Faculty Bibliography

BACKGROUND:Fetal smoke exposure is a common and key avoidable risk factor for birth complications and seems to influence later risk of overweight. It is unclear whether this increased risk is also present if mothers smoke during the first trimester only or reduce the number of cigarettes during pregnancy, or when only fathers smoke. We aimed to assess the associations of parental smoking during pregnancy, specifically of quitting or reducing smoking and maternal and paternal smoking combined, with preterm birth, small size for gestational age, and childhood overweight. METHODS AND FINDINGS/RESULTS:We performed an individual participant data meta-analysis among 229,158 families from 28 pregnancy/birth cohorts from Europe and North America. All 28 cohorts had information on maternal smoking, and 16 also had information on paternal smoking. In total, 22 cohorts were population-based, with birth years ranging from 1991 to 2015. The mothers' median age was 30.0 years, and most mothers were medium or highly educated. We used multilevel binary logistic regression models adjusted for maternal and paternal sociodemographic and lifestyle-related characteristics. Compared with nonsmoking mothers, maternal first trimester smoking only was not associated with adverse birth outcomes but was associated with a higher risk of childhood overweight (odds ratio [OR] 1.17 [95% CI 1.02-1.35], P value = 0.030). Children from mothers who continued smoking during pregnancy had higher risks of preterm birth (OR 1.08 [95% CI 1.02-1.15], P value = 0.012), small size for gestational age (OR 2.15 [95% CI 2.07-2.23], P value < 0.001), and childhood overweight (OR 1.42 [95% CI 1.35-1.48], P value < 0.001). Mothers who reduced the number of cigarettes between the first and third trimester, without quitting, still had a higher risk of small size for gestational age. However, the corresponding risk estimates were smaller than for women who continued the same amount of cigarettes throughout pregnancy (OR 1.89 [95% CI 1.52-2.34] instead of OR 2.20 [95% CI 2.02-2.42] when reducing from 5-9 to ≤4 cigarettes/day; OR 2.79 [95% CI 2.39-3.25] and OR 1.93 [95% CI 1.46-2.57] instead of OR 2.95 [95% CI 2.75-3.15] when reducing from ≥10 to 5-9 and ≤4 cigarettes/day, respectively [P values < 0.001]). Reducing the number of cigarettes during pregnancy did not affect the risks of preterm birth and childhood overweight. Among nonsmoking mothers, paternal smoking was associated with childhood overweight (OR 1.21 [95% CI 1.16-1.27], P value < 0.001) but not with adverse birth outcomes. Limitations of this study include the self-report of parental smoking information and the possibility of residual confounding. As this study only included participants from Europe and North America, results need to be carefully interpreted regarding other populations. CONCLUSIONS:We observed that as compared to nonsmoking during pregnancy, quitting smoking in the first trimester is associated with the same risk of preterm birth and small size for gestational age, but with a higher risk of childhood overweight. Reducing the number of cigarettes, without quitting, has limited beneficial effects. Paternal smoking seems to be associated, independently of maternal smoking, with the risk of childhood overweight. Population strategies should focus on parental smoking prevention before or at the start, rather than during, pregnancy.

Pulmonary disease after World Trade Center particulate matter(WTC-PM) exposure is associated with dyslipidemia and the receptor for advanced glycation end products (RAGE); however, the mechanisms are not well understood. We utilized a murine model and a multiOMIC assessment to understand the role of RAGE in the pulmonary long-term effects of a single high intensity exposure to WTC-PM. After 1-month(1-M), WTC-PM exposed wild-type(WT) mice had airway hyperreactivity(AHR) while RAGE-deficient(Ager-/-) were protected. PM-exposed WT mice also had histologic evidence of airspace disease while Ager-/- remained unchanged. Inflammatory mediators such as G-CSF, IP-10, and KC were differentially expressed after WTC-PM exposure. WTC-PM induced α-SMA, DIAPH1, RAGE and significant lung collagen deposition in WT compared to Ager-/-. Compared to WT with PM exposure, relative expression of phosphorylated to total CREB and JNK were significantly increased in the lung of PM-exposed Ager-/-, whereas Akt was decreased. Random forests of the refined lung metabolomic profile classified subjects with 92% accuracy; principal components analysis captured 86.7% of the variance in 3 components and demonstrated prominent sub-pathway involvement including known mediators of lung disease such as vitamin B6 metabolites, sphingolipids, fatty acids, and phosphatidylcholines. Treatment with a partial RAGE antagonist, pioglitazone, yielded similar fold-change expression of metabolites(N6-carboxymethyllysine, 1-methylnicotinamide, (N(1)+N(8))-acetylspermidine and Succinylcarnitine(C4-DC)) between WT and Ager-/- exposed to WTC-PM. RAGE can mediate WTC-PM-induced AHR, and warrants further investigation.

