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UC San Francisco Previously Published Works

Cover page of Atopic dermatitis and tobacco smoke exposure during childhood and adolescence

Atopic dermatitis and tobacco smoke exposure during childhood and adolescence

(2025)

Background

Tobacco smoke may affect atopic dermatitis (AD) because of its known effects on humoral and cellular immunity, but prior studies lack data on disease severity and biomarkers over time.

Objective

We investigated the association between passive and active tobacco smoke exposure (TSE) during childhood and adolescence and the activity and severity of AD.

Methods

A birth cohort of 10,521 individuals was followed through adolescence as part of the Avon Longitudinal Study of Parents and Children. We used mixed-effect models to determine the risk of AD (based on repeated assessments) with passive smoke exposure during childhood, active TSE during adolescence, and using a serum biomarker of tobacco exposure (cotinine) at 3 time points.

Results

After adjusting for confounding factors, there was no evidence of a relationship between passive TSE and concurrent AD activity in childhood (adjusted odds ratio, 0.95; 95% confidence interval, 0.83, 1.07) or of an increased risk between active smoking and AD activity in adolescence (adjusted odds ratio, 0.57; 95% confidence interval, 0.44, 0.75). Secondary analyses demonstrated no dose-response relationship and no increased severity of AD with passive or active TSE. Furthermore, we found no increased risk of AD with a cumulative measure of passive TSE across childhood (adjusted relative risk ratio, 0.98; 95% confidence interval, 0.96, 1.00).

Conclusion

Neither active nor passive TSE was associated with AD during childhood and adolescence.

Cover page of Concordance Between DASH Diet and Coronary Artery Calcification: Results From the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Prospective Cohort Study.

Concordance Between DASH Diet and Coronary Artery Calcification: Results From the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Prospective Cohort Study.

(2025)

INTRODUCTION: South Asian adults are at high risk for atherosclerotic cardiovascular disease, for which coronary artery calcification is an early predictor. Adherence to the Dietary Approaches to Stop Hypertension diet is a modifiable risk factor that may mitigate the progression of coronary artery calcification and atherosclerotic cardiovascular disease. METHODS: Using data from the Mediators of Atherosclerosis in South Asians Living in America cohort, the authors calculated a Dietary Approaches to Stop Hypertension dietary score (categorized as low, moderate, and high) to examine the associations of Dietary Approaches to Stop Hypertension diet adherence with coronary artery calcification after a 5-year follow up. RESULTS: The authors found that participants in the high Dietary Approaches to Stop Hypertension category were 41% less likely to have coronary artery calcification score >100 (age-adjusted incidence rate ratio=0.59; 95% CI=0.36, 0.95) than those in the low category; this association was attenuated in multivariable models. Differences were observed by sex. Men in the high Dietary Approaches to Stop Hypertension category were 51% less likely to have coronary artery calcification score >100 (adjusted incidence rate ratio=0.49; 95% CI=0.26, 0.95) and experienced 0.46-fold coronary artery calcification change (fold change=0.46; 95% CI=0.18, 0.90) in multivariable models. CONCLUSIONS: The findings indicate a relationship between Dietary Approaches to Stop Hypertension diet and early predictors of atherosclerotic cardiovascular disease risk among South Asians living in the U.S., particularly men.

Cover page of XOLARIS: A 24-Month, Prospective, Natural History Study of 201 Participants with Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa.

XOLARIS: A 24-Month, Prospective, Natural History Study of 201 Participants with Retinitis Pigmentosa GTPase Regulator-Associated X-Linked Retinitis Pigmentosa.

(2025)

