Publications

BACKGROUND: Asian people in the United States have different sociodemographic and health-related characteristics that might affect cardiovascular disease (CVD) risk by ethnicity and birthplace. However, they are often studied as a monolithic group in health care research. This study aimed to examine heterogeneity in CVD risk factors on the basis of birthplace among the 3 largest Asian subgroups (Chinese, Asian Indian, and Filipino) compared with US-born non-Hispanic White (NHW) adults.

METHODS AND RESULTS: A cross-sectional analysis was conducted using the 2010 to 2018 National Health Interview Survey data from 125 008 US-born and foreign-born Chinese, Asian Indian, Filipino, and US-born NHW adults. Generalized linear models with Poisson distribution were used to examine the prevalence and prevalence ratios of self-reported hypertension, diabetes, high cholesterol, physical inactivity, smoking, and overweight/obesity among Asian subgroups compared with US-born NHW adults. The study included 118 979 US-born NHW and 6029 Asian adults who self-identified as Chinese (29%), Asian Indian (33%), and Filipino (38%). Participants' mean (±SD) age was 49±0.1 years, and 53% were females. In an adjusted analysis, foreign-born Asian Indians had significantly higher prevalence of diabetes, physical inactivity, and overweight/obesity; foreign-born Chinese had higher prevalence of physical inactivity, and foreign-born Filipinos had higher prevalence of all 5 CVD risk factors except smoking compared with NHW adults.

CONCLUSIONS: This study revealed significant heterogeneity in the prevalence of CVD risk factors among Asian subgroups by ethnicity and birthplace, stressing the necessity of disaggregating Asian subgroup data. Providers should consider this heterogeneity in CVD risk factors and establish tailored CVD prevention plans for Asian subgroups.

BACKGROUND: Disparities in opioid prescribing among racial and ethnic groups have been observed in outpatient and emergency department settings, but it is unknown whether similar disparities exist at discharge among hospitalized older adults.

OBJECTIVE: To determine filled opioid prescription rates on hospital discharge by race/ethnicity among Medicare beneficiaries.

DESIGN: Retrospective cohort study.

PARTICIPANTS: Medicare beneficiaries 65 years or older discharged from hospital in 2016, without opioid fills in the 90 days prior to hospitalization (opioid-naïve).

MAIN MEASURES: Race/ethnicity was categorized by the Research Triangle Institute (RTI), grouped as Asian/Pacific Islander, Black, Hispanic, other (American Indian/Alaska Native/unknown/other), and White. The primary outcome was an opioid prescription claim within 2 days of hospital discharge. The secondary outcome was total morphine milligram equivalents (MMEs) among adults with a filled opioid prescription.

KEY RESULTS: Among 316,039 previously opioid-naïve beneficiaries (mean age, 76.8 years; 56.2% female), 49,131 (15.5%) filled an opioid prescription within 2 days of hospital discharge. After adjustment, Black beneficiaries were 6% less likely (relative risk [RR] 0.94, 95% CI 0.91-0.97) and Asian/Pacific Islander beneficiaries were 9% more likely (RR 1.09, 95% CI 1.03-1.14) to have filled an opioid prescription when compared to White beneficiaries. Among beneficiaries with a filled opioid prescription, mean total MMEs were lower among Black (356.9; adjusted difference - 4%, 95% CI - 7 to - 1%), Hispanic (327.0; adjusted difference - 7%, 95% CI - 10 to - 4%), and Asian/Pacific Islander (328.2; adjusted difference - 8%, 95% CI - 12 to - 4%) beneficiaries when compared to White beneficiaries (409.7).

CONCLUSIONS AND RELEVANCE: Black older adults were less likely to fill a new opioid prescription after hospital discharge when compared to White older adults and received lower total MMEs. The factors contributing to these differential prescribing patterns should be investigated further.

