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Patients with previously untreated pulmonary arterial hypertension who were randomly assigned to combination therapy with ambrisentan and tadalafil had a significantly lower risk of a composite clinical failure outcome at 20 months than did the pooled monotherapy group. Regardless of the initiating trigger, pulmonary arterial hypertension results in the altered synthesis of a variety of vasoactive substances derived from the endothelium. 1 Current therapies for pulmonary arterial hypertension 2 target abnormalities in one of three intracellular pathways with signaling dysfunction: the prostacyclin, nitric oxide, or endothelin pathway. 1 However, no single class of drug is consistently effective in treating all patients, which suggests that no single pathway plays a dominant pathogenic role. 3 , 4 Combination therapy with agents that target several different pathways may potentially increase the overall therapeutic effect on the mechanisms of this disease 5 and provide additional clinical benefits. 6 – . . .

BackgroundPatients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH), in particular systemic sclerosis (SSc), had an attenuated response compared with idiopathic PAH in most trials. Thus, there is uncertainty regarding the benefit of PAH-targeted therapy in some forms of CTD-PAH.ObjectiveTo explore the safety and efficacy of initial combination therapy with ambrisentan and tadalafil versus ambrisentan or tadalafil monotherapy in patients with CTD-PAH and SSc-PAH enrolled in the AMBITION trial.MethodsThis was a post hoc analysis of patients with CTD-PAH and SSc-PAH from AMBITION, an event-driven, double-blind trial in patients with WHO functional class II/III PAH. Treatment-naive patients were randomised 2:1:1 to once-daily initial combination therapy with ambrisentan plus tadalafil or monotherapy with ambrisentan or tadalafil, respectively. The primary endpoint was time to the first clinical failure event (first occurrence of death, hospitalisation for worsening PAH, disease progression or unsatisfactory long-term clinical response).ResultsIn the primary analysis set (N=500), 187 patients had CTD-PAH, of whom 118 had SSc-PAH. Initial combination therapy reduced the risk of clinical failure versus pooled monotherapy in each subgroup: CTD-PAH (HR 0.43 (95% CI 0.24 to 0.77)) and SSc-PAH (0.44 (0.22 to 0.89)). The most common AE was peripheral oedema, which was reported more frequently with initial combination therapy than monotherapy in the two PAH subgroups. The relative frequency of adverse events between those on combination therapy versus monotherapy was similar across subgroups.ConclusionsThis post hoc subgroup analysis provides evidence that CTD-PAH and SSc-PAH patients benefit from initial ambrisentan and tadalafil combination therapy.Trial registration number NCT01178073, post results.

The present article examines the effect of variable input on the acquisition of plural morphology in two varieties of Spanish: Chilean Spanish, where the plural marker is sometimes omitted due to a phonological process of syllable final /s/ lenition, and Mexican Spanish (of Mexico City), with no such lenition process. The goal of the study is to determine whether variable input for grammatical morphology affects the acquisition process. Does the ambiguous nature (sometimes present and sometimes absent) of a form affect acquisition? To address this question, Experiment 1 examines the production of the plural marker in Chilean- and Mexican Spanish-speaking children, and Experiments 2 and 3 examine children's use of plural and singular indefinite noun phrases in comprehension. The results indicate that variable input affects acquisition, with Chilean children taking longer to acquire the plural marker than Mexican children.

The aim of this study was to understand how nurses in a 25-bed critical-access hospital (CAH) led change to become the 1st to achieve Magnet®. Approximately 21% of the US population lives in rural areas served by CAHs. Rural nurse executives are particularly challenged with limited resources. Staff nurses, nurse managers, interprofessional care providers, the chief nursing officer, and board of directors (n = 27) were interviewed. Observations of hospital units and administrative meetings were done, and hospital reports were analyzed. Nine themes emerged to support a conceptual model of leading change. The CAH spent 3 years of its 6-year journey establishing organizational readiness. Nurses overcame complex challenges by balancing operational support and fostering relationships. The Magnet journey led to significantly improved nurse and patient outcomes. A new organizational culture centered on shared governance, evidence-based practice, and higher education emerged. The journey to Magnet leads to improved nurse, patient, and organization outcomes.

