Blurring the distinctions between on and off the job injuries: similarities and differences in circumstances.

OBJECTIVES: To compare the causes of non-fatal work and non-work injuries and the places or environments where they occur. It has been suggested that many injuries may have similar etiologies on and off the job and thus involve some common prevention strategies. However lack of comparable data on work relatedness has prevented testing this proposition. METHODS: The National Health Interview Survey (NHIS) now collects information on the cause, location, and work relatedness of all medically attended injuries. National US estimates of non-fatal work and non-work injuries were compared by cause and place/location for working age adults (18-64 years). RESULTS: Overall 28.6% of injuries to working age adults were work related (37.5% among employed people). The causes and locations of many work and non-work injuries were similar. Falls, overexertion, and struck/caught by were leading causes for work and non-work injuries. Motor vehicle injuries were less likely to be work related (3.4% at work v 19.5% non-work) and overexertion injuries more likely to be work related (27.1% v 13.8%). Assaults were less than 1% of work injuries and 1.8% of non-work injuries. Both work and non-work injuries occurred in every location examined-including the home where 3.5% of injuries were work related. CONCLUSIONS: Work and non-work injuries share many similarities suggesting opportunities to broaden injury prevention programs commonly restricted to one setting or the other. Comprehensive efforts to prevent both non-work and work injuries may result in considerable cost savings not only to society but also directly to employers, who incur much of the associated costs.     

Effect of posaconazole on cytochrome P450 enzymes: a randomized, open-label, two-way crossover study

Posaconazole is an antifungal with a wide-spectrum of activity against common and emerging fungal pathogens. In this randomised, open-label, two-way crossover study, the potential for drug interactions with posaconazole via the cytochrome P450 (CYP450) enzyme pathway was evaluated. Thirteen subjects received posaconazole tablets (2×100 mg) once daily for 10 days or no treatment; following a 14-day washout period, subjects were crossed over to the alternate treatment. The inhibition spectra of posaconazole were examined using a cocktail of the following probe substrates: caffeine (CYP1A2), tolbutamide (CYP2C8/9), dextromethorphan (CYP2D6 and total CYP3A4), chlorzoxazone (CYP2E1), and midazolam (hepatic CYP3A4). Except for midazolam, which was intravenously infused on Day 10, the cocktail probes were administered simultaneously on Day 9 during both treatment periods. Blood and urine samples were collected at specified times to quantitate probe substrates and/or metabolites. Based on insignificant differences in mean probe ratios, posaconazole did not inhibit CYP1A2, 2C8/9, 2D6, or 2E1. However, the midazolam AUC_(tf) was higher in the posaconazole than no-treatment group (93.4 ng h/ml versus 51.4 ng h/ml, P<0.01), indicating inhibition of hepatic CYP3A4. Drug interactions mediated by various CYP450 are common with the currently available triazole antifungals, however these results suggest that posaconazole may have an improved and more narrow drug interaction profile (CYP3A4 only) compared with other triazoles.     

Drop‐offs in the isoniazid preventive therapy cascade among children living with HIV in western Kenya, 2015–2019

