Faculty Bibliography

Cancer survivors benefit from evidence-based smoking cessation treatment. A crucial first step in this process is a clinician recommending that the patient quit smoking. However, contemporary delivery of advice to quit among patients with cancer is not well known. In a cross-sectional analysis of all adult smokers included in a prospective population-representative study of US adults, we analyzed the frequency that patients reported receiving advice to quit smoking from a healthcare professional according to reported cancer history (no cancer, tobacco-related cancer, non-tobacco related cancer history). Among an estimated 28.3 million smokers, 9.3% reported a history of cancer, 48.8% of which were tobacco-related cancers. In general, advice to quit was reported by more (67.8%) cancer survivors than those adults without any cancer (56.0%). After adjustment for sociodemographic factors, smokers with a non tobacco-related cancer (0.51, 95% CI 0.32-0.83) and those without any cancer history (0.43, 95% CI 0.30-0.63) were both less likely to report being advised to quit smoking than patients with a tobacco-related cancer history.

Air pollution poses a serious threat to children's respiratory health around the world. Satellite remote-sensing technology and air quality models can provide pollution data on a global scale, necessary for risk communication efforts in regions without ground-based monitoring networks. Several large centers, including NASA, produce global pollution forecasts that may be used alongside air quality indices to communicate local, daily risk information to the public. Here we present a health-based, globally applicable air quality index developed specifically to reflect the respiratory health risks among children exposed to elevated outdoor air pollution. Additive, excess-risk air quality indices were developed using 51 different coefficients derived from time-series health studies evaluating the impacts of ambient fine particulate matter, nitrogen dioxide, and ozone on children's respiratory morbidity outcomes. A total of four indices were created which varied based on whether or not the underlying studies controlled for co-pollutants and in the adjustment of excess risks of individual pollutants. Combined with historical estimates of air pollution provided globally at a 25 × 25 km² spatial resolution from the NASA's Goddard Earth Observing System composition forecast (GEOS-CF) model, each of these indices were examined in a global sample of 664 small and 140 large cities for study year 2017. Adjusted indices presented the most normal distributions of locally-scaled index values, which has been shown to improve associations with health risks, while indices based on coefficients controlling for co-pollutants had little effect on index performance. We provide the steps and resources need to apply our final adjusted index at the local level using freely-available forecasting data from the GEOS-CF model, which can provide risk communication information for cities around the world to better inform individual behavior modification to best protect children's respiratory health.

Plasma proteomic profiling may aid in the discovery of novel biomarkers upstream of the development of atrial fibrillation (AF). We used data from the Atherosclerosis Risk in Communities study to examine the relation between large-scale proteomics and incident AF in a cohort of older-aged adults in the United States. We quantified 4,877 plasma proteins in Atherosclerosis Risk in Communities participants at visit 5 (2011-2013) using an aptamer-based proteomic profiling platform. We used Cox proportional hazards models to assess the association between protein levels and incident AF, and explored relation of selected protein biomarkers using annotated pathway analysis. Our study included 4,668 AF-free participants (mean age 75 ± 5 years; 59% female; 20% Black race) with proteomic measures. A total of 585 participants developed AF over a mean follow-up of 5.7 ± 1.7 years. After adjustment for clinical factors associated with AF, N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with the risk of incident AF (hazard ratio, 1.82; 95% CI, 1.68 to 1.98; p, 2.91 × 10^-45 per doubling of NT-proBNP). In addition, 36 other proteins were also significantly associated with incident AF after Bonferroni correction. We further adjusted for medication use and estimated glomerular filtration rate and found 17 proteins, including angiopoietin-2 and transgelin, that remained significantly associated with incident AF. Pathway analyses implicated the inhibition of matrix metalloproteases as the top canonical pathway in AF pathogenesis. In conclusion, using a large-scale proteomic platform, we identified both novel and established proteins associated with incident AF and explored mechanistic pathways of AF development.

