Faculty Bibliography

IMPORTANCE:It remains unknown whether in an asymptomatic community-based cohort magnetic resonance imaging (MRI) measures of plaque characteristics are independently associated with incident cardiovascular disease (CVD) events when adjusted for carotid artery (CA) wall thickness, a measure of plaque burden. OBJECTIVE:To assess associations of CA MRI plaque characteristics with incident CVD events. DESIGN, SETTING, AND PARTICIPANTS:The Atherosclerosis Risk in Communities (ARIC) study is a prospective epidemiologic study of the incidence of CVD in 15 792 adults of which 2066 women and men were enrolled in the ARIC Carotid MRI substudy. ARIC participants were enrolled from 1987 to 1989, and the substudy was conducted between January 2004 and December 2005. Analysis began January 2017 and ended August 2020. EXPOSURES:Incident CVD events during a median (interquartile range [IQR]) follow-up time of 10.5 (8.1-10.9) years were assessed. MAIN OUTCOMES AND MEASURES:Proportional hazards Cox analyses were performed to ascertain associations between MRI variables of CA plaque burden and plaque characteristics. RESULTS:Of 15 792 ARIC participants, 2066 were enrolled in the substudy, of whom 1256 (701 women [55.8%]) had complete data and were eligible for incident CVD analyses. Carotid artery plaques in participants with incident CVD events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; P = .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; P = .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; P < .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; P = .03), respectively. The presence of a lipid core was independently associated with incident CVD events when adjusted for traditional CVD risk factors and maximum CA wall thickness (hazard ratio, 2.48 [95% CI, 1.36-4.51]; P = .003), whereas the presence of calcification was not. The frequency of intraplaque hemorrhage presence in this population of individuals free of CVD at baseline who were not recruited for carotid stenosis was too small to draw any meaningful conclusions (intraplaque hemorrhage presence: 68 of 1256 participants [5.4%]). Carotid artery lumen area and maximum stenosis, which were overall low, were independently associated with incident CVD events when adjusted for traditional CVD risk factors, as anticipated. CONCLUSIONS AND RELEVANCE:The presence of a CA lipid core on MRI is associated with incident CVD events independent of maximum CA wall thickness in asymptomatic participants.

BACKGROUND:The treatment, genotyping, and phenotyping of patients with World Health Organization Group 1 pulmonary arterial hypertension (PAH) have evolved dramatically in the last decade. RESEARCH QUESTION:The United States Pulmonary Hypertension Scientific Registry was established as the first US PAH patient registry to investigate genetic information, reproductive histories, and environmental exposure data in a contemporary patient population. STUDY DESIGN AND METHODS:Investigators at 15 US centers enrolled consecutively screened adults diagnosed with Group 1 PAH who had enrolled in the National Biological Sample and Data Repository for PAH (PAH Biobank) within 5 years of a cardiac catheterization demonstrating qualifying hemodynamic criteria. Exposure and reproductive histories were collected by using a structured interview and questionnaire. The biobank provided genetic data. RESULTS:, and 79% were women. Mean duration between symptom onset and diagnostic catheterization was 1.9 years. Sixty-six percent of patients were treated with more than one PAH medication at enrollment. Past use of prescription weight loss drugs (16%), recreational drugs (27%), and oral contraceptive pills (77%) was common. Women often reported miscarriage (37%), although PAH was rarely diagnosed within 6 months of pregnancy (1.9%). Results of genetic testing identified pathogenic or suspected pathogenic variants in 13% of patients, reclassifying 18% of IPAH patients and 5% of APAH patients to heritable PAH. INTERPRETATION:Patients with Group 1 PAH remain predominately middle-aged women diagnosed with IPAH or APAH. Delays in diagnosis of PAH persist. Treatment with combinations of PAH-targeted medications is more common than in the past. Women often report pregnancy complications, as well as exposure to anorexigens, oral contraceptives, and/or recreational drugs. Results of genetic tests frequently identify unsuspected heritable PAH.