Obesity is associated with increased diastolic stiffness and myocardial steatosis and dysfunction. The impact of aging on the protective effects of caloric restriction (CR) is not clear. We studied 2-month (younger) and 6–7-month (older)-old ob/ob mice and age-matched C57BL/6J controls (WT). Ob/ob mice were assigned to diet ad libitum or CR for 4 weeks. We performed echocardiograms, myocardial triglyceride assays, Oil Red O staining, and measured free fatty acids, superoxide, NOS activity, ceramide levels, and Western blots. In younger mice, CR restored diastolic function, reversed myocardial steatosis, and upregulated Akt phosphorylation. None of these changes was observed in the older mice; however, CR decreased oxidative stress and normalized NOS activity in these animals. Interestingly, myocardial steatosis was not associated with increased ceramide, but CR altered the composition of ceramides. In this model of obesity, aging attenuates the benefits of CR on myocardial structure and function.

The academic nursing practice has a role in replenishing the diminished resources that confront higher education and, if well conceived and managed, is a viable option to support existing academic program stability and growth. An alternative model for defining the academic practice—beyond traditional nurse-managed centers—is presented in this article. The cohesive interconnection of the education, research, and practice missions is addressed with examples of how each contributes to a variety of communities of interest and expands professional nursing roles through innovative care model testing and development. With effective business planning and infrastructure support, faculty practice plans can evolve to a second generation, with heightened societal accountability for service, academic, and collaborative research outcomes.

A partnership between a university school of nursing and a health care information technology supplier resulted in the Simulated E-hEalth Delivery System (SEEDS). This program enables nursing students to learn clinical skills in a state-of-the-art environment using a live-production, clinical information system designed for care delivery. (JOW)

In a democratic society, higher education can only remain credible if proportions of those enrolled and employed align to a reasonable extent with the demographic composition of the broader community. This chapter explores what is possible as administrators attempt to increase diversity in admissions under the 2003 decision in Grutter v. Bollinger as well as in employment, an issue the US Supreme Court has not addressed directly. It connects enhancing diversity and strategic advantage, applying three perspectives: creating value in organizations for those connected with them; external positioning, as for enhanced prestige; and internal resources alignment. Values influence administrators of institutions to want to reflect the overall US society in whom they admit or hire. The chapter shows that administrators of universities and colleges are most effective in enhancing values such as learning when they develop strategies particular to them, as opposed to the generic ones they tend to default to in the interest of achieving or maintaining legitimacy.

Left ventricular (LV) morphology may affect right ventricular (RV) function before and after Fontan palliation in patients with hypoplastic left heart syndrome (HLHS). We sought to assess the potential impact of LV morphology on RV function in patients with HLHS using cardiac magnetic resonance (CMR) imaging. A retrospective analysis of available CMR scans from all patients with HLHS was performed. LV morphology was categorized as absent/slit-like or globular/miniaturized. Volumetric analysis was performed using manual disc-summation method on steady-state free precession (SSFP) stack obtained in short-axis orientation of the ventricles. 4-chamber and short-axis SSFP images were used to measure strain on a semi-automated feature-tracking (FT) module. Two sample t-test was used to compare the groups. A total of 48 CMR scans were analyzed. Of those, 12 patients had absent/slit-like and 36 had globular/miniaturized LV morphology. Averaged 4-chamber longitudinal RV strain was significantly higher for absent/slit-like (− 17.6 ± 4.7%) than globular/miniaturized (− 13.4 ± 3.5; P  = 0.002). Averaged 4-chamber radial RV strain was also significantly higher for absent/slit-like (33.1 ± 14.9%) than globular/miniaturized (21.6 ± 7.1; P  = 0.001). For globular/miniaturized LV morphology, the decreases of 4-chamber longitudinal and radial strains were mainly attributable to the septal basilar and septal mid-ventricular segments. No differences were found in short-axis RV global circumferential strain between the morphologic subtypes (absent/slit-like − 15.0 ± 6.5, globular/miniaturized − 15.7 ± 4.7; P  = 0.68). Larger LV remnants, with globular/miniaturized LV morphology, demonstrated diminished strain in the septal base and mid-ventricle segments. Patients with globular/miniaturized LV morphology may benefit with closer monitoring and lower threshold to start heart failure medications. These results exemplify the utility of including both septal and regional deformation in systemic RV strain analysis.