Environmental Health Threats to Latino Migrant Farmworkers.

Approximately 75% of farmworkers in the United States are Latino migrants, and about 50% of hired farmworkers do not have authorization to work in the United States. Farmworkers face numerous chemical, physical, and biological threats to their health. The adverse effects of these hazards may be amplified among Latino migrant farmworkers, who are concurrently exposed to various psychosocial stressors. Factors such as documentation status, potential lack of authorization to work in the United States, and language and cultural barriers may also prevent Latino migrants from accessing federal aid, legal assistance, and health programs. These environmental, occupational, and social hazards may further exacerbate existing health disparities among US Latinos. This population is also likely to be disproportionately impacted by emerging threats, including climate change and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Latino migrant farmworkers are essential to agriculture in the United States, and actions are needed to protect this vulnerable population.

A Systems-based Approach to Reduce Deep Venous Thrombosis and Pulmonary Embolism in Trauma Patients.

BACKGROUND: Venous thromboembolism (VTE) in trauma patients carries significant morbidity and mortality. We previously described how titrating enoxaparin dosing by anti-Xa trough levels was associated with a lower VTE rate. We combined this strategy with a higher initial enoxaparin dose for a majority of patients and modified the electronic medical record (EMR) to encourage immediate dosing. We sought to determine if this systems-based approach was associated with a decrease in VTE rate. STUDY DESIGN: A retrospective review was conducted of all trauma patients on prophylactic enoxaparin at an academic, Level I Trauma Center from 01/2013 to 05/2014 (PRE) and 06/2015 to 02/2018 (POST). The patients in PRE were prescribed enoxaparin 30 mg twice daily without dose adjustments. The patients in POST received 40 mg twice daily unless exclusion criteria applied, with doses titrated to maintain anti-Xa trough levels between 0.1 and 0.2 IU/mL. RESULTS: There were 478 patients in the PRE and 1306 in the POST. Compared to PRE, POST patients were of similar age and were as likely to present after blunt trauma, although POST patients had lower injury severity scores (10 vs. 9, p < 0.01). The overall VTE rate was lower in POST (6.9% vs. 3.6%, p < 0.01). The adjusted risk of VTE (AOR 0.61, adjusted p = 0.04) was lower in POST and POST was independently protective for VTE (AOR 0.54; p = 0.01). CONCLUSION: By implementing system changes to improve enoxaparin dosing after trauma, a significant reduction in VTE rate was observed. Wider application of this strategy should be considered.

Real-world evidence on the safety and effectiveness of fingolimod in patients with multiple sclerosis from Taiwan.

BACKGROUND/PURPOSE: Multiple sclerosis is classified as a rare disease in Taiwan. This study evaluated the safety and effectiveness of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) from routine clinical practice in Taiwan. METHODS: In this retrospective, multicentre, observational study, we collected clinical data of patients treated with fingolimod 0.5 mg/day in routine clinical practice between September 2012 and December 2015. Primary outcome was the overall safety of fingolimod; secondary outcome was the annualized relapse rate (ARR). RESULTS: Overall, 62/69 (86.1%) patients were on fingolimod by the end of data collection period. Mean age (±standard deviation [SD]) at inclusion was 37.7 ± 10.10 years; mean duration of MS was 5.4 ± 4.52 years and mean duration of fingolimod exposure was 135.8 patient-years. The most common adverse events (AEs) were bradycardia (21.7%; first-dose related), upper respiratory tract infection, dizziness, and hypoaesthesia (numbness) (11.6% each), followed by urinary tract infection and back pain (7.2% each). Seven patients had liver enzyme-related AEs. Eight patients had absolute lymphocyte counts <0.2 × 103/uL over the study period. One patient developed second degree AV block after first-dosing. Serious AEs were observed in 11 patients (15.9%; mild-to-moderate). No newly developed macular oedema was detected. The ARR was 0.3 ± 0.74 in fingolimod-treated patients and 66.7% of patients were relapse-free. The mean (SD) change from baseline in expanded disability status scale score was -0.30 ± 1.353. CONCLUSION: Fingolimod 0.5 mg/day treatment with an average of 2 years of exposure was associated with a manageable safety profile, and maintained/improved effectiveness in RRMS patients from Taiwan.

