Reduction In Exposure Research Articles

Dry Powder Inhalation of Nintedanib in Dibasic Calcium Phosphate for Targeting the Lungs in Pulmonary Fibrosis.

We prepared three variants of nintedanib dry powder inhalations (DPIs), one with dibasic calcium phosphate dihydrate (CaHPO4·2H2O) and two with lactose monohydrate as the carrier. CaHPO4 is not reported as a DPI excipient. We compared nintedanib pharmacokinetics and efficacy of the CaHPO4 formulation against bleomycin-induced pulmonary fibrosis following oral (3.875 mg/q12h) and DPI (200 μg/12 h) dosing in rats. Blood plasma Cmax, Tmax, and AUC resulting from oral dosing and DPI were 780 versus 147.5 μg/mL, 2.47 versus 2.22 h, and 5562 versus 1094 μg/mL·h, respectively. Drug remaining in the lungs and airways at the end of 12 h of dosing with the DPI (2.41 ± 0.37 μg/g of tissue) was double the amount found after oral dosing (1.25 ± 0.56 μg/g). Lung fibrosis induced in rats using bleomycin was resolved equally well by the two interventions administered q12h for 14 days. We submit that the reduction in systemic exposure to nintedanib and enhanced exposure to target tissue could offer significant therapeutic and safety advantages, and CaHPO4 can be easily developed as an excipient for DPIs.

Interventions for reducing exposure to air pollution from landscape fires in a changing environment: A systematic review.

Emissions from more frequent and prolonged landscape fires (wildfires, risk reduction fires, agricultural burning) can expose populations to high levels of air pollution and exacerbate a range of health conditions. This systematic review aims to map, evaluate, and synthesise the scientific literature reporting interventions that can reduce exposure to landscape fire smoke (LFS). Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed, Scopus and Web of Science and reviewed relevant literature published until March 2024. Thirty-three studies from four countries met the eligibility criteria. Of the interventions evaluated, air filtration was the most frequently reported, and included use of portable air cleaners (PACs) with high efficiency particulate air (HEPA) filters, ventilation systems with standard and upgraded filters, and low-cost fan filter units (FFU). The effectiveness of PACs for fine particulate matter (PM2.5) reduction ranged between 54%-92%. In naturally ventilated residences, concentrations of PM2.5 were 0-44% lower indoors, and depended on the duration of LFS, building operation, and permeability. Mechanical ventilation with minimum efficiency reporting value (MERV) 5/8 filters in buildings reduced LFS PM2.5 levels by 18-58%; however, use of higher rated filters (e.g., MERV 12/13) achieved reductions of up to 87%. Communication interventions, including smartphone apps and alerts/messages from various media sources (e.g., radio, television, internet) had mixed results; nevertheless, inclusion of spirometry and asthma control surveys during app use could improve health outcomes for vulnerable groups. The efficacy of facemasks (N95/P2) was up to 94% for single pass PM2.5 removal, although they were relatively underutilised. Clean air shelters in public buildings can potentially provide a place for exposure reduction and social support, but have not been sufficiently tested during LFS events. Further research is needed on the effectiveness of interventions during prolonged smoke events, and in low- and middle-income countries.

P-1063. SCY-247: A Second-generation IV/Oral Triterpenoid Antifungal with Extensive Tissue Distribution and Pharmacokinetics, and Low Drug-Drug Interaction Potential

