An urgent call to address work-related psychosocial hazards and improve worker well-being.

Work-related psychosocial hazards are on the verge of surpassing many other occupational hazards in their contribution to ill-health, injury, disability, direct and indirect costs, and impact on business and national productivity. The risks associated with exposure to psychosocial hazards at work are compounded by the increasing background prevalence of mental health disorders in the working-age population. The extensive and cumulative impacts of these exposures represent an alarming public health problem that merits immediate, increased attention. In this paper, we review the linkage between work-related psychosocial hazards and adverse effects, their economic burden, and interventions to prevent and control these hazards. We identify six crucial societal actions: (1) increase awareness of this critical issue through a comprehensive public campaign; (2) increase etiologic, intervention, and implementation research; (3) initiate or augment surveillance efforts; (4) increase translation of research findings into guidance for employers and workers; (5) increase the number and diversity of professionals skilled in preventing and addressing psychosocial hazards; and (6) develop a national regulatory or consensus standard to prevent and control work-related psychosocial hazards.

Variability in Minimal Clinically Important Difference Calculation and Reporting in the Otolaryngology Literature.

OBJECTIVE: Best practices for calculation of the minimal clinically important difference (MCID) of outcome measures include the use of complementary methodologies (broadly classified as anchor-based and distribution-based) and reporting of the MCID's predictive ability. We sought to determine MCID calculation and reporting patterns within the otolaryngology literature. METHODS: A systematic search strategy of Embase, PubMed, and Web of Science databases was developed and implemented to identify studies reporting the determination of an MCID for an outcome measure. Studies specifically within the otolaryngology literature (defined as journals classified as "otorhinolaryngology" in the Journal Citation Reports database) were included. All those journals were additionally searched for relevant articles. RESULTS: There were 35 articles that met the inclusion criteria. Of these studies, 88.6% reported MCID of a patient-reported outcome measure and the remainder were for objective outcome measurements. Anchor-based methods were used by 82.9% of studies and distribution-based methods were used by 68.6% of studies. Of all studies, 31.4% utilized anchor-based methods alone, 17.1% utilized distribution-based methods alone, and 51.4% used both methods. Only 25.7% of studies reported the sensitivity (median: 60.8%, range: 40.5%-86.7%) and specificity (median: 80.4%, range: 63.5%-88.0%) of the MCID to detect patients experiencing clinically important change. CONCLUSION: Deviation from best practices in MCID calculation and reporting exists within the otolaryngology literature, with almost half of all studies only using one method of MCID calculation and almost three-quarters not reporting the predictive ability (sensitivity/specificity) of the calculated MCID. When predictive ability is reported, however, MCIDs appear to be more specific than sensitive. LEVEL OF EVIDENCE: NA Laryngoscope, 134:2059-2069, 2024.

Preparing the occupational safety and health workforce for future disruptions.

BACKGROUND: Despite some emerging lessons learned from the COVID-19 pandemic, evidence suggests the world remains largely underprepared for-and vulnerable to-similar threats in the future. METHODS: In 2022, researchers at the US National Institute for Occupational Safety and Health (NIOSH) led a team of volunteers to explore how future disruptions, such as pandemics, might impact work and the practice of occupational safety and health (OSH). This qualitative inquiry was framed as a strategic foresight project and included a series of activities designed to help better understand, prepare for, and influence the future. RESULTS: Findings from a thorough search for indicators of change were synthesized into nine critical uncertainties and four plausible future scenarios. Analysis of these outputs elucidated three key challenges that may impact OSH research, policy, and practice during future disruptions: (1) data access, (2) direct-to-worker communications, and (3) mis- and dis-information management. CONCLUSIONS: A robust strategic response is offered to address these challenges, and next steps are proposed to enhance OSH preparedness and institutionalize strategic foresight across the OSH community.

The adherence to the American Association for the Study of Liver Diseases 2018 guidelines in the management of hepatocellular carcinoma and its impact on survival.

