Generalized pustular psoriasis in Brazil: A public claims database study.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare and severe phenotype of psoriasis characterized by sudden outbreak of widespread coalescent sterile pustules associated with a spectrum of systemic symptoms. OBJECTIVE: We aimed to describe the epidemiology and treatment of GPP in Brazil from the public health care system perspective. METHODS: This was a retrospective public claims database study, using outpatient and inpatient databases, with information from January 2018 to August 2020, based on records of health resource utilization by patients with GPP. Outpatient treatment regimens and fatal inpatient outcomes were described. RESULTS: In total, 1458 outpatients of all ages were identified, of whom 53% were women. We estimated the GPP prevalence in Brazil to be between 0.7 and 0.9 per 100,000. Acitretin was the most commonly dispensed drug. Of all the outpatients, 769 outpatients could be tracked in the inpatient database, and 151 had hospital admissions during the study period. Of them, 5.3% had a fatal outcome during hospitalization. A primary skin condition or an infection was the most frequent hospitalization cause. LIMITATION: The International Classification of Diseases codes for GPP and psoriasis have not been previously validated in this context. CONCLUSION: GPP is a rare disease in Brazil and affects individuals of all ages and both sexes. Hospitalizations and disease-related deaths highlight the need for its prompt diagnosis, close medical follow-up, and effective treatment.

Custo-efetividade de alteplase no tratamento de acidente vascular cerebral isquêmico até quatro horas e meia após início dos sintomas: perspectiva do Sistema Único de Saúde do Brasil (SUS) / Cost-effectiveness of alteplase for treatment of ischemic stroke up to four and a half hours after the onset of symptoms: a Brazilian Public Health System (SUS) perspective

Objetivo: Analisar o custo-efetividade da trombólise com alteplase no tratamento de acidente vascular isquêmico (AVCi) agudo em até 4,5 horas após início dos sintomas em comparação com tratamento clínico conservador, sob a perspectiva do Sistema Único de Saúde (SUS) no Brasil. Métodos: Construiu-se um modelo de Markov para simular o tratamento de AVCi agudo e suas consequências em curto e longo prazo. Foram conduzidas análises de custo-efetividade (anos de vida ganhos, AVG) e custo-utilidade (anos de vida ajustados pela qualidade de vida, QALY), considerando um horizonte temporal de tempo de vida. Parâmetros de eficácia e segurança foram obtidos em uma metanálise de dados individuais, considerando tratamento em até 3 horas e 3-4,5 horas. Os custos agudos e crônicos foram obtidos por análise secundária de dados de um hospital público brasileiro e expressos em reais (R$). Foram conduzidas análises de sensibilidade determinística e probabilística. Utilizou-se como limiar de disposição a pagar (LDP) 1 PIB (produto interno bruto) per capita para 2019 no Brasil (R$ 31.833,50). Resultados: O tratamento com alteplase vs. conservador resultou em incremento de 0,22 AVG, 0,32 QALY e R$ 4.320,12 em custo, com razão de custo-efetividade incremental (RCEI) estimada em R$ 19.996,43/AVG e R$ 13.383,64/QALY. Ambas as estimativas foram mais sensíveis a variações na efetividade e nos custos de tratamento agudo com alteplase. Para RCEI/AVG e RCEI/QALY, 70,7% e 93,1% das simulações na análise de sensibilidade probabilística estavam abaixo do LDP, respectivamente. Conclusões: O tratamento com alteplase até 4,5 horas após o início dos sintomas tem elevada probabilidade de ser custo-efetivo na perspectiva do SUS.