Abstract Background SCY-247 is an IV/oral second-generation triterpenoid anti-fungal for systemic fungal infections including multidrug resistant pathogens. Here we present translational data for nonclinical pharmacokinetics (PK) including dose-related tissue disposition in a murine C. glabrata model and correlation to reductions in fungal burden. Further, in vitro CYP450 interactions were evaluated to assess potential for clinical drug-drug interactions (DDIs). Methods The PK of SCY-247 was determined in rats and dogs. Plasma and tissue exposures were compared to reductions in kidney and lung fungal burden in a model of invasive C. glabrata. Neutropenic mice were infected IV with C. glabrata (∼108 yeast cells/mouse) and sacrificed on Day +7. Potential for inhibiting or inducing CYP450 isoforms was assessed in vitro using methods supportive of an FDA Investigational New Drug (IND) Application. Results SCY-247 has low clearance (∼10% liver blood flow) with half-life ≥15 hours following oral and IV administration to rat and dog consistent with once-daily administration in humans. Volume of distribution is ∼3 L/kg supportive of extensive tissue distribution. Exposure increased on repeat administration. Solubility of oral SCY-247 as a salt is >30 mg/mL at gastric pH consistent with rapid dissolution in the stomach and rapid absorption - as demonstrated by an early Tmax (0.5-2hr) following oral administration. In a murine model of C. glabrata infection, SCY-247 demonstrated dose-related increases in exposure and corresponding reduction in fungal burden (right figure panel) with higher distribution in kidney and lung tissue compared to plasma (left figure panel). In vitro, SCY-247 did not induce human CYP450s 1A2, 2B6 or 3A4. The IC50 values for inhibition of human 2C9, 2C19 and 3A isoforms were >20 μM ( >10-fold higher than the anticipated clinical Cmax) supportive of low risk of DDI’s for these isoforms. Conclusion SCY-247 has demonstrated dose- and tissue-related exposure reductions in fungal burden, PK consistent with once daily dosing to humans and low risk for CYP450-related DDIs. Disclosures Steve Wring, PhD, SCYNEXIS, Inc.: Advisor/Consultant Katyna Borroto-Esoda, MS, Scynexis Inc: Advisor/Consultant Nathan P. Wiederhold, PharmD, BioMerieux: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mycovia: Grant/Research Support|Scynexis: Grant/Research Support|Sfunga: Grant/Research Support David A. Angulo, MD, SCYNEXIS, Inc.: Board Member|SCYNEXIS, Inc.: SCYNEXIS, INC Officer and Board Member, SCYNEXIS Patents|SCYNEXIS, Inc.: Stocks/Bonds (Public Company)

Assessment of blood lead and haemoglobin levels among battery technicians and local government office workers in South-western Nigeria

Introduction: Human exposure to lead has significant public health problems. Occupational exposure of lead has shifted from industrial sources to battery repair activities. Battery technicians are at risk of exposure to lead via inhalation of fumes, oral ingestion and skin absorption. Objectives: To assess and compare blood lead and haemoglobin levels of battery technicians and local government office workers in South-western Nigeria Methods: A cross-sectional study with multi-stage sampling was used to compare battery technicians and office workers in Lagos State. A structured interviewer-administered questionnaire was used for data collection while blood samples were collected for lead and haemoglobin measurements. Chi-squared test, Mann-Whitney U test, Fisher’s exact test and Student t-test were used to test for significance at p≤0.05.Results: A total of 150 battery technicians and 150 office workers participated in the study. The battery technicians were less educated and earned less but had more years of working experience (p≤0.001) when compared to office workers. The median (range) blood lead value for battery workers was 9.0 (1.0-24.0) μg/dl compared to office workers 0.3 (0.01-3.2) μg/dl, which was statistically significant. The age of office workers was associated with their blood haemoglobin level. Conclusions & Recommendations: Blood lead level of battery technicians was significantly higher than that of the office workers but their haemoglobin levels were non-significant. A switch to repair of non-lead batteries, changing the work process by enclosing the battery during repairs, more trainings on lead exposure reduction, use of personal protective devices and regular biological monitoring of lead may control elevated lead level among battery technicians.

Reactions to disclosed biofeedback information on skin DNA damage in individuals after a beach holiday: a mixed methods intervention study.

