
Sylvie Dobrota Lai
Ph.D. Student in Epidemiology and Clinical Research, admitted Autumn 2022
All Publications
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Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension.
Thorax
2025
Abstract
Pulmonary hypertension (PH) is a progressive cardiopulmonary condition associated with increased morbidity and mortality. The extracellular matrix component hyaluronan (HA) is linked to vascular remodelling and interstitial fibrosis in PH. We hypothesised that inhibition of HA synthesis with hymecromone could serve as a reverse-remodelling therapy in PH.We performed a proof-of-concept phase IIa randomised, double-blind, placebo-controlled study in adults with pulmonary arterial hypertension and PH associated with interstitial lung disease (PH-ILD). Patients were randomised to a 5:3 ratio and stratified by PH group to receive oral hymecromone or placebo two times per day over 24 weeks. The primary endpoint was change in pulmonary vascular resistance (PVR).We enrolled 16 patients with PH with a median age of 62.0 years. There were no treatment-related adverse events leading to hymecromone discontinuation. No statistically significant difference in PVR was observed at 24 weeks for the experimental group compared with the placebo group (mean difference 0.61 Wood unit, 95% CI -1.5 to 2.7). Five patients with PH-ILD treated with hymecromone demonstrated an unadjusted absolute mean increase in 6 min walk distance of 66 m (SD 69.6) from baseline to 24 weeks and improvements in quality-of-life measures.Our exploratory analyses suggest that treatment with hymecromone could lead to improvements in clinically meaningful functional parameters in patients with PH-ILD. Further investigations in larger patient cohorts are warranted.ClinicalTrials.gov: NCT05128929.
View details for DOI 10.1136/thorax-2024-222725
View details for PubMedID 40451287
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Association of Immune Cell Subsets with Longevity: The Cardiovascular Health Study.
The journals of gerontology. Series A, Biological sciences and medical sciences
2025
Abstract
BACKGROUND: Changes in the immune system are a potential biological mechanism of aging. We investigated the association of circulating immune cell subsets with age at death and survival to age 90.METHODS: Immune cell phenotypes were measured at baseline in 1,625 adults, aged 70 to 85 years, in the Cardiovascular Health Study. We selected five primary immune cell subsets: gamma-delta T-cells, natural killer cells, CD8+ T effector memory CD45RA expressing cells (TEMRA) cells, ratio of CD4+ to CD8+ cells, and ratio of naive to memory CD8+ cells. We used linear regression and Poisson models, adjusting for demographics and clinical factors; and tested for effect modification by sex and race. In a secondary analysis, we investigated 23 additional immune cell subsets, using the Holm-Bonferroni method to adjust for multiple comparisons.RESULTS: No primary immune cell subsets were significantly associated with longevity. Two secondary subsets were significantly associated with age at death. Each SD higher proportion of CD4+CD57+ cells was associated with a 0.64-year earlier death (95%CI:-0.99,-0.30) and each SD higher proportion of CD4+CD28-CD57+ cells was associated with a 0.54-year earlier death (95% CI:-0.87,-0.21). Several subsets had significant interactions with sex and race in the fully adjusted model of age at death. A higher proportion of CD4+CD57+ T-cells was significantly associated with lower likelihood of survival to age 90 (RR: 0.79) and 1.07-year earlier age at death in males, but not in females.CONCLUSIONS: Our results suggest that CD4+CD57+ cells are associated with earlier death and this relationship was stronger in males than females.
View details for DOI 10.1093/gerona/glaf094
View details for PubMedID 40378276
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Joint and Individual Mitochondrial DNA Variation and Cognitive Outcomes in Black and White Older Adults.
The journals of gerontology. Series A, Biological sciences and medical sciences
2024
Abstract
BACKGROUND: Mitochondrial dysfunction manifests in neurodegenerative diseases and other age-associated disorders. In this study, we examined variation in inherited mitochondrial DNA (mtDNA) sequences in Black and White participants from two large aging studies to identify variants related to cognitive function.METHODS: Participants included self-reported Black and White adults aged ≥ 70 years in the Lifestyle Interventions and Independence for Elders (LIFE; N=1319) and Health Aging and Body Composition (Health ABC; N=7888) studies. Cognitive function was measured by the digit-symbol substitution test (DSST), and the Modified Mini-Mental State Exam (3MSE) at baseline and over follow-up in LIFE (3.6 years) and Health ABC (10 years). We examined joint effects of multiple variants across 16 functional mitochondrial regions with cognitive function using a sequence kernel association test. Based on these results, we prioritized meta-analysis of common variants in Black and White participants using mixed effects models. A Bonferroni adjusted p-value of <0.05 was considered statistically significant.RESULTS: Joint variation in subunits ND1, ND2, and ND5 of Complex I, 12S RNA, and hypervariable region (HVR) were significantly associated with DSST and 3MSE at baseline. In meta-analyses among Black participants, variant m.4216T>C, ND1 was associated with a faster decline in 3MSE, and variant m.462C>T in the HVR was associated with a slower decline in DSST. Variant m.5460G>C, ND2 was associated with slower and m.182C>T in the HVR was associated with faster decline in 3MSE in White participants.CONCLUSION: Among Black and White adults, oxidative phosphorylation Complex I variants were associated with cognitive function.
View details for DOI 10.1093/gerona/glae170
View details for PubMedID 39007867
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The association of hearing problems with social network strength and depressive symptoms: the cardiovascular health study.