Objective: To assess the cost-effectiveness of thrombolysis with alteplase for the treatment of acute ischemic stroke up to 4.5 hours after the onset of symptoms as compared to conservative medical treatment from the perspective of the Brazilian Public Health System. Methods: A Markov model was used to simulate the treatment of acute stroke and the associated short- and long-term consequences. Cost-effectiveness (life-years gained, LYG) and cost-utility (quality-adjusted life years, QALY) analyses were performed considering a lifetime horizon. Efficacy and safety parameters were obtained from a meta-analysis of individual data, considering treatment within 3 hours and 3-4.5 hours after the onset of symptoms. Acute and chronic costs were derived from a secondary analysis of data obtained from a Brazilian public hospital and expressed in Brazilian reais (R$). Probabilistic and deterministic sensitivity analyses were performed. The willingness to pay threshold (WPT) was established as 1 GDP per capita for 2019 in Brazil (R$ 31,833.50). Results: Treatment with alteplase vs. conservative medical treatment was associated with an increase of 0.22 in LYG, 0.32 in QALY, and R$ 4,320.12 in cost. The incremental cost-effectiveness ratio (ICER) was estimated as R$ 19,996.43/LYG and R$ 13,383.64/QALY. Variations in effectiveness and costs of acute alteplase treatment had the greatest impact on sensitivity analyses. Considering ICER/LYG and ICER /QALY, 70.7% and 93.1% of the simulations in probabilistic sensitivity analysis were below the WPT, respectively. Conclusions: Treatment with alteplase up to 4.5 hours after the onset of symptoms has a high probability of being cost-effective from the perspective of the Brazilian Public Health System.

Custo-efetividade do afatinibe versus pemetrexede associado a cisplatina, erlotinibe e gefitinibe no tratamento de primeira linha de pacientes com câncer de pulmão não pequenas células localmente avançado ou metastático, com mutação do receptor do fator de crescimento epidermoide (EGFR+), na perspectiva do Sistema de Saúde Suplementar do Brasil / Cost-effectiveness of afatinib versus pemetrexed plus cisplatin, erlotinib and gefitinib as first line treatment in patients with locally advanced or metastatic epidermal growth factor receptor mutation (EFGR+) non-small cell lung cancer in the Brazilian private healthcare system

Objetivo: Comparar os custos e efetividade do afatinibe versus pemetrexede associado a cisplatina (PEM/CIS), erlotinibe e gefitinibe no tratamento de primeira linha de pacientes com câncer de pulmão não pequenas células (CPNPC) com mutação no receptor de fator de crescimento epidermoide (EGFR+) localmente avançado ou metastático, no Sistema de Saúde Suplementar brasileiro. Métodos: O modelo de Markov foi utilizado para estimar anos de vida livres de progressão (PFLY), anos de vida (LY), anos de vida ajustados pela qualidade (QALY) e desfechos clínicos por sete anos. Utilizaram-se dados de sobrevida, segurança e utilidade dos estudos LUX-Lung 1, 3 e 6 e LUCEOR. A eficácia comparativa versus gefitinibe e erlotinibe foi estimada utilizando modelos bayesianos de comparação indireta. A utilização dos recursos foi estimada por painel de especialistas, e custos diretos foram estimados utilizando-se bases de dados oficiais. Resultados: Afatinibe mostrou aumento da sobrevida livre de progressão (0,41 PFLY), sobrevida global (0,16 LY) e qualidade de vida (0,21 QALY) com custo incremental (R$ 8.549), resultando em razão de custo-efetividade incremental (RCEI) de R$ 20.639/PFLY. Comparado ao erlotinibe, o afatinibe mostrou aumento de 0,46 PFLY, 0,13 LY e 0,20 QALY, com menor custo (-R$ 21.327). Comparado ao gefitinibe, o afatinibe mostrou incrementos de 0,53 PFLY, 0,37 LY, 0,34 QALY, com custo incremental de R$ 24.890, resultando em RCEI de R$ 46.709/PFLY. Considerando-se três vezes o PIB per capita como limiar de custo-efetividade (R$ 86.628), o afatinibe é custo-efetivo versus PEM/CIS e gefitinibe e dominante quando comparado ao erlotinibe. Conclusão: Sugere-se que o afatinibe é uma opção custo-efetiva quando comparado ao PEM/CIS, erlotinibe e gefitinibe no tratamento de primeira linha de pacientes com CPNPC EGFR+.

