Quantifying 209 Polychlorinated Biphenyl Congeners in Silicone Wristbands to Evaluate Differences in Exposure among Demolition Workers.

A social housing estate in Denmark was designated for demolition due to exceedance of guidance values for polychlorinated biphenyls (PCBs) in indoor air. Here, we deployed precleaned silicone wristbands (n = 46) among demolition workers of these contaminated buildings during single workdays while conducting various work tasks. We established a method to analyze all 209 PCBs in wristbands to identify prominent congeners of exposure and evaluate differences between tasks. Wristbands were extracted using microwave-assisted extraction and then concentrated for gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis. Twenty-nine chromatographic peaks representing 37 congeners were detected in every wristband, and tetra-CBs were the dominant homologue group. PCB-66, -44, and -70 were the most abundant congeners measured in worker wristbands, none of which are included within the typical seven indicator or WHO 12 PCBs. Workers who cut PCB-containing sealants had wristbands with the highest PCB concentrations (geometric mean ∑209PCBs = 1963 ng/g wristband), which were followed by those handling concrete elements on the building roof. Additionally, wristbands captured a broader range of PCBs than has been previously measured in air and serum samples. Taken together, our results highlight the importance of total congener analysis in assessing current PCB exposure in demolition work and the utility of wristbands for assessing these exposures.

Organophosphate ester (OPE) exposure among waste recycling and administrative workers in Denmark using silicone wristbands.

In a recent estimate, 96 million tons of hazardous waste were produced in the European Union, most of which were handled among the member states. Organophosphate esters (OPEs) are applied as flame retardants and plasticizers and are present in many products, e.g., electronics, which end up in the hazardous waste stream upon disposal. Given the growing body of information suggesting potential adverse health effects of OPEs, waste recycling workers who handle hazardous waste could potentially be at risk of elevated exposure to these chemicals. Using silicone wristbands, we evaluated OPE exposure among waste recycling workers who handled hazardous waste and compared their exposure to that of administrative workers from the same waste companies. Wristbands were extracted and analyzed for six OPEs, which were all detected in >75% of wristbands. Overall, the sum of tris(2-chloroisopropyl) phosphate (∑TCIPP) isomers was the most abundant OPE across all wristbands collected within the study. In general, the sum of tri(methyl phenyl) phosphate isomers (∑TMPP) was elevated for all waste workers (10ß = 7.9), whereas tri-n-butyl phosphate (TnBP), tris(1,3-dichloroisopropyl) phosphate (TDCIPP), and ∑TMPP were 3-12 times higher among those specifically handling electronic and hazardous waste compared to the administrative workers (p < 0.05). Repeated wristband measurements from the same worker had fair to good consistency in OPE concentrations (intraclass correlation coefficients = 0.54-0.77), except for the two most volatile chlorinated OPEs. Taken together, our results suggest that waste recycling workers who handle electronic and hazardous waste have significantly elevated exposure to OPEs, and efforts to reduce these exposures should be considered.

Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial.

BACKGROUND: Inadequate dose titration and poor adherence to basal insulin can lead to suboptimal glycemic control in persons with type 2 diabetes (T2D). Once-weekly insulin icodec (icodec) is a basal insulin analogue that is in development and is aimed at reducing treatment burden. OBJECTIVE: To compare the effectiveness and safety of icodec titrated with a dosing guide app (icodec with app) versus once-daily basal insulin analogues (OD analogues) dosed per standard practice. DESIGN: 52-week, randomized, open-label, parallel-group, phase 3a trial with real-world elements. (ClinicalTrials.gov: NCT04760626). SETTING: 176 sites in 7 countries. PARTICIPANTS: 1085 insulin-naive adults with T2D. INTERVENTION: Icodec with app or OD analogue (insulin degludec, insulin glargine U100, or insulin glargine U300). MEASUREMENTS: The primary outcome was change in glycated hemoglobin (HbA1c) level from baseline to week 52. Secondary outcomes included patient-reported outcomes (Treatment Related Impact Measure for Diabetes [TRIM-D] compliance domain score and change in Diabetes Treatment Satisfaction Questionnaire [DTSQ] total treatment satisfaction score). RESULTS: The estimated mean change in HbA1c level from baseline to week 52 was greater with icodec with app than with OD analogues, with noninferiority (P < 0.001) and superiority (P = 0.009) confirmed in prespecified hierarchical testing (estimated treatment difference [ETD], -0.38 percentage points [95% CI, -0.66 to -0.09 percentage points]). At week 52, patient-reported outcomes were more favorable with icodec with app than with OD analogues (ETDs, 3.04 [CI, 1.28 to 4.81] for TRIM-D and 0.78 [CI, 0.10 to 1.47] for DTSQ). Rates of clinically significant or severe hypoglycemia were low and similar with both treatments. LIMITATION: Inability to differentiate the effects of icodec and the dosing guide app. CONCLUSION: Compared with OD analogues, icodec with app showed superior HbA1c reduction and improved treatment satisfaction and compliance with similarly low hypoglycemia rates. PRIMARY FUNDING SOURCE: Novo Nordisk A/S.

