Combination therapy with oral treprostinil for pulmonary arterial hypertension. A double-blind placebo-controlled clinical trial

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown. Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy. Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response. Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56–0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro–brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil–assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12–60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting. Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening. Clinical trial registered with www.clinicaltrials.gov (NCT01560624)

The “I” in us, or the eye on us? Regulatory focus, commitment and derogation of an attractive alternative person

When individuals are highly committed to their romantic relationship, they are more likely to engage in pro-relationship maintenance mechanisms. The present research expanded on the notion that commitment redirects self-oriented goals to consider broader relational goals and examined whether commitment interacts with a promotion and prevention focus to activate derogation of attractive alternatives. Three studies used cross-sectional and experimental approaches. Study 1 showed that romantically involved individuals predominantly focused on promotion, but not prevention, reported less initial attraction to an attractive target than single individuals, especially when highly committed to their relationship. Study 2 showed that romantically involved individuals induced in a promotion focus, compared to those in prevention focus, reported less initial attraction, but only when more committed to their relationship. Regardless of regulatory focus manipulation, more committed individuals were also less likely to perceive quality among alternative scenarios and to be attentive to alternative others in general. Finally, Study 3 showed that romantically involved individuals induced in promotion focus and primed with high commitment reported less initial attraction, than those primed with low commitment, or than those induced in prevention focus. Once again, for these latter no differences occurred according to commitment prime. Together, the findings suggest that highly committed promotion focused individuals consider broader relationship goals and activate relationship maintenance behaviors such as derogation of attractive alternatives to promote their relationship