Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus.

BACKGROUND: Oral treprostinil is a prostacyclin analogue approved to treat pulmonary arterial hypertension (PAH) by delaying disease progression and improving exercise capacity. Higher doses of oral treprostinil correlate with increased treatment benefit. Titrations may be challenging due to common side effects of prostacyclin-class therapies. STUDY DESIGN AND METHODS: The multicenter, prospective, real-world, observational ADAPT Registry study followed adult patients with PAH for up to 78 weeks after initiating oral treprostinil (NCT03045029). Dosing, titration, and transitions of oral treprostinil were at the discretion of the prescriber. Patient-reported incidence and treatment of common side effects were collected to understand side effect management and tolerability. Insights from literature and expert recommendations were added to provide a consolidated resource for oral treprostinil use. RESULTS: In total, 139 participants in ADAPT completed ≥1 weekly survey; (median age 60.0 years, 76 % female). Median treatment duration of oral treprostinil was 13.1 months. During early therapy (Months 1-5), 62 % (78/126) of patients reported headache and diarrhea, and 40 % (50/126) reported nausea. At Month 6, many patients who reported side effects during early therapy reported an improvement (61 % headache, 44 % diarrhea, 70 % nausea). Common side effect treatments, including acetaminophen, loperamide, and ondansetron, were effective. Approximately one-quarter of patients reporting the most common side effects were untreated at Month 6. CONCLUSION: Patient selection for, and initiation and titration of, oral treprostinil should be individualized and may include parenteral treprostinil induction-transition for faster titration. Assertive side effect management may help patients reach higher and more efficacious doses of oral treprostinil.

Why Living with Pulmonary Arterial Hypertension Requires a Holistic Approach: A Patient and Clinician Perspective.

Pulmonary arterial hypertension (PAH) is a rare disease caused by high pressure in the blood vessels leading from the heart to the lung. PAH affects many parts of a patient's life, which means that patients should be managed by a clinical team of different specialists, including doctors, advance practice providers, nurses, social workers, and therapists. This article is co-authored by a patient living with PAH and an acute care nurse practitioner specializing in the management of patients with pulmonary hypertension. In the first section of this commentary, the patient describes her experience of living with PAH. The specialist nurse practitioner then discusses the management of PAH, to provide a clinician perspective in the context of the patient's experiences.

This article describes the experience of a young patient with pulmonary arterial hypertension, or PAH, as well as the point of view of a PAH specialist nurse practitioner. PAH is a rare disease caused by high pressure in the blood vessels leading from the heart to the lung. This means the right side of the heart needs to work harder to pump blood through the lungs, which can make it weaker and eventually cause right heart failure and death. Although PAH cannot be cured and gets worse over time, effective treatment can delay worsening, reduce symptoms, and improve quality of life. Recognizing symptoms and diagnosing PAH early is important so that patients can be referred to specialists who understand PAH and can provide the most appropriate treatment. A patient's risk status shows the chance of the disease getting worse and the patient dying. The aim is to treat patients so that they stay low risk and improve their chance of living longer. Clinical guidelines give specialists advice on treating patients with PAH and say that regular risk assessment is important to guide treatment decisions. Because PAH affects many parts of a patient's life, the guidelines also say that patients should be managed by a clinical team of different specialists including doctors, advance practice providers, nurses, social workers, and therapists. Making sure that patients and carers understand PAH and the benefit of treatment is also important to help patients follow their treatment plan and actively help to manage their disease.

Clinical application of risk assessment in PAH: Expert center APRN recommendations.

Performing longitudinal and consistent risk assessments for patients with pulmonary arterial hypertension (PAH) is important to help guide treatment decisions to achieve early on and maintain a low-risk status and improve patient morbidity and mortality. Clinical gestalt or expert perception alone may over or underestimate a patient's risk status. Indeed, regular and continued use of validated risk assessment tools more accurately predict patients' survival. Effective PAH risk assessments are often underutilized even though many seasoned clinicians will attest to using these tools routinely. We present recommendations based on real-world experience in varied clinical practice settings around the United States for overcoming barriers to facilitate regular, serial formal risk assessment. Expert advanced practice provider clinicians from mid to large-size medical centers collaborated to formulate recommendations based on multiple discourses and discussions. Enlisting the help of support staff, such as medical assistants and nurses, to fill in available risk parameters in risk assessment tools can save time for providers and increase efficiency, as can technology-based solutions such as integrating risk assessments into electronic medical records. Modified, abbreviated risk assessment tools can be applied to a patient's clinical scenario when all of a patient's data are not available to complete a more comprehensive assessment. Initial discussions regarding the overall meaning and prognostic importance of risk scores may assist patients to take on a more active role in terms of informed decision-making regarding their care. A collaborative approach can help clinics establish consistent use of risk assessment.

