Inadequate Personal Protective Equipment Factors and Odds Related to Acute Pesticide Poisoning: A Meta-Analysis Report.

INTRODUCTION: Acute pesticide poisoning (APP) continues to affect farm workers, especially in low- and middle-income countries (LMIC). The dose-response relationship between exposure and APP is well-researched, but pesticide exposure assessment in a practical environment is difficult to perform, considering various work practices and protections in place. It is well known that inadequate personal protective equipment (PPE) use is a risk factor of APP. However, it is unknown which types of inadequate PPE use, such as face or other types of general protection, are most harmful. METHODS: This study aimed to identify if inadequate PPE use is an indicator of APP risk following established specifications for meta-analysis of epidemiological studies. Included studies reported an odds ratio (OR) between PPE use to APP in agricultural workers. Data extracted from selected articles included authors, publication year, country of origin, farm type, population size, method of data collection and time frame of reported symptoms, job task, type of PPE and pesticides used, adjustments made in analysis, OR for APP, and 95% confidence intervals (CI). Meta-analysis was performed using a random effects model, where ORs were pooled to assess an overall estimate for poisoning odds. RESULTS: Our findings suggested that inadequate PPE use was associated with increased odds (OR = 1.57, 95% CI = 1.16-2.12) of having APP. Failure to use general protection and inadequate face protection increased odds of APP by 1.29 times (95% CI = 0.88-1.90) and 1.92 times (95% CI = 1.23-3.00), respectively. CONCLUSIONS: The meta-analysis results indicate that improper facial protection and general protection are not differently associated with APP odds. Our study concludes that more robust protection against inhalation and dermal contact are critical because any gaps in comprehensive full-body PPE would put workers and exposed populations at APP risk.

Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study.

PURPOSE: Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy. METHODS: This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m2) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m2) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m2). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points. RESULTS: A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 (P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events. CONCLUSION: Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance (P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408).

The dependence of particle size on cell toxicity for modern mining dust.

Progressive massive pulmonary fibrosis among coal miners has unexpectedly increased. It would likely due to the greater generation of smaller rock and coal particles produced by powerful equipment used in modern mines. There is limited understanding of the relationship between micro- or nanoparticles with pulmonary toxicity. This study aims to determine whether the size and chemical characteristics of typical coal-mining dust contribute to cellular toxicity. Size range, surface features, morphology, and elemental composition of coal and rock dust from modern mines were characterized. Human macrophages and bronchial tracheal epithelial cells were exposed to mining dust of three sub- micrometer and micrometer size ranges at varying concentrations, then assessed for cell viability and inflammatory cytokine expression. Coal had smaller hydrodynamic size (180-3000 nm) compared to rock (495-2160 nm) in their separated size fractions, more hydrophobicity, less surface charge, and consisted of more known toxic trace elements (Si, Pt, Fe, Al, Co). Larger particle size had a negative association with in-vitro toxicity in macrophages (p < 0.05). Fine particle fraction, approximately 200 nm for coal and 500 nm for rock particles, explicitly induced stronger inflammatory reactions than their coarser counterparts. Future work will study additional toxicity endpoints to further elucidate the molecular mechanism causing pulmonary toxicity and determine a dose-response curve.

Incorporating field-based research into remote learning: An assessment of soil lead pollution in different land-use types in Los Angeles.