Exposure to airborne polychlorinated biphenyls and type 2 diabetes in a Danish cohort.

BACKGROUND: Previous research indicates an association between higher-chlorinated polychlorinated biphenyls (PCBs) and type 2 diabetes (T2D). However, less is known about the extent to which PCB exposure in indoor air, composed primarily of lower-chlorinated PCBs, affects T2D risk. We assessed the association between indoor air exposure to PCBs in residential buildings and T2D incidence. METHODS: The register-based 'Health Effects of PCBs in Indoor Air' (HESPAIR) cohort comprises 51,921 Danish residents of two residential areas with apartments built with and without PCB-containing materials (reference apartments). We assessed exposure status by combining register-based information on relocation history with extrapolated values of exposure based on PCB-measurements in indoor air from subsets of the apartments. T2D cases were identified in the Danish registers during 1977-2018. We estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression analyses with time-varying exposure. RESULTS: We identified 2737 incident T2D cases during the follow-up. Exposure to ≥3300 ng/m3 PCB × year (3rd tertile of PCByear) was associated with higher risk of T2D (HR 1.15, 95% CI 1.02-1.30) compared with exposure to <300 ng/m3 PCB × year (reference). However, among individuals with lower cumulated PCByear, the risk was similar to residents with exposure <300 ng/m3 PCB × year (300-899 ng/m3 PCB × year: HR 0.98, 95% CI 0.87-1.11; 900-3299 ng/m3 PCB × year: HR 0.96, 95% CI 0.83-1.10). DISCUSSION: We observed a marginally higher risk of T2D, but there was no evidence of an exposure-response relationship. The results should be interpreted with caution until confirmed in other independent studies of PCB exposure in indoor air.

Risk assessment of the asthma-induction potential of substances in spray products for car cabin detailing - based on EU's Chemical Agents Directive, using harmonised classifications and quantitative structure-activity relationship (QSAR).

Exposure to spray-formulated products for car cabin detailing is a potential risk for asthma induction. With a focus on the asthma-related endpoints sensitisation and irritation of the lungs, we performed an occupational risk assessment based on requirements in the EU Chemical Agents Directive. We identified 71 such spray products available in Denmark. We identified ingredient substances in safety data sheets and screened for harmonised classifications of respiratory sensitisation and airway irritation. For respiratory sensitisation, we also applied quantitative structure-activity relationship (QSAR). We modelled the exposure during 15 min of work inside a car cabin, and determined the risk ratio of the products by further applying occupational exposure limits - mainly derived no-effect levels (DNELs) from the European Chemicals Agency (ECHA) set on respiratory irritation. Four substances had a harmonised classification for respiratory irritation (bronopol, 2-phenoxyethanol, 2-methoxypropanol, and butan-1-ol). Seven substances were positive in the QSAR model for respiratory sensitisation (monoethanolamine, bronopol, glycerol, methyl salicylate, benzoic acid, ammonium benzoate, and sodium benzoate). Two vinyl treatment products had a risk ratio > 1 based on the level of sodium benzoate and its DNEL set on respiratory irritation. Two products had risk ratios of 0.69 and 0.73, respectively, based on 2-methyl-2 H-isothiazol-3-one and its acute DNEL set on respiratory irritation. In conclusion, 10 substances that may pose a risk for asthma induction were identified in the products. Two of the 71 products had a risk ratio > 1, meaning they may pose an asthma-induction risk in the modelled exposure scenario and using respiratory irritation DNELs from ECHA.