INTRODUCTION: Diabetic ketoacidosis (DKA) is a potentially life-threatening diabetic complication. Despite the high prevalence of DKA and the substantial associated healthcare burden, limited research on strategies to improve outcomes currently exists.Thiamine (vitamin B1) is a cofactor of pyruvate dehydrogenase, which plays a key role in aerobic glucose metabolism. Thiamine deficiency is common in patients with DKA, resulting in a shift to anaerobic metabolism and hyperlactatemia, which can prolong and complicate recovery. Therefore, we hypothesise that thiamine administration will improve aerobic metabolism and lead to faster resolution of acidemia in patients with DKA.

METHODS AND ANALYSIS: In this single centre, double-blind, randomised, placebo-controlled, parallel group interventional trial, 100 patients admitted to the hospital with DKA will be randomised to receive either intravenous thiamine (200 mg in 50 mL 0.9% saline) or placebo (0.9% saline identical in appearance and volume) two times per day for 2 days. The primary outcome will be the change in bicarbonate level over 24 hours as compared between the two treatment groups. Additional secondary outcomes include the change over time in anion gap, lactate levels, oxygen consumption by circulating mononuclear cells, intensive care unit and hospital length-of-stay and hospital resource usage when comparing the two study arms.

ETHICS AND DISSEMINATION: This trial was approved by the Committee on Clinical Investigations, the institutional review board of Beth Israel Deaconess Medical Center (protocol number 2018P000475). Findings will be disseminated through peer-reviewed publications and professional conference presentations.

TRIAL REGISTRATION NUMBER: NCT03717896; clinicaltrials.gov.

OBJECTIVE: With the recent expansion of the Centers for Medicare and Medicaid Services (CMS) coverage, transfemoral carotid artery stenting (tfCAS) is expected to play a larger role in the management of carotid disease. Existing research on the tfCAS learning curve, primarily conducted over a decade ago, may not adequately describe the current effect of physician experience on outcomes. Since about 30% of perioperative stroke/death post-CAS occur after discharge, appropriate thresholds for in-hospital event rates have been suggested to be <4% for symptomatic and <2% for asymptomatic patients. This study evaluates the tfCAS learning curve using Vascular Quality Initiative (VQI) data.

METHODS: We identified VQI patients undergoing tfCAS between 2005 and 2023. Each physician's procedures were chronologically grouped into 12 categories, from procedure counts 1-25 to 351+. Primary outcome was in-hospital stroke/death rate; secondary outcomes were in-hospital stroke/death/MI, 30-day mortality, in-hospital stroke/transient ischemic attack (stroke/TIA), and access site complications. The relationship between outcomes and procedure counts was analyzed using Cochran-Armitage test and a generalized linear model with restricted cubic splines. Our results were then validated using a generalized estimating equations model to account for the variability between physicians.

RESULTS: We analyzed 43,147 procedures by 2,476 physicians. In symptomatic patients, there was a decrease in rates of in-hospital stroke/death (procedure counts 1-25 to 351+: 5.2% to 1.7%), in-hospital stroke/death/MI (5.8% to 1.7%), 30-day mortality (4.6% to 2.8%), in-hospital stroke/TIA (5.0% to 1.1%), and access site complications (4.1% to 1.1%) as physician experience increased (all p-values<0.05). The in-hospital stroke/death rate remained above 4% until 235 procedures. Similarly, in asymptomatic patients, there was a decrease in rates of in-hospital stroke/death (2.1% to 1.6%), in-hospital stroke/death/MI (2.6% to 1.6%), 30-day mortality (1.7% to 0.4%), and in-hospital stroke/TIA (2.8% to 1.6%) with increasing physician experience (all p-values<0.05). The in-hospital stroke/death rate remained above 2% until 13 procedures.