Introduction: In two Korean and Italian studies, the adherence rate (AR) to ASSLD 2005 guidelines in the management of hepatocellular carcinoma (HCC) was 60%. In a US study, the AR to American Association for the Study of Liver Disease (AASLD) 2005 guidelines was 73.3%, 26.8%, 25.3%, and 58.8% for patients with Barcelona Clinic Liver Cancer (BCLC) Stage A, B, C, and D, respectively, and nonadherence to guidelines was associated with longer overall survival (OS) in patients with BCLC Stage D. Here, we explored the AR to AASLD 2018 guidelines and its impact on OS. Methods: Between 2017 and 2019, 148 unique treatment-naïve patients with HCC were identified. Patients were staged according to the BCLC staging system and their AR to AASLD 2018 guidelines was noted. OS was estimated using Kaplan-Meier method. Survivals among patients from different groups was compared using Log-rank test. Results: The overall AR to AASLD 2018 guidelines was 83%. The AR for BCLC Stages 0, A, B, C, and D were 100%, 97%, 77%, 77%, and 38%, respectively. In patients with BCLC Stage D, the OS of patients treated with modalities adherent versus nonadherent to AASLD 2018 guidelines was 0.03 vs. 5.2 months (P = 0.0005). Otherwise, adherence versus nonadherence to AASLD 2018 guidelines showed no statistically significant differences in OS for patients with BCLC Stages 0, A, B, and C. Conclusion: The overall AR to AASLD 2018 guidelines was 83%. Nonadherence to AASLD 2018 guidelines in patients with BCLC Stage D translated into better OS.

Clostridioides difficile infection in a skilled nursing facility (SNF): cost savings of an automated, standardized probiotic antimicrobial stewardship programme (ASP) policy.

Background: With multiple comorbidities and frequent exposures to antibiotics, patients in skilled nursing facilities (SNFs) are much more vulnerable to healthcare-acquired infections. We conducted a quality-improvement, retrospective analysis of all patients with Clostridioides difficile infection (CDI) from 2009 to 2021 at an SNF. Probiotics were initially added to a bundle of antimicrobial stewardship programme (ASP) CDI prevention strategies. Formulations and durations of probiotics were standardized for both oral and enteral administration. To reach all eligible patients, an ASP probiotic policy provided probiotics with every antibiotic course. Objectives: To assess the value of providing probiotic therapy to SNF patients at risk for CDI. Patients and methods: Patients receiving oral or enteral feeding with antibiotics ordered were eligible to receive probiotics. The incremental cost of CDI prevention, treatment and related care were calculated and compared for each phase of probiotic policy change and feeding type. ASP records for the oral probiotic and level of treatment were used in modelling the cost-effectiveness. Results: From quality improvement initiatives aimed at preventing facility-onset (FO) CDI, to ASP policies, probiotic formulations and delegation of ordering authority, the days of acute care treatment required was significantly reduced over the different phases of implementation [152 to 48, OR = 0.22 (0.16-0.31) to 4, OR = 0.08 (0.03-0.23)] after reducing total CDI from 5.8 to 0.3 cases per 10 000 patient-days. The annual cost of oral probiotics increased from $6019 to $14 652 but the modelled net annual savings for the facility was $72 544-$154 085. Conclusions: With optimization, the use of probiotics for CDI prevention at an SNF was safe, efficacious and cost-effective.

Pharmacokinetics of delta-9-tetrahydrocannabinol following acute cannabis smoke exposure in mice; effects of sex, age, and strain.