Characterization of the aerosol release from spray cleaning and disinfection products - Spray scenarios in a climate chamber.

Cleaning work using spray products has been associated with adverse respiratory effects but little is known of the exposure concentrations. The purpose of this study was to characterize aerosol generation at spray scenarios in a controlled climate chamber. Spraying on vertically and horizontally oriented surfaces, as well as spraying on a cloth, was investigated. Furthermore, the effect of nozzle geometry was tested. The average mass generation rates of six pressurized spray cans and 13 trigger sprays were about 1.7 g/s and did not differ significantly, but the average values of the individual sprays had large variations (0.5-3.1 g/s). The time required to halve the air concentration of aerosol particles, the half-life time, was determined for all spray products. The average half-life time of the total particle mass concentration (TPMC) of the pressurized spray cans was 0.5 h versus 0.25 h for trigger sprays. Gravimetrically determined airborne fractions of pressurized spray cans tended to be higher than those of trigger sprays. However, airborne fractions based on the measured peak TPMC were up to three orders of magnitude smaller. A comparison of different trigger spray nozzles when spraying the same product showed that the TPMC can be up to 18 times higher for the largest emitting nozzle. The distance of the nozzle to a cloth should be 1 cm to significantly reduce the concentration of the generated aerosols. ConsExpo modeling predicted the measured peak TPMC well but less well the decay.

Correlation Between Time in Range and HbA1c in People with Type 2 Diabetes on Basal Insulin: Post Hoc Analysis of the SWITCH PRO Study.

INTRODUCTION: Use of continuous glucose monitoring (CGM) in people with diabetes may provide a more complete picture of glycemic control than glycated hemoglobin (HbA1c) measurements, which do not capture day-to-day fluctuations in blood glucose levels. The randomized, crossover, phase IV SWITCH PRO study assessed time in range (TIR), derived from CGM, following treatment with insulin degludec or insulin glargine U100 in patients with type 2 diabetes at risk for hypoglycemia. This post hoc analysis evaluated the relationship between TIR and HbA1c, following treatment intensification during the SWITCH PRO study. METHODS: Correlation between absolute values for TIR (assessed over 2-week intervals) and HbA1c, at baseline and at the end of maintenance period 1 (M1; week 18) or maintenance period 2 (M2; week 36), were assessed by linear regression and using the Spearman correlation coefficient (rs). These methods were also used to assess correlation between change in TIR and change in HbA1c from baseline to the end of M1, both in the full cohort and in subgroups stratified by baseline median HbA1c (≥ 7.5% [≥ 58.5 mmol/mol] or < 7.5% [< 58.5 mmol/mol]). RESULTS: A total of 419 participants were included in the analysis. A moderate inverse linear correlation was observed between TIR and HbA1c at baseline (rs -0.54), becoming stronger following treatment intensification during maintenance periods M1 (weeks 17-18: rs -0.59) and M2 (weeks 35-36: rs -0.60). Changes in TIR and HbA1c from baseline to end of M1 were also linearly inversely correlated in the full cohort (rs -0.40) and the subgroup with baseline HbA1c ≥ 7.5% (rs -0.43). This was less apparent in the subgroup with baseline HbA1c < 7.5% (rs -0.17) (p-interaction = 0.07). CONCLUSION: Results from this post hoc analysis of data from SWITCH PRO, one of the first large interventional clinical studies to use TIR as the primary outcome, further support TIR as a valid clinical indicator of glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03687827.

Risk of cardiovascular diseases following residential exposure to airborne polychlorinated biphenyls: A register-based cohort study.