Objective: To compare costs and effectiveness of afatinib versus pemetrexed plus cisplatin (PEM/ CIS), erlotinib and gefitinib, as first line treatment in patients with locally advanced or metastatic epidermal growth factor receptor mutation (EGFR+) non-small cell lung cancer (NSCLC) in the Brazilian Private Healthcare System. Methods: A Markov model was used to estimate 7year progression-free life years (PFLY), life years (LY), quality-adjusted life years (QALY) and clinical outcomes of afatinib. Partitioned survival, safety and utility data from the LUX-Lung 1, 3 and 6 and LUCEOR trials were used. Comparative effectiveness versus gefitinib and erlotinib was estimated using Bayesian indirect treatment comparison. Resource use was estimated by an expert panel and direct costs were estimated from official databases. Results: Compared with PEM/CIS, afatinib was associated with increased progression free survival (0.41 PFLY), increased overall survival (0.16 LY) and increased quality of life (0.21 QALY) with incremental cost (BRL 8,549), resulting in an incremental cost-effectiveness ratio (ICER) of BRL 20.639/PFLY. Compared to erlotinib, afatinib was associated with additional 0.46 PFLY, 0.13 LY and 0.20 QALYs with lower cost (- BRL 21,327). When compared to gefitinib, afatinib was associated with incremental 0.53 PFLY, 0.37 LY and 0.34 QALY and increased cost (BRL 24,890), resulting in an ICER of BRL 46,709/PFLY. Considering 3 PIB per capita as a threshold (BRL 86,628), afatinib is a cost-effective technology versus PEM/CIS and gefitinib and dominant when compared to erlotinib. Conclusion: Findings suggest that afatinib is a cost-effective option, when compared to PEM/CIS, erlotinib and gefitinib, as first line treatment in EGFR+ NSCLC patients.

Nebivolol, a ß1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis.

UNLABELLED: Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. ß-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of ß1-blocker, on PM alterations induced by PD fluids (PDF).In vitro: We found that mesothelial cells (MCs) express ß1-adrenergic receptor. MCs were treated with TGF-ß to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-ß effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels. Moreover, Nebivolol partially inhibited MMT and decreased vascular endothelial growth factor (VEGF) and IL-6 levels in supernatants.In vivo: Twenty-one C57BL/6 mice were divided into 3 groups. Control group carried a catheter without PDF infusion. Study group received intraperitoneally PDF and oral Nebivolol during 30 days. PDF group received PDF alone. Nebivolol maintained the UFC and reduced PM thickness, MMT and angiogenesis promoted by PDF. It also improved the fibrinolytic capacity in PD effluents decreasing PAI-1 and IL-8 and increased tPA levels. CONCLUSION: Nebivolol protects PM from PDF-induced damage, promoting anti-fibrotic, anti-angiogenic, anti-inflammatory and pro-fibrinolytic effects.

Rapamycin Protects from Type-I Peritoneal Membrane Failure Inhibiting the Angiogenesis, Lymphangiogenesis, and Endo-MT.

Preservation of peritoneal membrane (PM) is essential for long-term survival in peritoneal dialysis (PD). Continuous presence of PD fluids (PDF) in the peritoneal cavity generates chronic inflammation and promotes changes of the PM, such as fibrosis, angiogenesis, and lymphangiogenesis. Mesothelial-to-mesenchymal transition (MMT) and endothelial-to-mesenchymal transition (Endo-MT) seem to play a central role in this pathogenesis. We speculated that Rapamycin, a potent immunosuppressor, could be beneficial by regulating blood and lymphatic vessels proliferation. We demonstrate that mice undergoing a combined PD and Rapamycin treatment (PDF + Rapa group) presented a reduced PM thickness and lower number of submesothelial blood and lymphatic vessels, as well as decreased MMT and Endo-MT, comparing with their counterparts exposed to PD alone (PDF group). Peritoneal water transport in the PDF + Rapa group remained at control level, whereas PD effluent levels of VEGF, TGF-ß, and TNF-α were lower than in the PDF group. Moreover, the treatment of mesothelial cells with Rapamycin in vitro significantly decreased VEGF synthesis and selectively inhibited the VEGF-C and VEGF-D release when compared with control cells. Thus, Rapamycin has a protective effect on PM in PD through an antifibrotic and antiproliferative effect on blood and lymphatic vessels. Moreover, it inhibits Endo-MT and, at least partially, MMT.