CONCLUSIONS: In-hospital stroke/death and 30-day mortality rates after tfCAS decreased with increasing physician experience, showing a lengthy learning curve consistent with previous reports. Given that physicians' early cases may not be included in the VQI, the learning curve was likely underestimated. Nevertheless, a substantially high rate of in-hospital stroke/death was found in physicians' first 25 procedures. With the recent CMS coverage expansion for tfCAS, a significant number of physicians would enter the early stage of the learning curve, potentially leading to increased post-operative complications.

IMPORTANCE: Guidelines recommend deprescribing opioids in older adults due to risk of adverse effects, yet little is known about patient-clinician opioid deprescribing conversations.

OBJECTIVE: To understand the experiences of older adults and primary care practitioners (PCPs) with using opioids for chronic pain and discussing opioid deprescribing.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study conducted semistructured individual qualitative interviews with 18 PCPs and 29 adults 65 years or older prescribed opioids between September 15, 2022, and April 26, 2023, at a Boston-based academic medical center. The PCPs were asked about their experiences prescribing and deprescribing opioids to older adults. Patients were asked about their experiences using and discussing opioid medications with PCPs.

MAIN OUTCOME AND MEASURES: Shared and conflicting themes between patients and PCPs regarding perceptions of opioid prescribing and barriers to deprescribing.

RESULTS: In total, 18 PCPs (12 [67%] younger that 50 years; 10 [56%] female; and 14 [78%] based at an academic practice) and 29 patients (mean [SD] age, 72 [5] years; 19 [66%] female) participated. Participants conveyed that conversations between PCPs and patients on opioid use for chronic pain were typically challenging and that conversations regarding opioid risks and deprescribing were uncommon. Three common themes related to experiences with opioids for chronic pain emerged in both patient and PCP interviews: opioids were used as a last resort, opioids were used to improve function and quality of life, and trust was vital in a clinician-patient relationship. Patients and PCPs expressed conflicting views on risks of opioids, with patients focusing on addiction and PCPs focusing on adverse drug events. Both groups felt deprescribing conversations were often unsuccessful but had conflicting views on barriers to successful conversations. Patients felt deprescribing was often unnecessary unless an adverse event occurred, and many patients had prior negative experiences tapering. The PCPs described gaps in knowledge on how to taper, a lack of clinical access to monitor patients during tapering, and concerns about patient resistance.

CONCLUSIONS AND RELEVANCE: In this qualitative study, PCPs and older adults receiving long-term opioid therapy viewed the use of opioids as a beneficial last resort for treating chronic pain but expressed dissonant views on the risks associated with opioids, which made deprescribing conversations challenging. Interventions, such as conversation aids, are needed to support collaborative discussion about deprescribing opioids.

BACKGROUND: Left ventricular ejection fraction (LVEF) is the most commonly clinically used imaging parameter for assessing cancer therapy-related cardiac dysfunction (CTRCD). However, LVEF declines may occur late, after substantial injury. This study sought to investigate cardiovascular magnetic resonance (CMR) imaging markers of subclinical cardiac injury in a miniature swine model.

METHODS: Female Yucatan miniature swine (n=14) received doxorubicin (2mg/kg) every 3 weeks for 4 cycles. CMR, including cine, tissue characterization via T1 and T2 mapping, and late gadolinium enhancement (LGE) was performed on the same day as doxorubicin administration and three weeks after the final chemotherapy cycle. In addition, MR spectroscopy (MRS) was performed during the 3 weeks after the final chemotherapy in 7 pigs. A single CMR and MRS exam was also performed in three Yucatan miniature swine that were age- and weight-matched to the final imaging exam of the doxorubicin-treated swine to serve as controls. CTRCD was defined as histological early morphologic changes, including cytoplasmic vacuolization and myofibrillar loss of myocytes, based on post-mortem analysis of humanely euthanized pigs after the final CMR exam.