IntroductionIsoniazid preventive therapy (IPT) can reduce the risk of tuberculosis (TB) in children living with HIV (CLHIV), but data on the outcomes of the IPT cascade in CLHIV are limited.MethodsWe evaluated the IPT cascade among CLHIV aged <15 years and newly enrolled in HIV care in eight HIV clinics in western Kenya. Medical record data were abstracted from September 2015 through July 2019. We assessed the proportion of CLHIV completing TB symptom screening, IPT eligibility assessment, IPT initiation and completion. TB incidence rate was calculated stratified by IPT initiation and completion status. Risk factors for IPT non‐initiation and non‐completion were assessed using Poisson regression with generalized linear models.ResultsOverall, 856 CLHIV were newly enrolled in HIV care, of whom 98% ([95% CI 97–99]; n = 841) underwent screening for TB symptoms and IPT eligibility. Of these, 13 (2%; 95% CI 1–3) were ineligible due to active TB and 828 (98%; 95% CI 97–99) were eligible. Five hundred and fifty‐nine (68%; 95% CI 64–71) of eligible CLHIV initiated IPT; median time to IPT initiation was 3.6 months (interquartile range [IQR] 0.5–10.2). Overall, 434 (78%; 95% CI 74–81) IPT initiators completed. Attending high‐volume HIV clinics (aRR = 2.82; 95% CI 1.20–6.62) was independently associated with IPT non‐initiation. IPT non‐initiation had a trend of being higher among those enrolled in the period 2017–2019 versus 2015–2016 (aRR = 1.91; 0.98–3.73) and those who were HIV virally non‐suppressed (aRR = 1.90; 95% CI 0.98–3.71). Being enrolled in 2017–2019 versus 2015–2016 (aRR = 1.40; 1.01–1.96) was independently associated with IPT non‐completion. By 24 months after IPT screening, TB incidence was four‐fold higher among eligible CLHIV who never initiated (8.1 per 1000 person years [PY]) compared to CLHIV who completed IPT (2.1 per 1000 PY; rate ratio [RR] = 3.85; 95% CI 1.08–17.15), with a similar trend among CLHIV who initiated but did not complete IPT (8.2/1000 PY; RR = 4.39; 95% CI 0.82–23.56).ConclusionsDespite high screening for eligibility, timely IPT initiation and completion were suboptimal among eligible CLHIV in this programmatic cohort. Targeted programmatic interventions are needed to address these drop‐offs from the IPT cascade by ensuring timely IPT initiation after ruling out active TB and enhancing completion of the 6‐month course to reduce TB in CLHIV.     

Systematic Evidence Map for Over One Hundred and Fifty Per- and Polyfluoroalkyl Substances (PFAS)

Background: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic (man-made) chemicals widely used in consumer products and industrial processes. Thousands of distinct PFAS exist in commerce. The 2019 U.S. Environmental Protection Agency (U.S. EPA) Per- and Polyfluoroalkyl Substances (PFAS) Action Plan outlines a multiprogram national research plan to address the challenge of PFAS. One component of this strategy involves the use of systematic evidence map (SEM) approaches to characterize the evidence base for hundreds of PFAS.Objective: SEM methods were used to summarize available epidemiological and animal bioassay evidence for a set of ∼150 PFAS that were prioritized in 2019 by the U.S. EPA’s Center for Computational Toxicology and Exposure (CCTE) for in vitro toxicity and toxicokinetic assay testing.Methods: Systematic review methods were used to identify and screen literature using manual review and machine-learning software. The Populations, Exposures, Comparators, and Outcomes (PECO) criteria were kept broad to identify mammalian animal bioassay and epidemiological studies that could inform human hazard identification. A variety of supplemental content was also tracked, including information on in vitro model systems; exposure measurement–only studies in humans; and absorption, distribution, metabolism, and excretion (ADME). Animal bioassay and epidemiology studies meeting PECO criteria were summarized with respect to study design, and health system(s) were assessed. Because animal bioassay studies with ≥21-d exposure duration (or reproductive/developmental study design) were most useful to CCTE analyses, these studies underwent study evaluation and detailed data extraction. All data extraction is publicly available online as interactive visuals with downloadable metadata.Results: More than 40,000 studies were identified from scientific databases. Screening processes identified 44 animal and 148 epidemiology studies from the peer-reviewed literature and 95 animal and 50 epidemiology studies from gray literature that met PECO criteria. Epidemiological evidence (available for 15 PFAS) mostly assessed the reproductive, endocrine, developmental, metabolic, cardiovascular, and immune systems. Animal evidence (available for 40 PFAS) commonly assessed effects in the reproductive, developmental, urinary, immunological, and hepatic systems. Overall, 45 PFAS had evidence across animal and epidemiology data streams.Discussion: Many of the ∼150 PFAS were data poor. Epidemiological and animal evidence were lacking for most of the PFAS included in our search. By disseminating this information, we hope to facilitate additional assessment work by providing the initial scoping literature survey and identifying key research needs. Future research on data-poor PFAS will help support a more complete understanding of the potential health effects from PFAS exposures. https://doi.org/10.1289/EHP10343     

