Open Access Policy Deposits

This series is automatically populated with publications deposited by UCSF Department of Epidemiology and Biostatistics researchers in accordance with the University of California’s open access policies. For more information see Open Access Policy Deposits and the UC Publication Management System.

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Differential Use of Diagnostic Ultrasound in U.S. Emergency Departments by Time of Day

(2011)

Background: Survey data over the last several decades suggests that emergency department (ED) access to diagnostic ultrasound performed by the radiology department is unreliable, particularly outside of regular business hours.

Objective: To evaluate the association between the time of day of patient presentation and the use of diagnostic ultrasound services in United States (U.S.) EDs.

Methods: This was a cross-sectional study of ED patient visits using the National Hospital Ambulatory Medical Care Survey for the years 2003 to 2005. Our main outcome measure was the use of diagnostic ultrasound during the ED patient visit as abstracted from the medical record. We performed multivariate analyses to identify any association between ultrasound use and time of presentation for all patients, as well as for two subgroups who are more likely to need ultrasound as part of their routine workup: patients at risk of deep venous thrombosis, and patients at risk for ectopic pregnancy.

Results: During the three-year period, we analyzed 110,447 patient encounters, representing 39 million national visits. Of all ED visits, 2.6% received diagnostic ultrasound. Presenting to the ED “off hours” (defined as Monday through Friday 7pm to 7am and weekends) was associated with a lower rate of ultrasound use independent of potential confounders (odds ratio [OR] 0.73, 95% confidence interval [CI]: 0.65 - 0.82). Patients at increased risk of deep venous thrombosis who presented to the ED during “off hours” were also less likely to undergo diagnostic ultrasound (OR 0.34, 95% CI: 0.15 - 0.79). Similarly, patients at increased risk of ectopic pregnancy received fewer diagnostic ultrasounds during “off hours” (OR 0.56, 95% CI 0.35 - 0.91).

Conclusion: In U.S. EDs, ultrasound use was lower during “off hours,” even among patient populations where its use would be strongly indicated. [West J Emerg Med. 2011;12(1):90-95.]

The Importance of Racially and Ethnically Inclusive Gait Speed Reference Values in Individuals 90 Years and Older: LifeAfter90

(2024)

Background and purpose

Clinicians use reference values to contextualize physical performance scores, but data are sparse in individuals 90 years and older and racial/ethnic diversity is limited in existing studies. Gait speed provides valuable information about an individual's health status. Slow gait speed is associated with falls, cognitive decline, and mortality. Here, we report gait speed reference values in a racially/ethnically diverse oldest-old cohort.

Methods

LifeAfter90 is a multiethnic cohort study of individuals 90 years and older. Participants are long-term members of an integrated healthcare delivery system without a dementia diagnosis at enrollment. We assessed gait speed using the 4-m walk test and calculated means, standard deviations, and percentiles by age, sex, assistive device use, and device type. We used linear regression to compare means by sex, age, device use and type, living situation and arrangement, and race/ethnicity.

Results and discussion

The mean age of the 502 participants was 92.9 (range 90.1-102.8) years. Of these, 62.6% were women, 34.7% were college educated, 90.8% lived in a private residence, 20.9% self-reported as Asian, 22.5% as Black, 11.8% as Hispanic, 35.7% as White, and 9.2% as multiple, "other," or declined to state. The overall mean gait speed was 0.54 m/s (women = 0.51 m/s, men = 0.58 m/s). Mean gait speeds were 0.58 m/s, 0.53 m/s, and 0.48 m/s in the 90 to 91, 92 to 93, and 94+ age categories, respectively. In those without a device, mean gait speed was 0.63 m/s compared to 0.40 m/s in those with a device (cane = 0.44 m/s, walker = 0.37 m/s). Mean gait speed was significantly slower in women compared to men, age category 94+ compared to 90 to 91, participants with a device compared to those without, participants with a walker compared to a cane, and Black participants compared to Asian and White participants. However, differences by race/ethnicity were attenuated when chronic health conditions were considered.

Conclusions

Reference values developed from this multiethnic 90+ cohort will help clinicians interpret gait speed measures and tailor recommendations toward a 90+ population that is growing in number and in racial/ethnic diversity.

Cover page of Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study

(2024)

Purpose

To assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).

Patients and methods

This was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.

Results

A total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).