A research-based course was developed to investigate the legacy of soil lead (Pb) pollution in Los Angeles, California. During the course, undergraduate and graduate students collected a total of 270 soil samples for analyses of metal (loid) concentrations in different land-use types (residential, park, and school). Residential soils had significantly higher Pb concentrations than other land uses (p < 0.01) exceeding the California recommended safety level for soil Pb (80 mg/kg) at the highest frequency (64% of samples), followed by schools (42%) and parks (6.0%). Soil Pb from all 87 census block groups was correlated with battery recycling plant and railroad proximity as geospatial indicators of childhood Pb exposure risk. Meanwhile, census block groups with higher Pb levels were correlated with higher percentages of the following population: those without health insurance, without college degrees, with a lower median household income and income below the poverty line, and ethnic and racial minorities (r = -0.46 to 0.59, p < 0.05). Principal component regression models significantly improved soil Pb estimation over correlation analysis by incorporating sociodemographic, economic, and geospatial risk factors for Pb exposure (R2 = 0.58, p < 0.05). This work provides new insights into how topsoil Pb prevails in various land-use types and their co-occurring sociodemographic, economic, and geospatial risk factors, indicating the need for multi-scalar assessment across urban land uses.

Prolonged Cefepime-Induced Neurotoxicity in a Patient with End-Stage Renal Disease.

BACKGROUND Cefepime, a fourth-generation cephalosporin, has a known adverse effect of neurotoxicity. It occurs notably in patients with end-stage renal disease, but symptom resolution typically occurs within a median of 2 days following drug discontinuation. CASE REPORT We present a patient with end-stage renal disease on hemodialysis (TWThSat) who developed prolonged neurotoxicity lasting longer than 1 week complicated by nonconvulsive status epilepticus 2 days after cefepime discontinuation. She presented initially with a right upper-extremity arteriovenous graft infection from extended-spectrum beta-lactamase Escherichia coli, and was treated with cefepime. She eventually developed acute encephalopathy, and cefepime was discontinued. However, 2 days later, she developed seizures with worsened mental status. She was stabilized on levetiracetam and lorazepam, but developed hypotension in the Neurological Intensive Care Unit (Neuro-ICU), delaying hemodialysis. Hemodialysis was performed 6 days after cefepime discontinuation once she was stabilized, and her mental status improved 1 to 2 days after, with full improvement 20 days after admission. She was discharged on levetiracetam and meropenem. In addition, we review risk factors and symptomology of cefepime-induced neurotoxicity and discuss important management issues. CONCLUSIONS Careful attention should be paid when administering cefepime to patients with end-stage renal disease. Patients showing signs of encephalopathy should not be on cefepime any longer, and more aggressive measures may be taken, such as prompt hemodialysis, assessment of cefepime blood levels, and electroencephalogram (EEG) to monitor for signs of seizures. Prolonging hemodialysis in patients with signs of cefepime neurotoxicity can pose a danger for more serious sequelae, such as status epilepticus. Close monitoring of patients at high risk of developing adverse events from cefepime administration can ensure patient safety and well-being.

Bovine HDL and Dual Domain HDL-Mimetic Peptides Inhibit Tumor Development in Mice.

A growing body of literature supports the role of apolipoproteins present in HDL in the treatment of pro-inflammatory diseases including cancer. We examined whether bovine HDL (bHDL) and three dual-domain peptides, namely AEM-28 and its analog AEM-28-2, and HM-10/10, affect tumor growth and development in mouse models of ovarian and colon cancer. We demonstrate that bHDL inhibits mouse colorectal cancer cell line CT26-mediated lung tumor development, and mouse ovarian cancer cell line ID8-mediated tumor burden. We also demonstrate that, although to different degrees, dual-domain peptides inhibit cell viability of mouse and human ovarian and colon cancer cell lines, but not that of normal human colonic epithelial cells or NIH3T3 mouse fibroblasts. Dual-domain peptides administered subcutaneously or in a chow diet decrease CT26 cell-mediated tumor burden, tumor growth, and tumor dissemination in BALB/c mice. Plasma levels of lysophosphatidic acid (LPA) are significantly reduced in mice that received bHDL and the dual-domain peptides, suggesting that reduction by effecting accumulation and/or synthesis of pro-inflammatory lipids may be one of the mechanisms for the inhibition of tumor development by bHDL and the dual-domain peptides. Our studies suggest that therapeutics based on apolipoproteins present in HDL may be novel agents for the treatment of epithelial adenocarcinomas of the ovary and colon.