BACKGROUND: Indoor air in buildings constructed with materials containing polychlorinated biphenyls (PCBs) may be contaminated with especially lower-chlorinated PCBs. So far, the cardiovascular consequences of living with such contamination are unknown. OBJECTIVES: To determine the risk of cardiovascular disease (CVD) following residential exposure to predominantly lower-chlorinated PCBs in indoor air. METHODS: The Health Effects of PCBs in Indoor Air (HESPAIR) cohort is register-based with 51 921 residents of two residential areas near Copenhagen: Farum Midtpunkt and Brøndby Strand Parkerne. Here, indoor air was contaminated with PCB in one third of the apartments due to construction with materials containing PCB. Individual PCB exposure was estimated based on register-based information on relocation dates and indoor air PCB measurements in subsets of the apartments. Information on CVD was retrieved from the Danish National Patient Register for the follow-up period of 1977-2018. We estimated adjusted hazard ratios using Cox regression with time-varying exposure. RESULTS: Cumulative residential exposure to airborne PCB was not associated with a higher overall risk for CVD (HR for highly exposed (≥3300 ng/m3 PCB × year): 1.02, 95% CI 0.94-1.10). This was also the case for most of the specific cardiovascular diseases, apart from acute myocardial infarction where a higher risk was observed for residents exposed to ≥3300 ng/m3 PCB × year compared to the reference group (HR 1.17, 95% CI 1.00-1.35). However, no exposure-response relationship was apparent and additional adjustment for education attenuated the risk estimate. DISCUSSION: In this, to our knowledge, first study ever to examine the risk of CVD following residential exposure to PCBs in indoor air, we observed limited support for cardiovascular effects of living in PCB-contaminated indoor air. Considering the prevalence of exposure to airborne PCBs and lack of literature on their potential health effects, these findings need to be corroborated in other studies.

Inhalation and dermal absorption as dominant pathways of PCB exposure for residents of contaminated apartment buildings.

Applications of polychlorinated biphenyls (PCBs) in buildings and their persistence in indoor environments have led to cases of current and highly elevated exposure in humans, despite the global cease of production decades ago. Personal exposure to PCBs was assessed among residents in a social housing estate in Denmark containing both contaminated (n = 67) and non-contaminated (n = 23) apartments. Samples and estimated daily intakes (EDIs) were assessed for 15 PCB congeners, and body burden, which was limited by the dietary data availability, was compared across 7 indicator PCBs, with its sum (PCBsum7) often applied in European regulation of PCBs. Median PCBsum7 EDI across measured pathways for exposed residents was 101 ng· (kg bodyweight)-1· day-1, with the majority of exposure (60%) coming from inhalation of contaminated indoor air. Calculated from both PCBs measured in indoor air and on hand wipes, dermal absorption estimates showed comparable results and served as a secondary exposure pathway, accounting for 35% of personal exposure and considering selected assumptions and sources of physical-chemical parameters. Estimates revealed that diet was the primary PCB source among the reference group, accounting for over 75% of the PCBsum7 EDI across exposure routes. When evaluating overall EDIs across the two study groups and including dietary estimates, PCB exposure among exposed residents was around 10 times higher than the reference group. Solely within the exposed population, pathway-specific body burdens were calculated to account for exposure across years of residence in contaminated apartments, where lower chlorinated PCBs were dominant in indoor air. Among these dominant congeners, estimated body burdens of PCB-28 and -52 were significantly correlated with measured serum (rs = 0.49, 0.45; p < 0.001). This study demonstrates that inhalation and dermal absorption serve as dominant exposure pathways for residents of apartments contaminated with predominantly lower chlorinated PCBs and suggest that predictions of body burden from indoor environment measurements may be comparable to measured serum PCBs.

Cancer Risk following Residential Exposure to Airborne Polychlorinated Biphenyls: A Danish Register-Based Cohort Study.

