Mediation Analysis of Maternal Smoking, Gestational Age, and Birth Weight on the Texas-Mexico Border.

OBJECTIVES: Published data on the indirect effect of maternal smoking on birth weight as mediated by gestational age in Hispanic populations are lacking. Our goal was to conduct such a mediation analysis using data from El Paso County, Texas. METHODS: El Paso County is located on the US-Mexico border. A simple mediation analysis was conducted using year 2010 El Paso County birth certificate data. The SAS macro PROCESS 3.5.3 was used to estimate the direct and indirect effects of active maternal smoking (by trimester) on birth weight (in grams) in the setting of linear regression. The single mediator was gestational age in weeks. A direct or indirect effect was deemed to be present if the 95% confidence limits (CLs) excluded 0. Analyses were adjusted for multiple variables, including maternal prepregnancy body mass index. The indirect effect was reported along with a 95% bootstrap CL. RESULTS: A total of 16,654 singleton births were included in the cohort. The majority of the mothers were White Hispanic (87.2%). The mean (standard deviation) birth weight was 3198.6 g (517.2). A direct effect of maternal smoking during each trimester on birth weight was detected. An indirect effect of maternal smoking on birth weight was not detected in any of the trimesters. In adjusted analyses for the third trimester, the indirect effect for every 1-U increase in the mean number of cigarettes smoked per day was -4.18 (95% bootstrap CL -10.64 to 1.99). CONCLUSIONS: In our large, predominantly Hispanic cohort, it appears that gestational age is not a mediator of the effect of maternal smoking on birth weight. Future studies in our population should explore other possible mediators of this association.

Sex and diet-dependent gene alterations in human and rat brains with a history of nicotine exposure.

Introduction: Chronic nicotine exposure induces changes in the expression of key regulatory genes associated with metabolic function and neuronal alterations in the brain. Many bioregulatory genes have been associated with exposure to nicotine, but the modulating effects of sex and diet on gene expression in nicotine-exposed brains have been largely unexplored. Both humans and rodents display motivation for nicotine use and the emergence of withdrawal symptoms during abstinence. Research comparing pre-clinical models with human subjects provides an important opportunity to understand common biomarkers of the harmful effects of nicotine as well as information that may help guide the development of more effective interventions for nicotine cessation. Methods: Human postmortem dorsolateral prefrontal cortex (dLPFC) tissue BA9 was collected from female and male subjects, smokers and non-smokers (N = 12 per group). Rat frontal lobes were collected from female and male rats that received a regular diet (RD) or a high-fat diet (HFD) (N = 12 per group) for 14 days following implantation of a osmotic mini-pump (Alzet) that delivered nicotine continuously. Controls (control-s) received a sham surgical procedure. RNA was extracted from tissue from human and rat samples and reversed-transcribed to cDNA. Gene expression of CHRNA10 (Cholinergic receptor nicotinic alpha 10), CERKL (Ceramide Kinase-Like), SMYD1 (SET and MYD Domin Containing 1), and FA2H (Fatty Acid 2-Hydrolase) in humans was compared to rats in each subset of groups and quantified by qPCR methods. Additionally, protein expression of FA2H was analyzed by immunohistochemistry (IHC) in human dLPFC. Results: Humans with a history of smoking displayed decreased CHRNA10 (p = 0.0005), CERKL (p ≤ 0.0001), and SMYD1 (p = 0.0005) expression and increased FA2H (p = 0.0097) expression compared to non-smokers (p < 0.05). Similar patterns of results were observed in nicotine exposed vs. control rats. Interestingly, sex-related differences in gene expression for CERKL and FA2H were observed. In addition, ANCOVA analysis showed a significant effect of nicotine in a sex-different manner, including an increase in CERKL in male and female rats with RD or HFD. In rats exposed to an HFD, FA2H gene expression was lower in nicotine-treated rats compared to RD rats treated with nicotine. Protein expression of FA2H (p = 0.001) by IHC was significantly higher in smokers compared to non-smokers. Conclusion: These results suggest that a history of long-term nicotine exposure in humans alters the expression of sphingolipid metabolism-related (CERKL, SMYD1, and FA2H) and neuronal (CHRNA10) marker genes similarly as compared to rats. Sex- and diet-dependent differences appear in nicotine-exposed rats, critical in regulating sphingolipid metabolism and nicotinic acetylcholine receptors. This research enhances the construct validity of rat models of nicotine usage by showing a similar pattern of changes in gene expression in human subjects with a smoking history.