Paired Phase II Studies of Erlotinib/Bevacizumab for Advanced Bronchioloalveolar Carcinoma or Never Smokers With Advanced Non-Small-cell Lung Cancer: SWOG S0635 and S0636 Trials.

BACKGROUND: Before mutation testing of the epidermal growth factor receptor (EGFR) gene was recognized as highly associated with the activity of EGFR tyrosine kinase inhibitors (TKIs), clinically defined patient populations with bronchioloalveolar carcinoma (BAC) and never smokers were identified as likely to benefit from EGFR TKIs. From preclinical and clinical data suggesting potentially improved efficacy with a combination of an EGFR TKI and the antiangiogenic agent bevacizumab, the Southwestern Oncology Group (SWOG) initiated paired phase II trials to evaluate the combination of erlotinib/bevacizumab in patients with advanced BAC (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636). MATERIALS AND METHODS: Eligible patients with BAC or adenocarcinoma with BAC features (SWOG S0635) or never smokers with advanced lung adenocarcinoma (SWOG S0636) received erlotinib 150 mg/day with bevacizumab 15 mg/kg until progression or prohibitive toxicity. Never smokers with BAC were preferentially enrolled to SWOG S0636. The primary endpoint for both trials was overall survival. RESULTS: A total of 84 patients were enrolled in the SWOG S0635 trial and 85 in the SWOG S0636 trial. The objective response rate was 22% (3% complete response) in the SWOG S0635 trial and 50% (38% confirmed; 3% complete response) in the SWOG S0636 trial. The median progression-free survival was 5 and 7.4 months in the S0635 and S0636 trials, respectively. The median overall survival was 21 and 29.8 months, respectively. Toxicity consisted mainly of rash and diarrhea in both trials. CONCLUSION: Although the field has moved toward molecular, rather than clinical, selection of patients as optimal candidates for EGFR TKI therapy, these results support the hypothesis that a subset of patients in whom erlotinib is particularly active could receive an incremental benefit from the addition of bevacizumab.

Osteoblastic bone flare on F18-FDG PET in non-small cell lung cancer (NSCLC) patients receiving bevacizumab in addition to standard chemotherapy.

Positron emission tomography (PET) is used routinely to follow therapeutic response in patients treated for non-small cell lung cancer (NSCLC). In responding patients it is generally expected that the observed decrease in fluorodeoxyglucose uptake should be similar in all lesions. In other disease entities though, isolated cases have been documented of asynchronous increases in activity in metastatic bone lesions ("bone flare") despite evidence of therapeutic response or stability in other lesions. Here, we describe four NSCLC cases in which the results of interim PET scans were misleading due to osteoblastic flare phenomenon. In all four cases, patients were treated with bevacizumab in addition to standard chemotherapy. All four patients developed isolated worsening of their skeletal metastases on PET/CT (computed tomography) analysis (increase in fluorodeoxyglucose activity) despite apparent response or stable disease elsewhere. Subsequent scans confirmed that the "worsening" was transient, consistent with a flare response. Awareness of the phenomena is important for physicians treating NSCLC patients, particularly with bevacizumab.

Cross-coupling between accommodation and convergence is optimized for a broad range of directions and distances of gaze.

