A modeling and simulation-based assessment of the impact of confounding factors on the readout of a sildenafil survival trial in pulmonary arterial hypertension
AbstractSildenafil (REVATIO®) was approved for the treatment of adult Pulmonary Arterial Hypertension (PAH) in the US and the EU. A pediatric study has been performed and sildenafil was approved in the EU for pediatric PAH. The long-term extension of this study revealed good survival but also an increased mortality with the high dose of sildenafil compared to lower doses. As a consequence, FDA required Pfizer to evaluate REVATIO®’s effect on the risk of death in adults with PAH. Following FDA’s rationale a survival model was developed to characterize the exposure–mortality relationship and assess its potential impact on an ongoing survival trial in adults in the context of confounding factors. Clinical trial simulatio ns were performed to assess the design of the survival trial in adults (AFFILIATE, NCT02060487), expected to last approximately 8 years according to both assumptions: absence or presence of an exposure–mortality relationship and to quantify the impact of confounding factors on its readout. Simulat ions showed that the trial would be robust in most conditions. But its interpretation will depend on the number of confounding factors such as additional treatments attempting to control disease progression.Clinical trial identifier NCT00159913 for STARTS-1, NCT00159874 for STARTS-2
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BP control is important for overall health and reduced mortality secondary to cardiovascular disease. Find out how teaching your patients about mindfulness can help.
University of Plymouth researchers have found that a mouthwash made from a material bees use to waterproof their hives could help combat high blood pressure and gum disease.
Publication date: Available online 9 December 2019Source: Biochimica et Biophysica Acta (BBA) - BiomembranesAuthor(s): Sofia Kiriakidi, Christos Chatzigiannis, Christina Papaemmanouil, Andreas G. Tzakos, Thomas MavromoustakosAbstractCardiovascular diseases and hypertension in particular are major health risks worldwide and the improvement on their treatment will be beneficial for the human health. AT1R antagonists belong to the sartans family that targets the renin-angiotensin aldosterone system (RAAS) through blocking the hormone angiotensin II to exert its detrimental effects in pathological states. As a consequence, the...
Conclusion: Our findings revealed that EL significantly reduced blood uric acid levels, prevented pathological changes of kidney in PO induced hyperuricemia animal model, and improved renal urate transports. We partly clarified the mechanism was related to suppressing effect of URAT1 by quassinoid in EL. This study is the first to demonstrate that EL plays a role in hyperuricemia by promoting renal uric acid excretion.
Resumo O aneurisma de art éria poplítea (AAP) é o mais frequente dos aneurismas periféricos, correspondendo a 85% do total de aneurismas. Normalmente, são assintomáticos, e o diagnóstico, em geral, é feito por meio do exame físico, tendo uma maior incidência no sexo masculino e em idosos. São bilaterais em 50% dos casos e, em 60% das vezes, estão associados a aneurisma de aorta abdominal. Apresentamos um paciente do sexo masculino com 72 anos de idade, com duas massas pulsáteis em ambas as regiões poplíteas, assintom&aac...
Publication date: Available online 9 December 2019Source: Canadian Journal of DiabetesAuthor(s): Lingning Huang, Yongze Zhang, Yunmin Wang, Ximei Shen, Sunjie YanAbstractAimsInvestigate association between diabetic peripheral neuropathy (DPN)and above normal blood pressure in non-hypertensive patients with type 2 diabetes mellitus(T2DM). Compare the achievement of clinical target for DPN and non-DPN withT2DM .MethodsA retrospective survey was administered to 3810 patients with type 2 diabetes. Cases were grouped according to the Toronto Clinical Scoring System (TCSS): Non-DPN, Mild DPN, Moderate DPN and Severe DPN. 1835 pa...
Conditions: Liver Cirrhoses; Portal Hypertension Interventions: Diagnostic Test: Esophagogastroduodenoscopy; Diagnostic Test: Endoscopic ultrasound Sponsor: Instituto Ecuatoriano de Enfermedades Digestivas Recruiting
Condition: Fatty Liver Disease Intervention: Other: A complete cardiovascular and liver characterization will be carried out Sponsors: Instituto de Investigación Marqués de Valdecilla; Hospital Universitario Puerta del Hierro Majadahonda.; Hospital Universitario Ramón y Cajal; Hospital General Universitario Gregorio Marañón Not yet recruiting
Conditions: Hypertension; Heart Failure; Hypertensive Heart Disease; Diastolic Dysfunction Intervention: Sponsor: Karolinska Institutet Enrolling by invitation