A narrative review and expert recommendations on the assessment of the clinical manifestations, follow-up, and management of post-OLT patients with ATTRv amyloidosis.

Orthotopic liver transplantation (OLT) was the first treatment able to modify the natural course of hereditary transthyretin (ATTRv) amyloidosis, which is a rare and fatal disorder caused by the accumulation of misfolded transthyretin (TTR) variants in different organs and tissues and which leads to a progressive and multisystem dysfunction. Because the liver is the main source of TTR, OLT dramatically reduces the production of the pathogenic TTR variant, which should prevent amyloid formation and halt disease progression. However, amyloidosis progression may occur after OLT due to wild-type TTR deposition, especially in the nerves and heart. In this review, we discuss the disease features influencing OLT outcomes and the clinical manifestations of ATTRv amyloidosis progression post-OLT to improve our understanding of disease worsening after OLT and optimize the follow-up and clinical management of these patients. By conducting a literature review on the PubMed database, we identified patient characteristics that have been associated with worse post-OLT outcomes, including late-onset V50M and non-V50M variants, age >40 years, long disease duration, advanced neuropathy and autonomic dysfunction, and malnutrition. Regarding post-OLT mortality, deaths occurring within the first year after OLT were mainly associated with fatal graft complications and infectious diseases, whereas cardiovascular-related deaths usually occurred later. Considering the diverse clinical manifestations of ATTRv amyloidosis progression post-OLT, including worsening neuropathy and/or cardiomyopathy, autonomic dysfunction, and oculoleptomeningeal involvement, we present advice on the most relevant tests for assessing disease progression post-OLT. Finally, we discuss the use of new therapies based on TTR stabilizers and TTR mRNA silencers for the treatment of ATTRv amyloidosis patients post-OLT.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Availability and characteristics of cardiovascular rehabilitation programs in South America.

PURPOSE: Cardiac rehabilitation (CR) programs decrease morbidity and mortality rates in patients with coronary artery disease, the leading cause of death in Latin America. This study was carried out to assess the characteristics and current level of CR program implementation in South America. METHODS: We carried out a survey of CR programs that were identified using the directory of the South American Society of Cardiology and through an exhaustive search by the investigators. RESULTS: We identified 160 CR programs in 9 of the 10 countries represented in the South American Society of Cardiology and 116 of those responded to our survey. On the basis of survey results from the responding programs, we estimate that the availability of CR programs in South America is extremely low, approximately 1 CR program for every 2 319 312 inhabitants. These CR programs provided services to a median of 180 patients per year (interquartile range, 60-400) and were most commonly led by cardiologists (84%) and physical therapists (72%). Phases I, II, III, and IV CR were offered in 49%, 91%, 89%, and 56% of the centers, respectively. The most commonly perceived barrier to participation in a CR program was lack of referral from the cardiologist or primary care physician, as reported by 70% of the CR program directors. CONCLUSIONS: The number of CR programs in South America appears to be insufficient for a population with a high and growing burden of cardiovascular disease. In addition, there appears to be a significant need for standardization of CR program components and services in the region.

[Assessment of venous thromboembolism risk in hospitalized medical patients. Concordance between PRETEMED guide and the recommendations of the viii conference of the American College of Chest Physicians]. / Riesgo de enfermedad tromboembólica venosa en pacientes hospitalizados no quirúrgicos. Grado de acuerdo entre la guía PRETEMED y las recomendaciones de la viii conferencia del American College of Chest Physicians.

BACKGROUND AND OBJECTIVE: The aim of this study is to evaluate the use of venous thromboembolism prophylaxis in hospitalized medical patients using 2 clinical practice guidelines and to analyze the agreement between them. PATIENTS AND METHODS: Cross-sectional study of medical services in a third level hospital. We calculated the thromboembolic risk and the thromboprophylaxis adequacy by implementing the recommendations of viii conference of the American College of Chest Physicians (ACCP) and PRETEMED guide as well as their agreement. RESULTS: One hundred and twenty eight patients were included in the study. According to the PRETEMED guide, 34.4% of patients were low risk, 6.3% moderate and 59.4% high, with appropriate prophylaxis in 72.7% of patients (CI95%: 64.4-79.9), 18.8% (CI95%: 12.7-26.2) were undertreated and 8.6% (CI95%: 4.6-14.4) overtreated. According to ACCP recommendations, 50% of patients were low risk and 50% high, with appropriate prophylaxis in 74.2% of patients (CI95%: 66.1-81.2), 10.9% (CI95%: 6.4-17.3) were undertreated and 14.8% (CI95%: 9.4-21.8) overtreated. When PRETEMED risk was classified into low or moderate-high group versus ACCP risk low or high, the grade of concordance between both guides was 0.68 (CI95%: 0.56-0.81). When PRETEMED risk was classified into low-moderate or high group versus ACCP risk low or high, the grade of concordance between both guides was 0.81 (CI95%: 0.71-0.91). CONCLUSIONS: About a quarter of hospitalized medical patients did not receive adequate prophylaxis, showing an important room for improvement. PRETEMED guide and ACCP recommendations differ in risk assessment mainly because PRETEMED guide overestimates the risk of venous thromboembolism since it includes more risk factors.