BACKGROUND:No study has comprehensively examined how the steroid metabolome is associated with breast cancer risk in women with familial risk. METHODS:We examined 36 steroid metabolites across the spectrum of familial risk (5-year risk ranged from 0.14% to 23.8%) in pre- and postmenopausal women participating in the New York site of the Breast Cancer Family Registry (BCFR). We conducted a nested case-control study with 62 cases/124 controls individually matched on menopausal status, age, and race. We measured metabolites using GC-MS in urine samples collected at baseline before the onset of prospectively ascertained cases. We used conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) per doubling in hormone levels. RESULTS:The average proportion of total steroid metabolites in the study sample were glucocorticoids (61%), androgens (26%), progestogens (11%), and estrogens (2%). A doubling in glucocorticoids (aOR = 2.7; 95% CI = 1.3-5.3) and androgens (aOR = 1.6; 95% CI = 1.0-2.7) was associated with increased breast cancer risk. Specific glucocorticoids (THE, THF αTHF, 6β-OH-F, THA, and α-THB) were associated with 49% to 161% increased risk. Two androgen metabolites (AN and 11-OH-AN) were associated with 70% (aOR = 1.7; 95% CI = 1.1-2.7) and 90% (aOR = 1.9; 95% CI = 1.2-3.1) increased risk, respectively. One intermediate metabolite of a cortisol precursor (THS) was associated with 65% (OR = 1.65; 95% CI = 1.0-2.7) increased risk. E1 and E2 estrogens were associated with 20% and 27% decreased risk, respectively. CONCLUSIONS:Results suggest that glucocorticoids and 11-oxygenated androgens are positively associated with breast cancer risk across the familial risk spectrum. IMPACT:If replicated, our findings suggest great potential of including steroids into existing breast cancer risk assessment tools.

BACKGROUND:Thirty years after the Mangled Extremity Severity Score (MESS) was developed, advances in vascular, trauma and orthopedic surgery have rendered the sensitivity of this score obsolete. A significant number of patients receive amputation during subsequent admissions, which are often missed in the analysis of amputation at the index admission. We aimed to identify risk factors for and predict amputation on initial admission or within 30 days of discharge (peritraumatic amputation or PTA). STUDY DESIGN/METHODS:The Nationwide Readmission Database for 2016 and 2017 was used in our analysis. Factors associated with PTA were identified. We used XGBoost, Random Forest, and Logistic Regression methods to develop a framework for machine learning (ML) based prediction models for PTA. RESULTS:We identified 1098 adult patients with traumatic lower extremity fracture and arterial injuries, 206 underwent amputation. 176 (85.4%) underwent amputation during the index admission and 30 (14.6%) underwent amputation within a 30-day readmission period. After identifying factors associated with PTA, we constructed machine learning models based on Random Forest, XGBoost, and Logistic Regression to predict PTA. We discovered that Logistic regression had the most robust predictive ability, with an accuracy of 0.88, sensitivity of 0.47, and specificity of 0.98. We then built on the Logistic Regression by the NearMiss algorithm, increasing sensitivity to 0.71, but decreasing accuracy to 0.74 and specificity to 0.75. CONCLUSIONS:ML-based prediction models combined with sampling algorithms (such as the NearMiss algorithm in this study), can help identify patients with traumatic arterial injuries at high risk for amputation and guide targeted intervention in the modern age of vascular surgery.

AIMS/OBJECTIVE:To determine whether loss of muscle mass (approximated using fat free mass [FFM]) is associated with risk for type 2 diabetes mellitus (T2DM) in Hispanic/Latino adults in the United States. METHODS:Participants were Hispanic/Latino adults (18-74-year-olds) who completed Visit 2 of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL; multi-site, prospective cohort study; 6.1-year follow-up) and did not have T2DM at baseline (n = 6264). At baseline and Visit 2, FFM was measured using bioelectrical impedance analysis and fasting glucose, HbA1c, and fasting insulin were measured by examiners. Diabetes was defined according to American Diabetes Association criteria. Survey-weighted Poisson regression models examined the association of percent change in relative FFM (%ΔFFM) with incident prediabetes and T2DM. Survey-weighted multivariable regression models examined associations of %ΔFFM with changes in glucose and insulin measures. RESULTS:Relative FFM declined by 2.1% between visits. %ΔFFM was inversely associated with incident prediabetes (p-for-trend = 0.001) and with changes in glucose and insulin measures (p-for-trend <0.0001). Findings were null, except for HOMA-IR, after adjustment for changes in adiposity measures. Associations were generally stronger for individuals with baseline overweight/obesity. CONCLUSIONS:Reducing loss of FFM during adulthood may reduce prediabetes risk (primarily insulin resistance), particularly among individuals with overweight/obesity.