The incidence of skin cancer among Danes is one of the highest in the world. Most skin cancers are, however, avoidable with sun protection and reduction of exposure. One way to increase awareness could be through personal biofeedback information about skin DNA damage. This study investigates the influence of biofeedback information about skin DNA damage on Danish beach holiday travelers' perception of risk of developing skin cancer and motivations for behaviour change. The intervention experiment included 20 participants aged 36-56 years, travelling to destinations with a high UV-index in February/March 2023. A new technology for detecting skin DNA damage in urine was used. Each participant was required to provide urine samples before and after travelling on holiday and participate in an interview about risk perceptions. The interviews were semi-structured and included the disclosure of DNA damage obtained during the holiday. Risk perceptions were assessed using a scale before and after the disclosure of biofeedback information. We identified key elements affecting perceived susceptibility of skin cancer as well as central barriers for behaviour change. The intervention increased risk perceptions for 35% of participants, and 30% expressed intentions to adopt more sun protective practices. However, most participants' perceived susceptibility to skin cancer did not change significantly, as the DNA damage still appeared too abstract. The findings suggest that biofeedback information can increase risk perceptions related to skin cancer and initiate intended behaviour change for some. Larger scale studies are needed and should include quantification of the individual DNA damage thereby making the assessed risk more relatable and personally relevant.

Extended Treatment Duration of Artemether-Lumefantrine in Ugandan Children with HIV on Efavirenz-Based Antiretroviral Therapy: A Randomized Controlled Pharmacokinetic and Pharmacodynamic Trial.

Malaria and HIV co-infection are prevalent in sub-Saharan Africa causing significant drug interactions with co-treatment. We previously reported a 30%-70% reduction in exposure to the standard 3-day (6-dose) artemether-lumefantrine (AL) treatment for malaria when given with efavirenz-based HIV therapy, impacting malaria reinfection risk. We conducted a prospective, randomized study comparing the 3-day regimen to an extended 5-day (10-dose) regimen with pharmacokinetic sampling for artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine (DBL) over 42 days. The primary outcome was comparative pharmacokinetics between regimens compared among children with HIV and among children without HIV receiving a 3-day regimen as controls (median age 5.3 years [range 1.4-13.9]; median weight 17.3 kg [range 8.7-39.1]). Children with HIV (n = 57; median age 10.8 years [range 3.4-17.1]; median weight 26.6 kg [range 14.6-54.5]) contributed 76 malaria episodes, with 71 included in the analysis. Another 97 children without HIV (median age 5.3 years [range 1.4-13.9]; median weight 17.3 kg [range 8.7-39.1]) contributed 114 episodes of malaria, with 109 included in the analysis. In the setting of efavirenz, artemether, dihydroartemisinin, lumefantrine, and DBL cumulative exposure was 2.09, 2.31, 1.90, and 1.65 fold higher with 5-day versus 3-day AL (all P <.001), and comparable to 3-day AL in children without HIV. The extended regimen in children with HIV did not result in a statistically significant reduction in recurrence risk at 28 or 42 days. Extending the duration of AL to 5 days compensated for a clinically significant reduction in all components of AL in the context of EFV-based antiretroviral therapy in young children.

Path Planning for Robots in Fire Scenarios based on Dijkstra Algorithm and Genetic Algorithm

Robots have emerged as a pivotal element in enhancing firefighting operations, offering a blend of efficiency and safety to human responders. This paper delves into the development of a path planning strategy for robots navigating through fire scenarios. Particularly we fused the Dijkstra Algorithm and Genetic Algorithm (GA). Our methodology commences with a simplified yet comprehensive definition of the fire environment, incorporating factors such as obstacle height, surface roughness, and fire sources. The environment and surroundings are represented by a 2.5-dimensional grid map. On the other hand, the robots traversal and ascent capabilities modeled to reflect varying velocities across different terrains. The Dijkstra Algorithm is subsequently utilized to identify the optimal path from the starting point to the destination, ensuring a balance between minimal traversal time and reduced thermal exposure. Our results, demonstrated through MATLAB simulations, reveal a marked improvement in path planning when GA optimization is applied. The comparative analysis across three scenarios underscores the versatility and effectiveness of our approach, showcasing a significant reduction in both traversal time and thermal exposure. Index TermsRobots, Firefighting, Path planning, Dijkstra, GA

Robotic pedicle screw placement for minimal invasive thoracolumbar spine surgery: a technical note.