[Physiology of fluid and solute transport across the peritoneal membrane]. / Fisiologia do transporte de fluidos e solutos atraves da membrana peritoneal.

In this review, phenomena involved in fluid and solute exchange through the peritoneal membrane, both in the physiologic and in the peritoneal dialysis settings, are explained. For that purpose, mathematical models developed for the study of molecule transport through the membrane, such as the "Pore Model" and the "Distributive Model" are used. Scientific accomplishments in the field are described and areas that require additional research are also cited. Knowledge about the physiologic mechanisms involved in this renal replacement therapy modality, concerning events directly related to the peritoneal membrane itself, is synthesized in this manuscript.

Fisiologia do transporte de fluidos e solutos atraves da membrana peritoneal / Physiology of fluid and solute transport across the peritoneal membrane

Nesta revisão, são explicados os fenômenos envolvidos nas trocas de fluidos e solutos através da membrana peritoneal, tanto na situação fisiológica quanto no contexto da diálise peritoneal. Para tanto, são utilizados os modelos matemáticos desenvolvidos para estudo do transporte pela membrana, tais como o "Modelo de Poros" e o "Modelo Distributivo". Os ganhos científicos com as pesquisas nesse campo são contemplados e as áreas que merecem pesquisas adicionais também são citadas. Assim, o estado atual do conhecimento fisiológico a respeito dessa modalidade de terapia renal substitutiva, no que se refere aos eventos relacionados à membrana peritoneal, encontra-se sintetizado nesse manuscrito.

In this review, phenomena involved in fluid and solute exchange through the peritoneal membrane, both in the physiologic and in the peritoneal dialysis settings, are explained. For that purpose, mathematical models developed for the study of molecule transport through the membrane, such as the "Pore Model" and the "Distributive Model" are used. Scientific accomplishments in the field are described and areas that require additional research are also cited. Knowledge about the physiologic mechanisms involved in this renal replacement therapy modality, concerning events directly related to the peritoneal membrane itself, is synthesized in this manuscript.

Protective measures against ultrafiltration failure in peritoneal dialysis patients.

Ultrafiltration failure in patients undergoing peritoneal dialysis is a condition with an incidence that increases over time. It is related to increased cardiovascular morbidity and mortality and is a major cause of the abandonment of the treatment technique. Because the number of patients undergoing renal replacement therapy is increasing with society aging and because approximately 10% of this population is treated with peritoneal dialysis, this matter is becoming more common in everyday practice for clinicians involved in the care of patients with chronic renal failure. In this review, we summarize the available measures used to prevent and treat ultrafiltration failure and the current state of research in the field, both in the experimental and clinical settings, focusing on the possible clinical applications of recent findings.

Protective measures against ultrafiltration failure in peritoneal dialysis patients

Ultrafiltration failure in patients undergoing peritoneal dialysis is a condition with an incidence that increases over time. It is related to increased cardiovascular morbidity and mortality and is a major cause of the abandonment of the treatment technique. Because the number of patients undergoing renal replacement therapy is increasing with society aging and because approximately 10 percent of this population is treated with peritoneal dialysis, this matter is becoming more common in everyday practice for clinicians involved in the care of patients with chronic renal failure. In this review, we summarize the available measures used to prevent and treat ultrafiltration failure and the current state of research in the field, both in the experimental and clinical settings, focusing on the possible clinical applications of recent findings.

Hypercalcemia and suppressed PTH levels in a renal transplant patient infected with Pneumocystis carinii.

Pneumocystis carinii pneumonia is a serious and relatively common complication of immunosuppressive therapy. In immunocompromised patients, P. carinii pneumonia can cause significant morbidity and mortality. Another common complication, typically seen in the subpopulation of renal transplant recipients, is hypercalcemia. The prevalence of hypercalcemia varies, reaching as high as 71%. We report the case of a renal transplant recipient who developed P. carinii pneumonia and hypercalcemia, the latter being resolved after the successful treatment of the former. We argue that there is a causal relationship between P. carinii pneumonia and hypercalcemia in renal transplant recipients. In immunocompromised patients, pulmonary infection accompanied by hypercalcemia should raise the suspicion of P. carinii pneumonia.