the presumably plausible principle was adopted, which stipulates that uncertainties in individual causality should be weighed in favour of a fast and transparent one-time compensation for (ex-)workers. RESULTS: In monocausal diseases, a limited workplace exposure assessment is considered sufficient to determine whether individual causality is presumably plausible in the Dutch context. For multicausal occupational diseases, individual causality assessment is more complicated. Modelling of existing data on the exposure-response relation helps establish the probability of causation, that is, the risk of the disease attributable to a work-related exposure. This operationalisation, applied in some protocols, makes use of the probability of causation, while being prudent in establishing exposure limits. An example from asbestos and lung cancer is provided in this short report. CONCLUSIONS: We propose a pragmatic approach to individual causality assessment of substance-related occupational diseases, considering statistical and diagnostic uncertainties. This approach substantiates protocols towards a one-time financial compensation without long-winding recognition procedures.

Wastewater Surveillance for Influenza A Virus and H5 Subtype Concurrent with the Highly Pathogenic Avian Influenza A(H5N1) Virus Outbreak in Cattle and Poultry and Associated Human Cases - United States, May 12-July 13, 2024.

As part of the response to the highly pathogenic avian influenza A(H5N1) virus outbreak in U.S. cattle and poultry and the associated human cases, CDC and partners are monitoring influenza A virus levels and detection of the H5 subtype in wastewater. Among 48 states and the District of Columbia that performed influenza A testing of wastewater during May 12-July 13, 2024, a weekly average of 309 sites in 38 states had sufficient data for analysis, and 11 sites in four states reported high levels of influenza A virus. H5 subtype testing was conducted at 203 sites in 41 states, with H5 detections at 24 sites in nine states. For each detection or high level, CDC and state and local health departments evaluated data from other influenza surveillance systems and partnered with wastewater utilities and agriculture departments to investigate potential sources. Among the four states with high influenza A virus levels detected in wastewater, three states had corresponding evidence of human influenza activity from other influenza surveillance systems. Among the 24 sites with H5 detections, 15 identified animal sources within the sewershed or adjacent county, including eight milk-processing inputs. Data from these early investigations can help health officials optimize the use of wastewater surveillance during the upcoming respiratory illness season.

Public health use and lessons learned from a statewide SARS-CoV-2 wastewater monitoring program (MiNET).

The global SARS-CoV-2 monitoring effort has been extensive, resulting in many states and countries establishing wastewater-based epidemiology programs to address the spread of the virus during the pandemic. Challenges for programs include concurrently optimizing methods, training new laboratories, and implementing successful surveillance programs that can rapidly translate results for public health, and policy making. Surveillance in Michigan early in the pandemic in 2020 highlights the importance of quality-controlled data and explores correlations with wastewater and clinical case data aggregated at the state level. The lessons learned and potential measures to improve public utilization of results are discussed. The Michigan Network for Environmental Health and Technology (MiNET) established a network of laboratories that partnered with local health departments, universities, wastewater treatment plants (WWTPs) and other stakeholders to monitor SARS-CoV-2 in wastewater at 214 sites in Michigan. MiNET consisted of nineteen laboratories, twenty-nine local health departments, 6 Native American tribes, and 60 WWTPs monitoring sites representing 45 % of Michigan's population from April 6 and December 29, 2020. Three result datasets were created based on quality control criteria. Wastewater results that met all quality assurance criteria (Dataset Mp) produced strongest correlations with reported clinical cases at 16 days lag (rho = 0.866, p < 0.05). The project demonstrated the ability to successfully track SARS-CoV-2 on a large, state-wide scale, particularly data that met the outlined quality criteria and provided an early warning of increasing COVID-19 cases. MiNET is currently poised to leverage its competency to complement public health surveillance networks through environmental monitoring for new and emerging pathogens of concern and provides a valuable resource to state and federal agencies to support future responses.

The critical role of parents within a Learning Health Network.