Pedicle screw placement in spine surgery is a complex and delicate procedure that requires precise and accurate placement of pedicle screws. This technical note describes the steps involved in performing robotic assistance pedicle screw insertion in thoracolumbar spine surgery using the ExcelsiusGPS platform. This paper outlines the surgical techniques and intraoperative workflow for pedicle screw placement using the ExcelsiusGPS system. It also covers the surgical process, including patient positioning, dynamic reference placement, intraoperative cone-beam tomography, screw planning, exposure, and insertion techniques for spinal stabilization. A meta-analysis highlighted the significant advantages of robotic spine surgery over traditional freehand techniques, including a notably lower complication rate (4.83% vs. 14.97%) and up to a tenfold reduction in surgeon radiation exposure compared to fluoroscopy. Additionally, robotic systems enhance pedicle screw placement accuracy, achieving a 91.7% success rate. This higher accuracy is attributed to real-time screw planning, trajectory guidance, and precise adjustments in robotic-assisted surgery. These advantages establish robotic assistance as a crucial innovation for enhancing surgical precision and patient safety, although it requires careful handling of technical challenges like alignment changes in highly flexible bones and ensuring accurate instrument trajectory during screw placement. Robotic-assisted spine surgery improves pedicle screw accuracy with real-time planning and trajectory adjustments, reducing complications and radiation exposure. However, higher costs and increased screw use warrant careful evaluation of its cost-effectiveness and impact on healthcare resources.

Use of teledentistry in pediatric dentistry in times of the covid-19 pandemic: literature review [English translation-Original in Spanish

At the beginning of 2020, the virus that initiates COVID-19 emerges. Therefore, limitations were imposed on the interactions in the pediatric dental office. Teledentistry became an option to provide dental services to pediatric patients. The purpose of this literature review was to determine the use of teledentistry in pediatric dentistry during COVID-19 pandemic. A search was conducted on platforms such as: Ebsco, Scielo, Lilacs, Pubmed and Google Scholar regarding it. It was found that teledentistry was used for the purposes like as the diagnosis and promotion of oral health, measurement of knowledge of parents about children’s oral health, to perform dental appliance checks, to measure the attitude and knowledge of teledentistry by the pediatric dentist and to carry out disease prevention and control in special patients. Objective: The purpose of this literature review was to determine the use of teledentistry in pediatric dentistry in times of the COVID-19 pandemic. Methodology: The selection criteria included case reports, original articles and randomized clinical trials in Spanish or English published from 2020 to 2022. Articles other than Spanish or English were excluded. The research question is: What is the use of teledentistry in Pediatric Dentistry in times of the Covid-19 pandemic? P= pediatric patients in need of dental care in times of the Covid-19 pandemic. I= teledentistry C= not receiving dental care O= reduction in viral exposure of the pediatric patient during dental consultation, guidelines for dental care in times of pandemic, appropriate use of teledentistry in pandemic. The article search strategy was conducted on platforms such as: EBSCO, Scielo, LILACS, Pubmed and Google Scholar. Results: It was found that teledentistry was used for diagnosis and promotion of oral health, to measure parents’ knowledge of children’s oral health, perform dental appliance checks, measure the attitude and knowledge of teledentistry by the pediatric dentist and to conduct prevention and control of diseases in special patients.

Impact of particulate matter exposure on melanoma risk: A multicentre case-control study.

The relationship between particulate matter (PM) exposure and melanoma risk remains largely unexplored. This study aims to investigate the association between PM10 and PM2.5 long-term exposure and melanoma risk. Case-control study involving 2575 participants, comprising 1473 melanoma patients and 1102 healthy controls attending Departments of Dermatology of University Hospital in North and Central Italy. Demographic data, smoking status, history of sunburns and skin type were collected. PM10 and PM2.5 exposure levels were estimated for each participant's residential address using a Bayesian hierarchical model, providing daily concentrations at a 1 km2 spatial resolution from 2013 to 2021. Logistic regression analyses were performed to evaluate the association between PM exposure and melanoma risk, adjusting for potential confounders. Melanoma patients and controls were 52% males and had a mean age of 63.89 and 61.66 years, respectively. The majority of melanoma patients had Fitzpatrick phototypes 2 (59%) and 3 (36%). There were no significant differences in the geographical distribution of cases and controls based on ZIP codes (p = 0.894). The average melanoma Breslow thickness was 1.01 mm, with 68.15% of cases diagnosed at stage 0 and IA. The multivariate logistic regression revealed a protective effect for higher PM10 (OR = 0.89, 95%CI: 0.86-0.92, p < 0.001) and PM2.5 levels (OR = 0.72, 95%CI: 0.68-0.76, p < 0.001). Darker skin phototypes (Fitzpatrick 4) and cigarette smoking were also associated with a reduced risk of melanoma. Higher levels of PM10 and PM2.5 may have a protective effect against melanoma, potentially due to the reduction in ultraviolet radiation exposure. Further research to understand the complex interactions between environmental factors and melanoma risk are needed.

