Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation in the United States.

BACKGROUND: Among patients hospitalized for atrial fibrillation, the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown. METHODS: Using the Get With The Guidelines-Atrial Fibrillation registry, patients admitted from January 1, 2014, to March 31, 2020, and discharged on DOACs were stratified according to receipt of underdosing, overdosing, or recommended dosing. Factors associated with off-label dosing (defined as underdosing or overdosing) were identified using logistic regression. Median odds ratio (OR) and time-series analyses were used to assess hospital-level variation and temporal trends, respectively. RESULTS: Of 22 470 patients (70.1±12.1 years, 48.1% female, 82.5% White) prescribed a DOAC at discharge from hospitalization for atrial fibrillation (66% apixaban, 29% rivaroxaban, and 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19 953 (88.8%). The overall rate of off-label dosing was 11.2%. Patient-related factors associated with off-label dose included age (underdosing: OR, 1.06 per 1-year increase [95% CI, 1.06-1.07]; overdosing: OR, 1.07 per 1-year increase [95% CI, 1.06-1.09]), dialysis dependence (underdosing: OR, 5.50 [95% CI, 3.76-8.05]; overdosing: OR, 5.47 [95% CI, 2.74-10.88]), female sex (overdosing: OR, 0.79 [95% CI, 0.63-0.99]), and weight (overdosing: OR, 0.96 per 1-kg increase [95% CI, 0.95-1.00]). Across hospitals, the adjusted median OR for off-label DOAC dose was 1.45 (95% CI, 1.34-1.65; underdosing: OR, 1.52 [95% CI, 1.39-1.76]; overdosing: OR, 1.32 [95% CI, 1.20-1.84]), indicating significant hospital-level variation. Over the study period, recommended dosing significantly increased over time (81.9%-90.9%; P<0.0001 for trend) with a corresponding decline in underdosing (14.4%-6.6%; P<0.0001 for trend) and overdosing (3.8%-2.5%; P=0.001 for trend). CONCLUSIONS: Over 1 in 10 patients hospitalized for atrial fibrillation are discharged on an off-label DOAC dose with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.

Cardiovascular disease and feminizing gender-affirming hormone therapy: Implications for the provision of safe and lifesaving care.

Sex recorded at birth, gender identity, and feminizing gender-affirming hormone therapy (fGAHT) likely contribute to cardiovascular disease (CVD) risk in transgender women. Understanding the interplay of these factors is necessary for the provision of safe, affirming, and lifesaving care. Among transgender women taking fGAHT, data show increases in CVD mortality and rates of myocardial infarction, stroke, and venous thromboembolism compared to reference populations, depending on study design and comparators. However, most studies are observational with a paucity of contextualizing information (e.g., dosing, route of administration, gonadectomy status), which makes it difficult to parse adverse fGAHT effects from confounders and interaction with known CVD risk factors (e.g., obesity, smoking, psychosocial and gender minority stressors). Increased CVD risk in transgender women points toward a need for greater attention to CVD management in this population including cardiology referral when indicated and additional research on the mechanisms and mediators of CVD risk.

Venous Thromboembolism for the Practicing Cardiologist.

Venous thromboembolism (VTE), encompassing pulmonary embolism (PE) and deep vein thrombosis (DVT), is encountered commonly. Acute PE may present as a high-risk cardiovascular emergency, and acute DVT can cause acute and chronic vascular complications. The goal of this review is to ensure that cardiologists are comfortable managing VTE-including risk stratification, anticoagulation therapy, and familiarity with primary reperfusion therapy. Clinical assessment and determination of degree of right ventricular dysfunction are critical in initial risk stratification of PE and determination of parenteral versus oral anticoagulation therapy. Direct oral anticoagulants have emerged as preferred first-line oral anticoagulation strategy in VTE scenarios.

Acute pulmonary embolism following recent hospitalization or surgery.

