Current status of clinician-educator tracks in internal medicine residency programmes.

BACKGROUND: Residents in internal medicine programmes lack formal training in leadership, curriculum development and clinical teaching. Residency programmes created clinician-educator tracks (CETs) to formally teach residents to become effective educators and to involve them in the science of medical education. However, the curricula in these tracks are often locally developed and remain at the discretion of the individual programmes. METHODS: This survey evaluates the frequency of CETs in internal medicine residency programmes in the USA and descriptively analyses their logistical and curricular content. During the academic year 2017-2018, directors of all Accreditation Council for Graduate Medical Education (ACGME) accredited internal medicine residency programmes in the USA were invited to participate in this survey (n=420). We developed a web-based 22-question survey to assess the logistics and curricular content of CET programmes. RESULTS: A total of 150 programmes responded to the survey invitation (response rate=35.7%). Only 24% (n=36) of programmes offered a CET, the majority of which have been available for only 5 years or less. The track is most frequently offered to postgraduate year (PGY)-2 and PGY-3 residents. Only a minority of participating faculty (27.8%) have protected time to fulfil their CET role. Bedside teaching, feedback, small group teaching and curriculum development are the most commonly taught topics, and faculty mentorship and small group teaching methods are the most commonly used types of instruction. CONCLUSIONS: CETs are offered in only 24% of internal medicine residency programmes in the USA. The curricula of these tracks vary across programmes, and their success is often countered by logistic and financial challenges.

Vitamin K2 Status and Arterial Stiffness Among Untreated Migraine Patients: A Case-Control Study.

OBJECTIVE: We aimed to examine arterial stiffness and vitamin K2 status in migraine subjects by comparison to controls. BACKGROUND: Migraine is a primary headache disorder that has been associated with an increased risk of cardiovascular events. Mechanisms underlying this increased risk, however, remain unclear. Vitamin K2 deficiency emerged as a cardiovascular risk factor, but vitamin K2 status has never been explored in migraine subjects. DESIGN AND METHODS: This is a case-control, single-center, observational study that includes a cohort of subjects with migraine and their age- and sex-matched controls. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV). Dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) was used as a marker for vitamin K2 status. A propensity-matched scoring method was used. RESULTS: A total of 146 patients (73 matched pairs) were included in this study, of whom 89% were women with a mean age of 31.9 ± 8.4 years. Compared with controls, migraine patients had statistically significantly higher mean cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, 95% confidence interval (CI) of mean difference [0.45, 1.08], P < .001), as well as higher dp-ucMGP (454.3 ± 116.7 pmol/L vs 379.8 ± 126.6 pmol/L, 95% CI of mean difference [34.63, 114.31], P < .001). Higher cfPWV was associated with higher dp-ucMGP concentrations only in the migraine with aura (MWA) group. Moreover, migraine subjects had a higher frequency of vitamin K2 deficiency (dp-ucMGP ≥ 500 pmol/L) compared to controls, but this association was not statistically significant (23/73 [31.5%] vs 16/73 [21.9%], P = .193). CONCLUSIONS: Individuals with migraine have worse indices of arterial stiffness as compared with their age- and sex-matched control subjects. This increase in arterial stiffness is associated with an increase in markers of vitamin K2 deficiency in the MWA group.

Increased Risk of Progression to Gastric Adenocarcinoma in Patients with Non-dysplastic Gastric Intestinal Metaplasia Versus a Control Population.