BACKGROUND: Polychlorinated biphenyls (PCBs) are biopersistent chemicals classified as human carcinogens. This classification is primarily based on evidence on higher-chlorinated PCBs found in food. The carcinogenic potential of airborne lower-chlorinated PCBs remains largely unexplored. OBJECTIVES: We aimed to investigate cancer risk following residential exposure to airborne PCBs. METHODS: Cancer risk was examined in the Health Effects of PCBs in Indoor Air (HESPAIR) cohort of 38,613 residents of two partly PCB-contaminated residential areas in Greater Copenhagen, identified by nationwide registries. PCB exposure was based on relocation dates and indoor air PCB measurements in subsets of apartments. Cancer diagnoses were extracted from the Danish Cancer Registry for the follow-up period of 1970-2018. We estimated adjusted hazard ratios with time-varying cumulative exposure and a 10-y lag using Cox regression. RESULTS: Overall risk of cancer was not associated with PCByear, [hazard ratio (HR) for high-exposed vs. low-exposed =0.98; 95% confidence interval (CI): 0.88, 1.09], but residents exposed to ≥3,000 ng/m3 PCB×year had higher risk of liver cancer (HR =2.81; 95% CI: 1.28, 6.15) and meningiomas (HR =3.49; 95% CI: 1.84, 6.64), with indications of exposure-response relationships. Results were suggestive of a higher risk of pancreatic cancer (HR =1.59; 95% CI: 0.95, 2.64) at the highest aggregated PCB level. For testis cancer, a higher risk was observed among residents exposed to 300-949 ng/m3 PCB×year relative to residents exposed to <300 ng/m3 PCB×year (HR =2.97; 95% CI: 1.41, 6.28), but the risk was not higher for residents exposed to ≥950 ng/m3 PCB×year. Apart from this, the risk of specific cancers was similar across exposure groups. DISCUSSION: In this, to our knowledge, first population-based cohort study of residential exposure to airborne PCBs, we found no association between exposure to PCBs in indoor air in private homes and the risk for most of the specific cancers. Higher risk of liver cancer and meningiomas were observed. https://doi.org/10.1289/EHP10605.

Silicone wristbands as personal passive samplers of exposure to polychlorinated biphenyls in contaminated buildings.

Polychlorinated biphenyls (PCBs) were used in a number of industrial products from 1950 to 80s, including building materials. As a result, some buildings exhibit high levels of PCBs in the indoor environment. The aim of this study was to test silicone wristbands as a method for estimating personal exposure to PCBs in buildings both in controlled experiments and field settings. In the controlled study, the sampling kinetics of silicone wristbands were investigated in a 31-day uptake study. The field study focused on the application of wristbands as a personal exposure measure. It included 71 persons in a contaminated housing estate and 23 persons in a reference group. The linear uptake of PCBs ranged from 2 to 24 days for PCB-8, 18, 28, 31, 40, 44, 49, 52, 66, 99, and 101 under controlled conditions. A generic sampling rate (Rk) of 2.3 m3 d-1 corresponding to a mass transfer coefficient of 17 m h-1 was found in the controlled kinetic study. Partitioning coefficients were also determined for the nine congeners. In the field study, an apparent generic field sampling rate (Rf) of 2.6 m3 d-1 was found; when adjusted to reported hours exposed, it increased to 3.5 m3 d-1. The wristbands were shown to be a good tool for predicting airborne exposure, as there was a highly significant difference between the exposed and reference group as well as a clear trend when used for ranking of exposure. In correlation analyses, highly significant correlations were observed between air and wristband levels, though adjusting by self-reported exposure time only increased the correlation marginally in the field study. The obtained kinetic data can be used for estimating the magnitude of external exposure. The advantages provided by the wristbands in the form of easy use and handling are significant, though the limitations should also be acknowledged.

Identification of substances with a carcinogenic potential in spray-formulated engine/brake cleaners and lubricating products, available in the European Union (EU) - based on IARC and EU-harmonised classifications and QSAR predictions.

Spray-formulated engine/brake cleaners and lubricating agents are widely used to maintain machines. The occupational exposure to their aerosols is evident. To assess the carcinogenic potential of these products, we identified such products available in the European Union (EU). We built a database with CAS numbers of 1) mono-constituent substances, and 2) multi-constituent-substances, and unknown-or-variable-composition,-complex-reaction-products-and-biological-materials (multi-constituent/UVCBs). The compositions of multi-constituent/UVCBs were unravelled with European Chemicals Agency (ECHA) registration dossiers. To identify carcinogenic potentials, we searched for 1) International Agency for Research on Cancer (IARC) classification; 2) Harmonised classifications in Annex VI to the EU classification, labelling and packaging (CLP) Regulation; and 3) whether they had a Danish Environmental Protection Agency advisory CLP self-classification based on quantitative structure-activity relationships (QSARs) for genotoxicity and carcinogenicity in the Danish (Q)SAR Database. In 82 products, we identified 332 mono-constituent substances and 44 multi-constituent/UVCBs. Six substances were either IARC 1 or 2B classified. Twelve mono-constituent substances and 22 multi-constituent/UVCBs had harmonised classifications as Carcinogenic Category 1A, 1B or 2, while nine substances fulfilled the QSAR-based advisory self-classification algorithms for mutagenicity or carcinogenicity. At the product level, 39 products contained substances of carcinogenic concern by either IARC, harmonised classification or QSAR. We conclude that in the investigated EU marketed spray-formulated engine/brake cleaners and lubricants, 24 of 332 mono-constituent substances and 28 of 44 multi-constituent/UVCBs had a carcinogenic potential. At the product level, 39 of 82 contained substances with an identified carcinogenic potential. Regulators and manufacturers can use this determination of carcinogenic potential to decrease occupational risk.