An expert panel Delphi consensus statement on the use of palliative care in the management of patients with pulmonary arterial hypertension.

Mortality in pulmonary arterial hypertension (PAH) remains high and referral to palliative or supportive care (P/SC) specialist services is recommended when appropriate. However, access to P/SC is frequently a challenge for patients with a noncancer diagnosis and few patients living with PAH report P/SC involvement in their care. A modified Delphi process of three questionnaires completed by a multidisciplinary panel (N = 15) was used to develop expert consensus statements regarding the use of P/SC to support patients with PAH. Panelists rated their agreement with each statement on a Likert scale. There was a strong consensus that patients should be referred to P/SC when disease symptoms become unmanageable or for end-of-life care. Services that achieved consensus were pain management techniques, end-of-life care, and psychosocial recommendations. Palliative or supportive care should be discussed with patients, preferably in-person, when disease symptoms become unmanageable, when starting treatment, when treatment-related adverse events occur or become refractory to initial intervention. Care partners and patient support groups were considered important in improving a patient's overall health outcomes, treatment adherence, and perception of care. Most patients with PAH experience cognitive and/or psychosocial changes and those who receive psychosocial management have better persistence and/or compliance with their treatment. These consensus statements provide guidance to healthcare providers on the "who and when" of referral to palliative care services, as well as the importance of focusing on the psychosocial aspects of patient care and quality of life.

Current clinical utilization of risk assessment tools in pulmonary arterial hypertension: a descriptive survey of facilitation strategies, patterns, and barriers to use in the United States.

Practice guidelines suggest that treatment decisions in pulmonary arterial hypertension be informed by periodic assessment of patients' clinical risk. Several tools, well validated for risk discrimination, such as the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management calculator, were developed to assess pulmonary arterial hypertension patients' risk of death based on multiple parameters, including functional class, hemodynamics, biomarkers, comorbidities, and exercise capacity. Using an online survey, we investigated the use of risk assessment tools by pulmonary hypertension healthcare providers in the United States. Of 121 survey respondents who make treatment decisions, 59% reported using risk assessment tools. The use of these tools was lower for non-physicians (48% vs. 65% physicians) and for practitioners at centers with 1 to 100 pulmonary arterial hypertension patients compared with centers with >100 patients (47% vs. 64%). Risk was most frequently assessed by decision makers at the time of diagnosis (cited by 54%) and at the time of worsening symptoms (cited by 42%), suggesting that use of pulmonary arterial hypertension risk assessment tools remains low. In our survey, non-physicians compared with physicians cited two major barriers to increased tool use: lack of education and training (20% vs. 4%) and lack of clarity on the best tool to use (30% vs. 18%). Information technology tools, such as electronic medical record integration and web or phone-based risk calculating applications, were cited most frequently as ways to increase the use of risk assessment tools.

Development of droplet digital PCR for the detection of Babesia microti and Babesia duncani.

Babesia spp. are obligate protozoan parasites of red blood cells. Transmission to humans occurs through bites from infected ticks or blood transfusion. Infections with B. microti account for the majority of the reported cases of human babesiosis in the USA. A lower incidence is caused by the more recently described species B. duncani. The current gold standard for detection of Babesia is microscopic examination of blood smears. Recent PCR-based assays, including real-time PCR, have been developed for B. microti. On the other hand, molecular assays that detect and distinguish between B. microti and B. duncani infections are lacking. Closely related species of Babesia can be differentiated due to sequence variation within the internal transcribed spacer (ITS) regions of nuclear ribosomal RNAs. In the present study, we targeted the ITS regions of B. microti and B. duncani to develop sensitive and species-specific droplet digital PCR (ddPCR) assays. The assays were shown to discriminate B. microti from B. duncani and resulted in limits of detection of ~10 gene copies. Moreover, ddPCR for these species were useful in DNA extracted from blood of experimentally infected hamsters, detecting infections of low parasitemia that were negative by microscopic examination. In summary, we have developed sensitive and specific quantitative ddPCR assays for the detection of B. microti and B. duncani in blood. Our methods could be used as sensitive approaches to monitor the progression of parasitemia in rodent models of infection as well as serve as suitable molecular tests in blood screening.