AIM: In previous studies, the 5-year progression rate of gastric intestinal metaplasia to gastric adenocarcinoma has varied substantially. We investigated the incidence rate of dysplasia and gastric adenocarcinoma and the rate of progression among a cohort of patients with non-dysplastic gastric intestinal metaplasia. METHODS: This is a single-center, single-cohort retrospective study. Patients who had undergone an EGD with biopsies from 01/01/1993 to 12/31/2013 were included. The primary outcome of interest was the composite of low-grade dysplasia, high-grade dysplasia, or adenocarcinoma. Time to progression and risk factor subgroup analyses were performed. RESULTS: A total of 1628 subjects were screened, of whom 358 met the inclusion criteria. A total of 21 first-time events were recorded. The annual incidence rate of low-grade dysplasia was 2.1 (95% CI 1.3-3.5) cases per 1000 person-years, 0.5 (95% 0.2-1.3) per 1000 person-years for high-grade dysplasia, and 0.8 (95% CI 0.3-1.6) cases per 1000 person-years for gastric adenocarcinoma. The historical control group had an annual adenocarcinoma incidence rate of 0.07 per 1000 person-years. The event rate in Asians was also noted to be significantly higher between years 0-8 as compared with patients of non-Asian race, and extensive intestinal metaplasia was an independent risk factor (HR = 4.06 (95% CI 1.45-11.34), p = 0.007). CONCLUSIONS: Patients with non-dysplastic gastric intestinal metaplasia may progress to dysplasia and gastric adenocarcinoma. The incidence rate of gastric adenocarcinoma is higher than that of the historical control population (0.07 per 1000 person-years). The presence of extensive intestinal metaplasia was a risk factor for progression of disease. Triennial EGD may be warranted in patients with non-dysplastic gastric intestinal metaplasia.

Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI.

BACKGROUND: In patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) with placement of stents, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding. The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain. METHODS: We randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to Thrombolysis in Myocardial Infarction [TIMI] criteria or bleeding requiring medical attention). RESULTS: The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3; hazard ratio for group 1 vs. group 3, 0.59; 95% confidence interval [CI], 0.47 to 0.76; P<0.001; hazard ratio for group 2 vs. group 3, 0.63; 95% CI, 0.50 to 0.80; P<0.001). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan-Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3; P values for all comparisons were nonsignificant). CONCLUSIONS: In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y12 inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy. (Funded by Janssen Scientific Affairs and Bayer Pharmaceuticals; PIONEER AF-PCI ClinicalTrials.gov number, NCT01830543 .).

The CSL112-2001 trial: Safety and tolerability of multiple doses of CSL112 (apolipoprotein A-I [human]), an intravenous formulation of plasma-derived apolipoprotein A-I, among subjects with moderate renal impairment after acute myocardial infarction.

BACKGROUND: CSL112 (apolipoprotein A-I [human]) is a plasma-derived apolipoprotein A-I developed for early reduction of cardiovascular risk following an acute myocardial infarction (AMI). The safety of CSL112 among AMI subjects with moderate, stage 3 chronic kidney disease (CKD) is unknown. METHODS: CSL112_2001, a multicenter, placebo-controlled, parallel-group, double-blind, randomized phase 2 trial, enrolled patients with moderate CKD within 7 days following AMI. Enrollment was stratified on the basis of estimated glomerular filtration rate and presence of diabetes requiring treatment. Patients were randomized in a 2:1 ratio to receive 4 weekly infusions of CSL112 6 g or placebo. The co-primary safety end points were renal serious adverse events (SAEs) and acute kidney injury, defined as an increase ≥26.5 µmol/L in baseline serum creatinine for more than 24 hours, during the treatment period. RESULTS: A total of 83 patients were randomized (55 CSL112 vs 28 placebo). No increase in renal SAEs was observed in the CSL112 group compared with placebo (CSL112 = 1 [1.9%], placebo = 4 [14.3%]). Similarly, no increase in acute kidney injury events was observed (CSL112 = 2 [4.0%], placebo = 4 [14.3%]). Rates of other SAEs were similar between groups. CSL112 administration resulted in increases in ApoA-I and cholesterol efflux similar to those observed in patients with AMI and normal renal function or stage 2 CKD enrolled in the ApoA-I Event Reducing in Ischemic Syndromes I trial. CONCLUSIONS: These results demonstrate the acceptable safety of the 6-g dose of CSL112 among AMI subjects with moderate stage 3 CKD and support inclusion of these patients in a phase 3 cardiovascular outcomes trial powered to assess efficacy.

Extended-Duration Betrixaban Reduces the Risk of Stroke Versus Standard-Dose Enoxaparin Among Hospitalized Medically Ill Patients: An APEX Trial Substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban).