Parent members of the Pediatric Rheumatology Care & Outcomes Improvement Network are an integral part of the Learning Health Network's work. Since early in the creation of the network, they have been a part of every Quality Improvement project, committee, and work group and have a role in governance on the Executive and Steering Committees. Members of the Parent Working Group (PWG) have played a role in developing QI measures used in the clinical setting as well as initiatives and projects like the guiding work of Treat-to-Target. The PWG also creates self-management supports, including toolkits for families and patients at all stages of life. This article will discuss how integrating parents as partners in a pediatric Learning Health Network is critical for the quality of care received by children with chronic illnesses and to improving outcomes.

Spatiotemporal modeling of occupational particulate matter using personal low-cost sensor and indoor location tracking data.

Occupational exposure to particulate matter (PM) can result in multiple adverse health effects and should be minimized to protect workers' health. PM exposure at the workplace can be complex with many potential sources and fluctuations over time, making it difficult to control. Dynamic maps that visualize how PM is distributed throughout a workplace over time can help in gaining better insights into when and where exposure occurs. This study explored the use of spatiotemporal modeling followed by kriging for the development of dynamic PM concentration maps in an experimental setting and a workplace setting. Data was collected using personal low-cost PM sensors and an indoor location tracking system, mounted on a moving robot or worker. Maps were generated for an experimental study with one simulated robot worker and a workplace study with four workers. Cross-validation was performed to evaluate the performance and robustness of three types of spatiotemporal models (metric, separable, and summetric) and, as an additional external validation, model estimates were compared with measurements from sensors that were placed stationary in the laboratory or workplace. Spatiotemporal models and maps were generated for both the experimental and workplace studies, with average root mean squared error (RMSE) from 10-fold cross-validation ranging from 7-12 and 73-127 µg/m3, respectively. Workplace models were relatively more robust compared to the experimental study (relative SD ranging from 8-14% of the average RMSE vs. 27-56%, respectively), presumably due to the larger number of parallel measurements. Model estimates showed low to moderate fits compared to stationary sensor measurements (R2 ranging from 0.1-0.5), indicating maps should be interpreted with caution and only used indicatively. Together, these findings show the feasibility of using spatiotemporal modeling for generating dynamic concentration maps based on personal data. The described method could be applied for exposure characterization within comparable study designs or can be expanded further, for example by developing real-time, location-based worker feedback systems, as efficient tools to visualize and communicate exposure risks.

Who do you ask? predicting injury rates from survey responses.

BACKGROUND: Few studies have addressed whether using manager or worker perceptions of safety policies and practices alone predict reported injury rates less accurately than using both. OBJECTIVE: This study provides an example and describes a method that can be used to address this issue with survey instruments designed to measure safety climate, policies, or practices. METHODS: Using multilevel logistic regression, we estimated the relationship between worker and manager perceptions of a given exposure and the odds of worker injury during the post-survey year for three safety scales. We tested whether surveying both workers and managers provides additional predictive value compared with surveying just one group. RESULTS: Injury in the year following the survey was significantly associated with worker scores on two of the three scales. Manager responses were not significantly associated with injury and did not significantly improve injury rate prediction when added to a model with only worker survey responses. CONCLUSIONS: The capacity of manager-only or worker-only perceptions of safety policies and practices to predict worker injuries should be established before choosing to survey just one or the other. The approach and findings in this paper can be applied to other survey instruments and in other settings to help make this choice.

Air pollution exposure and mortality from neurodegenerative diseases in the Netherlands: A population-based cohort study.