Increased use of cannabis and cannabinoids for recreational and medical purposes has led to a growth in research on their effects in animal models. The majority of this work has employed cannabinoid injections; however, smoking remains the most common route of cannabis consumption. To better model real-world cannabis use, we exposed mice to cannabis smoke to establish the pharmacokinetics of Δ9THC and its metabolites in plasma and brain. To determine the time course of Δ9THC and two major metabolites [11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (11-COOH-THC)], male and female C57BL/6J mice were exposed to smoke from sequentially burning 5 cannabis cigarettes. Following smoke exposure, trunk blood and brains were collected at 6 time points (10-240 min). Plasma and brain homogenates were analyzed for Δ9THC and metabolites using a validated ultraperformance liquid chromatography-tandem mass spectrometry method. To assess effects of age, sex, and mouse strain, we exposed mice of four strains (C57BL/6J, FVB, Swiss Webster, and 129S6/SvEv, aged 4-24 months) to cannabis using the same smoke regimen. Samples were collected 10 and 40 min following exposure. Lastly, to assess effects of dose, C57BL/6J mice were exposed to smoke from burning 3 or 5 cannabis cigarettes, with samples collected 40 min following exposure. The pharmacokinetic study revealed that maximum plasma Δ9THC concentrations (Cmax) were achieved at 10 and 40 min for males and females, respectively, while Cmax for brain Δ9THC was observed at 20 and 40 min for males and females, respectively. There were no age or strain differences in plasma Δ9THC concentrations at 10 or 40 min; however, 129S6/SvEv mice had significantly higher brain Δ9THC concentrations than FVB mice. Additionally, 3 cigarettes produced significantly lower plasma 11-COOH-THC concentrations compared to 5 cigarettes, although dose differences were not evident in plasma or brain concentrations of Δ9THC or 11-OH-THC. Across all experiments, females had higher levels of 11-COOH-THC in plasma compared to males. The results reveal robust sex differences in Δ9THC pharmacokinetics, and lay the groundwork for future studies using mice to model the pharmacodynamics of smoked cannabis.

Visco-Elastic Honeycomb Structures with Increased Energy Absorption and Shape Recovery Performance Using Buckling Initiators.

Energy-absorbing materials have extensive applications in aerospace and automotive applications. Research has shown buckling initiators, or triggers, in energy-absorbing tubular structures increase the energy absorbed by encouraging the side panels to fold when loaded out of plane in compression conditions. Additively manufactured TPE honeycombs were designed in this study to include these buckling initiators, which introduced a slight decrease in initial weight, as well as initial stress concentrations, while improving crashworthiness characteristics. The samples with buckling initiators (1BI) showed an increase in crush efficiency when directly compared to their no buckling initiator (0BI) counterparts. The 1BI samples maintained an increased crush efficiency regardless of the strain rate used. The samples with 1BI were able to better equilibrate the peak stress with the plateau stress. These honeycomb samples were found to maintain their crush efficiency, even after multiple rounds of compression testing. The quasi-static 0BI samples experienced a 23.4% decrease in the peak stress after multiple rounds of compression testing, while the 1BI samples saw approximately a 23.0% decrease. The 1BI samples averaged a decrease in crush efficiency of 0.5%, while the 0BI samples saw a decrease in crush efficiency of 5%. As the strain rate increased, the crush efficiency for the 1BI samples showed an increase in performance, with a smaller degradation in crush efficiency over multiple uses. Visco-elastic honeycomb with buckling initiators has a higher energy absorption than samples with no buckling initiators when exposed to multiple impact cycles.

Time-resolved assessment of single-cell protein secretion by sequencing.

Secreted proteins play critical roles in cellular communication. Methods enabling concurrent measurement of cellular protein secretion, phenotypes and transcriptomes are still unavailable. Here we describe time-resolved assessment of protein secretion from single cells by sequencing (TRAPS-seq). Released proteins are trapped onto the cell surface and probed by oligonucleotide-barcoded antibodies before being simultaneously sequenced with transcriptomes in single cells. We demonstrate that TRAPS-seq helps unravel the phenotypic and transcriptional determinants of the secretion of pleiotropic TH1 cytokines (IFNγ, IL-2 and TNF) in activated T cells. In addition, we show that TRAPS-seq can be used to track the secretion of multiple cytokines over time, uncovering unique molecular signatures that govern the dynamics of single-cell cytokine secretions. Our results revealed that early central memory T cells with CD45RA expression (TCMRA) are important in both the production and maintenance of polyfunctional cytokines. TRAPS-seq presents a unique tool for seamless integration of secretomics measurements with multi-omics profiling in single cells.

Four Futures for Occupational Safety and Health.