BACKGROUND: Stroke is a morbid and potentially mortal complication among patients hospitalized with acute medical illness. The potential of extended-duration thromboprophylaxis with the factor Xa inhibitor betrixaban to reduce the risk of stroke compared with standard-dose enoxaparin in this population was assessed in this retrospective APEX trial substudy (Acute Medically Ill Venous Thromboembolism Prevention With Extended Duration Betrixaban). METHODS: Hospitalized acutely medically ill subjects (n=7513) were randomized in a double-dummy double-blind fashion to either extended-duration oral betrixaban (80 mg once daily for 35-42 days) or standard-dose subcutaneous enoxaparin (40 mg once daily for 10±4 days) for venous thromboprophylaxis. Stroke events were adjudicated by an independent, blinded event adjudication committee. RESULTS: The mean age of study participants was 76 years; 45% were male; 13% had had a stroke; and 45% had congestive heart failure. There were fewer all-cause strokes (0.54% versus 0.97%; relative risk [RR]=0.56; 95% confidence interval, 0.32-0.96; P=0.032; adjusted RR=0.43%; number needed to treat=233) and ischemic strokes (0.48% versus 0.91%; RR=0.53; 95% confidence interval, 0.30-0.94; P=0.026; adjusted RR=0.43%; number needed to treat=233) among patients treated with betrixaban versus enoxaparin through 77 days of follow-up. Among high-risk subjects, those with congestive heart failure or ischemic stroke as their index event, betrixaban reduced the risk of all-cause stroke (0.72% versus 1.48%; RR=0.49; 95% confidence interval, 0.26-0.90; P=0.019; adjusted RR=0.76%; number needed to treat=132) and ischemic stroke (0.63% versus 1.38%; RR=0.45; 95% confidence interval, 0.24-0.87; P=0.014; adjusted RR=0.75%; number needed to treat=134) compared with enoxaparin. CONCLUSIONS: Among hospitalized medically ill patients, extended-duration betrixaban significantly reduced all-cause stroke and ischemic stroke through 77 days of follow-up CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01583218.

Recurrent Hospitalization Among Patients With Atrial Fibrillation Undergoing Intracoronary Stenting Treated With 2 Treatment Strategies of Rivaroxaban or a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy.

BACKGROUND: Patients with atrial fibrillation who undergo intracoronary stenting traditionally are treated with a vitamin K antagonist (VKA) plus dual antiplatelet therapy (DAPT), yet this treatment leads to high risks of bleeding. We hypothesized that a regimen of rivaroxaban plus a P2Y12 inhibitor monotherapy or rivaroxaban plus DAPT could reduce bleeding and thereby have a favorable impact on all-cause mortality and the need for rehospitalization. METHODS: Stented subjects with nonvalvular atrial fibrillation (n=2124) were randomized 1:1:1 to administration of reduced-dose rivaroxaban 15 mg daily plus a P2Y12 inhibitor for 12 months (group 1); rivaroxaban 2.5 mg twice daily with stratification to a prespecified duration of DAPT of 1, 6, or 12 months (group 2); or the reference arm of dose-adjusted VKA daily with a similar DAPT stratification (group 3). The present post hoc analysis assessed the end point of all-cause mortality or recurrent hospitalization for an adverse event, which was further classified as the result of bleeding, a cardiovascular cause, or another cause blinded to treatment assignment. RESULTS: The risk of all-cause mortality or recurrent hospitalization was 34.9% in group 1 (hazard ratio=0.79; 95% confidence interval, 0.66-0.94; P=0.008 versus group 3; number needed to treat=15), 31.9% in group 2 (hazard ratio=0.75; 95% confidence interval, 0.62-0.90; P=0.002 versus group 3; number needed to treat=10), and 41.9% in group 3 (VKA+DAPT). Both all-cause death plus hospitalization potentially resulting from bleeding (group 1=8.6% [P=0.032 versus group 3], group 2=8.0% [P=0.012 versus group 3], and group 3=12.4%) and all-cause death plus rehospitalization potentially resulting from a cardiovascular cause (group 1=21.4% [P=0.001 versus group 3], group 2=21.7% [P=0.011 versus group 3], and group 3=29.3%) were reduced in the rivaroxaban arms compared with the VKA arm, but other forms of rehospitalization were not. CONCLUSIONS: Among patients with atrial fibrillation undergoing intracoronary stenting, administration of either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy or 2.5 mg rivaroxaban twice daily plus DAPT was associated with a reduced risk of all-cause mortality or recurrent hospitalization for adverse events compared with standard-of-care VKA plus DAPT. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01830543.

