Advancing hospital-based health technology assessment: evaluating genomic panel contracting strategies for blood tumors through a multimethodology.

INTRODUCTION: The adoption of genomic technologies in the context of hospital-based health technology assessment presents multiple practical and organizational challenges. OBJECTIVE: This study aimed to assist the Instituto Português de Oncologia de Lisboa Francisco Gentil (IPO Lisboa) decision makers in analyzing which acute myeloid leukemia (AML) genomic panel contracting strategies had the highest value-for-money. METHODS: A tailored, three-step approach was developed, which included: mapping clinical pathways of AML patients, building a multicriteria value model using the MACBETH approach to evaluate each genomic testing contracting strategy, and estimating the cost of each strategy through Monte Carlo simulation modeling. The value-for-money of three contracting strategies - "Standard of care (S1)," "FoundationOne Heme test (S2)," and "New diagnostic test infrastructure (S3)" - was then analyzed through strategy landscape and value-for-money graphs. RESULTS: Implementing a larger gene panel (S2) and investing in a new diagnostic test infrastructure (S3) were shown to generate extra value, but also to entail extra costs in comparison with the standard of care, with the extra value being explained by making available additional genetic information that enables more personalized treatment and patient monitoring (S2 and S3), access to a broader range of clinical trials (S2), and more complete databases to potentiate research (S3). CONCLUSION: The proposed multimethodology provided IPO Lisboa decision makers with comprehensive and insightful information regarding each strategy's value-for-money, enabling an informed discussion on whether to move from the current Strategy S1 to other competing strategies.

Reversible contrast-induced encephalopathy after coil embolization of epistaxis. / Encefalopatia reversível induzida por contraste após embolização com espiras por epistaxe.

A 37-year-old woman (35 weeks pregnant) was admitted to a local hospital due to severe epistaxis resulting in shock and the need for emergency cesarean section. After failure to tamponade the bleeding, angiographic treatment was provided. After the procedure, she was admitted to the neurocritical intensive care unit and was confused and agitated, requiring sedation and endotracheal intubation. In the intensive care unit, diagnostic investigations included brain magnetic resonance imaging, lumbar puncture with viral panel, electroencephalogram, tests for autoimmunity, and hydroelectrolytic and metabolic evaluations. Magnetic resonance imaging showed a puntiform restricted diffusion area on the left corona radiata on diffusion weighted imaging and mild cortical posterior edema (without restricted diffusion), and an electroencephalogram showed moderate diffuse slow activity and fronto-temporal slow activity of the left hemisphere with associated scarce paroxysmal components. The other exams did not show any relevant alterations. Due to the temporal relationship, the clinical history and the magnetic resonance imaging results, a diagnosis of contrast-induced encephalopathy was made. After 2 days in the intensive care unit, sedation was withdrawn, the patient was extubated, and total neurological recovery was verified within the next 24 hours.

Uma mulher com 37 anos de idade, gestante de 35 semanas, foi admitida em um hospital local em razão de epistaxe grave, que resultou em choque e em necessidade de realização de cesárea emergencial. Após falha do tamponamento para controlar a hemorragia, decidiu-se por tratamento angiográfico. Após o procedimento, ela foi admitida à unidade de terapia intensiva neurocrítica, encontrando-se confusa e agitada, com necessidade de sedação e intubação orotraqueal. Na unidade de terapia intensiva, as investigações incluíram exames de ressonância magnética, punção lombar com painel viral, eletroencefalograma, testes para autoimunidade e avaliações hidroeletrolítica e metabólica. O exame de ressonância magnética mostrou área puntiforme restrita na corona radiata esquerda nas sequências de imagens pesadas em difusão, além de leve edema cortical posterior (sem restrição à difusão), e o eletroencefalograma mostrou atividade lenta difusa moderada, atividade frontoparietal lenta e escassos componentes paroxísticos associados no hemisfério esquerdo. Outros exames não mostraram alterações relevantes. Por causa da relação temporal e da história clínica, assim como imagens de ressonância magnética, formulou-se o diagnóstico de encefalopatia induzida por contraste. A sedação foi retirada após 2 dias na unidade de terapia intensiva, e a paciente foi extubada, verificando-se completa recuperação neurológica dentro das 24 horas seguintes.