The risk factors of venous thromboembolism in massively transfused patients.

BACKGROUND: Massive transfusion protocols (MTPs) are necessary for hemodynamically unstable trauma patients with active bleeding. Thrombotic events have been associated with blood transfusion; however, the risk factors for the development of venous thromboembolism (VTE) in trauma patients receiving MTP are unknown. METHODS: A retrospective review was conducted by reviewing the electronic medical records of all trauma patients admitted to a Level I trauma center who received MTP from 2011 to 2016. Data were collected on patient demographics, mechanism of injury, injury severity scores, quantity of blood products transfused during MTP activation, incidence of VTE, intensive care unit length of stay (LOS), hospital LOS, and ventilator days. The primary outcome was VTE. RESULTS: Of the 59 patients who had MTP activated, 15 (25.4%) developed a VTE during their hospital admission. Patients who developed VTE were compared with those who did not. Age (40 y versus 35 y, P = 0.59), sex (60% versus 73% male, P = 0.52), and mechanism of injury (47% versus 59% blunt, P = 0.40) were similar. Intensive care unit LOS, hospital LOS, and ventilator days were longer in the patients who were diagnosed with a VTE. Multivariable analysis revealed an increase in the odds for developing a VTE with increasing packed red blood cell transfusion (adjusted odds ratio = 2.61, P = 0.03). CONCLUSIONS: The risk for VTE in trauma patients requiring massive transfusion is proportional to the number of packed red blood cells transfused. Liberal screening protocols and maintenance of a high index of suspicion for VTE in these high-risk patients is justified.

Relation Detection to Identify Stroke Assertions from Clinical Notes Using Natural Language Processing.

According to the World Stroke Organization, 12.2 million people world-wide will have their first stroke this year almost half of which will die as a result. Natural Language Processing (NLP) may improve stroke phenotyping; however, existing rule-based classifiers are rigid, resulting in inadequate performance. We report findings from a pilot study using NLP to improve relation detection for stroke assertion detection to support research studies and healthcare operations.

Balancing Act: Acute and Contextual Vestibular Sensations of Cranial Electrotherapy Stimulation Using Survey and Sensor Outcomes in a Non-Clinical Sample.

Cranial electrotherapy stimulation (CES) delivers low-intensity electrical currents to the brain to treat anxiety, depression, and pain. Though CES is considered safe and cost-effective, little is known about side effects emerging across different contexts. Our objective was to investigate how varying physical and cognitive demands impact the frequency and intensity of CES vestibular sensations in a sample of healthy young adults. We used a 2 (stimulation: sham, active) × 2 (physical demand: static sway, dynamic sit-to-stand) × 2 (cognitive demand: single-task remain silent, dual-task count backward) repeated measures design. Vestibular sensations were measured with surveys and wearable sensors capturing balance changes. Active stimulation did not influence reported vestibular sensations. Instead, high physical demand predicted more sensation reports. High cognitive demand, but not active stimulation, predicted postural sway unsteadiness. Significant effects of active stimulation on balance were observed only during the dynamic sit-to-stand transitions. In summary, CES induces vestibular sensations only for a specific outcome under certain circumstances. Our findings imply that consumers can safely maximize the benefits of CES while ensuring they are taking steps to minimize any potential side effects by considering their context and circumstances.

Drinking water and the implications for gender equity and empowerment: A systematic review of qualitative and quantitative evidence.