Effect of bromhexine in hospitalized patients with COVID-19.

BACKGROUND: Bromhexine is a potent inhibitor of transmembrane serine protease 2 and appears to have an antiviral effect in controlling influenza and parainfluenza infection; however, its efficacy in COVID-19 is controversial. METHODS: A group of hospitalized patients with confirmed COVID-19 pneumonia were randomized using 1:1 allocation to either standard treatment lopinavir/ritonavir and interferon beta-1a or bromhexine 8 mg four times a day in addition to standard therapy. The primary outcome was clinical improvement within 28 days, and the secondary outcome measures were time to hospital discharge, all-cause mortality, duration of mechanical ventilation, the temporal trend in 2019-nCoV reverse transcription-polymerase chain reaction positivity and the frequency of adverse drug events within 28 days from the start of medication. RESULTS: A total of 111 patients were enrolled in this randomized clinical trial and data from 100 patients (48 patients in the treatment arm and 52 patients in the control arm) were analyzed. There was no significant difference in the primary outcome of this study, which was clinical improvement. There was no significant difference in the average time to hospital discharge between the two arms. There were also no differences observed in the mean intensive care unit stay, frequency of intermittent mandatory ventilation, duration of supplemental oxygenation or risk of death by day 28 noted between the two arms. CONCLUSION: Bromhexine is not an effective treatment for hospitalized patients with COVID-19. The potential prevention benefits of bromhexine in asymptomatic postexposure or with mild infection managed in the community remain to be determined.

An Evacuation Simulation in Multiple Neonatal Intensive Care Units Across a Single City: Lessons Learned.

OBJECTIVE: Evacuations of neonatal intensive care units (NICUs) in emergency situations pose specialized challenges given their population of critically-ill neonates. Most of the literature on this topic describes planned evacuations and simulations due to natural disasters, usually involving only NICU staff. This study examines a unique emergent NICU evacuation simulation involving multiple responders occurring on a citywide scale. METHODS: A simulated evacuation in response to a fire was conducted in 6 different NICUs in El Paso, Texas. The exercise utilized response from NICU staff and first responders. A standardized tool, by independent evaluators, was used to evaluate staff competencies while reactions were assessed using post-exercise surveys. RESULTS: This city-wide multidisciplinary simulation improved NICU personnel skills in evacuation and also introduced first responders to this specialized patient population. Areas of strength across all NICUs included teamwork, knowledge of evacuation equipment, and patient tracking. Areas for improvement included lack of adequate equipment for post-evacuation care, understanding implications of smoke exposure, alternative evacuation routes, incident command structure, and unified communication. CONCLUSIONS: This successful, citywide NICU evacuation simulation improved knowledge among participants, introduced first responders to a specialized patient population, and provided valuable lessons on neonate-specific themes that can be incorporated to improve citywide emergency preparedness.

An imbalance-aware deep neural network for early prediction of preeclampsia.

Preeclampsia (PE) is a hypertensive complication affecting 8-10% of US pregnancies annually. While there is no cure for PE, aspirin may reduce complications for those at high risk for PE. Furthermore, PE disproportionately affects racial minorities, with a higher burden of morbidity and mortality. Previous studies have shown early prediction of PE would allow for prevention. We approached the prediction of PE using a new method based on a cost-sensitive deep neural network (CSDNN) by considering the severe imbalance and sparse nature of the data, as well as racial disparities. We validated our model using large extant rich data sources that represent a diverse cohort of minority populations in the US. These include Texas Public Use Data Files (PUDF), Oklahoma PUDF, and the Magee Obstetric Medical and Infant (MOMI) databases. We identified the most influential clinical and demographic features (predictor variables) relevant to PE for both general populations and smaller racial groups. We also investigated the effectiveness of multiple network architectures using three hyperparameter optimization algorithms: Bayesian optimization, Hyperband, and random search. Our proposed models equipped with focal loss function yield superior and reliable prediction performance compared with the state-of-the-art techniques with an average area under the curve (AUC) of 66.3% and 63.5% for the Texas and Oklahoma PUDF respectively, while the CSDNN model with weighted cross-entropy loss function outperforms with an AUC of 76.5% for the MOMI data. Furthermore, our CSDNN model equipped with focal loss function leads to an AUC of 66.7% for Texas African American and 57.1% for Native American. The best results are obtained with 62.3% AUC with CSDNN with weighted cross-entropy loss function for Oklahoma African American, 58% AUC with DNN and balanced batch for Oklahoma Native American, and 72.4% AUC using either CSDNN with weighted cross-entropy loss function or CSDNN with focal loss with balanced batch method for MOMI African American dataset. Our results provide the first evidence of the predictive power of clinical databases for PE prediction among minority populations.