Symptomatic event reduction with extended-duration betrixaban in acute medically ill hospitalized patients.

BACKGROUND: Approximately 15%-30% of patients in trials of medical thromboprophylaxis will have missing compression ultrasound (CUS) data. The goal of the present analysis was to perform analyses to minimize missing data. METHODS: The APEX trial randomized 7,513 acutely medically ill hospitalized patients to thromboprophylaxis with either betrixaban for 35-42 days or enoxaparin for 6-14 days. A modified intent-to-treat (mITT) analysis was performed and included all subjects administered study drug, irrespective of CUS performance, and an analysis of symptomatic events which do not require performance of a CUS (symptomatic deep vein thrombosis, nonfatal pulmonary embolism, and venous thromboembolism (VTE)-related mortality). RESULTS: In the mITT population, betrixaban significantly reduced the primary end point (which included both symptomatic and CUS events) (165 [4.4%] vs 223 [6.0%]; relative risk = 0.75; 95% CI 0.61-0.91; P = .003; absolute risk reduction [ARR] = 1.6%; number needed to treat [NNT] = 63). Betrixaban also reduced symptomatic VTE through day 42 (35 [1.28%] vs 54 [1.88%], hazard ratio [HR] = 0.65; 95% CI 0.42-0.99; P = .044; ARR = 0.6%; NNT=167) as well as through day 77 (37 [1.02%] vs 67 [1.89%]; HR= 0.55; 95% CI 0.37-0.83; P = .003; ARR = 0.87%; NNT=115) as well as the individual end point of nonfatal pulmonary embolism (9 [0.25%] vs 20 [0.55%]; HR= 0.45; 95% CI 0.21-0.99; P = .041; ARR = 0.30%; NNT=334). On an "as-treated" basis, 80 mg of betrixaban reduced VTE-related mortality through day 77 (10 [0.34%] vs. 22 [0.79%]; HR=0.46; 95% CI 0.22-0.96; P = .035; ARR = 0.45%; NNT=223). CONCLUSION: In an mITT analysis of all patients administered study drug, extended-duration betrixaban reduced the primary end point as well as symptomatic events. In an as-treated analysis, 80 mg of betrixaban reduced VTE-related death.

Increased benefit of betrixaban among patients with a history of venous thromboembolism: a post-hoc analysis of the APEX trial.

Hospitalized acute medically ill patients with a history of venous thromboembolism (VTE) are at increased risk for recurrent VTE. We characterized the efficacy and safety of betrixaban for prevention of recurrent VTE in these high risk patients. The APEX trial randomized 7513 acutely ill hospitalized medical patients at risk for developing VTE to receive either betrixaban for 35-42 days or enoxaparin for 10 ± 4 days to prevent VTE. This exploratory post-hoc analysis assessed the efficacy and safety of betrixaban versus enoxaparin among subjects with and without prior VTE. Time-to-multiple symptomatic VTE events was also calculated. Approximately 8% of subjects in both arms had prior VTE, which was associated with a fourfold increase in adjusted risk of VTE [MV OR 4.03, 95% CI 3.06-5.30, p < 0.001]. Betrixaban reduced VTE compared with enoxaparin among subjects with prior VTE [32 (10.4%) vs. 55 (18.9%), RR 0.57, 95% CI 0.38-0.86, p = 0.006, ARR 8.5%, NNT 12] and without prior VTE [133 (3.9%) vs. 168 (4.9%), RR 0.79, 95% CI 0.64-0.99, p = 0.042, ARR 1.0%, NNT 100] (interaction p > 0.05). Additionally, four subjects in the enoxaparin arm and one subject in the betrixaban arm experienced a recurrent VTE. Compared with enoxaparin, betrixaban use was associated with reduction of recurrent VTE events through the active treatment period [36 vs. 57, HR 0.63, 95% CI 0.41-0.97, p = 0.045] and through the end of study [38 vs. 71, HR 0.54, 95% CI 0.36-0.81, p = 0.004]. Prior VTE is associated with a fourfold increase in the risk of VTE among hospitalized medically ill patients. Only 12 such patients would need to be treated with betrixaban versus enoxaparin to prevent an additional VTE endpoint. Betrixaban reduced not only the first but also all recurrent VTE events in a time-to-any-event analysis. TRIAL REGISTRATION: http://www.clinicaltrials.gov , Unique identifier: NCT01583218.