BACKGROUND/OBJECTIVES/OBJECTIVE:Use of cannabis is increasing in a variety of populations in the United States; however, few investigations about how and for what reasons cannabis is used in older populations exist. DESIGN/METHODS:Anonymous survey. SETTING/METHODS:Geriatrics clinic. PARTICIPANTS/METHODS:A total of 568 adults 65 years and older. INTERVENTION/METHODS:Not applicable. MEASUREMENTS/METHODS:Survey assessing characteristics of cannabis use. RESULTS:Approximately 15% (N = 83) of survey responders reported using cannabis within the past 3 years. Half (53%) reported using cannabis regularly on a daily or weekly basis, and reported using cannabidiol-only products (46%). The majority (78%) used cannabis for medical purposes only, with the most common targeted conditions/symptoms being pain/arthritis (73%), sleep disturbance (29%), anxiety (24%), and depression (17%). Just over three-quarters reported cannabis "somewhat" or "extremely" helpful in managing one of these conditions, with few adverse effects. Just over half obtained cannabis via a dispensary, and lotions (35%), tinctures (35%), and smoking (30%) were the most common administration forms. Most indicated family members (94%) knew about their cannabis use, about half reported their friends knew, and 41% reported their healthcare provider knowing. Sixty-one percent used cannabis for the first time as older adults (aged ≥61 years), and these users overall engaged in less risky use patterns (e.g., more likely to use for medical purposes, less likely to consume via smoking). CONCLUSION/CONCLUSIONS:Most older adults in the sample initiated cannabis use after the age of 60 years and used it primarily for medical purposes to treat pain, sleep disturbance, anxiety, and/or depression. Cannabis use by older adults is likely to increase due to medical need, favorable legalization, and attitudes.

BACKGROUND:Studies suggest that migraine is often underdiagnosed and inadequately treated in the primary care setting, despite many patients relying on their primary care provider (PCP) to manage their migraine. Many women consider their women's healthcare provider to be their PCP, yet very little is known about migraine knowledge and practice patterns in the women's healthcare setting. OBJECTIVE:The objective of this study was to assess women's healthcare providers' knowledge and needs regarding migraine diagnosis and treatment. METHODS:The comprehensive survey assessing migraine knowledge originally developed for PCPs was used in this study, with the addition of a section regarding the use of hormonal medications in patients impacted by migraine. Surveys were distributed online, and primarily descriptive analyses were performed. RESULTS:The online survey was completed by 115 women's healthcare providers (response rate 28.6%; 115/402), who estimated that they serve as PCPs for approximately one-third of their patients. Results suggest that women's healthcare providers generally recognize the prevalence of migraine, but experience some knowledge gaps regarding migraine management. Despite 82.6% (95/115) of survey respondents feeling very comfortable or somewhat comfortable with diagnosing migraine, only 57.9% (66/114) reported routinely asking patients about headaches during annual visits. Very few were familiar with the American Academy of Neurology guidelines on preventative treatment (6.3%; 7/111) and the Choosing Wisely Campaign recommendations on migraine treatment (17.3%; 19/110), and many prescribed medications known to contribute to medication overuse headache. In addition, only 24.3% (28/115) would order imaging for a new type of headache, 35.7% (41/115) for worsening headache, and 47.8% (55/115) for headache with neurologic symptoms; respondents cited greater tendency with sending patients to an emergency department for the same symptoms. Respondents had limited knowledge of evidence-based, non-pharmacological treatments for migraine (i.e., biofeedback or cognitive behavioral therapy), with nearly none placing referrals for these services. Most providers were comfortable prescribing hormonal contraception (mainly progesterone only) to women with migraine without aura (80.9%; 89/110) and with aura (72.5%; 79/109), and followed American College of Obstetricians and Gynecologists (ACOG) guidelines to limit combination hormonal contraception for patients with aura. When queried, 6.3% or less (5/79) of providers would prescribe estrogen-containing contraception for women with migraine with aura. Only 37.3% (41/110) of respondents reported having headache/migraine education. Providers indicated interest in education pertaining to migraine prevention and treatment (96.3%; 105/109), migraine-associated disability (74.3%; 81/109), and diagnostic testing (59.6%; 65/109). CONCLUSION/CONCLUSIONS:Women's healthcare providers appear to have several knowledge gaps regarding the management of migraine in their patients. These providers would likely benefit from access to a headache-specific educational curriculum to improve provider performance and patient outcomes.