Gut decontamination in the poisoned patient.

Poisoning management includes gastrointestinal decontamination strategies to decrease the burden of poison entering the body and change the expected severe toxicity expected to a less toxic, more favourable outcome. Common modalities are orogastric lavage, oral-activated charcoal and whole-bowel irrigation. Endoscopic retrieval and laparotomy are rare options reserved for severe ingestions and body packers. Although supporting data are generally of low quality, gastrointestinal decontamination is likely to improve patient outcome in many situations. Unfortunately, technical limitations and contraindications can explain their infrequent use. Orogastric lavage can be useful for early lethal ingestions, albeit with significant complications such as aspiration and perforation. Activated charcoal cannot adsorb every substance. Usual dosing is 1g/kg per dose. Whole-bowel irrigation is reserved for charged molecules or substances not adsorbed to activated charcoal but requires intact gut motility. Indications depend on several factors inherent to the ingestion (dose, time, poison) and patient's characteristics. During recent decades, studies of newer pharmaceuticals or modified-release formulations showed that significant amounts of poison, especially pharmacobezoars, persist in the gut hours postingestion, thus are amenable to gastrointestinal decontamination. Improved understanding of gut motility in volunteer studies and overdose showed clinically significant reduction in drug exposure with activated charcoal. The 1-h dogma for gastrointestinal decontamination, especially activated charcoal, is now obsolete. Clinicians must perform a risk assessment for each ingestion to determine the expected benefit at the time of decision-making, choosing the modality to achieve reduction in the toxicity burden while planning for complications or contraindications.

The hidden danger from farm to table: transforming food safety through innovative approaches to reducing harmful chemicals in the American food system

The American food system faces significant challenges in ensuring food safety, particularly in mitigating the presence of harmful chemicals from farm to table. From pesticide residues in crops to chemical additives in processed foods, these contaminants pose risks to public health and the environment. This paper explores innovative approaches to reducing harmful chemicals in the food supply chain, emphasizing technological advancements, regulatory reforms, and sustainable agricultural practices. Key strategies include the adoption of precision agriculture to minimize pesticide use, the integration of biopesticides and organic fertilizers, and the development of advanced food processing techniques to limit chemical exposure. The role of regulatory frameworks is also examined, highlighting the need for stricter enforcement of safety standards and enhanced monitoring systems to track chemical use and contamination levels. Furthermore, this study underscores the importance of public awareness and consumer advocacy in driving change within the food industry. Collaborative efforts between policymakers, agricultural producers, food manufacturers, and researchers are essential to achieving a safer food system. The paper demonstrates how leveraging technology such as blockchain for traceability and artificial intelligence for real-time monitoring can significantly reduce chemical risks while improving transparency across the supply chain. Case studies from successful initiatives provide actionable insights into how these approaches have led to measurable reductions in harmful chemical exposure. By addressing these challenges and opportunities, this research contributes to a deeper understanding of the hidden dangers in the food system and outlines a path toward a safer, more sustainable future. Key findings reveal that an integrated approach combining innovation, policy, and consumer engagement is critical to transforming food safety standards and protecting public health. Keywords: Food Safety, Harmful Chemicals, American Food System, Precision Agriculture, Biopesticides, Regulatory Frameworks, Sustainable Practices, Blockchain Traceability, Public Health, Chemical Reduction.