Safety and Tolerability of CSL112, a Reconstituted, Infusible, Plasma-Derived Apolipoprotein A-I, After Acute Myocardial Infarction: The AEGIS-I Trial (ApoA-I Event Reducing in Ischemic Syndromes I).

BACKGROUND: Human or recombinant apolipoprotein A-I (apoA-I) has been shown to increase high-density lipoprotein-mediated cholesterol efflux capacity and to regress atherosclerotic disease in animal and clinical studies. CSL112 is an infusible, plasma-derived apoA-I that has been studied in normal subjects or those with stable coronary artery disease. This study aimed to characterize the safety, tolerability, pharmacokinetics, and pharmacodynamics of CSL112 in patients with a recent acute myocardial infarction. METHODS: The AEGIS-I trial (Apo-I Event Reducing in Ischemic Syndromes I) was a multicenter, randomized, double-blind, placebo-controlled, dose-ranging phase 2b trial. Patients with myocardial infarction were stratified by renal function and randomized 1:1:1 to CSL112 (2 g apoA-I per dose) and high-dose CSL112 (6 g apoA-I per dose), or placebo for 4 consecutive weekly infusions. Coprimary safety end points were occurrence of either a hepatic safety event (an increase in alanine transaminase >3 times the upper limit of normal or an increase in total bilirubin >2 times the upper limit of normal) or a renal safety event (an increase in serum creatinine >1.5 times the baseline value or a new requirement for renal replacement therapy). RESULTS: A total of 1258 patients were randomized, and 91.2% received all 4 infusions. The difference in incidence rates for an increase in alanine transaminase or total bilirubin between both CSL112 arms and placebo was within the protocol-defined noninferiority margin of 4%. Similarly, the difference in incidence rates for an increase in serum creatinine or a new requirement for renal replacement therapy was within the protocol-defined noninferiority margin of 5%. CSL112 was associated with increases in apoA-I and ex vivo cholesterol efflux similar to that achieved in patients with stable coronary artery disease. In regard to the secondary efficacy end point, the risk for the composite of major adverse cardiovascular events among the groups was similar. CONCLUSIONS: Among patients with acute myocardial infarction, 4 weekly infusions of CSL112 are feasible, well tolerated, and not associated with any significant alterations in liver or kidney function or other safety concern. The ability of CSL112 to acutely enhance cholesterol efflux was confirmed. The potential benefit of CSL112 to reduce major adverse cardiovascular events needs to be assessed in an adequately powered phase 3 trial. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02108262.

The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial.

BACKGROUND: The APEX trial assessed the safety and efficacy of extended-duration thromboprophylaxis using betrixaban versus standard dosing of enoxaparin among hospitalized, acutely ill medical patients. The 80-mg betrixaban dose was halved to 40 mg among subjects with severe renal insufficiency and those receiving a concomitant strong P-glycoprotein inhibitor. METHODS: This analysis assessed the pharmacokinetics, efficacy, and safety of full- (80 mg) and reduced-dose (40 mg) betrixaban relative to enoxaparin in the APEX trial. RESULTS: The median concentration of betrixaban among subjects administered the 80-mg dose was higher than that of the 40-mg dose (19 ng/mL vs 11 ng/mL, P<.001). In the primary analysis cohort 1 (d-dimer ≥2× upper limit of normal), the primary efficacy outcome (asymptomatic proximal deep vein thrombosis, symptomatic proximal or distal deep vein thrombosis, symptomatic nonfatal pulmonary embolism, or venous thromboembolism-related death) was significantly reduced among subjects treated with 80 mg of extended-duration betrixaban versus enoxaparin (6.27% [95/1516] vs 8.39% [130/1549], relative risk reduction=0.26 [0.04-0.42], P=.023), and similarly in the entire primary efficacy outcome population (4.87% [122/2506] vs 7.06% [181/2562], relative risk reduction=0.30 [0.13-0.44], P=.001). There was no difference in the primary outcome for subjects treated with 40 mg betrixaban vs enoxaparin across cohorts. In addition, there was no excess of major bleeding associated with either betrixaban dose compared with enoxaparin. CONCLUSIONS: The 80-mg betrixaban dose achieves higher plasma concentrations than the 40-mg dose and, in contrast to the 40-mg dose, is associated with improved efficacy across all cohorts relative to standard-dose enoxaparin without an excess risk of major bleeding in the management of medically ill subjects.

