Torcetrapib therapy resulted in an increased risk of mortality and morbidity of unknown mechanism. Although there was evidence of an off-target effect of torcetrapib, we cannot rule out adverse effects related to CETP inhibition. (ClinicalTrials.gov number, NCT00134264 [ClinicalTrials.gov].).

Purpose To determine whether a structured mentoring curriculum improves research mentoring skills. Method The authors conducted a randomized controlled trial (RCT) at 16 academic health centers (June 2010 to July 2011). Faculty mentors of trainees who were conducting clinical/translational research ≥50% of the time were eligible. The intervention was an eight-hour, case-based curriculum focused on six mentoring competencies. The primary outcome was the change in mentors’ self-reported pretest to posttest composite scores on the Mentoring Competency Assessment (MCA). Secondary outcomes included changes in the following: mentors’ awareness as measured by their self-reported retrospective change in MCA scores, mentees’ ratings of their mentors’ competency as measured by MCA scores, and mentoring behaviors as reported by mentors and their mentees. Results A total of 283 mentor–mentee pairs were enrolled: 144 mentors were randomized to the intervention; 139 to the control condition. Self-reported pre-/posttest change in MCA composite scores was higher for mentors in the intervention group compared with controls (P < .001). Retrospective changes in MCA composite scores between the two groups were even greater, and extended to all six subscale scores (P < .001). More intervention-group mentors reported changes in their mentoring practices than control mentors (P < .001). Mentees working with intervention-group mentors reported larger changes in retrospective MCA pre-/posttest scores (P = .003) and more changes in their mentors’ behavior (P = .002) than those paired with control mentors. Conclusions This RCT demonstrates that a competency-based research mentor training program can improve mentors’ skills.

Objective To examine the mortality and cardiovascular disease (CVD) burden among a population-based cohort of patients with systemic lupus erythematosus (SLE) with previously described late mean onset and low rates of organ-threatening disease. Methods This retrospective population-based cohort study investigated incident cases of SLE diagnosed from 1991–2008 and followed through March 2009 to examine rates of death and CVD events: myocardial infarction, stroke, or congestive heart failure hospitalization. Cases were identified using the 1997 update of 1982 American College of Rheumatology SLE criteria. Searches included electronic records, chart audits, and state death matches, with physician review. Age and sex-matched population comparisons facilitated relative event rate calculations. Results 70 incident SLE cases had late mean onset (52 years), with an incidence of 5 cases per 100,000/year. Matched comparisons showed similar baseline rates of hypertension, hyperlipidemia, and diabetes. However, SLE patients experienced more CVD in the 2 years preceding SLE diagnosis, odds ratio 3.8 (95% CI 1.8, 8.0). The estimated 10-year mortality rates were 26% for SLE subjects versus 19% for comparisons, hazard ratio (HR) 2.1, p<0.01. Adjusted for prior CVD, SLE cases still demonstrated increased hazards of mortality (HR 1.9, p=0.01) and CVD event or death (HR 1.8, p=0.01). Conclusion This incident SLE cohort demonstrated approximately doubled mortality and CVD event hazards compared to age and sex-matched comparisons, even after accounting for higher CVD events in the 2 years preceding SLE diagnosis. This raises future research questions regarding delayed lupus diagnosis versus accelerated CVD prior to SLE, particularly in older-onset SLE.

; for the BETonMACE Investigators and Committees IMPORTANCE Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes. OBJECTIVE To test whether apabetalone significantly reduces major adverse cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019. INTERVENTIONS Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care. MAIN OUTCOMES AND MEASURES The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke. RESULTS Among 2425 patients who were randomized (mean age, 62 years; 618 women [25.6%]), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalonetreated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 [95% CI, 0.65-1.04]; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 [9.4%] vs 69 [5.7%]) for reasons including elevations of liver enzyme levels (35 [2.9%] vs 11 [0.9%]). CONCLUSIONS AND RELEVANCE Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events.

In the COMPANION trial, a machine learning algorithm produced a model that predicted clinical outcomes after CRT. Applied before device implant, this model may better differentiate outcomes over current clinical discriminators and improve shared decision-making with patients.