Obesity and type 2 diabetes mellitus are highly prevalent and increasing in the United States among racial/ethnic minority groups. Type 2 diabetes mellitus, which is driven by many factors including elevated levels of adiposity, is an exemplar health disparities disease. Pervasive disparities exist at every level from risk factors through outcomes for U.S. racial/ethnic minority groups, including African American, Hispanic/LatinX American, and Asian American populations. Disparities in clinical care exist including hemoglobin A1c control, lower prescription rates of newer antihyperglycemic medications, along with greater rates of complications postbariatric surgery. Underpinning these disparities are the social determinants of health affecting provider-patient interactions, access to resources, and healthy built environments. We review the best practices to address cardiometabolic disparities in the current cardiovascular guidelines and describe recommendations for cross-cutting strategies to advance equity in obesity and type 2 diabetes across U.S. racial/ethnic groups.

A library of well-characterized human induced pluripotent stem cell (hiPSC) lines from clinically healthy human subjects could serve as a useful resource of normal controls for in vitro human development, disease modeling, genotype-phenotype association studies, and drug response evaluation. We report generation and extensive characterization of a gender-balanced, racially/ethnically diverse library of hiPSC lines from 40 clinically healthy human individuals who range in age from 22 to 61 years. The hiPSCs match the karyotype and short tandem repeat identities of their parental fibroblasts, and have a transcription profile characteristic of pluripotent stem cells. We provide whole-genome sequencing data for one hiPSC clone from each individual, genomic ancestry determination, and analysis of mendelian disease genes and risks. We document similar transcriptomic profiles, single-cell RNA-sequencing-derived cell clusters, and physiology of cardiomyocytes differentiated from multiple independent hiPSC lines. This extensive characterization makes this hiPSC library a valuable resource for many studies on human biology.

OBJECTIVE:Pain specialists treat patients with headache and interface with those who use opioids more so than neurologists and headache specialists. We assessed headache medicine knowledge and needs of pain specialists. DESIGN/SETTING/METHODS:Cross-sectional online survey. SUBJECTS/METHODS:Members of the American Academy of Pain Medicine. METHODS:Survey was based on a prior survey on primary care providers' knowledge and needs and was iteratively updated by four headache specialists, two with pain medicine affiliations. RESULTS:Of the 105 respondents, 71.4% were physicians, 34.3% were women, and they averaged 20.0 ± 13.6 years in practice. The most common specialty was anesthesia (36.1%, n = 35/97) followed by neurology (14.4%, n = 14/97). About half of providers (55.7%, n = 34/61 and 53.3%, n = 32/60) were familiar with the American Academy of Neurology Guidelines for pharmacological migraine prevention and the Choosing Wisely Campaign recommendations for limiting neuroimaging and opioids. Less than half of all providers (39.7%, n = 23/58) were familiar with the American Headache Society guidelines for emergency management of migraine. Providers were aware of Level A evidence-based nonpharmacological therapies, with over three-fourths recognizing cognitive behavioral therapy (80.7%, n = 50/62) and biofeedback (75.8%, n = 47/62) as evidence-based interventions. About 80% of providers (n = 50/64) estimate making migraine diagnoses in ≤ 50% of their patients with headache. Providers consider starting preventive headache therapy at 7.1 ± 3.9 days/month and report referring 34.3%±34.2% of patients to behavioral interventions. CONCLUSIONS:Dissemination and implementation of headache guidelines is needed for pain medicine specialists. Providers may need help diagnosing migraine based on currently accepted guidelines and referring for evidence-based behavioral therapies.