N-terminal pro-B-type natriuretic peptide and the risk of stroke among patients hospitalized with acute heart failure: an APEX trial substudy.

BACKGROUND: Among patients hospitalized with acute heart failure (HF), the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in short-term stroke prediction remains unclear. METHODS: In the APEX trial, 7513 patients hospitalized for an acute medical illness were randomized to receive either extended-duration betrixaban (80 mg once daily for 35-42 days) or standard-of-care enoxaparin (40 mg once daily for 10 ± 4 days) for venous thromboprophylaxis. Baseline NT-proBNP concentrations were obtained in 3261 patients admitted for HF. Stroke events were adjudicated by an independent clinical events committee blinded to thromboprophylaxis allocation. The association of NT-proBNP level and other risk factors and biomarkers with stroke was assessed at 77 days after randomization. RESULTS: In univariate analysis, the risk of stroke at 77 days was associated with baseline NT-proBNP (HR 3.63 [95% CI 1.47-8.99]; P = 0.005), D-dimer (HR 2.73 [95% CI 1.03-7.20]; P = 0.043), and hsCRP (HR 3.03 [95% CI 1.36-6.75]; P = 0.007). In multivariable analysis adjusting for hsCRP and thromboprophylaxis, NT-proBNP was associated with the risk of stroke (adjusted HR 3.64 [95% CI 1.35-9.83]; P = 0.011). The interaction of NT-proBNP with the treatment effect was not significant (Pint = 0.30). CONCLUSIONS: Baseline NT-proBNP concentration was associated with short-term stroke among patients hospitalized with acute HF. Stroke risk assessment models should consider incorporation of NT-proBNP measurement.

EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention.

AIMS: Among patients with ST-elevation myocardial infarction (STEMI), reperfusion injury contributes to additional myocardial damage. MTP-131 is a cell-permeable peptide that preserves the integrity of cardiolipin, enhances mitochondrial energetics, and improves myocyte survival during reperfusion. METHODS AND RESULTS: EMBRACE STEMI is a multicentre, randomized, double-blind Phase 2a trial that evaluated the efficacy and safety of MTP-131 vs. placebo infused at a rate of 0.05 mg/kg/h for 1 h among first-time anterior STEMI subjects undergoing primary percutaneous coronary intervention (PCI) for a proximal or mid left anterior descending (LAD) artery occlusion. Administration of MTP-131 was not associated with a significant reduction in the primary endpoint, infarct size by creatine kinase-myocardial band (CK-MB) area under the curve (AUC) over 72 h (5785 ± 426 ng h/mL in placebo vs. 5570 ± 486 ng h/mL in MTP-131; ITALIC! P = NS). MTP-131 was not associated with an improvement in pre-specified magnetic resonance imaging, angiographic, electrocardiographic, or clinical outcomes. CONCLUSION: Among subjects with first-time anterior STEMI due to a proximal or mid LAD lesion who undergo successful PCI, administration of MTP-131 was safe and well tolerated. Treatment with MTP-131 was not associated with a decrease in myocardial infarct size as assessed by AUC0-72 of CK-MB.

Rationale and design of Apo-I Event Reduction in Ischemic Syndromes I (AEGIS-I): A phase 2b, randomized, placebo-controlled, dose-ranging trial to investigate the safety and tolerability of CSL112, a reconstituted, infusible, human apoA-I, after acute myocardial infarction.

BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease. DESIGN: The AEGIS-I trial (ClinicalTrials.govNCT02108262) is a phase 2b, multicenter, randomized, placebo-controlled, dose-ranging clinical trial to evaluate the hepatic and renal safety of multiple administrations of 2 doses of CSL112 among subjects with acute myocardial infarction (AMI). Approximately 1,200 subjects (400 per treatment group) with either normal renal function or mild renal impairment will be enrolled up to 7 days after an AMI and will be stratified by renal function and randomized in a 1:1:1 ratio to either 1 of 2 doses of CSL112 (either 2 g or 6 g) or placebo as a weekly 2-hour infusion over the course of 4 consecutive weeks. The coprimary safety endpoints will be the incidence of hepatic and renal toxicity, defined as either confirmed ALT >3 × ULN, total bilirubin >2 × ULN, serum creatinine ≥1.5×baseline value, or a new requirement for renal replacement therapy through the end of the active treatment period. SUMMARY: The AEGIS-I trial will characterize the safety profile of CSL112, a reconstituted formulation of apolipoprotein A-I, and will assess if administration to patients with a recent AMI is associated with a clinically significant alteration in either liver or kidney function when compared with placebo.

Medical education in a foreign language and history-taking in the native language in Lebanon - a nationwide survey.

BACKGROUND: With the adoption of the English language in medical education, a gap in clinical communication may develop in countries where the native language is different from the language of medical education. This study investigates the association between medical education in a foreign language and students' confidence in their history-taking skills in their native language. METHODS: This cross-sectional study consisted of a 17-question survey among medical students in clinical clerkships of Lebanese medical schools. The relationship between the language of medical education and confidence in conducting a medical history in Arabic (the native language) was evaluated (n = 457). RESULTS: The majority (88.5%) of students whose native language was Arabic were confident they could conduct a medical history in Arabic. Among participants enrolled in the first clinical year, high confidence in Arabic history-taking was independently associated with Arabic being the native language and with conducting medical history in Arabic either in the pre-clinical years or during extracurricular activities. Among students in their second clinical year, however, these factors were not associated with confidence levels. CONCLUSIONS: Despite having their medical education in a foreign language, the majority of students in Lebanese medical schools are confident in conducting a medical history in their native language.

Renal function decline in recipients and donors of kidney grafts: role of aortic stiffness.

BACKGROUND/AIMS: Renal function decreases over time as a result of reduction in the number of functioning nephrons with age. In recipients and donors of kidney grafts, renal function decline may be linked differently to various parameters, namely arterial stiffness. METHODS: We conducted a prospective cohort study including 101 recipients of kidney grafts and their donors aiming at determining the factors correlated to the renal function decline over time. Aortic stiffness was evaluated by the non-invasive measurement of aortic pulse wave velocity. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease (MDRD) equation and the annualized change was determined. RESULTS: Decline in renal function was estimated at 1-year post-transplantation and annually thereafter (median follow-up 8 years, range 3.6-18.3), as the mean of the annualized decrease in the glomerular filtration rate. In recipients, filtration rate decreased by 4.8 ± 19.7 ml/min/1.73 m(2) the first post-transplant year and at a yearly rate of 2.2 ± 3.8 ml/min/1.73 m(2) thereafter. The first-year decline was related to smoking and acute rejection. Later decline was significantly associated with donor age and aortic stiffness. In living donors, renal function decline after the first year corresponded to 0.7 ml/min/1.73 m(2), was significantly lower than that of recipients (p < 0.001), and was determined by donor age at nephrectomy. CONCLUSION: Recipients of kidney grafts show a glomerular filtration rate decline over time that is significantly associated with donor age and aortic stiffness after the first post-transplant year, while donors demonstrate a lower decline that is mostly determined by age at nephrectomy.

D-Dimer elevation and adverse outcomes.

