Cost effectiveness of first-line oral therapies for pulmonary arterial hypertension: A modelling study

Background: In recent years, a significant number of costly oral therapies have become available for the treatment of pulmonary arterial hypertension (PAH). Funding decisions for these therapies requires weighing up their effectiveness and costs. Objective: The aim of this study was to assess the cost effectiveness of monotherapy with oral PAH-specific therapies versus supportive care as initial therapy for patients with functional class (FC) II and III PAH in Canada. Methods: A cost-utility analysis, from the perspective of a healthcare system and based on a Markov model, was designed to estimate the costs and quality-adjusted life-years (QALYs) associated with bosentan, ambrisentan, riociguat, tadalafil, sildenafil and supportive care for PAH in treatment-naïve patients. Separate analyses were conducted for cohorts of patients commencing therapy at FC II and III PAH. Transition probabilities, based on the relative risk of improving and worsening in FC with treatment versus placebo, were derived from a recent network meta-analysis. Utility values and costs were obtained from published data and clinical expert opinion. Extensive sensitivity analyses were conducted. Results: Analysis suggests that sildenafil is the most cost-effective therapy for PAH in patients with FC II or III. Sildenafil was both the least costly and most effective therapy, thereby dominating all other treatments. Tadalafil was also less costly and more effective than supportive care in FC II and III; however, sildenafil was dominant over tadalafil. Even given the uncertainty within the clinical inputs, the probabilistic sensitivity analysis showed that apart from sildenafil and tadalafil, the other PAH therapies had negligible probability of being the most cost effective. Conclusion: The results show that initiation of therapy with sildenafil is likely the most cost-effective strategy in PAH patients with either FC II or III disease.This research was supported by funds from the Canadian Agency for Drugs and Technologies in Health (CADTH)

Differential expression and properties of mammalian CAP and CAP2

Bibliography: p. 47-53

Diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin: a systematic review and meta-analysis

Background: Several studies have been published in the literature on the diagnostic accuracy of NT-pro-BNP for pleural effusions from heart failure in the last decade. The purpose of our study was to perform a systematic review and meta-analysis on the diagnostic accuracy of pleural fluid NT-pro-BNP for pleural effusions of cardiac origin. Methods: MEDLINE, EMBASE, PapersFirst, and the Cochrane collaboration and the Cochrane Register of controlled trials were searched. All searches were inclusive as of March 2010. Studies were only included if the absolute number of true-positive, false-negative, true-negative, and false-positive observations were available, and the "reference standards" were described clearly. Two investigators independently reviewed articles and extracted data. Quality was assessed with the Quality Assessment for Diagnostic Accuracy Studies (QUADAS). The bivariate model for diagnostic meta-analysis was used to obtain a pooled sensitivity and a pooled specificity. Results: Ten studies (total number of patients 1120) were included in the meta-analysis. The average pleural fluid NT-pro-BNP level in effusions of cardiac origin was 6140 pg/mL. The pooled sensitivity and specificity of all studies combined was 94% (95% CI: 90-97) and 94% (95% CI: 89-97) respectively. The pooled positive likelihood ratio was 15.2 (95% CI: 8.1-28.7) and the pooled negative likelihood ratio was 0.06 (95% CI: 0.03-0.11). The area under the ROC curve was 0.98 (95% CI: 0.96-0.99) and the diagnostic odds ratio was 246 (95% CI: 81-745). Conclusions: Pleural fluid NT-pro-BNP is a very useful biomarker with high diagnostic accuracy for distinguishing pleural effusions of cardiac origin.Medicine, Department ofMedicine, Faculty ofRespiratory Medicine, Division ofReviewedFacult

Clinical manifestations and diagnostic methods in pulmonary angiosarcoma: protocol for a scoping review

Background: Angiosarcoma involving the lung can represent either primary or metastatic malignancy. Due to the rarity of this condition, knowledge surrounding the natural history and clinical presentation is scarce. The aim of this scoping review is to summarize the existing literature on pulmonary angiosarcoma, particularly as it pertains to the clinical presentation and ancillary tests used for diagnosis in addition to histopathology. Methods We will conduct a systematic search using Ovid MEDLINE and EMBASE electronic databases. Two investigators will independently screen identified titles and abstracts to select articles reporting on pulmonary angiosarcoma. The data will be summarized in a narrative fashion and organized according to aspects of epidemiology, risk factors, clinical presentation, diagnostic methods, and treatment. Discussion Scoping reviews are increasingly used to synthesize the evidence on a particular topic, to identify gaps in the literature, and to determine if future systematic reviews are feasible. In order to improve the care of patients with angiosarcoma, earlier recognition and diagnosis is required. This review will be valuable for highlighting the range of clinical presentations and the role of imaging and other diagnostic tools in the diagnosis of metastatic and primary pulmonary angiosarcoma. Systematic review registration PROSPERO registration: CRD42017059052Medicine, Faculty ofOther UBCNon UBCMedicine, Department ofReviewedFacult

Isolated native tricuspid valve endocarditis caused by viridans streptococcus

The present report describes a case of native tricuspid valve endocarditis caused by viridans group streptococcus in a 43-year-old man who had recently undergone dental extraction. The patient had no history of intravenous drug use, heart disease or right heart catheterization. Although there have been scattered reports of unusual organisms, to the authors' knowledge, this is the first case of viridans group streptococcal endocarditis involving only the tricuspid valve after dental manipulation

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: General management for pulmonary hypertension

Treatment of pulmonary hypertension (PH) patients is challenging and should only be initiated after a comprehensive diagnostic evaluation. Such treatment should ideally be done in specialized centers with full capability for hemodynamic measurements, having access to a broad range of PAH therapies, and adequate experience in the management of critically ill patients. The following discussion is intended to review the general measures and the non-specific (supportive) therapy used in managing PH patients, while the specific therapy will be discussed in a subsequent different article

Factors that prognosticate mortality in idiopathic pulmonary arterial hypertension: A systematic review of the literature

SummaryRationaleThere is a lack of consensus on factors that predict mortality in idiopathic pulmonary arterial hypertension (IPAH). Tests that can accurately predict prognosis are needed to guide treatment and counsel patients.MethodsWe conducted a systematic review to identify factors that prognosticate mortality in IPAH. Study design, cohort size, comparison method, measured value, and statistical significance was extracted for eight pre-selected parameters [pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (mPAP), mean right atrial pressure (mRAP), cardiac output, right ventricular end diastolic pressure, functional class, 6 min walk distance (6MWD), and diffusing capacity of carbon monoxide].Results107 factors have been associated with mortality in IPAH. A reproducible predictive association with mortality was demonstrated for only 10 factors: functional class (14 studies), heart rate (10 studies), 6MWD (8 studies), pericardial effusion (5 studies), mPAP (10 studies), mRAP (17 studies), cardiac index (13 studies), stroke volume index (4 studies), PVR (10 studies), mixed venous PaO2 or saturations (4 studies). Of the 8 factors chosen for detailed evaluation, there were at least half as many studies that evaluated the variable and did not find an association with mortality compared to those that did.ConclusionsThere is a large body of literature describing numerous factors that predict mortality in IPAH. Most factors have been assessed in very few studies. There are conflicting reports on the prognostic value of many factors. These discrepancies highlight the need to evaluate the literature in total when considering the utility of variables as prognostic factors in IPAH