AIMS AND OBJECTIVES/OBJECTIVE:To evaluate the knowledge and attitudes towards sexual and gender minority (SGM) oncology patients' needs among advanced practice providers (APPs). BACKGROUND:SGM individuals experience health disparities, in part due to lack of access to knowledgeable providers. Despite the important role of APPs in cancer care, less is known about their attitudes and knowledge towards SGM cancer patients. DESIGN/METHODS:Cross-sectional study. METHODS:A survey of APPs at a National Cancer Institute-Designated Comprehensive Cancer Center assessed self-reported demographics, attitudes, knowledge and postsurvey confidence in knowledge of SGM oncology patient needs. Reporting of this study adheres to STROBE guidelines. RESULTS:Knowledge of health needs was low with an average of 2.56 (SD = 1.27) items answered correctly out of 6. The majority of APPs self-reported being comfortable treating SGM patients (93.6% and 87.2%, respectively), but less confident in knowledge of their health needs (68.0% and 53.8%, respectively). Although less than half of APPs believed education should be mandatory (44.9%), 79.5% were interested in education about SGMs' unique health needs. Political affiliation, medical specialty, licensure, and having SGM friends or family were associated with various attitude items, but not knowledge. Moderation analyses indicated that APPs who had greater overall knowledge scores were more likely to agree, on average, that knowing sexual orientation, gender identity and sex assigned at birth are important to providing quality oncology care. CONCLUSION/CONCLUSIONS:APPs report being comfortable providing care for SGMs with cancer, but knowledge gaps remain that may inhibit the quality of care provided. Given the interest in education, results would support the development of SGM-related healthcare training for oncology APPs. RELEVANCE TO CLINICAL PRACTICE/CONCLUSIONS:Targeted education for providers during training and continuing education is likely to improve the provision of quality care for SGMs with cancer.

BACKGROUND:In 2016, the Food and Drug Administration (FDA) changed labeling regarding metformin contraindications in patients with diabetes and CKD from using serum creatinine-based thresholds to using eGFR-based thresholds. Because race and sex affect serum creatinine levels independently of GFR, the earlier creatinine-based contraindication may have inadvertently caused racial and sex disparities in metformin prescription among patients with low eGFR. METHODS:in a large health system (the primary cohort), we assessed the association of race and sex with metformin prescription across eGFR level before and after the FDA label change. For a replication cohort, we meta-analyzed data from 36 cohorts with 1,051,723 patients from OptumLabs Data Warehouse. RESULTS:value for interaction by period <0.001). CONCLUSIONS:The metformin label change to an eGFR-based contraindication may have reduced racial and sex disparities in metformin prescription in moderate kidney dysfunction.

We advance a tripartite framework of language use to encompass language skills, the practice of language skills, and the subjective experiences associated with language use among Mexican-origin adolescents who function as language brokers by translating and interpreting for their English-limited parents. Using data collected over 2 waves from a sample of 604 adolescents (Wave 1: Mage = 12.41, SD = 0.97), this study identified 4 types of bilingual language broker profiles that capture the tripartite framework of language use: efficacious, moderate, ambivalent, and nonchalant. All 4 profiles emerged across waves and brokering recipients (i.e., mothers, fathers), except for Wave 1 brokering for mother, in which case only 3 profiles (i.e., efficacious, moderate, and ambivalent) emerged. Three profiles emerged across time: stable efficacious, stable moderate, and other. The efficacious and stable efficacious profiles showed the most consistent relation to adolescents' academic competence. Improving bilingual language proficiency, together with fostering more frequently positive brokering experiences, may be an avenue to improving academic competence among Mexican-origin adolescents in the United States. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BACKGROUND:It is poorly understood how cardiovascular screening in asymptomatic childhood cancer survivors (CCS) is applied to and impacts clinical care. OBJECTIVES:To describe the current role of cardiovascular screening in the clinical care of asymptomatic CCS. METHODS:At 50 pediatric academic medical centers, a childhood cancer survivorship clinic director, pediatric cardiologist, and adult cardiologist with a focus on CCS were identified and invited to participate in a survey. Surveys were managed electronically. Categorical data were analyzed using nonparametric methods. RESULTS:Of the 95 (63%) respondents, 39% were survivorship practitioners, and 61% were cardiologists. Eighty-eight percent of survivorship practitioners reported that greater than half of CCS received cardiovascular screening. CCS followed by adult cardiology were more likely to be seen by a cardio-oncologist. Those followed by pediatric cardiology were more likely to be seen by a heart failure/transplant specialist. Common reasons for referral to cardiology were abnormal cardiovascular imaging or concerns a CCS was at high risk for cardiovascular disease. Ninety-two percent of cardiologists initiated angiotensin converting enzyme inhibitor or angiotensin receptor blocker therapy for mild systolic dysfunction. Adult cardiologists initiated beta-blocker therapy for less severe systolic dysfunction compared to pediatric cardiologists (P < .001). Pediatric cardiologists initiated mineralocorticoid therapy for less severe systolic dysfunction compared to adult cardiologists (P = .025). Practitioners (93%) support a multi-institutional collaboration to standardize cardiovascular care for CCS. CONCLUSIONS:While there is much common ground in the clinical approach to CCS, heterogeneity is evident. This highlights the need for cohesive, multi-institutional, standardized approaches to cardiovascular management in CCS.