D-Dimer is a biomarker of fibrin formation and degradation. While a D-dimer within normal limits is used to rule out the diagnosis of deep venous thrombosis and pulmonary embolism among patients with a low clinical probability of venous thromboembolism (VTE), the prognostic association of an elevated D-dimer with adverse outcomes has received far less emphasis. An elevated D-dimer is independently associated with an increased risk for incident VTE, recurrent VTE, and mortality. An elevated D-dimer is an independent correlate of increased mortality and subsequent VTE across a broad variety of disease states. Therefore, medically ill subjects in whom the D-dimer is elevated constitute a high risk subgroup in which the prospective evaluation of the efficacy and safety of antithrombotic therapy is warranted.

Learning Theories Versus Practice: How Do Internal Medicine Residents Study for Licensing Examinations?

OBJECTIVE:  The ability to recall relevant medical knowledge within clinical contexts is a critical aspect of effective and efficient patient diagnosis and management. The ever-growing and changing body of medical literature requires learners to develop effective life-long learning techniques. Learners can more successfully build their fund of knowledge and ability to retrieve it by using evidence-based learning strategies. Our objective was to evaluate the study habits of internal medicine (IM) residents at an academic institution to understand if they apply key learning strategies for the American Board of Internal Medicine (ABIM) exam preparation. We also briefly review various learning strategies that can be applied to IM residency curricula. METHODS: A web-based survey consisting of 16 multiple-response questions on study habits was filled out by the IM residents in 2019 at Tufts Medical Center. RESULTS: Of the 75 residents invited to participate in the study, 69 responded (response rate = 92%). Of the responders, n=25 (36.2%) were post-graduate year (PGY)-1, n=20 (29.0%) were PGY-2, and n=24 (34.8%) were PGY-3 residents. More than half the residents (n=40, 58%) had Step 2 Clinical Knowledge (CK) scores > 250. Residents self-reported applying spaced learning (67%), interleaving (64%), retrieval (64%), and elaboration practices (46%) for exam preparation. There was a significant association between the Step 2 CK score and elaboration (p=0.017) technique but not with spaced learning, interleaving, or retrieval. The majority of residents felt not at all prepared (n=42, 60.9%) for the ABIM exam. CONCLUSIONS: Despite two years of clinical training, 33% of the third-year residents felt inadequately prepared for the board certification exam. Incorporating evidence-based learning strategies into their daily curriculum may help them better prepare for the ABIM exam.

Patient Adherence to Secondary Prevention Therapies After an Acute Coronary Syndrome: A Scoping Review.

PURPOSE: Adherence to guideline-recommended, long-term secondary preventative therapies among patients with acute coronary syndrome (ACS) is fundamental to improving long-term outcomes. The purpose of this scoping review was to provide a broad synopsis of pertinent studies in a structured and comprehensive way regarding factors that influence patient adherence to medical therapy after ACS. METHODS: Relevant articles focusing on adherence to medical therapy after ACS were retrieved from the EMBASE and MEDLINE databases (search date, September 7, 2021). Studies were independently screened, and relevant information was extracted. FINDINGS: A total of 58 studies were identified by using the EMBASE and MEDLINE databases. Adherence to secondary prevention was moderate to low and steadily decreased over time. Nearly 30% of patients discontinued one or more medications within 90 days of their primary ACS, and adherence decreased to 50% to 60% at 1 year postdischarge. There were no major differences in adherence between drug classes. Factors influencing patient adherence can be broadly divided into 3 categories: patient related, health care system related, and disease related. Patients managed with percutaneous coronary interventions were more adherent to follow-up treatment than medically managed patients. Depression was reported as a major psychological factor that negatively affected adherence. Improved adherence was observed when higher levels of patient education and provider engagement were delivered during postdischarge follow-up, particularly when scheduled early. Notably, the incidence of major adverse cardiovascular events was lower in hospitals with high 90-day medication adherence than those with moderate or low adherence. IMPLICATIONS: Patient nonadherence to guideline-recommended long-term pharmacologic secondary preventative therapies after ACS is multifactorial. A comprehensive multifaceted approach should be implemented to improve adherence and clinical outcomes. This approach should include key interventions such as early follow-up visits, high medication adherence at 90 days, patient engagement and education, and development of novel interventions that support the 3 broad categories influencing patient adherence as discussed in this review.