Accommodation and convergence systems are cross-coupled so that stimulation of one system produces responses by both systems. Ideally, the cross-coupled responses of accommodation and convergence match their respective stimuli. When expressed in diopters and meter angles, respectively, stimuli for accommodation and convergence are equal in the mid-sagittal plane when viewed with symmetrical convergence, where historically, the gains of the cross coupling (AC/A and CA/C ratios) have been quantified. However, targets at non-zero azimuth angles, when viewed with asymmetric convergence, present unequal stimuli for accommodation and convergence. Are the cross-links between the two systems calibrated to compensate for stimulus mismatches that increase with gaze-azimuth? We measured the response AC/A and stimulus CA/C ratios at zero azimuth, 17.5 and 30 deg of rightward gaze eccentricities with a Badal Optometer and Wheatstone-mirror haploscope. AC/A ratios were measured under open-loop convergence conditions along the iso-accommodation circle (locus of points that stimulate approximately equal amounts of accommodation to the two eyes at all azimuth angles). CA/C ratios were measured under open-loop accommodation conditions along the iso-vergence circle (locus of points that stimulate constant convergence at all azimuth angles). Our results show that the gain of accommodative-convergence (AC/A ratio) decreased and the bias of convergence-accommodation increased at the 30 deg gaze eccentricity. These changes are in directions that compensate for stimulus mismatches caused by spatial-viewing geometry during asymmetric convergence.

Blood donor satisfaction and intention of future donation.

BACKGROUND: New regulatory requirements for donor eligibility challenge blood centers to recruit and retain enough donors. This study evaluated correlations between overall satisfaction with the donation process and donor demographics and the effect of both on a donor's intent to return. STUDY DESIGN AND METHODS: An anonymous, self-administered questionnaire was given to donors at multiple sites of one blood center over a 3-week period. First-time and repeat donors were asked questions on demographic characteristics, satisfaction with the current donation process, motivation for current and future donations, and intent to return. RESULTS: More than 75 percent of donors rated the overall donation process at 9 or 10 on a scale of 10 (mean, 9.19; standard deviation, 1.09), with female, high school-educated, and first-time donors giving higher satisfaction ratings than male, college-educated, and repeat donors, respectively (all p < 0.001). Donor satisfaction was correlated with intent to return for another donation (p = 0.002). For the current donation, donors rated altruistic motivations most highly. Medical testing was the most highly rated incentive for future donations, followed by frequent donor programs and convenient donation times and locations; preferences varied by demographic subgroup. CONCLUSIONS: Blood donor satisfaction varies among demographic and donation history subgroups and is positively correlated with the intent to return for future donation. Although the primary motivation among all donors was altruism, incentives to future donation may need to be tailored according to demographic subgroups.

Cytomegalovirus viremia during Campath-1H therapy for relapsed and refractory chronic lymphocytic leukemia and prolymphocytic leukemia.

Campath-1H is effective therapy for patients with relapsed and refractory chronic lymphocytic leukemia (CLL) and prolymphocytic leukemia (PLL), but it is associated with profound lymphopenia and deficiencies in cell-mediated immunity. We report the incidence of cytomegalovirus (CMV) viremia in 34 patients treated with Campath-1H for relapsed or refractory CLL and PLL. All patients received infection prophylaxis during therapy and continuing for at least 2 months following Campath-1H. Five patients (15%) developed CMV viremia at a median of 28 days (range, 20-30 days) after the first dose of Campath-1H. The median CMV viral load was 860/mL (range, 420-2100/mL), as determined by quantitative plasma polymerase chain reaction (PCR). All 5 patients had a temperature > 38.5 degrees C, normal chest radiographs, normal liver function tests, and negative bacterial blood cultures with no clinical evidence of CMV disease at the time of presentation with CMV viremia. The median absolute neutrophil count (ANC) was 740/ microL (range, 340-1600/ microL), and the median absolute lymphocyte count (ALC) was 16/microL (range, 11-169/ microL) for the 5 patients at the time of CMV viremia. All 5 patients received ganciclovir therapy followed by prompt fever resolution and clearance of CMV viremia by plasma PCR. By univariate regression analysis, the following were not risk factors for CMV viremia: age, number of prior regimens, prior rituximab therapy, prior splenectomy, modified Rai stage at Campath-1H therapy (low/intermediate vs. high), ANC, and ALC; although, there was a trend towards significance for prior rituximab therapy (P = 0.07). Cytomegalovirus viremia may be a significant infectious complication during Campath-1H therapy and should be investigated further in future studies.