BACKGROUND: Safe drinking water is a fundamental human right, yet more than 785 million people do not have access to it. The burden of water management disproportionately falls on women and young girls, and they suffer the health, psychosocial, political, educational, and economic effects. While water conditions and disease outcomes have been widely studied, few studies have summarized the research on drinking water and implications for gender equity and empowerment (GEE). METHODS: A systematic review of primary literature published between 1980 and 2019 was conducted on drinking water exposures and management and the implications for GEE. Ten databases were utilized (EMBASE, PubMed, Web of Science, Cochrane, ProQuest, Campbell, the British Library for Development Studies, SSRN, 3ie International Initiative for Impact Evaluation, and clinicaltrials.gov). Drinking water studies with an all-female cohort or disaggregated findings according to gender were included. RESULTS: A total of 1280 studies were included. GEE outcomes were summarized in five areas: health, psychosocial stress, political power and decision-making, social-educational conditions, and economic and time-use conditions. Water quality exposures and implications for women's health dominated the literature reviewed. Women experienced higher rates of bladder cancer when exposed to arsenic, trihalomethanes, and chlorine in drinking water and higher rates of breast cancer due to arsenic, trichloroethylene, and disinfection byproducts in drinking water, compared to men. Women that were exposed to arsenic experienced higher incidence rates of anemia and adverse pregnancy outcomes compared to those that were not exposed. Water-related skin diseases were associated with increased levels of psychosocial stress and social ostracization among women. Women had fewer decision-making responsibilities, economic independence, and employment opportunities around water compared to men. CONCLUSION: This systematic review confirms the interconnected nature of gender and WaSH outcomes. With growing attention directed towards gender equity and empowerment within WaSH, this analysis provides key insights to inform future research and policy.

Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort.

BACKGROUND: Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. METHODS: We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, 17ß-estradiol, and testosterone was assessed using structural equation modeling. RESULTS: The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration (ß)=-0.19 95% confidence interval (CI): -0.31, -0.07], language [ß=-0.12 (95% CI: -0.23, -0.01)], and memory/learning [ß=-0.11 (95% CI: -0.22, 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ß=-0.08 (95% CI: -0.14, -0.01)]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. CONCLUSION: This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

The Role of NK Cells in EBV Infection and EBV-Associated NPC.

A vast majority of the population worldwide are asymptomatic carriers of Epstein-Barr Virus (EBV). However, some infected individuals eventually develop EBV-related cancers, including Nasopharyngeal Carcinoma (NPC). NPC is one of the most common EBV-associated epithelial cancers, and is highly prevalent in Southern China and Southeast Asia. While NPC is highly sensitive to radiotherapy and chemotherapy, there is a lack of effective and durable treatment among the 15%-30% of patients who subsequently develop recurrent disease. Natural Killer (NK) cells are natural immune lymphocytes that are innately primed against virus-infected cells and nascent aberrant transformed cells. As EBV is found in both virally infected and cancer cells, it is of interest to examine the NK cells' role in both EBV infection and EBV-associated NPC. Herein, we review the current understanding of how EBV-infected cells are cleared by NK cells, and how EBV can evade NK cell-mediated elimination in the context of type II latency in NPC. Next, we summarize the current literature about NPC and NK cell biology. Finally, we discuss the translational potential of NK cells in NPC. This information will deepen our understanding of host immune interactions with EBV-associated NPC and facilitate development of more effective NK-mediated therapies for NPC treatment.

Poor Corticospinal Motor Neuron Health Is Associated with Increased Symptom Severity in the Acute Phase Following Repetitive Mild TBI and Predicts Early ALS Onset in Genetically Predisposed Rodents.

Traumatic brain injury (TBI) is a well-established risk factor for several neurodegenerative disorders including Alzheimer's disease and Parkinson's disease, however, a link between TBI and amyotrophic lateral sclerosis (ALS) has not been clearly elucidated. Using the SOD1G93A rat model known to recapitulate the human ALS condition, we found that exposure to mild, repetitive TBI lead ALS rats to experience earlier disease onset and shortened survival relative to their sham counterparts. Importantly, increased severity of early injury symptoms prior to the onset of ALS disease symptoms was linked to poor health of corticospinal motor neurons and predicted worsened outcome later in life. Whereas ALS rats with only mild behavioral injury deficits exhibited no observable changes in corticospinal motor neuron health and did not present with early onset or shortened survival, those with more severe injury-related deficits exhibited alterations in corticospinal motor neuron health and presented with significantly earlier onset and shortened lifespan. While these studies do not imply that TBI causes ALS, we provide experimental evidence that head injury is a risk factor for earlier disease onset in a genetically predisposed ALS population and is associated with poor health of corticospinal motor neurons.