A Longitudinal Cohort Study of Youth Mental Health and Substance use Before and During the COVID-19 Pandemic in Ontario,Canada: An Exploratory Analysis

BackgroundYouth mental health appears to have been negatively impacted by the COVID-19 pandemic. The impact on substance use is less clear, as is the impact on subgroups of youth, including those with pre-existing mental health or substance use challenges.ObjectiveThis hypothesis-generating study examines the longitudinal evolution of youth mental health and substance use from before the COVID-19 pandemic to over one year into the pandemic among youth with pre-existing mental health or substance use challenges.MethodA total of 168 youth aged 14–24 participated. Participants provided sociodemographic data, as well as internalizing disorder, externalizing disorder, and substance use data prior to the pandemic’s onset, then every two months between April 2020–2021. Linear mixed models and Generalized Estimating Equations were used to analyze the effect of time on mental health and substance use. Exploratory analyses were conducted to examine interactions with sociodemographic and clinical characteristics.ResultsThere was no change in internalizing or externalizing disorder scores from prior to the pandemic to any point throughout the first year of the pandemic. Substance use scores during the pandemic declined compared to pre-pandemic scores. Exploratory analyses suggest that students appear to have experienced more mental health repercussions than non-students; other sociodemographic and clinical characteristics did not appear to be associated with mental health or substance use trajectories.ConclusionsWhile mental health remained stable and substance use declined from before the COVID-19 pandemic to during the pandemic among youth with pre-existing mental health challenges, some youth experienced greater challenges than others. Longitudinal monitoring among various population subgroups is crucial to identifying higher risk populations. This information is needed to provide empirical evidence to inform future research directions.     

Trichodermamides A and B,cytotoxic modified dipeptides from the marine-derived fungus Trichoderma virens

Trichodermamides A (1) and B (2), two modified dipeptides, have been isolated from cultures of the marine-derived fungus Trichoderma virens. The trichodermamides possess a rare cyclic O-alkyl-oxime functionality incorporated into a six-membered ring. The structure of trichodermamide B was established by X-ray diffraction analysis, while the structure assignment of trichodermamide A, and determination of the absolute stereochemistry, was accomplished by spectral and chemical methods. Trichodermamide B displayed significant in vitro cytotoxicity against HCT-116 human colon carcinoma with an IC(50) of 0.32 microg/mL.     

Optimal timing and mode of delivery after cesarean with previous classical incision or myomectomy: a review of the data

Uterine rupture is an obstetrical emergency that can be catastrophic for the mother and fetus. Previous uterine surgery, including previous cesarean delivery or myomectomy, is an established risk factor, although the exact magnitude of the associated risk remains uncertain. We reviewed the literature related to uterine rupture after previous cesarean delivery with classical incision or myomectomy in an attempt to quantify outcomes associated with various management strategies. Although cesarean delivery with a classical incision is relatively uncommon (representing 0.3%-0.4% of deliveries), it presents a significant risk of rupture in subsequent pregnancies (1%-12% on the basis of published reports). Available data suggest that scheduled cesarean at 36-37 weeks optimizes both maternal and fetal outcomes in these cases. Patients with previous myomectomy are more frequently encountered in the obstetrical population. The risk of uterine rupture in subsequent pregnancies in these women is substantially lower than those with a history of previous classical incision (0.5%-0.7% on the basis of published reports). Although less common, given the potentially devastating consequences of uterine rupture, scheduled delivery at 38 weeks is suggested in those women requiring cesarean delivery. Despite the lack of well-controlled studies, preferred management strategies can be gleaned from previously published data to optimize maternal and fetal outcomes in women with these risk factors.     

Embryotoxicity of micropore filters used in liquid sterilization

Microfiltration is the usual method of sterilization of tissue culture media. The filtrates of eight commercial filters were tested for embryotoxicity using mouse embryo growth. Four of five disk filters tested showed embryotoxicity in the first 5 ml of filtrate and the three largercapacity filters showed embryotoxicity for up to the first 10 ml of filtrate. The ethylene oxide-sterilized filters appeared to give poorer results than the gamma-irradiated filters. The importance of discarding the initial filtrate or preflushing such filters before use is emphasized.