Encefalopatia reversível induzida por contraste após embolização com espiras por epistaxe / Reversible contrast-induced encephalopathy after coil embolization of epistaxis

RESUMO Uma mulher com 37 anos de idade, gestante de 35 semanas, foi admitida em um hospital local em razão de epistaxe grave, que resultou em choque e em necessidade de realização de cesárea emergencial. Após falha do tamponamento para controlar a hemorragia, decidiu-se por tratamento angiográfico. Após o procedimento, ela foi admitida à unidade de terapia intensiva neurocrítica, encontrando-se confusa e agitada, com necessidade de sedação e intubação orotraqueal. Na unidade de terapia intensiva, as investigações incluíram exames de ressonância magnética, punção lombar com painel viral, eletroencefalograma, testes para autoimunidade e avaliações hidroeletrolítica e metabólica. O exame de ressonância magnética mostrou área puntiforme restrita na corona radiata esquerda nas sequências de imagens pesadas em difusão, além de leve edema cortical posterior (sem restrição à difusão), e o eletroencefalograma mostrou atividade lenta difusa moderada, atividade frontoparietal lenta e escassos componentes paroxísticos associados no hemisfério esquerdo. Outros exames não mostraram alterações relevantes. Por causa da relação temporal e da história clínica, assim como imagens de ressonância magnética, formulou-se o diagnóstico de encefalopatia induzida por contraste. A sedação foi retirada após 2 dias na unidade de terapia intensiva, e a paciente foi extubada, verificando-se completa recuperação neurológica dentro das 24 horas seguintes.

ABSTRACT A 37-year-old woman (35 weeks pregnant) was admitted to a local hospital due to severe epistaxis resulting in shock and the need for emergency cesarean section. After failure to tamponade the bleeding, angiographic treatment was provided. After the procedure, she was admitted to the neurocritical intensive care unit and was confused and agitated, requiring sedation and endotracheal intubation. In the intensive care unit, diagnostic investigations included brain magnetic resonance imaging, lumbar puncture with viral panel, electroencephalogram, tests for autoimmunity, and hydroelectrolytic and metabolic evaluations. Magnetic resonance imaging showed a puntiform restricted diffusion area on the left corona radiata on diffusion weighted imaging and mild cortical posterior edema (without restricted diffusion), and an electroencephalogram showed moderate diffuse slow activity and fronto-temporal slow activity of the left hemisphere with associated scarce paroxysmal components. The other exams did not show any relevant alterations. Due to the temporal relationship, the clinical history and the magnetic resonance imaging results, a diagnosis of contrast-induced encephalopathy was made. After 2 days in the intensive care unit, sedation was withdrawn, the patient was extubated, and total neurological recovery was verified within the next 24 hours.

Experimental protoporphyria: effect of bile acids on liver damage induced by griseofulvin.

The effect of bile acids administration to an experimental mice model of Protoporphyria produced by griseofulvin (Gris) was investigated. The aim was to assess whether porphyrin excretion could be accelerated by bile acids treatment in an attempt to diminish liver damage induced by Gris. Liver damage markers, heme metabolism, and oxidative stress parameters were analyzed in mice treated with Gris and deoxycholic (DXA), dehydrocholic (DHA), chenodeoxycholic, or ursodeoxycholic (URSO). The administration of Gris alone increased the activities of glutathione reductase (GRed), superoxide dismutase (SOD), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), and glutathione-S-transferase (GST), as well as total porphyrins, glutathione (GSH), and cytochrome P450 (CYP) levels in liver. Among the bile acids studied, DXA and DHA increased PROTO IX excretion, DXA also abolished the action of Gris, reducing lipid peroxidation and hepatic GSH and CYP levels, and the activities of GGT, AP, SOD, and GST returned to control values. However, porphyrin accumulation was not prevented by URSO; instead this bile acid reduced ALA-S and the antioxidant defense enzymes system activities. In conclusion, we postulate that DXA acid would be more effective to prevent liver damage induced by Gris.

Ethical, legal and organizational issues in the ICU: prediction of outcome.

PURPOSE OF REVIEW: Since the development of the first general outcome prediction models, these instruments have been widely used in the intensive care unit. Last updated in the early 1990s, these models are now severely outdated. RECENT FINDINGS: In recent months, researchers and users assisted in several attempts at improving the existing models through customization or expansion or in the development of new models, such as the Simplified Acute Physiology Score (SAPS) 3 and the Acute Physiology and Chronic Health Evaluation (APACHE) IV. SUMMARY: Although not similar, especially in the choice of the reference population, these models aim at replacing older general outcome models, the predictions from which no longer reflect the current case-mix outcomes of intensive care. The objective of this review is to present and discuss, to the clinician working in the intensive care unit, these different strategies and to give an updated version of the general outcome prediction models available in 2006.

Incidence of sepsis in hospitalized patients.

In recent years, several epidemiological studies have helped expand our knowledge of the incidence of sepsis at the intensive care unit (ICU) and population levels. However, more data are needed from developing countries. Overall, even with a lack of standardized definitions--particularly of sepsis-associated organ dysfunction, hypoperfusion or hypotension, and septic-induced cardiovascular failure despite adequate fluid resuscitation--the incidence of sepsis seems higher in Brazil, the United Kingdom, and Portugal. In the future, in order to better identify patients that need early ICU admission, aggressive care, and new therapies, we must develop and apply better instruments for definition and risk stratification, especially for evaluating the risk of progressing from sepsis to severe sepsis and septic shock.