Conclusion

Treatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

Cover page of Gender differences in the association between education and late‐life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest–old

Gender differences in the association between education and late‐life cognitive function in the LifeAfter90 Study: A multiethnic cohort of the oldest–old

(2024)

Introduction

Few studies have examined the relationship between education and cognition among the oldest-old.

Methods

Cognitive assessments were conducted biannually for 803 participants (62.6% women) of LifeAfter90, a longitudinal study of individuals ≥ 90 years old. Gender differences in associations between education (< high school, high school, some college, and ≥ college) and cognition (verbal episodic memory, semantic memory, and executive function) were examined at baseline and longitudinally using linear mixed models.

Results

Higher education levels were associated with better cognitive performance at baseline for both men and women. College completion was more strongly associated with better baseline executive function among women. Education-cognition associations for baseline verbal episodic memory and baseline semantic memory did not differ by gender. Education was not associated with a decline in any domain-specific cognitive scores, regardless of gender.

Discussion

Education is associated with cognitive function among the oldest-old and varies by gender and cognitive domain at baseline but not over time.

Highlights

In the oldest-old, higher education was associated with better cognitive function. College completion was more strongly associated with executive function in women. Education was not associated with cognitive decline after age 90 regardless of gender. Improving education could decrease gaps in cognitive level among older individuals.

Early-life tobacco exposure is causally implicated in aberrant RAG-mediated recombination in childhood acute lymphoblastic leukemia

(2024)

Cover page of Folate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium

Folate metabolism and risk of childhood acute lymphoblastic leukemia: a genetic pathway analysis from the Childhood Cancer and Leukemia International Consortium

(2024)

Background

Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

Methods

We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls). Each study followed a standardized protocol for quality control and imputation of genome-wide data and summary statistics were meta-analyzed for all children combined and by major ancestry group using METAL software.

Results

None of the selected SNPs reached statistical significance, overall and for major ancestry groups (using adjusted Bonferroni P-value of 5 × 10-6 and less-stringent P-value of 3.5 × 10-5 accounting for the number of "independent" SNPs). None of the 10 top (nonsignificant) SNPs and corresponding genes overlapped across ancestry groups.

Conclusions

This large meta-analysis of original data does not reveal associations between many common genetic variants in the folate metabolism pathway and childhood ALL in various ancestry groups.

Impact

Genetic variants in the folate pathway alone do not appear to substantially influence childhood acute lymphoblastic leukemia risk. Other mechanisms such as gene-folate interaction, DNA methylation, or maternal genetic effects may explain the observed associations with self-reported prenatal folate intake.

Frontotemporal lobar degeneration targets brain regions linked to expression of recently evolved genes

(2024)

In frontotemporal lobar degeneration (FTLD), pathological protein aggregation in specific brain regions is associated with declines in human-specialized social-emotional and language functions. In most patients, disease protein aggregates contain either TDP-43 (FTLD-TDP) or tau (FTLD-tau). Here, we explored whether FTLD-associated regional degeneration patterns relate to regional gene expression of human accelerated regions (HARs), conserved sequences that have undergone positive selection during recent human evolution. To this end, we used structural neuroimaging from patients with FTLD and human brain regional transcriptomic data from controls to identify genes expressed in FTLD-targeted brain regions. We then integrated primate comparative genomic data to test our hypothesis that FTLD targets brain regions linked to expression levels of recently evolved genes. In addition, we asked whether genes whose expression correlates with FTLD atrophy are enriched for genes that undergo cryptic splicing when TDP-43 function is impaired. We found that FTLD-TDP and FTLD-tau subtypes target brain regions with overlapping and distinct gene expression correlates, highlighting many genes linked to neuromodulatory functions. FTLD atrophy-correlated genes were strongly enriched for HARs. Atrophy-correlated genes in FTLD-TDP showed greater overlap with TDP-43 cryptic splicing genes and genes with more numerous TDP-43 binding sites compared with atrophy-correlated genes in FTLD-tau. Cryptic splicing genes were enriched for HAR genes, and vice versa, but this effect was due to the confounding influence of gene length. Analyses performed at the individual-patient level revealed that the expression of HAR genes and cryptically spliced genes within putative regions of disease onset differed across FTLD-TDP subtypes. Overall, our findings suggest that FTLD targets brain regions that have undergone recent evolutionary specialization and provide intriguing potential leads regarding the transcriptomic basis for selective vulnerability in distinct FTLD molecular-anatomical subtypes.