Rapid changes to the nature of work have challenged the capacity of existing occupational safety and health (OSH) systems to ensure safe and productive workplaces. An effective response will require an expanded focus that includes new tools for anticipating and preparing for an uncertain future. Researchers at the U.S. National Institute for Occupational Safety and Health (NIOSH) have adopted the practice of strategic foresight to structure inquiry into how the future will impact OSH. Rooted in futures studies and strategic management, foresight creates well-researched and informed future scenarios that help organizations better prepare for potential challenges and take advantage of new opportunities. This paper summarizes the inaugural NIOSH strategic foresight project, which sought to promote institutional capacity in applied foresight while exploring the future of OSH research and practice activities. With multidisciplinary teams of subject matter experts at NIOSH, we undertook extensive exploration and information synthesis to inform the development of four alternative future scenarios for OSH. We describe the methods we developed to craft these futures and discuss their implications for OSH, including strategic responses that can serve as the basis for an action-oriented roadmap toward a preferred future.

Gastrointestinal conditions related to tooth wear.

Gastro-oesophageal reflux disease (GORD) is a relatively common condition that occurs in adults and less commonly in children. It develops when the reflux of stomach contents into the oesophagus causes troublesome symptoms and/or complications. Signs and symptoms include heartburn, retrosternal discomfort, epigastric pain and hoarseness, dental erosion, chronic cough, burning mouth syndrome, halitosis and laryngitis. A proportion of patients will, however, have silent reflux. Strongly associated risk factors include family history, age, hiatus hernia, obesity and neurological conditions, such as cerebral palsy. There are different treatment options which may be considered for GORD, consisting of conservative, medical and surgical therapy. Dentists should be aware of the symptoms of GORD and dental signs of intrinsic erosion indicative of possible GORD so that they can question patients about this and, if appropriate, initiate a referral to a general medical practitioner.

Psychological distress and quality of life among Opioid Agonist Treatment service users with a history of injecting and non-injecting drug use: A cross-sectional study in Kathmandu, Nepal.

BACKGROUND: Opioid use disorder is a serious public health problem in Nepal. People who use opioids often experience psychological distress and poor quality of life. Opioid agonist Treatment (OAT) is central in managing opioid dependence. This study aimed to examine factors associated with quality of life and serious psychological distress among OAT service users in the Kathmandu Valley, Nepal and compare those who had injected opioids prior to OAT and those who had not. METHODS: A cross-sectional study with 231 was conducted using a semi-structured questionnaire, the Nepalese versions of the Kessler 6 psychological distress scale and World Health Organization Quality of Life scale (WHOQOL-BREF). Bivariate and multivariate analyses were undertaken to examine factors associated with quality of life and serious psychological distress. RESULTS: Most participants were males (92%) and about half had injected opioids before initiating OAT. Serious psychological distress in the past four weeks was significantly more prevalent among participants with a history of injecting (32.2%) than those who did not inject (15.9%). In the adjusted linear regression model, those who had history of injecting were likely to have lower physical quality of life compared to non-injectors. Those self-reporting a past history of mental illness were more than seven times and those with medical comorbidity twice more likely to have serious psychological distress over last four weeks. Lower socioeconomic status and a history of self-reported mental illness in the past were found to be significantly associated with lower quality of life on all four domains. CONCLUSION: Those who had history of injecting were younger, had frequent quit attempts, higher medical comorbidity, lower socioeconomic status and remained longer in OAT services. Alongside OAT, the complex and entangled needs of service users, especially those with a history of injecting drugs, need to be addressed to improve quality of life and lessen psychological distress.

Four Cases of Acute Kidney Injury Requiring Dialysis in Ultramarathoners.