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Recent hospitalization or surgery is a leading risk factor for PE, yet there are minimal data examining its effect on treatment and outcomes. We conducted a retrospective review of institutional billing codes for hospitalized patients with acute PE from August 2012 to August 2018. Patients were stratified based on whether they had a recent major medical encounter (MME), defined as surgery or hospitalization within 90 days. Primary outcomes included in-hospital mortality and 30- and 90-day readmission rates. Secondary outcomes included length of stay (LOS), use of advanced therapies, major bleeding, discharge anticoagulation and recurrent venous thromboembolism (VTE) at 90 days. Outcomes were adjusted for confounders using multivariable regression modeling. 2063 patients were hospitalized for an acute PE; 633 (30.7%) had a recent MME. Patients with a recent MME had a higher average Charlson Comorbidity Index (4.6 vs. 4.0, p < 0.01). Both 30- and 90-day readmission rates were higher in patients with a recent MME (21.7% vs. 14.4%; adjusted OR 1.06 [1.00, 1.12], p = 0.037; 30.8% vs 18.7%; adjusted OR 1.11 [1.11, 1.62], p = 0.003, respectively). After adjustment, there were no between-group differences in in-hospital mortality, LOS, use of advanced therapies, major bleeding, or recurrent VTE at 90 days. In-hospital mortality was higher for patients with a recent medical hospitalization compared to those with a recent surgery (10.2% vs. 5.6%, adjusted OR 1.08 [1.01, 1.15] p = 0.032). Despite recent hospitalization and/or surgery and greater number of comorbidities, patients admitted with a PE and recent MME had similar in-hospital outcomes, but experienced higher readmission rates. In-hospital mortality was higher in those with a recent medical compared to surgical encounter. Clinicians should optimize post-discharge transitional care in this subset of patients.

Sex differences in presentation, management, and outcomes among patients hospitalized with acute pulmonary embolism.

While the presence of gender disparities in cardiovascular disease have been described, there is a paucity of data regarding the impact of sex in acute pulmonary embolism (PE). We identified all patients admitted to a tertiary care hospital with acute PE between August 1, 2012 through July 1, 2018. We stratified the presenting characteristics, management, and outcomes between women and men. Of the 2031 patients admitted with acute PE, 1081 (53.2%) were women. Women were more likely to present with dyspnea (59.8% vs 52.0%, p < 0.001) and less likely to present with hemoptysis (1.9% vs 4.0%, p = 0.01). Women were older (63.8 ± 17.4 years vs 62.3 ± 15.0 years, p = 0.04), but had lower rates of myocardial infarction, liver disease, smoking history, and prior DVT. PE severity was similar between women and men (massive: 4.9% vs 3.6%; submassive: 43.9% vs 41.8%; p = 0.19), yet women were more likely to present with normal right ventricular size on a surface echocardiogram (63.2% vs 54.8%, p = 0.01). In unadjusted analyses, women were less likely to survive to discharge (92.4% vs 94.7%, p = 0.04), but after adjustment, there was no sex-based survival difference. There were no sex differences in the PE-related diagnostic studies performed, use of advanced therapies, or short-term outcomes, before and after adjustment (p > 0.05 for all). In this large PE cohort from a tertiary care institution, women had different comorbidity profiles and PE presentations compared with men. Despite these differences, there were no sex disparities in PE management or outcomes.

Changes in Care for Acute Pulmonary Embolism Through A Multidisciplinary Pulmonary Embolism Response Team.

BACKGROUND: Optimal management of acute pulmonary embolism requires expertise offered by multiple subspecialties. As such, pulmonary embolism response teams (PERTs) have increased in prevalence, but the institutional consequences of a PERT are unclear. METHODS: We compared all patients that presented to our institution with an acute pulmonary embolism in the 3 years prior to and 3 years after the formation of our PERT. The primary outcome was in-hospital pulmonary embolism-related mortality before and after the formation of the PERT. Sub-analyses were performed among patients with elevated-risk pulmonary embolism. RESULTS: Between August 2012 and August 2018, 2042 patients were hospitalized at our institution with acute pulmonary embolism, 884 (41.3%) pre-PERT implementation and 1158 (56.7%) post-PERT implementation, of which 165 (14.2%) were evaluated by the PERT. There was no difference in pulmonary embolism-related mortality between the two time periods (2.6% pre-PERT implementation vs 2.9% post-PERT implementation, P = .89). There was increased risk stratification assessment by measurement of cardiac biomarkers and echocardiograms post-PERT implementation. Overall utilization of advanced therapy was similar between groups (5.4% pre-PERT implementation vs 5.4% post-PERT implementation, P = 1.0), with decreased use of systemic thrombolysis (3.8% pre-PERT implementation vs 2.1% post-PERT implementation, P = 0.02) and increased catheter-directed therapy (1.3% pre-PERT implementation vs 3.3% post-PERT implementation, P = 0.05) post-PERT implementation. Inferior vena cava filter use decreased after PERT implementation (10.7% pre-PERT implementation vs 6.9% post-PERT implementation, P = 0.002). Findings were similar when analyzing elevated-risk patients. CONCLUSION: Pulmonary embolism response teams may increase risk stratification assessment and alter application of advanced therapies, but a mortality benefit was not identified.

A Review of Nonanesthetic Uses of Ketamine.