BACKGROUND: Long-term exposure to ambient air pollution has been linked with all-cause mortality and cardiovascular and respiratory diseases. Suggestive associations between ambient air pollutants and neurodegeneration have also been reported, but due to the small effect and relatively rare outcomes evidence is yet inconclusive. Our aim was to investigate the associations between long-term air pollution exposure and mortality from neurodegenerative diseases. METHODS: A Dutch national cohort of 10.8 million adults aged ≥30 years was followed from 2013 until 2019. Annual average concentrations of air pollutants (ultra-fine particles (UFP), nitrogen dioxide (NO2), fine particles (PM2.5 and PM10) and elemental carbon (EC)) were estimated at the home address at baseline, using land-use regression models. The outcome variables were mortality due to amyotrophic lateral sclerosis (ALS), Parkinson's disease, non-vascular dementia, Alzheimer's disease, and multiple sclerosis (MS). Hazard ratios (HR) were estimated using Cox models, adjusting for individual and area-level socio-economic status covariates. RESULTS: We had a follow-up of 71 million person-years. The adjusted HRs for non-vascular dementia were significantly increased for NO2 (1.03; 95% confidence interval (CI) 1.02-1.05) and PM2.5 (1.02; 95%CI 1.01-1.03) per interquartile range (IQR; 6.52 and 1.47 µg/m3, respectively). The association with PM2.5 was also positive for ALS (1.02; 95%CI 0.97-1.07). These associations remained positive in sensitivity analyses and two-pollutant models. UFP was not associated with any outcome. No association with air pollution was found for Parkinson's disease and MS. Inverse associations were found for Alzheimer's disease. CONCLUSION: Our findings, using a cohort of more than 10 million people, provide further support for associations between long-term exposure to air pollutants (PM2.5 and particularly NO2) and mortality of non-vascular dementia. No associations were found for Parkinson and MS and an inverse association was observed for Alzheimer's disease.

Distinct Responses to Menin Inhibition and Synergy with DOT1L Inhibition in KMT2A-Rearranged Acute Lymphoblastic and Myeloid Leukemia.

Pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) exhibit favorable survival rates. However, for AML and ALL patients carrying KMT2A gene translocations clinical outcome remains unsatisfactory. Key players in KMT2A-fusion-driven leukemogenesis include menin and DOT1L. Recently, menin inhibitors like revumenib have garnered attention for their potential therapeutic efficacy in treating KMT2A-rearranged acute leukemias. However, resistance to menin inhibition poses challenges, and identifying which patients would benefit from revumenib treatment is crucial. Here, we investigated the in vitro response to revumenib in KMT2A-rearranged ALL and AML. While ALL samples show rapid, dose-dependent induction of leukemic cell death, AML responses are much slower and promote myeloid differentiation. Furthermore, we reveal that acquired resistance to revumenib in KMT2A-rearranged ALL cells can occur either through the acquisition of MEN1 mutations or independently of mutations in MEN1. Finally, we demonstrate significant synergy between revumenib and the DOT1L inhibitor pinometostat in KMT2A-rearranged ALL, suggesting that such drug combinations represent a potent therapeutic strategy for these patients. Collectively, our findings underscore the complexity of resistance mechanisms and advocate for precise patient stratification to optimize the use of menin inhibitors in KMT2A-rearranged acute leukemia.

Thriving from work questionnaire: German translation and validation.

BACKGROUND: The Thriving from Work questionnaire is a comprehensive indicator of positive well-being for employees, applicable in both research and practical contexts. Current discussions underline the crucial impact that employment should have in enriching workers' lives positively and meaningfully, along with the necessity for accurate and dependable tools to assess employee well-being. This study investigated the reliability, validity, and dimensionality of the translated German adaptation of the Thriving from Work questionnaire developed by Peters and colleagues [1, 2]. The questionnaire assesses work-related well-being with 30 items clustered in six domains: emotional and psychological well-being, social well-being, work-life integration, physical and mental well-being, basic needs for thriving, and experiences of work. METHODS: This study aimed to convert the Thriving at Work Questionnaire from English into German. We assessed the psychometric characteristics of the German version of the questionnaire by using item response theory with a sample of 567 German employees and examined its criterion validity. RESULTS: We found that the long and short German Thriving from Work questionnaire versions are reliable with good construct validity. Criterion validity was demonstrated by relationships with important work and life outcomes, such as life satisfaction, trust in the organizations' management, general well-being, work-related fatigue, and work stress. CONCLUSIONS: The current study demonstrated that the German language version of the questionnaire is both a reliable and valid measure of employee well-being. We discuss recommendations for further adaptation and future research.

Occupational exposure to respirable crystalline silica and incident idiopathic interstitial pneumonias and pulmonary sarcoidosis: a national prospective follow-up study.

BACKGROUND: Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. METHODS: The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. RESULTS: Mean cumulative exposure was 125 µg/m3-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m3-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m3-years of 1.20 (95% CI 1.17 to 1.23). CONCLUSION: This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.