Professional cleaning and risk of asthma - a Danish nationwide register-based study.

OBJECTIVE: This study aimed to investigate the risk of asthma among professional cleaners in a nationwide population-based study. METHODS: Professional cleaners, aged 16-50 years, were identified according to the yearly assigned administrative job and industrial codes in a register-based, matched cohort study with other manual workers as references (1995-2016). Asthma was defined from national registers based on hospitalization and medication. Associations between recent and cumulative cleaning years and risk of asthma were estimated using Poisson regression, first in a full cohort and then in an inception cohort, among workers aged 16-20 years at the start of follow-up. RESULTS: The risk of asthma was not increased for recent cleaning compared to references [adjusted incidence rate ratio (IRRadj) 1.02 [95% confidence interval (CI) 0.99-1.04]. Similar results were seen for the inception cohort, where cumulative years of cleaning were associated with increased risk of asthma, more prominent for the group with the maximum of six years of cleaning IRRadj 2.53 (95% CI 1.38-4.64). Cumulative years of cleaning were associated with decreased risk of asthma, more pronounced for the maximum of ten compared to one year of cleaning [IRRadj 0.74 (95% CI 0.63-0.88)]. CONCLUSIONS: Asthma risk was increased in the inception cohort for cumulative years of cleaning but decreased in the full cohort. We could not confirm that recent work within cleaning was associated with increased risk of asthma. This may be due to healthy worker bias. Thus, we cannot rule out that long-term professional cleaning may be associated with increased risk of asthma.

Asthma-inducing potential of 28 substances in spray cleaning products-Assessed by quantitative structure activity relationship (QSAR) testing and literature review.

Exposure to spray cleaning products constitutes a potential risk for asthma induction. We set out to review whether substances in such products are potential inducers of asthma. We identified 101 spray cleaning products for professional use. Twenty-eight of their chemical substances were selected. We based the selection on (a) positive prediction for respiratory sensitisation in humans based on quantitative structure activity relationship (QSAR) in the Danish (Q)SAR Database, (b) positive QSAR prediction for severe skin irritation in rabbits and (c) knowledge on the substances' physico-chemical characteristics and toxicity. Combining the findings in the literature and QSAR predictions, we could group substances into four classes: (1) some indication in humans for asthma induction: chloramine, benzalkonium chloride; (2) some indication in animals for asthma induction: ethylenediaminetetraacetic acid (EDTA), citric acid; (3) equivocal data: hypochlorite; (4) few or lacking data: nitriloacetic acid, monoethanolamine, 2-(2-aminoethoxy)ethanol, 2-diethylaminoethanol, alkyldimethylamin oxide, 1-aminopropan-2-ol, methylisothiazolinone, benzisothiazolinone and chlormethylisothiazolinone; three specific sulphonates and sulfamic acid, salicylic acid and its analogue sodium benzoate, propane-1,2-diol, glycerol, propylidynetrimethanol, lactic acid, disodium malate, morpholine, bronopol and benzyl alcohol. In conclusion, we identified an asthma induction potential for some of the substances. In addition, we identified major knowledge gaps for most substances. Thus, more data are needed to feed into a strategy of safe-by-design, where substances with potential for induction of asthma are avoided in future (spray) cleaning products. Moreover, we suggest that QSAR predictions can serve to prioritise substances that need further testing in various areas of toxicology.