Cover page of Disparities in awareness and treatment among women with hypertension: Insights from the American Heart Association Research Goes Red Registry.

Disparities in awareness and treatment among women with hypertension: Insights from the American Heart Association Research Goes Red Registry.

(2024)

Hypertension is an important modifiable risk factor for cardiovascular disease and affects nearly one-third of women in the U.S. Prior research has demonstrated declining rates of blood pressure (BP) control nationally among women, and there are significant racial and ethnic disparities in both hypertension prevalence and outcomes among U.S. women. However, national-level data on attitudes and awareness of women with hypertension are limited. To address this gap, data were analyzed from participants with self-reported hypertension enrolled in the American Heart Associations Research Goes Red Registry. Of 6170 women who responded as of February 2023, 1835 (30 %) reported a history of hypertension. The top health concerns reported among women with hypertension were weight, healthcare access and costs, and hypertension. Health concerns varied significantly by age, race, and ethnicity; younger women and Black and Hispanic women were more likely to report hypertension as their top concern. Among women with self-reported hypertension, 77 % reported knowing their BP, and 90 % reported being on an anti-hypertensive. Black and Hispanic women were less likely to know their BP compared to White women. Younger women were less likely to be treated for hypertension, and there were also disparities in treatment by employment status and among uninsured women. In this national registry of women in the U.S., gaps and disparities exist in awareness and treatment of hypertension, highlighting targets for quality improvement in hypertension care for women.

Cover page of Our Needs Have Been Ignored for a Long Time: Factors Affecting the Willingness of Black and Hispanic/Latinx Sexual and Gender Minority Communities to Donate Biospecimens

Our Needs Have Been Ignored for a Long Time: Factors Affecting the Willingness of Black and Hispanic/Latinx Sexual and Gender Minority Communities to Donate Biospecimens

(2024)

The study aimed to document factors affecting the willingness to engage in biospecimen donation for substance use research among Black and Hispanic/Latinx sexual and gender minority (SGM) people. From May to July 2022, we interviewed 22 Black and Hispanic/Latinx SGM people from The Population Research in Identity and Disparities for Equality Study, a cohort of SGM people in the United States and its territories, using Zoom videoconferencing software. Fourteen participants were cisgender sexual minority people, and eight participants were gender minority people who were also sexual minority. We took an inductive, collaborative qualitative analytic approach to identify themes. Themes included the following: (1) community benefits, (2) personal benefits, (3) community exploitation, (4) personal risks, (5) convenience, (6) trustworthiness of the research team, (7) perceived value in donating, and (8) normalization of biospecimen collection. Participants were generally motivated to engage in biospecimen donation for altruistic purposes. The most cited concerns were related to data security, misuse, and privacy. Researchers must be proactive in building trust with Black and Hispanic/Latinx SGM communities to increase engagement, diversify biospecimen repositories, and reduce health inequities. Future research involving biospecimens should provide biospecimen education during the consent process and prioritize participant convenience.

Cover page of Predictors of weight and waist gain in US South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study

Predictors of weight and waist gain in US South Asians: Findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study

(2024)

Background

Weight and waist gain are significant concerns in adulthood. Both weight and waist gain are particularly important among South Asians, known to have an increased risk of developing chronic cardiometabolic complications at any body mass index compared to other racial and ethnic groups. The aim of this study was to investigate factors predicting weight and waist gain in a longitudinal cohort of South Asians living in the US (United States).

Methods

This was a prospective analysis using data from exam 1 (2010-2013) and exam 2 (2015-2018) of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, a prospective cohort study of South Asians (recruited from San Francisco and Chicago), with a mean 4.8 years of follow-up.

Results

Of 634 participants studied (42.7 % women, mean age 55 years, BMI 25.7 kg/m2, weight 70.4 kg at exam 1), 34.7 % had gained ≥5 % weight and 32.3 % gained ≥5 % waist at exam 2. In the adjusted models, older age, higher number of years of US residence, and having diabetes were associated with lower odds of weight gain; being female and having higher adiponectin were associated with higher odds of weight gain. Being female and being employed full/part time or being retired predicted lower likelihood of waist gain. Being single, separated/divorced, having a higher leptin and a higher C-reactive protein level predicted higher likelihood of waist gain.

Conclusions

The current study identified several social, demographic, and clinical factors that can serve as targets for obesity interventions among US South Asians. In addition, this study also raises hypotheses about associations of adipokine levels with weight and waist gain.