Adding injury to insult: Unfair treatment at work and occupational injury among hospital patient-care workers.

BACKGROUND: Hospital patient-care workers have high occupational injury rates. While physical hazards within hospital work environments are established determinants of injury, social exposures may also contribute. This study examined how reports of unfair treatment at work, a dimension of work-related experiences of discrimination, were associated with injury among hospital-based patient-care workers. METHODS: We used data from the Boston Hospital Workers Health Study, a longitudinal cohort of nurses and nursing assistants at two Boston-area hospitals. In 2018, we conducted a worker survey asking about three types of unfair treatment at work and occupational injuries during the past year. We used mixed-effects logistic regression models to evaluate associations between specific types, total load, and high-frequency exposure of unfair treatment with injury, adjusting for age, gender, race and ethnicity, job title, and unit type. RESULTS: Among 1001 respondents, 21% reported being humiliated in front of others at work, 28% reported being watched more closely than other workers, and 47% reported having to work twice as hard as others for the same treatment. For each type of unfair treatment, we observed a monotonic relationship with occupational injury wherein increasing frequency of exposure was associated with increased odds of injury. We also observed monotonic relationships between total load and high-frequency exposure to unfair treatment and odds of injury. CONCLUSIONS: Work-related unfair treatment is associated with injury among hospital workers. Programs and policies that focus on preventing unfair treatment may lessen injury burden in hospital workers.

Rose geranium in sesame oil nasal spray to improve nasal vestibulitis symptoms: a randomized controlled trial.

PURPOSE: The purpose of this phase III randomized double-blinded controlled trial was to investigate the efficacy of a rose geranium in sesame oil (RG) nasal spray compared with an isotonic saline (IS) nasal spray for alleviating nasal vestibulitis symptoms among patients undergoing chemotherapy. METHODS: Patients undergoing active chemotherapy who reported associated nasal symptoms were randomized 1:1 to receive RG or IS, administered twice daily for 2 weeks. Consenting participants completed nasal symptom questionnaires at baseline and then weekly while on treatment. The proportion of patients experiencing improvements in their nasal symptoms 2 weeks after initiating the nasal spray, using a six-point global impression of change score, was estimated within and between each randomized arm, and compared between arms, using Fisher's exact test. The estimated odds ratio was determined (95% confidence interval). RESULTS: One hundred and six patients consented to this study; 43 participants in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Participants had a mean age of 57.8 years (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. Of the evaluable participants who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the participants who received IS (P = 0.009). Adverse events were sparse and did not differ between arms. CONCLUSION: Rose geranium in sesame oil significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. TRIAL REGISTRATION: NCT04620369.

Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.

Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure.

BACKGROUND: Organic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and hypersensitivity pneumonitis and other ILDs in a cohort study. METHODS: The study population included all residents of Denmark born in 1956 or later with at least 1 year of gainful employment since 1976. Incident cases of hypersensitivity pneumonitis and other ILDs were identified in the Danish National Patient Register 1994-2015. Job exposure matrices were used to assign individual annual levels of exposure to organic dust, endotoxin and wood dust from 1976 to 2015. We analysed exposure-response relations by different exposure metrics using a discrete-time hazard model. RESULTS: For organic dust, we observed increasing risk with increasing cumulative exposure with incidence rate ratios (IRR) per 10 unit-years of 1.19 (95% CI 1.12 to 1.27) for hypersensitivity pneumonitis and 1.04 (95% CI 1.02 to 1.06) for other ILDs. We found increasing risk with increasing cumulative endotoxin exposure for hypersensitivity pneumonitis and other ILDs with IRRs per 5000 endotoxin units/m3-years of 1.55 (95% CI 1.38 to 1.73) and 1.09 (95% CI 1.00 to 1.19), respectively. For both exposures, risk also increased with increasing duration of exposure and recent exposure. No increased risks were observed for wood dust exposure. CONCLUSION: Exposure-response relations were observed between organic dust and endotoxin exposure and hypersensitivity pneumonitis and other ILDs, with lower risk estimates for the latter. The findings indicate that organic dust should be considered a possible cause of any ILD. TRIAL REGISTRATION NUMBER: j.no.: 1-16-02-196-17.