Effectiveness of the 10 cm2 Rivastigmine Patch in Taiwanese Patients with Mild-to-Moderate Alzheimer's Dementia: A 48-Week Real-World Observational Study.

INTRODUCTION: The current study aimed to provide data on the effectiveness of the 10 cm2 rivastigmine patch in patients with Alzheimer's disease (AD) in a real-world setting in Taiwan. METHODS: This was a 48-week, single-arm, open-label, observational, and post-marketing study conducted across seven centers in Taiwan between May 5, 2016 and July 10, 2017. Eligible patients (aged 55-95 years) treated with the 10 cm2rivastigmine patch were enrolled based on physicians' judgment and according to the Taiwan reimbursement criteria of the drug. Data were prospectively collected at Week 0 (baseline), Week 24, and Week 48. The primary endpoint was the change in the cognitive assessment screening instrument (CASI) scores at Week 48 versus baseline. The changes from baseline in clinical dementia rating (CDR), mini-mental state examination (MMSE), and neuropsychiatric inventory (NPI) scores were evaluated, as were treatment persistence and the safety profile. RESULTS: Of the 285 eligible patients [full analysis set (FAS)], 216 (75.8%) completed the study protocol while 180 (63.2%) persisted on the 10 cm2 rivastigmine patch for the full 48 weeks. At baseline, 89.8% of patients had a CDR score of 0.5 or 1, while the change in CDR score at Week 48 was not significant. In the FAS, both the CASI and MMSE scores had numerical improvement at Week 24 but declined by 2.1 and 0.4 points, respectively, at Week 48 (p = 0.005 and p = 0.022). The increment in NPI scores was not significant. The most common drug-related adverse events (AEs) were pruritus (11.2%), nausea (3.5%), rash (3.2%), and vomiting (2.8%). CONCLUSIONS: The use of the 10 cm2 rivastigmine patch in the mild stage of AD maintained cognitive function at Week 24 and neuropsychiatric function at Week 48. The treatment persistency and safety profile support the clinical tolerability of the rivastigmine patch in the management of mild-to-moderate AD in Taiwan.

How repetitive traumatic injury alters long-term brain function.

BACKGROUND: How recurrent traumatic brain injury (rTBI) alters brain function years after insult is largely unknown. This study aims to characterize the mechanistic cause for long-term brain deterioration following rTBI using a rat model. METHODS: Eighteen Sprague-Dawley wild-type rats underwent bilateral rTBI using a direct skull impact device or sham treatment, once per week for 5 weeks, and were euthanized 56 weeks after the first injury. Weekly rotarod performance measured motor deficits. Beam walk and grip strength were also assessed. Brain tissue were stained and volume was computed using Stereo Investigator's Cavalieri Estimator. The L5 cortical layer proximal to the injury site was microdissected and submitted for sequencing with count analyzed using R "DESeq2" and "GOStats." Brain-derived neurotrophic factor (BDNF) levels were determined using enzyme-linked immunosorbent assay. RESULTS: Rotarod data demonstrated permanent deficits 1 year after rTBI. Decreased beam walk performance and grip strength was noted among rTBI rodents. Recurrent traumatic brain injury led to thinner cortex and thinner corpus callosum, enlarged ventricles, and differential expression of 72 genes (25 upregulated, 47 downregulated) including dysregulation of those associated with TBI (BDNF, NR4A1/2/3, Arc, and Egr) and downregulation in pathways associated with neuroprotection and neuroplasticity. Over the course of the study, BDNF levels decreased in both rTBI and sham rodents, and at each time point, the decrease in BDNF was more pronounced after rTBI. CONCLUSION: Recurrent traumatic brain injury causes significant long-term alteration in brain health leading to permanent motor deficits, cortical and corpus callosum thinning, and expansion of the lateral ventricles. Gene expression and BDNF analysis suggest a significant drop in pathways associated with neuroplasticity and neuroprotection. Although rTBI may not cause immediate neurological abnormalities, continued brain deterioration occurs after the initial trauma in part due to a decline in genes associated with neuroplasticity and neuroprotection.