RESULTS: Of 13 swine completing five serial CMR scans, 10 (77%) had histological evidence of CTRCD. Three animals had neither histological evidence nor changes in LVEF from baseline. No absolute LVEF <40% or LGE were observed. Native T1, extracellular volume (ECV), and T2 at 12 weeks were significantly higher in swine with CTRCD than those without CTRCD (1178 ms vs. 1134 ms, p=0.002, 27.4% vs. 24.5%, p=0.03, and 38.1 ms vs. 36.4 ms, p=0.02, respectively). There were no significant changes in strain parameters. The temporal trajectories in native T1, ECV, and T2 in swine with CTRCD showed similar and statistically significant increases. At the same time, there were no differences in their temporal changes between those with and without CTRCD. MRS myocardial triglyceride content substantially differed among controls, swine with and without CTRCD (0.89%, 0.30%, 0.54%, respectively, ANOVA, p=0.01), and associated with the severity of histological findings and incidence of vacuolated cardiomyocytes.

CONCLUSIONS: Serial CMR imaging alone has a limited ability to detect histologic CTRCD beyond LVEF. Integrating MRS myocardial triglyceride content may be useful for detection of early potential CTRCD.

BACKGROUND: Non-invasive biomarkers that predict surgical treatment response would inform personalized treatments and provide insight into potential biological pathways underlying endometriosis-associated pain and symptom progression. Thus, we evaluated plasma proteins in relation to persistence of pelvic pain following laparoscopic surgery in predominantly adolescents and young adults with endometriosis using a multiplex aptamer-based proteomics biomarker discovery platform.

METHODS: We conducted a prospective analysis including 142 participants with laparoscopically- confirmed endometriosis from the Women's Health Study: From Adolescence to Adulthood (A2A) observational longitudinal cohort with study enrollment from 2012-2018. Biologic samples and patient data were collected with modified World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonization Project (EPHect) tools. In blood collected before laparoscopic ablation or excision of endometriosis, we simultaneously measured 1,305 plasma protein levels including markers for immunity, angiogenesis and inflammation using SomaScan. Worsening or persistent post-surgical pelvic pain was defined as having newly developed, persistent (i.e., stable), or worsening severity, frequency, or persistent life-interference of dysmenorrhea or acyclic pelvic pain at one-year post-surgery compared to pre-surgery. We calculated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression adjusted for age, body mass index, and fasting status and hormone use at blood draw. We applied Ingenuity Pathway Analysis and STRING analysis to identify pathophysiologic pathways and protein interactions.

RESULTS: Median age at blood draw was 17 years (interquartile range 15-19), and most participants were white race (90%). All had superficial peritoneal lesions only and were treated by excision or ablation. One-year post-surgery, pelvic pain worsened or persisted for 76 (54%) of these participants with endometriosis, while pelvic pain improved for 66 (46%). We identified 83 proteins associated with worsening or persistent pelvic pain one-year post-surgery (nominal p<0.05). Compared to those with improved pelvic pain one year post-surgery, those with worsening or persistent pelvic pain had higher plasma levels of CD63 antigen (OR=2.98, 95% CI:1.44-6.19) and CD47 (OR=2.68, 95%CI=1.28-5.61), but lower levels of Sonic Hedgehog protein (SHH; OR=0.55, 95%CI=0.36-0.84) in pre-surgical blood. Pathways related to cell migration were upregulated and pathways related to angiogenesis were downregulated in those with worsening/persistent post-surgical pelvic pain compared to those with improved pain. When we examined change in proteins levels from pre- to post-surgery and its subsequent risk of worsening/persistent post-surgical pain at one-year follow-up, we observed increasing levels of SHH from pre- to post-surgery was associated with four-fold increase in risk of post-surgical pain (OR quartile 4 vs. 1=3.86, 1.04-14.33).

CONCLUSION: Using an aptamer-based proteomics platform, we identified plasma proteins and pathways associated with worsening or persistent pelvic pain post-surgical treatment of endometriosis among adolescents and young adults that may aid in risk stratification of individuals with endometriosis.

Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5 K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 × 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.