Occupational exposure and markers of genetic damage, systemic inflammation and lung function: a Danish cross-sectional study among air force personnel.

Air force ground crew personnel are potentially exposed to fuels and lubricants, as raw materials, vapours and combustion exhaust emissions, during operation and maintenance of aircrafts. This study investigated exposure levels and biomarkers of effects for employees at a Danish air force military base. We enrolled self-reported healthy and non-smoking employees (n = 79) and grouped them by exposure based on job function, considered to be potentially exposed (aircraft engineers, crew chiefs, fuel operators and munition specialists) or as reference group with minimal occupational exposure (avionics and office workers). We measured exposure levels to polycyclic aromatic hydrocarbons (PAHs) and organophosphate esters (OPEs) by silicone bands and skin wipes (PAHs only) as well as urinary excretion of PAH metabolites (OH-PAHs). Additionally, we assessed exposure levels of ultrafine particles (UFPs) in the breathing zone for specific job functions. As biomarkers of effect, we assessed lung function, plasma levels of acute phase inflammatory markers, and genetic damage levels in peripheral blood cells. Exposure levels of total PAHs, OPEs and OH-PAHs did not differ between exposure groups or job functions, with low correlations between PAHs in different matrices. Among the measured job functions, the UFP levels were higher for the crew chiefs. The exposure level of the PAH fluorene was significantly higher for the exposed group than the reference group (15.9 ± 23.7 ng/g per 24 h vs 5.28 ± 7.87 ng/g per 24 h, p = 0.007), as was the OPE triphenyl phosphate (305 ± 606 vs 19.7 ± 33.8 ng/g per 24 h, p = 0.011). The OPE tris(1,3-dichlor-2-propyl)phosphate had a higher mean in the exposed group (60.7 ± 135 ng/g per 24 h) compared to the reference group (8.89 ± 15.7 ng/g per 24 h) but did not reach significance. No evidence of effects for biomarkers of systemic inflammation, genetic damage or lung function was found. Overall, our biomonitoring study show limited evidence of occupational exposure of air force ground crew personnel to UFPs, PAHs and OPEs. Furthermore, the OH-PAHs and the assessed biomarkers of early biological effects did not differ between exposed and reference groups.

Semaglutide single-dose pen-injector: Post hoc analysis of summative usability testing for weight management.

Subcutaneous semaglutide, at a 2.4 mg once-weekly maintenance dose, is approved in the United States for weight management in individuals with a body mass index (BMI) of 30 kg/m2 or higher, or with a BMI of 27 kg/m2 or higher and at least one obesity-related co-morbidity. To investigate the usability of the semaglutide pen-injector in individuals who met these criteria, we report post hoc analysis of the summative (human factors validation) usability testing and safety analysis involving patients with type 2 diabetes (an obesity-related co-morbidity) with the same pen-injector, limited to the 26 out of 30 patients with a BMI of 27 kg/m2 or higher (11 pen-injector-naïve, 15 pen-injector-experienced) and 15 non-pharmacist healthcare professionals (HCPs). Participants performed two simulated injections into an injection pad. No potentially serious use errors occurred. Mean subjective ease-of-use rating on a seven-point scale, where 1 = difficult and 7 = easy, was 6.9 for the second injection in all three groups. These results suggest that the semaglutide pen-injector is easy to use and not associated with serious use errors when used by pen-injector-naïve or pen-injector-experienced patients meeting the requirement for weight management with semaglutide treatment, and by non-pharmacist HCPs.

Couple Counseling and Pelvic Floor Muscle Training for Men Operated for Prostate Cancer and for Their Female Partners: Results From the Randomized ProCan Trial.