Ketamine, a nonselective NMDA receptor antagonist, is used widely in medicine as an anesthetic agent. However, ketamine's mechanisms of action lead to widespread physiological effects, some of which are now coming to the forefront of research for the treatment of diverse medical disorders. This paper aims at reviewing recent data on key nonanesthetic uses of ketamine in the current literature. MEDLINE, CINAHL, and Google Scholar databases were queried to find articles related to ketamine in the treatment of depression, pain syndromes including acute pain, chronic pain, and headache, neurologic applications including neuroprotection and seizures, and alcohol and substance use disorders. It can be concluded that ketamine has a potential role in the treatment of all of these conditions. However, research in this area is still in its early stages, and larger studies are required to evaluate ketamine's efficacy for nonanesthetic purposes in the general population.

Fluoropyrimidine-Associated Cardiotoxicity: A Retrospective Case-Control Study.

BACKGROUND: The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS: In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION: Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.

Chronic Disease Burden of the Homeless: A Descriptive Study of Student-Run Free Clinics in Tampa, Florida.

Variation between homeless populations due to socioeconomic and environmental factors necessitates tailoring medical, health policy, and public health interventions to the unique needs of the homeless population served. Despite the relatively large size of the homeless population in Florida, there is a paucity of research that characterizes the homeless population who frequent homeless clinics within the state. This project describes the demographics, disease prevalence, and other risk factors among homeless individuals in Tampa, Florida. We conducted a retrospective chart review on adult homeless patients seen in 2015 and 2016 at two free clinic sites operated by Tampa Bay Street Medicine, a medical student-run organization from the University of South Florida in Tampa, Florida. Rates of diseases and substance use were recorded and Charlson Comorbidity Index (CCI) was calculated to assess mortality risk. Of the 183 homeless patients in this study, 34.4% reported hypertension, 13.7% reported diabetes, 27.1% reported a respiratory disease, 5.6% reported hyperlipidemia, and 32.8% reported a psychiatric disorder. Tobacco use was reported by 65.6% of patients, 32.2% reported alcohol use, and 17.5% reported illicit drug use. CCI was positively associated with age. Females reported higher rates of anemia, anxiety, chronic obstructive pulmonary disease, and psychiatric disorders. Hypertension, diabetes, certain respiratory diseases, and mental health disorders were more prevalent in the homeless population than in the general population in Tampa, Florida. Homeless women appeared to have higher morbidity than homeless men. Rates of tobacco and illicit drug use were significantly higher whereas alcohol use was lower in the study population than the general population. This study underscores the critical need for mental health initiatives, substance abuse treatment programs, and women's health programs that are accessible to the homeless in Tampa.

Postoperative atrial fibrillation after cesarean delivery.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most common arrhythmia seen clinically. Due to the lack of literature and guidelines on maternal AF as a postoperative complication following cesarean delivery (CD), we undertook a study to characterize parturients who developed AF following CD and to evaluate arrhythmia management and outcomes in this patient population. METHODS: After receiving ethics committee approval, a retrospective chart review was performed to determine the incidence, possible risk factors, treatment, and outcome of women who developed AF following CD performed between 2003 and 2012 at New York Methodist Hospital in Brooklyn, New York. RESULTS: A total of 17,039 CDs were performed at New York Methodist Hospital from 2003 to 2012. Of these, seven parturients developed AF after CD. The incidence of AF following CD in this patient population was 1:2,434 (0.04%). The age range was 26-41 years, with a median of 33 years. All 7 parturients were at term or postterm. Two deliveries were elective and five were emergent. Two of the seven parturients had prior history of paroxysmal AF. One patient was identified as having mitral regurgitation. All seven had low levels of serum magnesium postoperatively. Out of the seven, two parturients had spontaneous conversion to normal sinus rhythm, one required electrical cardioversion and four required pharmacologic cardioversion. CONCLUSIONS: Postoperative AF (POAF) exists as a rare complication in women who undergo CD with an incidence of 0.04% in our patient population. All parturients in our study were noted to have hypomagnesemia in the postoperative period. Occurrence of AF increased length of hospital stay and utilization of hospital resources.

Burden of Chronic Conditions among Patients from Free Clinics: A Retrospective Chart Review of 2015.

INTRODUCTION: There is limited research about the poor and uninsured patients who visit free clinics. METHODS: We conducted a retrospective chart review of uninsured adult patients in four free clinics seen between January and December 2015. Prevalence of chronic conditions and their association with socioeconomic factors were investigated. RESULTS: In 2015, 3,196 adult patients with chronic conditions were managed in four free clinics. Many of these patients were women (60.8%) and Hispanic (44.7%); the group had a mean age of 47.9 years (SD=14.1) and a median income of $14,400. The top five prevalent conditions were hypertension (33.6%), hyperlipidemia (20.7%), diabetes (14%), major depression (11.7%), and arthritis (8.7%). In the multivariable analysis, clinic site, age, marital status, employment status, and household size were significantly associated with the Disease Burden Index. DISCUSSION: Public health prevention programs should focus on uninsured patients of free clinics who are mainly low-income, sicker, and unemployed, and often women and Hispanics.