Age and ageing
2022; 51 (8)
Abstract
BACKGROUND: research on the association between hearing impairment and psychosocial outcomes is not only limited but also yielded mixed results.METHODS: we investigated associations between annual self-reports of hearing problems, depressive symptoms and social network strength among 5,888 adults from the Cardiovascular Health Study over a period of 9 years. Social network strength and depressive symptoms were defined using the Lubben Social Network Scale (LSNS), and the Center for Epidemiological Studies Depression Scale (CES-D).RESULTS: hearing problems were associated with weaker social networks and more depressive symptoms. These association differed for prevalent versus incident hearing problems. Participants with prevalent hearing problems scored an adjusted 0.47 points lower (95% CI: -2.20, -0.71) on the LSNS and 0.71 points higher (95% CI: 0.23, 1.19) on the CES-D than those without hearing problems. Participants with incident hearing problems had a greater decline of 0.12 points (95% CI: -0.12, -0.03) per year in social network score than individuals with no hearing problems after adjusting for confounders. Females appeared to be more vulnerable to changes in social network strength than males (P-value for interaction=0.02), but not for changes in depressive score. Accounting for social network score did not appear to attenuate the association between hearing problems and depressive score.CONCLUSION: findings suggest that older adults with prevalent hearing problems may be more at risk for depression, but individuals with incident hearing problems may be at greater risk for a winnowing of their social network.
View details for DOI 10.1093/ageing/afac181
View details for PubMedID 35977151
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The Burnout Dyad: A Collaborative Approach for Including Patients in a Model of Provider Burnout.
The Journal of continuing education in the health professions
2021
Abstract
ABSTRACT: Both patients and providers in the United States (US) suffer from burnout, which can impact the clinical relationship and quality of care. Among providers, burnout is a state of exhaustion including heightened depersonalization; among patients, burnout can negatively affect clinical outcomes. More than half of clinical providers in the United States suffer from burnout; less is known about the magnitude and prevalence among patients. Understanding patient burnout will improve our recognition of treatment barriers, understanding of patient-provider communication, and perceived quality of care. The purpose of the 2019 Stanford University MedicineX Burnout Workgroup was to use a collaborative approach to expand on the National Academy of Medicine (NAM) Wellness and Resilience Model, which does not currently include the patient as an influential member of the care team potentially experiencing burnout. This collaboration among patients, physicians, students, caregivers, technologists, and researchers used a convenience sample of conference attendees, broken into three focus groups to (1) provide an expanded definition of burnout that includes patients' perspectives, (2) analyze the NAM burnout model for inclusion of the patient experience, and (3) define a care experience that includes both patients and providers. The design of this workgroup was informed by Everyone Included, a model that recognizes and rejects hierarchical traditions in clinical practice. This approach allowed for the creation of a safe space for the exchange of knowledge between the various stakeholders. The resulting inclusive conceptual model, The Burnout Dyad, describes a cocreated care experience informed by both patient and provider characteristics.
View details for DOI 10.1097/CEH.0000000000000391
View details for PubMedID 34609356
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Improving Health-Related Quality of Life of Patients With an Ostomy Using a Novel Digital Wearable Device: Protocol for a Pilot Study.
JMIR research protocols
2018; 7 (3): e82
Abstract
Ostomy surgeries involving the placement of an ostomy bag (eg, colostomy, ileostomy, urostomy, etc) have been shown to have a negative impact on health-related quality of life. To date, no studies have been conducted examining what impact, if any, wearable biosensors have on the health-related quality of life of ostomy patients.In the present study, we plan to assess the quality of life of ostomy patients using the Ostom-i alert sensor, a portable, wearable, Bluetooth-linked biosensor that facilitates easier ostomy bag output measurements. We hypothesize that using the Ostom-i alert sensor will result in an improved, ostomy-specific, health-related quality of life as compared to baseline measurement before the use of the sensor.A total of 20 ostomy patients will be screened and recruited to participate in this prospective, observational, cross-over pilot study using an Ostom-i alert sensor for one month. The primary outcome of this study will compare ostomy-specific, health-related quality of life at baseline (prior to Ostom-i alert sensor use) to ostomy-specific, health-related quality of life after 2 and 4 weeks of Ostom-i use by utilizing the City of Hope Quality of Life Questionnaire for Patients with an Ostomy. Secondary outcomes of general health-related quality of life and adjustment to ostomy will be evaluated using the Medical Outcomes Study 36-item short form health survey and the Olbrisch Ostomy Adjustment Scale Short Form 2.The project was funded by the Department of Anesthesiology, Perioperative and Pain Medicine at Stanford University School of Medicine. Enrollment is currently underway and data analysis is expected to be completed in 2018.Proposed benefits of mobile, internet-linked personal health monitors, such as the Ostom-i, include a reduction in the cost of care by reducing resource utilization and infection rates, improving patient-provider communication, reducing time spent as an inpatient as well as improved quality of life. Prior studies have demonstrated decreased health-related quality of life in patients with an ostomy bag. We aim to examine the extent to which the Ostom-i alert sensor affects the health-related quality of life of its users. The Ostom-i alert sensor has the potential to improve quality of life of users by giving them the freedom and confidence to partake in daily activities with the knowledge that they can check how full their ostomy bag is in a private, discrete manner.ClinicalTrials.gov NCT02319434; https://clinicaltrials.gov/ct2/show/NCT02319434 (Archived at WebCite at http://www.webcitation.org/6xhFDThmq).
View details for PubMedID 29581087