Ethnic and border differences on blood cancer presentation and outcomes: A Texas population-based study.

BACKGROUND: The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population-based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. METHODS: Data from the Texas Cancer Registry (1995-2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non-Hispanic) and geographic location (border vs non-border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel-Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. RESULTS: Hispanic patients were diagnosed at a younger age than non-Hispanic patients and presented with increased comorbidities. Whereas non-Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79-2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) compared with Hispanics living elsewhere in Texas. CONCLUSIONS: Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.

Predictors of timely diagnostic follow-up after an abnormal Pap test among Hispanic women seeking care in El Paso, Texas.

BACKGROUND: Diagnostic follow-up of women with an abnormal Pap test is necessary to resolve the risk developing cervical cancer. The purpose of this study is to describe patient characteristics associated with timely receipt of a diagnostic colposcopy after an abnormal Pap test among Hispanic women in El Paso, a Texas-Mexico border city. METHODS: We conducted a retrospective chart review of Hispanic patients seen at an academic colposcopy clinic following an abnormal Pap test. An optimal diagnostic interval to colposcopy was based on a National Breast and Cervical Cancer Early Detection Program (NBCCEDP) quality indicator and was defined as receipt of colposcopy within 90 days or less from the date of an abnormal Pap test. Risk ratios (RR) were calculated by building a generalized linear model fit using a Poisson distribution, log link, and robust variance. RESULTS: Overall, 177 of the 270 women (65.6%) received follow-up within an optimal diagnostic interval. After adjusting for other variables in the model, women who were 30 years of age or older were 32% more likely to have an optimal interval than younger women (adjusted RR = 1.32, P < 0.01). High school graduates were less likely than more educated women to have an optimal interval (adjusted RR = 0.68, P < 0.01). Participation in the NBCCEDP was not associated with receipt of follow-up within an optimal diagnostic interval. CONCLUSIONS: Compared with women with greater educational attainment, high school graduates were less likely to receive follow-up within an optimal diagnostic interval, as were younger (≤ 30 years) women compared with older women. Participation in the NBCCEDP was not associated with receipt of care within an optimal diagnostic interval.

Analysis of count data in the setting of cervical cancer detection.

Women with an abnormal Pap smear are often referred to colposcopy, a procedure during which endocervical curettage (ECC) may be performed. ECC is a scraping of the endocervical canal lining. Our goal was to compare the performance of a naïve Poisson (NP) regression model with that of a zero-inflated Poisson (ZIP) model when identifying predictors of the number of distress/pain vocalizations made by women undergoing ECC. Data on women seen in the colposcopy clinic at a medical school in El Paso, Texas, were analyzed. The outcome was the number of pain vocalizations made by the patient during ECC. Six dichotomous predictors were evaluated. Initially, NP regression was used to model the data. A high proportion of patients did not make any vocalizations, and hence a ZIP model was also fit and relative rates (RRs) and 95% CIs were calculated. AIC was used to identify the best model (NP or ZIP). Of the 210 women, 154 (73.3%) had a value of 0 for the number of ECC vocalizations. NP identified three statistically significant predictors (language preference of the subject, sexual abuse history and length of the colposcopy), while ZIP identified one: history of sexual abuse (yes vs no; adjusted RR=2.70, 95% CI 1.47 to 4.97). ZIP was preferred over NP. ZIP performed better than NP regression. Clinicians and epidemiologists should consider using the ZIP model (or the zero-inflated negative binomial model) for zero-inflated count data.

The Cost of Hospitalized Ocular Injuries in Texas, 2013-2014.