Influence of Hospital Bed Count on the Positioning of Cardiovascular Interventional Radiology (IR) Nurses: Online Questionnaire Survey of Japanese IR-Specialized Radiological Technologists.

Interventional radiology (IR) utilizing X-rays can lead to occupational radiation exposure, posing health risks for medical personnel in the field. We previously conducted a survey on the occupational radiation exposure of IR nurses in three designated emergency hospitals in Japan. Our findings indicated that a hospital with 214 beds showed a higher lens-equivalent dose than hospitals with 678 and 1182 beds because the distance between the X-ray irradiation field and the IR nurse's position of the hospital with 214 beds was shorter than those of 678 and 1182 beds. Based on these observations, we hypothesized that the number of hospital beds affects the distance between the X-ray irradiation field and the IR nurse's position. To verify this hypothesis, we conducted a more extensive online questionnaire survey, focusing exclusively on hospitals that perform cardiovascular IR. We analyzed data from 78 facilities. The results of this study confirmed our earlier findings, showing that both the number of physicians performing IR procedures and the distance from the X-ray irradiation field to the IR nurse's position are influenced by the number of hospital beds. Additionally, factors such as the type of hospital, emergency medical system, annual number of IR sessions, location of medical equipment, and the positioning of IR nurses appear to be associated with the number of hospital beds. Understanding these relationships could enable the development of individualized and prioritized radiation exposure reduction measures for IR nurses in high-risk settings, provided that comprehensive occupational radiation risk assessments for cardiovascular IR consider the number of hospital beds and related factors. This study was not registered.

Reductions in exposures to simulated respiratory aerosols by a ceiling-mounted HEPA air filtration unit

Reductions in exposures to simulated respiratory aerosols by a ceiling-mounted HEPA air filtration unit

Evaluation of three diagnostic algorithms to reduce normal scan rates, radiation exposure and costs in patients with suspected chronic coronary syndrome referred for 82Rb-Positron Emission Tomography (82Rb-PET)

BackgroundThe majority of functional ischemia tests in patients with suspected chronic coronary syndromes (CCS) yield normal results. Implementing gatekeepers for patient preselection, such as pretest probability (PTP) and/or coronary artery...

Estimating Maxillary Sinus Volume Using Smartphone Camera.

Goal: This study aims to introduce a novel method for estimating maxillary sinus volume using smartphone technology, providing an accessible alternative to traditional imaging techniques. Methods: We recruited 40 participants to conduct a comparative analysis between Computed Tomography (CT) and face scans obtained using an Apple iPhone. Utilizing Apple's ARKit for 3D facial mesh modeling, we estimated sinus dimensions based on established craniofacial landmarks and calculated the volume through a geometric approximation of the maxillary sinus. Results: We demonstrated a high degree of agreement between CT and face scans, with Mean Absolute Percentage Errors (MAPE) of 8.006 ± 8.839% (Width), 6.725 ± 4.595% (Height), 9.952 ± 6.733% (Depth), and 10.429 ± 7.409% (Volume). These results suggest the feasibility of this non-invasive approach for clinical use. Conclusions: This method aligns with the growing focus on telemedicine, presenting significant reductions in healthcare costs and radiation exposure from CT scans. It marks a substantial advancement in otolaryngology and maxillofacial surgery, showcasing the integration of smartphone technology in medical diagnostics and opening avenues for innovative, patient-friendly, and cost-effective healthcare solutions.

Annual trends in mercury contamination are associated with changing trophic niches of giant petrels.