OBJECTIVE: To improve the understanding of the natural disease progression of retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP). DESIGN: A multicenter, prospective, observational natural history study over 24 months. PARTICIPANTS: Male participants aged ≥7 years with a pathogenic variant in the RPGR gene, a best-corrected visual acuity (BCVA) score of ≥34 ETDRS letters, and a mean 68-loci retinal sensitivity (assessed by microperimetry) of 0.1 to 20 decibels (dB). METHODS: Participants were divided into subgroups based on their BCVA score at baseline: 34 to 73 (lower BCVA) or ≥74 (higher BCVA) ETDRS letters. There were 7 visits over 24 months. MAIN OUTCOME MEASURES: Change from baseline in BCVA, retinal sensitivity, low luminance visual acuity (LLVA), fixation stability, contrast sensitivity, visual field, anatomical measures, 25-item Visual Function Questionnaire (VFQ-25), intraocular pressure, and adverse events (AEs). RESULTS: Overall, 201 participants were included. The mean (standard deviation [SD]) age was 30.3 (11.9) years in the lower BCVA subgroup (n = 170) and 27.7 (10.1) years in the higher BCVA subgroup (n = 31). The study eye baseline mean (SD) BCVA scores were 59.4 (10.30) and 77.3 (3.95) in the lower and higher BCVA subgroups, respectively; the lower BCVA subgroup had lower retinal sensitivity in the study eye at baseline than the higher BCVA subgroup. Over 24 months, there were small observed changes in BCVA, retinal sensitivity, LLVA, fixation, contrast sensitivity, and fundus photography findings. There were observed mean (SD) changes at 24 months in the lower and higher BCVA subgroups of -1.01 (4.67) and 0.03 (5.83) dB-steradians in the volume of full-field hill of vision, -330.6 (869.51) and -122.7 (22.01) μm in distance from foveal center to the nearest border of preserved fundus autofluorescence, -104.3 (277.80) and -207.1 (171.01) μm in central ellipsoid width, and -2.8 (9.7) and -0.6 (7.6) in VFQ-25 composite score, respectively. There was 1 death from completed suicide. There were no ocular serious adverse events, and most AEs were mild/moderate. CONCLUSIONS: This study provides evidence of the slow natural progression of XLRP over 24 months in both subgroups and provides important functional, anatomical, and safety data. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cover page of Hypertension control and risk of age-associated dementia in people with HIV infection.

Hypertension control and risk of age-associated dementia in people with HIV infection.

(2025)

OBJECTIVE: Hypertension is a major risk factor for dementia, but sustained blood pressure control is difficult to achieve. We evaluated whether inadequately controlled hypertension may contribute to excess dementia risk among people with HIV. DESIGN: A retrospective cohort study. METHODS: We studied demographically matched people with and without HIV between July 1, 2013, and December 31, 2021, who were at least 50 years old and had a hypertension diagnosis but no dementia diagnosis. Hypertension control was calculated using a disease management index (DMI), which captured degree and duration above the hypertension treatment goals of SBP less than 140 mmHg and DBP less than 90 mmHg. DMI values ranged from 0 to 100% (perfect control); hypertension was considered inadequately controlled if DMI was less than 80% (i.e., in control for <80% of the time). Annual, time-updated DMI was calculated for SBP and DBP. Associations of SPB and DPB control with incident dementia were evaluated using extended Cox regression models. RESULTS: The study included 3099 hypertensive people with HIV (mean age: 58.3 years, 90.2% men) and 66 016 people without HIV. Each year of inadequate SBP control was associated with greater dementia risk in both people with HIV (adjusted hazard ratio [aHR] = 1.26, 0.92-1.64) and people without HIV (aHR = 1.27 (1.21-1.33); P- interaction = 0.85). Similarly, inadequate DBP control was associated with greater dementia risk in both people with HIV (aHR = 1.43, 0.90-1.95) and people without HIV (aHR = 1.71, 1.50-1.93; P -interaction = 0.57). CONCLUSION: Findings suggest the association of inadequate hypertension control with greater dementia risk is similar by HIV status. Stronger associations of DBP control with dementia merit further investigation.

Cover page of Prolonged venous transit is associated with lower odds of excellent recovery after reperfusion in anterior large-vessel occlusion stroke.

Prolonged venous transit is associated with lower odds of excellent recovery after reperfusion in anterior large-vessel occlusion stroke.

(2025)

BACKGROUND AND PURPOSE: Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion. METHODS: In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days. RESULTS: Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p < 0.001). After adjusting for possible confounders, PVT positivity was independently associated with lower odds of excellent recovery (adjusted odds ratio 0.11, 95% confidence interval 0.02 to 0.48; p = 0.006). CONCLUSIONS: Among patients with AIS-LVO who achieved successful reperfusion, PVT positivity was independently associated with a decreased likelihood of excellent functional outcome at 90 days. Assessment of PVT on CTP may provide valuable prognostic information and aid in clinical decision making for patients with AIS-LVO.