Transient acute kidney injury (AKI) following ultraendurance footraces is a common biochemical diagnosis. However, severe AKI requiring renal replacement therapy is uncommon in ultramarathoners. We report 4 runners (3 men; mean age, 44 ± 3 y) who required prolonged (10-42 d) dialysis following the Western States 100 Mile Endurance Run over a 3-y span (0.38% of starters). The maximum ambient temperatures on the race day ranged from 36.6° to 38.3°C. The runners presented to local hospitals 17 to 32 h after running, with laboratories confirming rhabdomyolysis, hyponatremia (mean serum sodium concentration, 127±2 mmol⋅L-1), and AKI (mean serum creatinine concentration, 8.5±2 mg⋅dL-1). The case-cluster report highlights the potential synergistic effects of high ambient temperatures, muscle damage, and electrolyte imbalance on protracted renal dysfunction in ultramarathoners competing in a warming world.

Quantification of spatial pharmacogene expression heterogeneity in breast tumors.

BACKGROUND: Chemotherapeutic drug concentrations vary across different regions of tumors and this is thought to be involved in development of chemotherapy resistance. Insufficient drug delivery to some regions of the tumor may be due to spatial differences in expression of genes involved in the disposition, transport, and detoxification of drugs (pharmacogenes). Therefore, in this study, we analyzed the spatial expression of 286 pharmacogenes in six breast cancer tissues using the recently developed Visium spatial transcriptomics platform to (1) determine if these pharmacogenes are expressed heterogeneously across tumor tissue and (2) to determine which pharmacogenes have the most spatial expression heterogeneity. METHODS AND RESULTS: The spatial transcriptomics technology sequences the transcriptome of 55 um diameter barcoded sections (spots) across a tissue sample. We analyzed spatial gene expression profiles of four biobank-sourced breast tumor samples in addition to two breast tumor sample datasets from 10× Genomics. We define heterogeneity as the interquartile range of read counts. Collectively, we identified 8887 spots in tumor regions, 3814 in stroma, 44 in lymphocytes, and 116 in normal regions based on pathologist annotation of the tissues. We showed statistically significant differences in expression of pharmacogenes in tumor regions compared to surrounding non-tumor regions. We also observed that the most heterogeneously expressed genes within tumor regions were involved in reactive oxygen species (ROS) handling and detoxification mechanisms. GPX4, GSTP1, MGST3, SOD1, CYP4Z1, CYB5R3, GSTK1, and NAT1 showed the most heterogeneous expression within tumor regions. CONCLUSIONS: The heterogeneous expression of these pharmacogenes may have important implications for cancer therapy due to their ability to impact drug distribution and efficacy throughout the tumor. Our results suggest that chemoresistance caused by expression of GPX4, GSTP1, MGST3, and SOD1 may be intrinsic, not acquired, since the heterogeneity is not specific to chemotherapy-treated samples or cell type. Additionally, we identified candidate chemoresistance pharmacogenes that can be further tested through focused follow-up studies.

Adjuvant Radiation Does Not Affect Locoregional Control Following Resection of Melanoma Satellitosis or In-Transit Disease.

BACKGROUND: This study evaluates the association of adjuvant radiation therapy (RT) with improved locoregional (LR) recurrence for resected melanoma satellitosis and in-transit disease (ITD). MATERIALS AND METHODS: Data were collected retrospectively for resected melanoma satellitosis/ITD from 1996 to 2017. RESULTS: 99 patients were identified. 20 patients (20.2%) received adjuvant RT while 79 (79.8%) did not. Mean follow-up in the RT group was 4.3 years and 4.7 years in the non-RT group. 80% of patients who underwent RT suffered a complication, most commonly dermatitis. Locoregional recurrence occurred in 9 patients (45%) treated with adjuvant RT and 30 patients (38%) in the non-RT group (P = 0.805). Median LR-DFS was 5.8 years in the RT group and 9.5 years in the non-RT group (P = 0.604). On multivariable analysis, having a close or positive margin was the only independent predictor of LR-DFS (HR 3.8 95% CI 1.7-8.7). In-transit disease was associated with improved overall survival when compared to satellitosis (HR 0.260, 95% CI 0.08-0.82). DISCUSSION: The use of adjuvant RT is not associated with improved locoregional control in resected melanoma satellitosis or ITD. Close or positive margin was the only treatment-related factor associated with decreased LR-DFS after surgical resection of satellitosis/ITD.