Rosechelle Ruggiero

Ambrisentan, an endothelin receptor type A-selective endothelin receptor antagonist, for the treatment of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by vasoconstriction and vascular proliferation, which leads to right heart failure and death. Prostacyclin, NO and endothelin are felt to be key mediators in the development of PAH. We present the available published and presented data about ambrisentan, an ETA-selective endothelin receptor antagonist (ERA) and newest ERA agent to be approved by the FDA for the treatment of PAH in patients with WHO functional class II and III symptoms. Randomized, placebo-controlled trials have demonstrated a significant improvement in exercise capacity and decrease in time to clinical worsening, along with evidence to support an improvement in WHO functional class and quality of life for patients receiving ambrisentan. Long-term data have shown a 1-year survival of 95%; of the survivors, 94% remained on ambrisentan monotherapy. Endothelin receptor antagonists as a drug class have previously been associated with peripheral edema, aminotransferases abnormalities and a teratogenic risk to a developing fetus. Peripheral edema was observed in patients receiving ambrisentan; however, a greater percentage was experienced in patients aged > 65 years. In contrast, significant aminotransferase abnormalities were not observed with ambrisentan treatment in the placebo-controlled trials, and in all clinical trials combined the 1-year risk seems to be low (< 3%). Despite these data, the FDA requires monthly liver function tests monitoring. As with other ERAs, monthly pregnancy testing is required in all women of child bearing potential.

Long-term therapy with oral treprostinil in pulmonary arterial hypertension failed to lead to improvement in important physiologic measures: results from a single center

Sustained-release oral treprostinil, an oral prostacyclin, led to significant improvement in 6-minute walk distance (6MWD) versus placebo in treatment-naive patients with pulmonary arterial hypertension (PAH) but failed to lead to significant improvement in two 16-week trials in patients receiving background PAH therapies (FREEDOM studies). Long-term studies are lacking. Our objective was to evaluate 6MWD, functional class, hemodynamics, and other long-term outcomes during oral treprostinil administration in PAH. Patients receiving oral treprostinil through the FREEDOM studies at our institution were included and were followed for up to 7 years. The primary end point was change in pulmonary vascular resistance (PVR) at first follow-up catheterization. Other end points included 6MWD, functional class, and other hemodynamic results. Thirty-seven patients received oral treprostinil for a median of 948 days, with 81%, 61%, and 47% continuing therapy at 1, 2, and 3 years, respectively. Mean treprostinil dose at 3, 12, and 24 months was 4.3 ± 2.3, 8.6 ± 3.2, and 11.7 ± 5.8 mg/24 h, respectively. Compared with pretreatment values, there was no significant change in 6MWD at 3 or 12 months, no improvement in functional class at 12 months, and no significant change in hemodynamics at the first follow-up catheterization (N = 34). Oral treprostinil dose was inversely associated with change in PVR (r = −0.42, P < 0.05), and change in PVR was numerically better among patients in the highest dosing quartile. No significant improvement in 6MWD, functional class, or hemodynamics versus pretreatment values was seen with long-term oral treprostinil therapy, potentially because of inability to achieve a clinically effective dose.

Pulmonary Hypertension in Parenchymal Lung Disease

The pathophysiology of pulmonary hypertension (PH) in parenchymal lung diseases is partially related to hypoxic pulmonary vasoconstriction. PH treatment is controversial for these patients. This article focuses on group III PH, namely PH attributable to lung diseases and/or hypoxia. Group III includes chronic obstructive pulmonary disease and interstitial lung diseases, the most common parenchymal lung diseases associated with PH. It also includes sleep-disordered breathing and hypoventilation from any cause. Other parenchymal lung diseases associated with PH, namely sarcoidosis and systemic vasculitides (group V), are discussed. The data describing PH in specific parenchymal diseases are reviewed.

Chronic Critical Illness: The Limbo Between Life and Death

The entity of chronic critical illness (CCI) has shown a rise in the past decades for popularity and prevalence. CCI is loosely defined as the group of patients who require the intensive care setting for weeks to months; its hallmark is prolonged mechanical ventilation. The outcomes of chronically critically ill patients have been dismal and have not improved over time; 1-year survival hovers at approximately 50%. Given the high mortality, prognostic variables are important when making medical decisions. CCI encompasses a syndrome that includes altered pathophysiology across a variety of organ systems. Another crucial element of CCI is the symptom burden that patients experience which include feelings of dyspnea, difficulty communicating and pain. This patient population necessitates the combined efforts of multiple care teams and the early integration of palliative and critical care. Future directions need to include improving the symptom management and communication for patients with CCI.

Sepsis at a Safety Net Hospital: Risk Factors Associated With 30-Day Readmission

Background: Sepsis is a leading cause of hospitalization, and subsequent readmissions are frequent and costly. There is an expanding body of literature describing risk factors for readmissions in patients with sepsis. However, there are little data studying medically underserved patients who typically receive their care at a safety net hospital. Methods: In a retrospective cohort study, we evaluated 1355 sepsis survivors at risk of hospital readmission in fiscal year 2013 at a safety net hospital. We described patient characteristics during their initial and readmission hospitalizations and analyzed risk factors associated with 30-day readmission. Results: The 30-day readmission rate among sepsis survivors was 22.6%. Comorbid conditions associated with readmissions included end-stage renal disease (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.17-1.36), malignancy (OR, 1.14; 95% CI, 1.08-1.21), and cirrhosis (OR, 1.11; 95% CI, 1.02-1.20). Bacteremia during the initial hospitalization (OR, 1.07; 95% CI, 1.01-1.15) and being discharged with a vascular catheter (OR, 1.10; 95% CI, 1.01-1.20) were associated with readmission. Less severe sepsis during the initial hospitalization was associated with a reduced risk of 30-day readmission (OR, 0.91; 95% CI, 0.87-0.94). Conclusions: At a safety net hospital, patients who survived their initial sepsis hospitalization had a 30-day readmission rate to our institution of 22.6% that is comparable to rates described in prior studies. Readmission was commonly due to infection. Factors associated with readmission included multiple comorbid medical conditions, bacteremia, and being discharged with a vascular catheter. Further studies in this population are needed to determine potential modifiability of these risk factors in an attempt to reduce sepsis readmissions.