This study assessed the prevalence of prenatal smoking, factors associated with prenatal smoking, and its association with birth outcomes in a sample of pregnant women in Egypt. Pregnant women were recruited during their last trimester from antenatal clinics in Cairo from June 2015 to May 2016. Participants completed an interviewer-administered survey that assessed tobacco use and attitudes, and exhaled carbon monoxide (CO) was measured. Gestational age at delivery and offspring birth weight were collected via a postnatal phone interview. Two hundred pregnant women ages 16-37 years participated. More than a quarter (29.0%) of women reported smoking (cigarettes, hookah, or both) during their current pregnancy, and hookah was more popular than cigarettes. Most women who smoked prior to their current pregnancy either maintained their current smoking habits (46.6%) or switched from dual to hookah-only smoking (46.6%). Current smokers during pregnancy had a higher mean (±SD) exhaled CO level (2.97 ± 1.45 vs. 0.25 ± 0.60 ppm, p < 0.001) and had babies with a lower mean birth weight (2583 ± 300 vs. 2991 ± 478 g, p < 0.001) than non-smokers. Smokers during pregnancy had greater odds of premature birth and/or low birth weight babies compared to non-smokers. Dual cigarette-hookah smokers had the highest risk. Additional focused programs are required to prevent women of childbearing age from initiating tobacco use and empower women to stop tobacco use during the preconception and gestational periods.

Physical activity (PA) has numerous health benefits. Personalized coaching may increase adherence to PA recommendations, but it is challenging to deliver personalized coaching in a scalable manner. The objective of our study was to determine whether novel artificially intelligent (AI) coaching interventions increase PA among overweight or obese, physically inactive cancer survivors compared to a control arm that receives health information. We conducted a single-center, three-arm randomized trial with equal allocation to (1) voice-assisted AI coaching delivered by smart speaker (MyCoach), (2) autonomous AI coaching delivered by text message (SmartText), and (3) control. Data collection was automated via sensors and voice technology, effectively masking outcome ascertainment. The primary outcome was change in mean steps per day from baseline to the end of follow-up at 4 weeks. Of the 42 randomized participants, 91% were female, and 36% were Black; mean age was 62.1 years, and mean BMI was 32.9 kg/m². The majority were breast cancer survivors (85.7%). At the end of 4 weeks follow-up, steps increased in the MyCoach arm by an average of 3618.2 steps/day; the net gain in this arm was significantly greater [net difference = 3568.9 steps/day (95% CI: 1483-5655), P value <0.001] compared to control arm, and [net difference = 2160.6 steps/day (95% CI: 11-4310), P value 0.049] compared to SmartText. In conclusion, AI-based voice-assisted coaching shows promise as a practical method of delivering scalable, individualized coaching to increase physical activity in sedentary cancer survivors. Additional research is needed to replicate these findings in a broader population of cancer survivors and to investigate the effects of these interventions in the general population.ClinicalTrials.gov Identifier: NCT03212079, July 11, 2017, https://clinicaltrials.gov/ct2/show/NCT03212079 .

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

COVID-19 mortality disproportionately affected specific occupations and industries. The Occupational Safety and Health Administration (OSHA) protects the health and safety of workers by setting and enforcing standards for working conditions. Workers may file OSHA complaints about unsafe conditions. Complaints may indicate poor workplace safety during the pandemic. We evaluated COVID-19-related complaints filed with California (Cal)/OSHA between January 1, 2020 and December 14, 2020 across seven industries. To assess whether workers in occupations with high COVID-19-related mortality were also most likely to file Cal/OSHA complaints, we compared industry-specific per-capita COVID-19 confirmed deaths from the California Department of Public Health with COVID-19-related complaints. Although 7,820 COVID-19-related complaints were deemed valid by Cal/OSHA, only 627 onsite inspections occurred and 32 citations were issued. Agricultural workers had the highest per-capita COVID-19 death rates (402 per 100,000 workers) but were least represented among workplace complaints (44 per 100,000 workers). Health Care workers had the highest complaint rates (81 per 100,000 workers) but the second lowest COVID-19 death rate (81 per 100,000 workers). Industries with the highest inspection rates also had high COVID-19 mortality. Our findings suggest complaints are not proportional to COVID-19 risk. Instead, higher complaint rates may reflect worker groups with greater empowerment, resources, or capacity to advocate for better protections. This capacity to advocate for safe workplaces may account for relatively low mortality rates in potentially high-risk occupations. Future research should examine factors determining worker complaints and complaint systems to promote participation of those with the greatest need of protection.