Background/UNASSIGNED:The COVID-19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID-19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow-up trial using the widely available tissue-plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective/UNASSIGNED:To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID-19-induced ARDS. Patients/Methods/UNASSIGNED:A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard-of-care). Inclusion criteria are known/suspected COVID-19 infection with PaO2/FiO2 ratio<150mmHg for >4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re-dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results/UNASSIGNED:The primary outcome is improvement in PaO2/FiO2 at 48 hours post-randomization. Other outcomes include: ventilator- and ICU-free-days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped-wedge design with four looks at the data. Conclusion/UNASSIGNED:Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial. (NCT04357730; FDA IND 149634).

Diabetes is the leading cause of kidney failure worldwide, whereas glomerulonephritis has been predominant in developing countries such as China. The prevalence of obesity and diabetes has increased dramatically in developing countries, substantially affecting the patterns of chronic kidney disease (CKD) observed in these regions. Using data from the Hospital Quality Monitoring System to evaluate changes in the spectrum of non-dialysis-dependent CKD in China, we have observed an increase in the percentage of patients with CKD due to diabetes, which has exceeded that of CKD due to glomerulonephritis since 2011, as well as an increase in hypertensive nephropathy and, in some regions, obstructive kidney disease (mostly associated with kidney stones). The growth of noncommunicable diseases under profound societal and environmental changes has shifted the spectrum of CKD in China toward patterns similar to those of developed countries, which will have enormous impacts on the Chinese health care system. There is much to be done regarding public health interventions, including the establishment of a national CKD surveillance system, improvement in the management of diabetes and hypertension, and enhancement of the affordability and accessibility of kidney replacement therapy. Reducing the burden of CKD will require joint efforts from government, the medical community (including practitioners other than nephrologists), and the public.

INTRODUCTION/BACKGROUND:The prevalence of e-cigarette use has increased dramatically in the last decade in the U.S. Understanding the prevalence, patterns of use, and risk factor associations of e-cigarette use in pregnant women is particularly important, as this could have potential health implications for the mother and the developing child. METHODS:Using Behavioral Risk Factor Surveillance System Survey data from 2016 to 2018, adult women of reproductive age (18-49 years) who reported being pregnant (n=7,434) were studied. Self-reported current e-cigarette use was the main exposure. Other measures included combustible cigarette smoking status and high-risk behaviors (including other tobacco, marijuana, or heavy alcohol use; binge drinking; and others). All analyses were done in 2019. RESULTS:Approximately 2.2% of pregnant women reported current e-cigarette use, of whom 0.6% reported daily use. The highest prevalence of e-cigarette use was observed in the youngest age group of pregnant women (3.2%), with 41.7% of all pregnant current e-cigarette users being aged 18-24 years. There was a marked increase in the prevalence of current use of e-cigarettes among pregnant women from 1.9% in 2016 to 3.8% in 2018. Approximately 46% of pregnant current e-cigarette users reported concomitant cigarette smoking. Compared with pregnant never e-cigarette users, pregnant current e-cigarette users had a higher prevalence of other tobacco product use, marijuana use, heavy alcohol intake, binge drinking, and other high-risk behaviors. CONCLUSIONS:These findings underscore the need to strengthen prevention and policy efforts, specifically in the vulnerable subgroup of pregnant women.