PURPOSE: Healthcare costs are a continual concern. To improve our cost-efficiency we must identify the direct costs of ocular injuries requiring hospitalization. The purpose of this study was to evaluate the direct costs of hospitalized ocular injuries in Texas. METHODS: Retrospective cohort study using the Texas Hospital Inpatient Discharge Public Use Data File, 2013-2014. Persons hospitalized for ocular trauma were identified using ICD-9-CM codes. Injuries were subcategorized as ocular adnexal, open globe, or closed globe based on diagnosis and procedure codes and analyzed across three age groups: 18-44, 45-64, and >65 years. RESULTS: From 2013 to 2014, 1498 patients were hospitalized with ocular adnexal injuries, 644 with open globe injuries, and 2877 with closed globe injuries. Length of stay ranged from 2 to 4 days. The median total charges ranged between $34,576 and $55,409 across all injuries and groups. The largest portion of medical costs were due to radiology in the ocular adnexal and closed globe groups, and operating room charges in the open globe group. CONCLUSIONS: Median hospitalization costs for ocular injuries were between $34,576 and $55,409 for a 2-4 day length of stay. Open globe injuries had the shortest median lengths of stay, 2-3 days, and lower median total costs. Only in the open globe group were operative costs higher than radiology costs. Operative charges were lowest in the oldest age group, who also had longer lengths of stay. Our reported costs were lower than other nationally reported ocular injury costs for similar lengths of hospital stay.

Novel coronavirus, novel faculty development programs: rapid transition to eLearning during the pandemic.

The novel coronavirus disease 2019 (COVID-19) has caused a rapid and massive transition to online education. We describe the response of our Office of Faculty Development at Texas Tech University Health Sciences Center El Paso (TTUHSC EP) to this unprecedented challenge during and after this post-pandemic crisis. The initiatives for emergency transition to eLearning and faculty development described in this paper may serve as a model for other academic health centers, schools, colleges and universities.

Evaluating the performance of a low-cost mobile phone attachable microscope in cervical cytology.

BACKGROUND: Cervical cancer remains a global health problem especially in remote areas of developing countries which have limited resources for cervical cancer screening. In this study, we evaluated the performance of a low-cost, smartphone attachable paper-based microscope when used for classifying images of cervical cytology. METHODS: Cervical cytology samples included: 10 Normal, 10 Low-grade squamous intraepithelial lesion (LSIL), 10 High-grade squamous intraepithelial lesion (HSIL), and 10 Malignant Pap Smears. The agreement between conventional microscopy vs. Foldscope imaging was calculated using a weighted kappa coefficient. A confusion matrix was created with three classes: Normal, LSIL, and HSIL/malignant, to evaluate the performance of the Foldscope by calculating the accuracy, sensitivity, and specificity. RESULTS: We observed a kappa statistic of 0.68 for the agreement. This translates into a substantial agreement between the cytological classifications by the Foldscope vs. conventional microscopy. The accuracy of the Foldscope was 80%, with a sensitivity and specificity of 85 and 90% for the HSIL/Mal category, 80 and 83.3%, for LSIL, and 70 and 96.7% for Normal. CONCLUSIONS: This study highlights the usefulness of the Foldscope in cervical cytology, demonstrating it has substantial agreement with conventional microscopy. Its use could improve cytologic interpretations in underserved areas and, thus, improve the quality of cervical cancer screening. Improvements in existing limitations of the device, such as ability to focus, could potentially increase its accuracy.

A Simulation-Based Workshop to Improve Residents' Collaborative Clinical Practice.

BACKGROUND: The Accreditation Council for Graduate Medical Education expects residents to attain competency in systems-based practice by advocating for quality patient care, working in interprofessional teams, and implementing system solutions to prevent errors. Diabetes in pregnancy was identified as an area for improvement through comprehensive interdisciplinary and interprofessional care. OBJECTIVE: An interdisciplinary and interprofessional workshop was created by 3 regional academic institutions to improve collaborative practice, clinical knowledge, and clinical judgment of residents. METHODS: A workshop consisting of 4 clinical simulation stations for ultrasound assessment, glycemic control, hyperglycemic emergencies, and macrosomia complications was designed to address gaps in quality of care. Workshop participants were residents from 6 programs and students in nursing, pharmacy, and sonography. Attitude and clinical knowledge were measured preworkshop and postworkshop, and at 3-month and 6- to 7-month follow-up. RESULTS: There were increases in average clinical knowledge scores across time points from residents: 56.4% preworkshop, 64.8% postworkshop, 66.0% at 3-month follow-up, and 68.1% at 6- to 7-month follow-up. Additionally, participants reported positive attitudes toward interprofessional education and indicated high overall satisfaction. CONCLUSIONS: Residents demonstrated improved knowledge and attitudes toward interprofessional training after participating in a large-scale simulation workshop focused on the care of patients with diabetes in pregnancy.

Spanish Language Pelvic Floor Disorders Patient Information Handouts: How Readable Are They?

