Faculty Bibliography
Searched for:
school:SOM
Department/Unit:Population Health
Total Results:
12260
STudy of Alteplase for Respiratory failure in SARS-Cov2/COVID-19: Study Design of the Phase IIa STARS Trial
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).
PMCID:7280574
PMID: 32838109
ISSN: 2475-0379
CID: 4575272
Mapping geographical inequalities in oral rehydration therapy coverage in low-income and middle-income countries, 2000-17
BACKGROUND:Oral rehydration solution (ORS) is a form of oral rehydration therapy (ORT) for diarrhoea that has the potential to drastically reduce child mortality; yet, according to UNICEF estimates, less than half of children younger than 5 years with diarrhoea in low-income and middle-income countries (LMICs) received ORS in 2016. A variety of recommended home fluids (RHF) exist as alternative forms of ORT; however, it is unclear whether RHF prevent child mortality. Previous studies have shown considerable variation between countries in ORS and RHF use, but subnational variation is unknown. This study aims to produce high-resolution geospatial estimates of relative and absolute coverage of ORS, RHF, and ORT (use of either ORS or RHF) in LMICs. METHODS:We used a Bayesian geostatistical model including 15 spatial covariates and data from 385 household surveys across 94 LMICs to estimate annual proportions of children younger than 5 years of age with diarrhoea who received ORS or RHF (or both) on continuous continent-wide surfaces in 2000-17, and aggregated results to policy-relevant administrative units. Additionally, we analysed geographical inequality in coverage across administrative units and estimated the number of diarrhoeal deaths averted by increased coverage over the study period. Uncertainty in the mean coverage estimates was calculated by taking 250 draws from the posterior joint distribution of the model and creating uncertainty intervals (UIs) with the 2·5th and 97·5th percentiles of those 250 draws. FINDINGS:While ORS use among children with diarrhoea increased in some countries from 2000 to 2017, coverage remained below 50% in the majority (62·6%; 12 417 of 19 823) of second administrative-level units and an estimated 6 519 000 children (95% UI 5 254 000-7 733 000) with diarrhoea were not treated with any form of ORT in 2017. Increases in ORS use corresponded with declines in RHF in many locations, resulting in relatively constant overall ORT coverage from 2000 to 2017. Although ORS was uniformly distributed subnationally in some countries, within-country geographical inequalities persisted in others; 11 countries had at least a 50% difference in one of their units compared with the country mean. Increases in ORS use over time were correlated with declines in RHF use and in diarrhoeal mortality in many locations, and an estimated 52 230 diarrhoeal deaths (36 910-68 860) were averted by scaling up of ORS coverage between 2000 and 2017. Finally, we identified key subnational areas in Colombia, Nigeria, and Sudan as examples of where diarrhoeal mortality remains higher than average, while ORS coverage remains lower than average. INTERPRETATION:To our knowledge, this study is the first to produce and map subnational estimates of ORS, RHF, and ORT coverage and attributable child diarrhoeal deaths across LMICs from 2000 to 2017, allowing for tracking progress over time. Our novel results, combined with detailed subnational estimates of diarrhoeal morbidity and mortality, can support subnational needs assessments aimed at furthering policy makers' understanding of within-country disparities. Over 50 years after the discovery that led to this simple, cheap, and life-saving therapy, large gains in reducing mortality could still be made by reducing geographical inequalities in ORS coverage. FUNDING:Bill & Melinda Gates Foundation.
PMCID:7388204
PMID: 32710861
ISSN: 2214-109x
CID: 4851412
Patient Perspectives on the Implementation of Risk-Aligned Bladder Cancer Surveillance: Systematic Evaluation Using the Tailored Implementation for Chronic Diseases Framework
PURPOSE/UNASSIGNED:Many patients living with bladder cancer do not undergo surveillance that is aligned with their risk for recurrence or progression, which exposes them to unnecessary risk and burden of procedures. To implement risk-aligned surveillance as recommended by multiple guidelines, we need to understand patient-, provider-, and system-level factors contributing to the delivery of risk-aligned surveillance. In this study, we sought to systematically assess patient-level factors. PARTICIPANTS AND METHODS/UNASSIGNED:not aligned with cancer risk). Interview transcripts were analyzed using a priori codes from the Tailored Implementation for Chronic Diseases framework. Quantitative and qualitative data were integrated by cross-tabulating determinants across risk and surveillance categories. RESULTS/UNASSIGNED:Participants included seven low-risk and 15 high-risk patients; 10 underwent risk-aligned surveillance and 12 did not. In mixed-methods analyses, perception of risk appropriately differed by risk but not by surveillance category. Participants understood the recommended surveillance schedule according to their risk category. Participants emphatically expressed that adhering to providers' recommendations is prudent; intentions to adhere did not vary across risk and surveillance categories. CONCLUSION/UNASSIGNED:Participants intended to adhere to providers' recommendations and strongly endorsed the importance of adherence. These findings suggest implementation strategies to improve risk-aligned surveillance may be most effective when targeting provider- and system-level factors rather than patient-level factors.
PMID: 32119595
ISSN: 2688-1535
CID: 4563562
CKD in China: Evolving Spectrum and Public Health Implications
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.
PMID: 31492486
ISSN: 1523-6838
CID: 5585492
American journal of respiratory cell & molecular biology. 2020:63(2):219-233.DOI: 10.1165/rcmb.2019-0064OC
MultiOMICs of WTC-Particulate Induced Persistent Airway Hyperreactivity: Role of Receptor for Advanced Glycation End Products
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.