INTRODUCTION: Patients with prostate cancer (PC) who undergo radical prostatectomy (RP) experience impaired sexual and urinary function. AIM: To compare the effect of early couple counseling and pelvic floor muscle training (PFMT) with usual care for sexual and urinary dysfunction after RP. METHODS: The ProCan study was a randomized controlled trial (RCT) with two parallel treatment arms and 1:1 allocation. Between January 2016 and December 2017, candidates for RP were invited to a longitudinal questionnaire study and provided baseline measures before surgery. Patients who underwent RP, had a female partner, and were sexually active were invited to the ProCan RCT. Couples who provided informed consent were allocated to usual care or usual care and up to six couple counseling sessions, up to three instructions in PFMT and a video home-training program. All couples filled in follow-up questionnaires at 8 and 12 months and non-participants provided 12 months' follow-up. Linear mixed-effect models and 95% confidence intervals were used to measure effects of the intervention. MAIN OUTCOME MEASURE: Primary outcome was erectile function, measured with The International Index of Erectile Function, at 8 and 12 months follow-up. Secondary outcomes were sexual and urinary function and use of treatment for erectile dysfunction (ED) by patients; sexual function in female partners; and relationship function, health-related quality of life, anxiety, depression, and self-efficacy in both patients and female partners. RESULTS: Thirty-five couples were randomized. No significant effect of the intervention was found on erectile function at 8 months (estimated difference in change, 1.41; 95% CI; -5.51 ; 8.33) or 12 months (estimated difference in change, 0.53; 95% CI; -5.94; 6.99) or in secondary outcomes, except for significantly increased use of ED treatment at 8 months. CONCLUSION: We found no effect of early couple counseling and PFMT, possibly because of the limited number of participants. Karlsen RV, Bidstrup PE, Giraldi A, et al. Couple Counseling and Pelvic Floor Muscle Training for Men Operated for Prostate Cancer and for Their Female Partners. Results From the Randomized ProCan Trial. Sex Med 2021;9:100350.

Toxicity of boric acid, borax and other boron containing compounds: A review.

Boron, often in the form of boric acid, is widely used as a flame retardant in insulation products, and although humans ingest boron through food, high exposure may lead to unwanted health effects. We assessed the toxicity of boric acid, borax and other forms of boron, after inhalation, dermal and oral exposure. After oral exposure, boron is absorbed over the gastrointestinal tract. Intact skin seems to pose a more effective barrier to boron than compromised skin. Boron excretion seems to mainly occur via the urine, although after skin exposure boron has been demonstrated in bile and gastrointestinal contents. Inhalation toxicity data are sparse, but one animal study showed reduced foetal weight after inhalation of cellulose that had a boric acid content of 20%. Skin exposure to boric acid has proven fatal in some cases, and the range of toxicity effects include abdominal as well as local effects on the skin. Fatalities from boric acid also have occurred after oral ingestion, and the endpoints in animals are weight loss and reproductive toxicity. Concerning genotoxicity studies, the overall picture indicates that boron-containing compounds are not genotoxic. There was no evidence of the carcinogenicity of boric acid in a 2-year study in mice.

Is the health literacy of informal caregivers associated with the psychological outcomes of breast cancer survivors?

PURPOSE: To investigate whether health literacy (HL) among informal caregivers of breast cancer (BC) survivors is associated with patient psychological outcomes. METHODS: We used data (n = 340 pairs) from baseline questionnaires administered in the MyHealth trial investigating nurse-led BC follow-up. All BC survivors and their invited caregivers were included immediately after completion of primary treatment. We performed multivariate regression analyses to examine the association between caregiver HL (nine dimensions as measured by the Health Literacy Questionnaire) as exposure and patient depression, anxiety, and health-related quality of life (HQoL) as outcomes. We further examined whether any association differed according to type of caregiver, patient HL, and patient activation (skill in managing one's health). RESULTS: Three dimensions, "ability to engage with providers" (ß = - 0.2), "navigating the system" (ß = - 0.2), and "understand health information" (ß = - 0.2), were significantly associated with lower patient depression (p < 0.05), while four dimensions, "having sufficient information" (ß = 0.3), "navigating the system" (ß = 0.2), "find health information" (ß = 0.2), and "understand health information" (ß = 0.2), were significantly associated with better patient HQoL (p < 0.05). No significant associations were found for anxiety. Patient HL and activation did not significantly modify the associations, while certain associations for depression were stronger in patients with non-partner caregivers. CONCLUSIONS: The HL of informal caregivers may play an important role in optimizing psychological outcomes in cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Involving informal caregivers, who can provide support related to health information and services, may be beneficial for the psychological well-being of cancer survivors.