Annual variation in prey availability can influence seabird diets and hence their exposure to pollutants, including mercury (Hg). Among seabirds, those species that scavenge carrion of marine mammals and other top predators may be especially vulnerable to accumulating high Hg concentrations. In this study, total Hg (THg) concentrations and carbon (δ13C) and nitrogen (δ15N) stable isotope values were measured in chick feathers of northern giant petrels Macronectes halli and southern giant petrels M. giganteus at Bird Island, South Georgia (2013-2020). Both species are opportunistic predator-scavengers which feed mainly on penguins and Antarctic fur seal Arctocephalus gazella carrion, and to lesser extents on marine prey and other seabirds. THg concentrations were not significantly different between northern giant petrels and southern giant petrels (means ± SDs, 2.49 ± 0.92 μg g-1 dw and 2.34 ± 0.85 μg g-1 dw, respectively), but concentrations in both species declined signficantly over time, as did δ13C and δ15N values. Annual feather THg concentrations of giant petrels were positively correlated with the number of dead Antarctic fur seal pups and their mortality rate at Bird Island, but not with population sizes or breeding success of penguins. Accordingly, these results suggest a shift away from carrion (associated with the decreasing size and productivity of the Antarctic fur seal population) and towards the consumption of prey from lower trophic levels (e.g., Antarctic krill Euphausia superba), with a corresponding reduction in dietary Hg exposure. Future work should investigate the consequences of changing prey availability for diets and pollutant exposure of other marine predators within the South Georgia and Scotia Sea marine ecosystems, given the ongoing environmental changes in the region.

Salt exposure and emission reduction strategies in typical industrial wastewater treatment processes

Salt exposure and emission reduction strategies in typical industrial wastewater treatment processes

A Phase 1, Open-Label, Randomized, Two-Part Study in Healthy Adult Volunteers to Evaluate the Bioavailability of the Maribavir Powder for Oral Suspension, as Well as Food Effect and Impact of Rabeprazole.

The relative bioavailability and impact of food and the proton pump inhibitor rabeprazole on the pharmacokinetics of a maribavir powder-for-oral-suspension formulation was investigated in a Phase 1 open-label study in healthy adult volunteers. A single 200-mg maribavir dose was administered as the commercial tablet (Treatment A), powder formulation (Treatment B), or powder formulation with a high-fat/high-calorie meal (Treatment C) in Part 1, and as the powder formulation alone (Treatment D) or following administration of rabeprazole 20mg once daily for 5 days (Treatment E) in Part 2. Maribavir maximum plasma concentration following Treatment B was 18% lower versus Treatment A, whereas the area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration or infinity were similar. Maribavir maximum plasma concentration, AUC from time 0 to the last quantifiable concentration, and AUC from time 0 to infinity were reduced by 42%, 18%, and 18% (Treatment C vs Treatment B), and by 51%, 30%, and 11% (Treatment E vs Treatment D), respectively. A clinically significant reduction in maribavir exposure is not expected when maribavir powder formulation is taken with food or proton pump inhibitors. Participants assessed the powder for oral suspension as easy to swallow and having an acceptable taste/texture. Safety profiles for maribavir formulations in this study were consistent with those previously published.

Hearing Loss Is Associated With Increased Mortality in a Cohort of Older Construction Trades Workers.

Hearing loss has been associated with increased mortality, and there is evidence that regular use of hearing aids reduces the mortality risk. However, these associations have not been sufficiently studied in worker populations at high risk for noise-induced hearing loss. Medical examination data for 19,379 workers employed in US Department of Energy (DOE) facilities were used. Speech-frequency pure-tone average hearing loss and hearing aid use were ascertained. Mortality status through 2021 was obtained from the National Death Index. Cox regression examined the association between hearing loss and mortality and the impact of hearing aid use. Eight thousand eighty-one workers (41.3%) had speech-frequency hearing loss and 2228 (15.3%) of these workers reported use of hearing aids. A total of 5398 deaths occurred over a median follow-up of 11.1 years. Hearing loss was an independent risk factor for higher mortality with an adjusted hazard ratio (HR) of 1.10 (95% CI = 1.03-1.17). The HR increased with hearing loss severity but the relationship was non-linear. Hearing aid users were at 30% reduced risk of mortality compared to those not using hearing aids (HR = 0.70, 95% CI = 0.63-0.77). Results are consistent with research linking hearing loss with increased mortality and the preventive impact of hearing aid use. These findings should inform workers' compensation programs in favor of: (1) better coverage of hearing loss for noise-exposed workers, and (2) inclusion of hearing aids in medical benefits. Reduction in noise exposures is a priority and workers with hearing loss should be encouraged to use hearing aids.