T1 Paravertebral Catheter for Postoperative Pain Management After First Rib Resection for Venous Thoracic Outlet Syndrome: A Case Report.

While it has been shown that a paravertebral block provides effective postoperative analgesia for patients undergoing thoracic surgeries, including first rib resection, this is the first reported case of a paravertebral catheter used for perioperative analgesia in a patient undergoing first rib resection. We present the case of a 76-year-old woman with right upper extremity swelling who underwent infraclavicular first rib resection for venous thoracic outlet syndrome. Continuous infusion of ropivacaine through a T1 paravertebral catheter, which was placed before induction of general anesthesia but after T1 and T2 paravertebral blocks, provided effective postoperative pain control. Our experience suggests that paravertebral catheter infusions of local anesthetics may be effective adjuncts to general anesthesia in patients undergoing first rib resection and warrants further investigation.

Pudendal nerve blocks in men undergoing urethroplasty: a case series.

The pudendal nerve block (PNB) is widely used for regional anesthesia during obstetric and anorectal procedures, but its role in urologic procedures has not been thoroughly studied. While transvaginal PNB is relatively straightforward, PNB in male patients often requires imaging guidance due to difficulty appreciating anatomic landmarks. We review the PNB and relevant sonoanatomy, and describe its analgesic efficacy in three male patients undergoing urethroplasty for urethral stricture. In this procedure, the patient was placed in lithotomy position, the ischial tuberosity was palpated, and the sacrotuberous ligament and pudendal artery were identified using ultrasound. Ropivacaine was injected medial to the pudendal artery and disappearance of muscle twitch was demonstrated. Two patients reported well-controlled pain at 24 hours postoperatively. One reported perineal pain requiring additional analgesia. All patients were discharged on postoperative day 1 without complications. Ultrasound-guided PNB provides safe and reasonably effective pain control to male patients undergoing urologic procedures.

Alcohol Intake Increases in Adolescent C57BL/6J Mice during Intermittent Cycles of Phase-Delayed, Long-Light Conditions.

Adolescents naturally go to bed and awaken late, but are forced to awaken early for school and work. This leads to "social jetlag", a state of circadian desynchrony (CD), in which internal biological rhythms are out of sync with behavioral rhythms. CD is associated with increased alcohol intake in adults, but has been less well-studied in adolescents. The goal of this study was to model adolescent alcohol intake during similar CD conditions in male C57BL/6J mice. Free access alcohol intake, water intake and wheel-running activity were measured during a normal 12HR photoperiod or during alternating photoperiod (Experiment 1: 12 h light for 4 days followed by 18 h light for 3 days, with dark (activity onset) delayed 9 h during the 18HR photoperiod; Experiment 2: 12 h light for 4 days followed by 6 h light for 3 days, with dark onset delayed 3 h during the 6HR photoperiod). In Experiment 1, CD produced a small but significant increase in the total alcohol intake per day as well as in intake in bouts, with the greatest increase over controls in the hours following the 6HR dark period. Additionally, the pattern of alcohol intake in bouts shifted to increase alcohol intake during the shorter dark period. In Experiment 2, the opposite effect occurred-the longer dark cycle led to lower alcohol drinking in the second half of the dark period. However, in Experiment 2, CD produced no significant changes in either total alcohol intake or alcohol intake in bouts. CONCLUSION: shifts in the light cycle that disrupt the regular pattern of day and night, and increase the length of the night phase, are sufficient to increase both drinking in bouts and restricted drinking in adolescent mice, modeling increased alcohol intake in adolescents during CD.

Estrogen receptor-positive primary squamous cell carcinoma of the breast.

Pure primary squamous cell carcinoma of the breast (SCCB) represents around 0.1% of breast carcinomas. Diagnosis requires independence from adjacent skin without metastatic disease. SCCB is often large at presentation with nonspecific mammographic and ultrasound findings. It is typically hormone receptor negative and aggressive. Mastectomy and adjuvant chemotherapy is the most common treatment, although treatment guidelines are not well established. We present a case of pure primary SCCB detected by high risk screening mammogram and treated with breast conserving surgery, chemotherapy, and radiation. We discuss clinical, radiologic, and pathologic findings.