OBJECTIVE: This study aimed to determine the readability of commonly available patient information materials for pelvic floor disorders written in Spanish and compare their readability based on type of content and source. METHODS: Spanish patient information handouts, including pamphlets from the National Institutes of Health, International Urogynecology Association, American Congress of Obstetricians and Gynecologists, online printable handouts, and industry-sponsored brochures were assessed for readability. Online materials for patients were obtained from Google searches using key words (pelvic floor disorders, urogynecology, patient information handouts, Spanish). Reading difficulty was assessed using INFLESZ v1.0, (Barrio-Cantalejo IM, Spain) a free software developed to calculate the readability of Spanish written texts. Three index scales were used: Flesch-Szigriszt Index, Word correlation Index, and the Fernandez-Huerta Index. RESULTS: Forty patient information handouts were analyzed. All pamphlets analyzed had readability scores within the "average" to "very difficult" reading difficulty levels as per the index scales used. None of the analyzed pamphlets met the sixth grade reading level criteria suggested by the National Institutes of Health and American Medical Association, including government-developed materials. There were no differences in readability scores between type of leaflet content or source. CONCLUSIONS: Current available free, industry-, organization-, and government-provided reading materials in Spanish do not serve the Spanish-speaking only or low English-speaking literacy population. Future work should aim to simplify the language in such documents to the suggested sixth grade reading level.

Parental Age and the Risk of Gestational Hypertension and Preeclampsia.

OBJECTIVES: To determine the effect of maternal age (MA) and paternal age (PA) on the risk of gestational hypertension, preeclampsia, and eclampsia in women who delivered on the Texas-Mexico border. METHODS: A cohort study using birth certificate data (singleton pregnancies, years 2005-2010) from El Paso County, Texas, was conducted. Six parental age-exposure categories were created with MA 20 to 34 years and PA younger than 35 years serving as the referent. A directed acyclic graph was created. Adjusted risk ratios for the composite outcome of gestational hypertension, preeclampsia, or eclampsia were calculated using Poisson regression. RESULTS: A total of 85,114 records were identified, with a majority of the mothers being of Hispanic ethnicity (89.2%). The incidence of the composite outcome ranged from 2.8% in the MA 20 to 34 years old and PA 35 years and older group to 4.4% in the MA younger than 20 years old and PA 35 years and older group. Compared to the MA 20 to 34 years old and PA younger than 35 years group, women in the MA 35 years and older and PA 35 years and older groups were more likely to experience the outcome (adjusted risk ratio 1.57, 95% confidence interval 1.39-1.77, P < 0.0001). CONCLUSIONS: Couples in which both parents are 35 years old and older should be counseled on the increased risk of gestational hypertension or preeclampsia/eclampsia.

Outcomes of Women Delivering at Very Advanced Maternal Age.

BACKGROUND: The purpose of this study was to evaluate the maternal outcome in women with very advanced maternal age (VAMA) at childbirth (>45 years) compared to advanced maternal age (35-39 and 40-44 years). METHODS: Retrospective cohort study using the Texas Public Use Data File, years 2013-2014. Maternal age was a three-level variable: 35-39 (referent), 40-44, and 45-59 years (VAMA). Adjusted risk ratios (aRRs) for the two older age groups for various obstetrical and nonobstetrical complications were calculated from log-binomial regression models. RESULTS: The sample consisted of 96,879 deliveries. In univariate analyses, a higher frequency (p < 0.05) of gestational diabetes, pregestational diabetes, chronic hypertension, pregnancy related hypertensive disorders, multiple gestation, oligohydramnios, polyhydramnios, placenta previa, postpartum hemorrhage, small for gestational age, intrauterine fetal death, and length of stay were noted in the two older maternal age groups compared to the youngest maternal age group. Multiple gestations were noted to be more frequent in the two older groups: the VAMA group had a 336% increase in their risk (aRR = 4.36, 95% CI: 3.68-5.17), while women 40-44 years of age experienced a 17% increase in their risk (aRR = 1.17, 95% CI: 1.07-1.29) compared to women in the 35-39 year group. The risk of the following outcomes was approximately doubled in VAMA women compared to the referent (all statistically significant): small for gestational age (aRR = 1.92), stillbirth (aRR = 2.12), and intrauterine fetal death (aRR = 1.96). CONCLUSIONS: This population-based study detected a dose-response association between maternal age and the risk of multiple maternal and fetal complications.