The Impact of IV Electrolyte Replacement on the Fluid Balance of Critically Ill Surgical Patients.

Avoiding excess fluid administration is necessary when managing critically ill surgical patients. The aim of this study was to delineate the current practices of IV electrolyte (IVE) replacement in a surgical ICU and quantify their contribution to the fluid balance (FB) status. Patients admitted to the surgical ICU over a six-month period were reviewed. Patients undergoing dialysis and those with ICU stay <72 hours were excluded. A total of 248 patients were included. The median age was 60 years, and 57 per cent were male. Overall, 1131 patient ICU days were analyzed. The median daily FB was 672 mL. IVEs were administered in 62 per cent of ICU days. In days that IVEs were used, negative FB was significantly less likely to be achieved (62% vs 69%, P = 0.02). The most commonly administered IVE was calcium (32% of ICU days); however, the largest volume of IVE was administered in the form of phosphorus (median 225 mL). Diuretics were administered in 17 per cent of ICU days. Patients who received diuretics were significantly more likely to receive IVE (70% vs 61%, P = 0.02). Administration of IVE may contribute to the daily positive FB of surgical ICU patients. Implementation of practices that can ameliorate this effect is encouraged.

Unexpected complicated appendicitis in the elderly diagnosed with acute appendicitis.

BACKGROUND: This study determined the prevalence of complicated appendicitis in elderly patients diagnosed preoperatively with uncomplicated appendicitis. METHODS: Patients with a preoperative diagnosis of uncomplicated appendicitis at an academic hospital from 11/2013 to 05/2017 were reviewed. Patients ≥65 years were compared to those younger. Pathology reports were categorized as either uncomplicated or complicated (COMP). The primary outcome was the prevalence of COMP appendicitis. RESULTS: The prevalence of COMP appendicitis increased with age after 20 years with an abrupt increase after 65 years. Patients ≥65 years were more likely to have COMP appendicitis (48.1% vs. 15.5%; OR: 5.1; p < 0.01) and prolonged stays (3.8 vs. 2.3 days; p < 0.01). CONCLUSION: Nearly half of elderly patients had pathologic confirmation of complicated appendicitis despite no preoperative clinical or radiographic suspicion for complicated appendicitis. Nonoperative management of acute appendicitis in the elderly may not be appropriate due to the high rate of unexpected complicated appendicitis.

Evaluation of three polygenic risk score models for the prediction of breast cancer risk in Singapore Chinese.

Genome-wide association studies (GWAS) have proven highly successful in identifying single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. The majority of these studies are on European populations, with limited SNP association data in other populations. We genotyped 51 GWAS-identified SNPs in two independent cohorts of Singaporean Chinese. Cohort 1 comprised 1294 BC cases and 885 controls and was used to determine odds ratios (ORs); Cohort 2 had 301 BC cases and 243 controls for deriving polygenic risk scores (PRS). After age-adjustment, 11 SNPs were found to be significantly associated with BC risk. Five SNPs were present in <1% of Cohort 1 and were excluded from further PRS analysis. To assess the cumulative effect of the remaining 46 SNPs on BC risk, we generated three PRS models: Model-1 included 46 SNPs; Model-2 included 11 statistically significant SNPs; and Model-3 included the SNPs in Model-2 but excluded SNPs that were in strong linkage disequilibrium with the others. Across Models-1, -2 and -3, women in the highest PRS quartile had the greatest ORs of 1.894 (95% CI = 1.157-3.100), 2.013 (95% CI = 1.227-3.302) and 1.751 (95% CI = 1.073-2.856) respectively, suggesting a direct correlation between PRS and BC risk. Given the potential of PRS in BC risk stratification, our findings suggest the need to tailor the selection of SNPs to be included in an ethnic-specific PRS model.