INTRODUCTION: The COVID-19 pandemic overwhelmed New York City hospitals. Shortages of ventilators and sedatives prompted tracheostomy earlier than recommended by professional societies. The objective of this study was to determine the impact of percutaneous dilational tracheostomy (PDT) in COVID-19 patients on critical care capacity.
METHOD(S): This is a single-institution prospective case series of SARS-CoV-2 infected patients undergoing PDT from April 1-June 4, 2020 with follow-up through June 25, 2020 at a public tertiary care center. Clinical data were obtained through medical record review. Mechanically ventilated COVID-19 patients were screened for intervention based on the following criteria: >= 6 days of intubation with further need for mechanical ventilation, a fractional inspired oxygen concentration of <= 60%, positive end expiratory pressure <=12, no significant organ dysfunction except acute kidney injury, and minimal pressor requirements. The main outcomes measured were change in 48-hour periprocedural sedative/analgesia requirements, liberation from the ventilator, rate of transfer from the ICU, decannulation, PDT-related complications, and in-hospital survival.
RESULT(S): Fifty-five patients met PDT criteria and underwent PDT a median of 13 days from intubation. Patient characteristics are found in Table 1. Intravenous midazolam equivalents, fentanyl equivalents and cisatracurium equivalents were significantly reduced post- PDT (Table 2). Thirty-five patients were transferred from the ICU and liberated from the ventilator. Median time from PDT to ventilator liberation and ICU discharge was 10 and 12 days respectively. Decannulation occurred in 45.5% and 52.7% were discharged from acute inpatient care. Median follow-up for the study was 62 days. Four patients had bleeding complications postoperatively and 11 died during the study period. Older age was associated with increased odds of complication (OR 1.12, 95% CI 1.04, 1.23) and death (OR=1.15, 95% CI 1.05, 1.30).
CONCLUSION(S): Mechanically ventilated COVID-19 patients undergoing PDT using standard criteria improves ventilator and medication utilization in areas strained by the SARS-CoV-2 pandemic. Long term outcomes after PDT in this population deserve further study

OBJECTIVE:To develop a 180-day readmission risk model for older adults with acute myocardial infarction (AMI) that considered a broad range of clinical, demographic and age-related functional domains. METHODS:We used data from ComprehenSIVe Evaluation of Risk in Older Adults with AMI (SILVER-AMI), a prospective cohort study that enrolled participants aged ≥75 years with AMI from 94 US hospitals. Participants underwent an in-hospital assessment of functional impairments, including cognition, vision, hearing and mobility. Clinical variables previously shown to be associated with readmission risk were also evaluated. The outcome was 180-day readmission. From an initial list of 72 variables, we used backward selection and Bayesian model averaging to derive a risk model (N=2004) that was subsequently internally validated (N=1002). RESULTS:Of the 3006 SILVER-AMI participants discharged alive, mean age was 81.5 years, 44.4% were women and 10.5% were non-white. Within 180 days, 1222 participants (40.7%) were readmitted. The final risk model included 10 variables: history of chronic obstructive pulmonary disease, history of heart failure, initial heart rate, first diastolic blood pressure, ischaemic ECG changes, initial haemoglobin, ejection fraction, length of stay, self-reported health status and functional mobility. Model discrimination was moderate (0.68 derivation cohort, 0.65 validation cohort), with good calibration. The predicted readmission rate (derivation cohort) was 23.0% in the lowest quintile and 65.4% in the highest quintile. CONCLUSIONS:Over 40% of participants in our sample experienced hospital readmission within 180 days of AMI. Our final readmission risk model included a broad range of characteristics, including functional mobility and self-reported health status, neither of which have been previously considered in 180-day risk models.