Cover page of Post-intervention control in HIV immunotherapy trials

Post-intervention control in HIV immunotherapy trials

(2025)

Purpose of review

While post-treatment control following interruption of standard-of-care antiretroviral therapy (ART) is well described, post-intervention control following immunotherapy in HIV cure-related clinical trials is less well understood. We provide an overview of recent studies that have identified post-intervention controllers and review the mechanisms that may drive this biologically important phenotype.

Recent findings

Post-intervention controllers have been identified in recent immunotherapy trials testing broadly neutralizing antibodies, immune modulators, modified T cells, checkpoint inhibitors, and gene therapy administered individually or in combination. Currently, there is substantial variability in how each trial defines post-intervention control, as well as in how the mechanisms underlying such control are evaluated. Such mechanisms include ongoing activity of both exogenous and autologous antibodies, as well as changes in HIV-specific T cell function.

Summary

While no therapeutic strategy to date has succeeded in definitively inducing HIV control, many studies have identified at least a small number of post-intervention controllers. The field would benefit from a standardized approach to defining and reporting this phenotype, as well as standardization in the approach to assessment of how it is achieved. Such efforts would allow for comparisons across clinical trials and could help accelerate efforts toward an HIV cure.

Cover page of The Role of Gender Norms on Intimate Partner Violence Among Newly Married Adolescent Girls and Young Women in India: A Longitudinal Multilevel Analysis.

The Role of Gender Norms on Intimate Partner Violence Among Newly Married Adolescent Girls and Young Women in India: A Longitudinal Multilevel Analysis.

(2025)

Gender norms have been posited to impact intimate partner violence (IPV), but there is scant evidence of the longitudinal association between community-level gender norms and IPV. Using longitudinal data on 3,965 married girls surveyed in India, we fitted mixed-effects ordinal and binary logistic regression models for physical IPV intensity and occurrence of sexual IPV. We found a 26% increase in the odds that women experience frequent physical IPV per one unit increase in greater community-level equitable gender norms. We did not find an association between community-level equitable gender norms and sexual IPV. Findings suggest that the relationship between gender norms and physical and sexual IPV differs, indicating the need for tailored interventions for different types of IPV.

Cover page of Defining and Validating Criteria to Identify Populations Who May Benefit From Home-Based Primary Care.

Defining and Validating Criteria to Identify Populations Who May Benefit From Home-Based Primary Care.

(2025)

BACKGROUND: Home-based primary care (HBPC) is an important care delivery model for high-need older adults. Currently, target patient populations vary across HBPC programs, hindering expansion and large-scale evaluation. OBJECTIVES: Develop and validate criteria that identify appropriate HBPC target populations. RESEARCH DESIGN: A modified Delphi process was used to achieve expert consensus on criteria for identifying HBPC target populations. All criteria were defined and validated using linked data from Medicare claims and the National Health and Aging Trends Study (NHATS) (cohort n=21,727). Construct validation involved assessing demographics and health outcomes/expenditures for selected criteria. SUBJECTS: Delphi panelists (n=29) represented diverse professional perspectives. Criteria were validated on community-dwelling Medicare beneficiaries (age ≥70) enrolled in NHATS. MEASURES: Criteria were selected via Delphi questionnaires. For construct validation, sociodemographic characteristics of Medicare beneficiaries were self-reported in NHATS, and annual health care expenditures and mortality were obtained via linked Medicare claims. RESULTS: Panelists proposed an algorithm of criteria for HBPC target populations that included indicators for serious illness, functional impairment, and social isolation. The algorithms Delphi-selected criteria applied to 16.8% of Medicare beneficiaries. These HBPC target populations had higher annual health care costs [Med (IQR): $10,851 (3316, 31,556) vs. $2830 (913, 9574)] and higher 12-month mortality [15% (95% CI: 14, 17) vs. 5% (95% CI: 4, 5)] compared with the total validation cohort. CONCLUSIONS: We developed and validated an algorithm to define target populations for HBPC, which suggests a need for increased HBPC availability. By enabling objective identification of unmet demands for HBPC access or resources, this algorithm can foster robust evaluation and equitable expansion of HBPC.