PMID: 32315541
ISSN: 1535-4989
CID: 4392852
E-Cigarette Use Patterns and High-Risk Behaviors in Pregnancy: Behavioral Risk Factor Surveillance System, 2016-2018
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.
PMID: 32362509
ISSN: 1873-2607
CID: 4429802
Sex workers are returning to work and require enhanced support in the face of COVID-19: results from a longitudinal analysis of online sex work activity and a content analysis of safer sex work guidelines
Sex workers confront unique challenges in the face of COVID-19. Data from an international sex work website popular with cisgender men and transgender men and women suggest that, after a period of physical distancing, many sex workers are returning to in-person work: from May to August 2020, active sex work profiles increased 9.4% (P < 0.001) and newly created profiles increased by 35.6% (P < 0.001). Analysis of sex work and COVID-19 guidelines published by five community-based organisations found that they focused on altering sexual practices, enhancing hygiene and pivoting to virtual work. To capitalise on these guidelines, funding and research for implementation and evaluation are needed to support COVID-19 risk reduction strategies for sex workers.
PMID: 32838836
ISSN: 1449-8987
CID: 4652242
Exposures to phthalates and bisphenols in pregnancy and postpartum weight gain in a population-based longitudinal birth cohort
BACKGROUND:Experimental evidence suggests that exposures to phthalates and bisphenols may interfere with processes related to glucose and lipid metabolism, insulin sensitivity, and body weight. Few studies have considered the possible influence of chemical exposures during pregnancy on maternal weight gain or metabolic health outcomes postpartum. OBJECTIVE:To examine the associations of early and mid-pregnancy bisphenol and phthalate urine concentrations with maternal weight gain 6 years postpartum. METHODS:We analyzed urine samples for bisphenol, phthalate and creatinine concentrations from early and mid-pregnancy in 1192 women in a large, population-based birth cohort in Rotterdam, the Netherlands, and examined postpartum weight gain using maternal anthropometrics before pregnancy and 6 years postpartum. We have used covariate-adjusted linear regressions to evaluate associations of early and mid-pregnancy bisphenols and phthalate metabolites with weight change. Mediator and interaction models have been used to assess the role of gestational weight gain and breastfeeding, respectively. Sensitivity analysis is performed among women without subsequent pregnancies. RESULTS:Among all 1192 mothers included in the analysis, each log unit increase in the average bisphenol A and all assessed phthalate groupings were associated with increased maternal weight gain. As a proxy for phthalate exposure, each log unit increase in averaged phthalic acid was associated with 734 g weight gain (95% CI 273-1196 g) between pre-pregnancy and 6 years postpartum. Mediation by gestational weight gain was not present. Breastfeeding and ethnicity did not modify the effects. Stratification revealed these associations to be strongest among overweight and obese women. Among women without subsequent pregnancies (n = 373) associations of bisphenols, HMW phthalate metabolites and di-2-ethylhexylphthalate metabolites attenuated. For phthalic acid, LMW phthalate metabolites and di-n-octylphthalate metabolites associations increased. Similarly to the whole group, stratification yielded significant results among overweight and obese women. DISCUSSION/CONCLUSIONS:In a large population-based birth cohort, early and mid-pregnancy phthalate exposures are associated with weight gain 6 years postpartum, particularly among overweight and obese women. These data support ongoing action to replace phthalates with safer alternatives.
PMID: 32745783
ISSN: 1873-6750
CID: 4581282
International journal of environmental research & public health. 2020:17(15).DOI: 10.3390/ijerph17155493
Genome-Wide DNA Methylation Profiles in Community Members Exposed to the World Trade Center Disaster
The primary goal of this pilot study was to assess feasibility of studies among local community members to address the hypothesis that complex exposures to the World Trade Center (WTC) dust and fumes resulted in long-term epigenetic changes. We enrolled 18 WTC-exposed cancer-free women from the WTC Environmental Health Center (WTC EHC) who agreed to donate blood samples during their standard clinical visits. As a reference WTC unexposed group, we randomly selected 24 age-matched cancer-free women from an existing prospective cohort who donated blood samples before 11 September 2001. The global DNA methylation analyses were performed using Illumina Infinium MethylationEpic arrays. Statistical analyses were performed using R Bioconductor package. Functional genomic analyses were done by mapping the top 5000 differentially expressed CpG sites to the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway database. Among cancer-free subjects, we observed substantial methylation differences between WTC-exposed and unexposed women. The top 15 differentially methylated gene probes included BCAS2, OSGIN1, BMI1, EEF1A2, SPTBN5, CHD8, CDCA7L, AIDA, DDN, SNORD45C, ZFAND6, ARHGEF7, UBXN8, USF1, and USP12. Several cancer-related pathways were enriched in the WTC-exposed subjects, including endocytosis, mitogen-activated protein kinase (MAPK), viral carcinogenesis, as well as Ras-associated protein-1 (Rap1) and mammalian target of rapamycin (mTOR) signaling. The study provides preliminary data on substantial differences in DNA methylation between WTC-exposed and unexposed populations that require validation in further studies.
PMID: 32751422
ISSN: 1660-4601
CID: 4553982
Diffusion of Ecstasy in the Electronic Dance Music Scene
BACKGROUND:Results provide insight regarding diffusion and initiation of ecstasy in the EDM scene. Findings can inform prevention and harm reduction efforts.
PMID: 32729760
ISSN: 1532-2491
CID: 4560602