Thriving from work questionnaire: Spanish translation and validation.

BACKGROUND: Thriving from Work is a construct that has been highlighted as an important integrative positive worker well-being indicator that can be used in both research and practice. Recent public discourse emphasizes the important contributions that work should have on workers' lives in positive and meaningful ways and the importance of valid and reliable instruments to measure worker well-being. The Thriving from Work Questionnaire measures how workers' experiences of their work and conditions of work contributes in positive ways to their thriving both at and outside of work. METHODS: The purpose of this study was to translate the Thriving from Work Questionnaire from English to Spanish, and then validate the translated questionnaire in a sample of 8,795 finance workers in Peru and Mexico. We used item response theory models replicating methods that were used for the original validation studies. We conducted a differential item functioning analysis to evaluate any differences in the performance of models between Peru and Mexico. We evaluated criterion validity with organizational leadership, flourishing, vitality, community well-being, and worker's home location socio-economic position. RESULTS: The current study demonstrates that the Spanish (Peru/Mexico) questionnaire was found to be a reliable and valid measure of workers' thriving from work. One item was dropped from the long-form version of the original U.S. questionnaire. Both the long and short form versions of the questionnaire had similar psychometric properties. Empirical reliability was high. Criterion validity was established as hypothesized relationships between constructs was supported. There were no differences in the performance of the model between countries suggesting utility across Latin American countries. CONCLUSIONS: The current study demonstrated that the Spanish (Peru and Mexico) version of the questionnaire is both a reliable and valid measure of worker well-being in Latin America. Specific recommendations are made for the adaptation of the questionnaire and directions of future research.

Feasibility of a Capacity Building Organizational Intervention for Worker Safety and Well-being in the Transportation Industry: Pivoting to Address the COVID-19 Pandemic and Social and Political Unrest in Chile.

OBJECTIVE: This study developed, implemented, and evaluated the feasibility of executing an organizational capacity building intervention to improve bus driver safety and well-being in a Chilean transportation company. Method: Through an implementation science lens and using a pre-experimental mixed methods study design, we assessed the feasibility of implementing a participatory organizational intervention designed to build organizational capacity. Result: We identified contextual factors that influenced the intervention mechanisms and intervention implementation and describe how the company adapted the approach for unexpected external factors during the COVID-19 pandemic and social and political unrest experienced in Chile. Conclusions: The intervention enabled the organization to create an agile organizational infrastructure that provided the organization's leadership with new ways to be nimbler and more responsive to workers' safety and well-being needs and was robust in responding to strong external forces that were undermining worker safety and well-being.

The asbestos-asbestosis exposure-response relationship: a cohort study of the general working population.

OBJECTIVES: The association between asbestos exposure and asbestosis in high-exposed industrial cohorts is well-known, but there is a lack of knowledge about the exposure-response relationship for asbestosis in a general working population setting. We examined the exposure-response relationship between occupational asbestos exposure and asbestosis in asbestos-exposed workers of the Danish general working population. METHODS: We followed all asbestos-exposed workers from 1979 to 2015 and identified incident cases of asbestosis using the Danish National Patient Register. Individual asbestos exposure was estimated with a quantitative job exposure matrix (SYN-JEM) from 1976 onwards and back-extrapolated to age 16 for those exposed in 1976. Exposure-response relations for cumulative exposure and other exposure metrics were analyzed using a discrete time hazard model and adjusted for potential confounders. RESULTS: The range of cumulative exposure in the population was 0.001 to 18 fibers per milliliter-year (f/ml-year). We found increasing incidence rate ratios (IRR) of asbestosis with increasing cumulative asbestos exposure with a fully adjusted IRR per 1 f/ml-years of 1.18 [95% confidence interval (CI) 1.15- -1.22]. The IRR was 1.94 (95% CI 1.53-2.47) in the highest compared to the lowest exposure tertile. We similarly observed increasing risk with increasing cumulative exposure in the inception population. CONCLUSIONS: This study found exposure-response relations between cumulative asbestos exposure and incident asbestosis in the Danish general working population with mainly low-level exposed occupations, but there is some uncertainty regarding the exposure levels.