Cover page of Association of Hyperautofluorescence Signals with Geographic Atrophy Progression in the METformin for the MINimization of Geographic Atrophy Progression Trial

Association of Hyperautofluorescence Signals with Geographic Atrophy Progression in the METformin for the MINimization of Geographic Atrophy Progression Trial

(2025)

Purpose

To investigate the association between rim area focal hyperautofluorescence (RAFH) signals and geographic atrophy (GA) growth rates, as well as the impact of oral metformin on the longitudinal change of RAFH.

Design

Secondary analysis of a randomized controlled trial.

Participants

Seventy-one eyes from 44 participants with GA and ≥6 months of follow-up in the METformin for the MINimization of geographic atrophy progression study.

Methods

Fundus autofluorescence images were captured using a 488 nm excitation wavelength. Two masked graders identified and measured RAFH lesions using proprietary semiautomatic segmentation software and ImageJ. We calculated RAFH by dividing the areas of hyperautofluorescence within a 450-μm rim circumscribing the GA by the total area enclosed within this rim.

Main outcome measures

Longitudinal changes in RAFH and GA area.

Results

Baseline RAFH was positively associated with the baseline square root of GA area 0.065/year (P < 0.001). In the entire study cohort, higher baseline RAFH was associated with a faster GA area growth rate in mm2/year (Spearman's ρ = 0.53; P < 0.001). The association became weaker in square root-transformed GA area growth (ρ = 0.19, P = 0.11) and perimeter-adjusted GA growth rate (ρ = 0.28, P = 0.02), achieving statistical significance only in the latter. When this analysis was stratified into 3 baseline GA tertiles, the first and second tertiles showed weak to moderate association with statistical significance in all 3 modes of GA growth rates. Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). Rim area focal hyperautofluorescence increased slightly but significantly over time at 0.020/year (P < 0.01). The use of oral metformin was not significantly associated with the change in RAFH over time compared with the observation group (0.023/year vs. 0.016/year; P = 0.29).

Conclusions

Increased baseline RAFH is associated with faster GA area progression. However, the effect size of this association may depend on the baseline GA lesion size such that small to medium-sized GA lesions display this relationship regardless of the mode of the calculation of GA growth rate.

Financial disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Cover page of A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy.

A Predictive Nomogram for Development of Lymph Node Metastasis in Muscle-Invasive Bladder Cancer Following Neoadjuvant Therapy.

(2025)

PURPOSE: Pelvic lymph node metastases (ypN+) after multiagent neoadjuvant chemotherapy (NAC) is a poor prognostic sign in nonmetastatic muscle-invasive bladder cancer (nmMIBC). We sought to create a nomogram predicting probability of ypN+ after NAC for cN0 nmMIBC and determine association with overall survival (OS). METHODS AND MATERIALS: We reviewed the National Cancer Database for patients with cT2-4N0M0 urothelial carcinoma of the bladder receiving multiagent NAC and surgery from 2004 to 2020. Following a data split, univariate logistic regression identified variables associated with ypN+ at P < .05. Eligible variables were used for multivariate logistic regression and nomogram generation. A threshold for 95% sensitivity defined high- and low-risk groups for ypN+. Fine-Gray models assessed ypN+ risk group and OS, accounting for competing risks of surgical mortality. RESULTS: A total of 6194 patients were identified with a median follow-up of 39.5 months (interquartile range [IQR], 20.5-67.2 months). Most patients had high-grade (97.7%) cT2 disease (70.8%) with nonpapillary urothelial histology (67.3%) and initiated NAC at a median of 41.0 days after diagnosis (IQR, 28.0-59.0 days).The nomogram included age in decades (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.87-1.03; P = .172), weeks from diagnosis to NAC (OR, 1.02; 95% CI, 1.01-1.04; P = .004), nonpapillary histology (OR, 1.17; 95% CI, 0.99-1.39; P = .068), and clinical T-stage. Within the testing cohort, ypN+ was found in 392 (22.8%) high-risk and 12 (8.0%) low-risk patients (P < .001), with median OS of 36.1 and 74.0 months, respectively (P < .001). High-risk patients had worse OS despite competing risks of 30-day (subdistribution hazard ratio [SHR], 1.80; 95% CI, 1.49-2.18; P < .001) and 90-day surgical mortality (SHR, 1.68; 95% CI, 1.39-2.04; P < .001). CONCLUSIONS: This is the first study to provide a tool for predicting ypN+ and prognosticate worse OS in primarily high-grade nmMIBC and could select patients for alternative neoadjuvant therapy and facilitate future study.