RESUMO
AIMS: Diagnosis of idiopathic inflammatory myopathies (IIM) is based on morphological characteristics and the evaluation of disease-related proteins. However, although broadly applied, substantial bias is imposed by the respective methods, observers and individual staining approaches. We aimed to quantify the protein levels of major histocompatibility complex (MHC)-1, (MHC)-2 and intercellular adhesion molecule (ICAM)-1 using an automated morphometric method to mitigate bias. METHODS: Double immunofluorescence staining was performed on whole muscle sections to study differences in protein expression in myofibre and endomysial vessels. We analysed all IIM subtypes including dermatomyositis (DM), anti-synthetase syndrome (ASyS), inclusion body myositis (IBM), immune-mediated-necrotising myopathy (IMNM), dysferlinopathy (DYSF), SARS-CoV-2 infection and vaccination-associated myopathy. Biopsies with neurogenic atrophy (NA) and normal morphology served as controls. Bulk RNA-Sequencing (RNA-Seq) was performed on a subset of samples. RESULTS: Our study highlights the significance of MHC-1, MHC-2 and ICAM-1 in diagnosing IIM subtypes and reveals distinct immunological profiles. RNASeq confirmed the precision of our method and identified specific gene pathways in the disease subtypes. Notably, ASyS, DM and SARS-CoV-2-associated myopathy showed increased ICAM-1 expression in the endomysial capillaries, indicating ICAM-1-associated vascular activation in these conditions. In addition, ICAM-1 showed high discrimination between different subgroups with high sensitivity and specificity. CONCLUSIONS: Automated morphometric analysis provides precise quantitative data on immune-associated proteins that can be integrated into our pathophysiological understanding of IIM. Further, ICAM-1 holds diagnostic value for the detection of IIM pathology.
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Molécula 1 de Adesão Intercelular , Músculo Esquelético , Miosite , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Miosite/patologia , Miosite/diagnóstico , Miosite/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/metabolismo , COVID-19/patologia , COVID-19/diagnóstico , Masculino , Feminino , Diagnóstico Diferencial , Antígenos de Histocompatibilidade Classe II/metabolismoRESUMO
Posterior reversible encephalopathy syndrome (PRES) is an acute neurological condition associated with different etiologies, including antibiotic therapy. To date, most data regarding antibiotic-related PRES are limited to case reports and small case series. Here, we report a novel case description and provide a systematic review of the clinico-radiological characteristics and prognosis of available cases of PRES associated with antibiotic therapy. We performed a systematic literature search in PubMed and Scopus from inception to 10 January 2024, following PRISMA guidelines and a predefined protocol. The database search yielded 12 subjects (including our case). We described the case of a 55-year-old female patient with PRES occurring one day after administration of metronidazole and showing elevated serum neurofilament light chain protein levels and favorable outcome. In our systematic review, antibiotic-associated PRES was more frequent in female patients (83.3%). Metronidazole and fluoroquinolones were the most reported antibiotics (33.3% each). Clinical and radiological features were comparable to those of PRES due to other causes. Regarding the prognosis, about one third of the cases were admitted to the intensive care unit, but almost all subjects (90.0%) had a complete or almost complete clinical and radiological recovery after prompt cessation of the causative drug. Antibiotic-associated PRES appears to share most of the characteristics of classic PRES. Given the overall good prognosis of the disease, it is important to promptly diagnose antibiotic-associated PRES and discontinue the causative drug.
Assuntos
Antibacterianos , Síndrome da Leucoencefalopatia Posterior , Humanos , Síndrome da Leucoencefalopatia Posterior/induzido quimicamente , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Metronidazol/efeitos adversosRESUMO
Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of the thyroid. Selective molecular markers and drivers distinguishing ATC from other thyroid carcinomas of follicular origin remain largely unknown, limiting advances in diagnosis and treatment. In a retrospective study, we analyzed gene expression in 36 ATC, 18 poorly differentiated, 132 papillary, and 55 follicular thyroid carcinoma, as well as 124 paired and unpaired normal thyroid tissues in three independent cohorts by RNA-sequencing and immunohistochemistry. RNA-sequencing data in the test cohort suggested selective ATC protein biomarkers. Evaluation of these revealed that ATCs are characterized by the de novo expression of various testis antigens, including melanoma-associated antigen A3 (MAGEA3), but most importantly the oncofetal IGF2 mRNA binding protein 1 (IGF2BP1). Shallow whole genome sequencing essentially excluded that IGF2BP1 upregulation results from gene copy number alterations. Immunohistochemical analyses in all three tumor cohorts confirmed the selective de novo expression of IGF2BP1 protein in ATC. In sum, 75% (27/36) of all tested ATC and 0.5% (1/204) of poorly and well-differentiated thyroid carcinoma tissue samples were positive for IGF2BP1 protein. This indicates that IGF2BP1 protein expression identifies ATC with a diagnostic odds ratio of 612 (95% CI: 74.6-5021). In addition, we found that MAGEA3 is exclusively, although less consistently upregulated in ATC, presenting with an odds ratio of 411 (95% CI: 23.8-7098.7). Importantly, we provide confirmatory evidence that IGF2BP1 and MAGEA3 expression distinguishes ATC from poorly differentiated thyroid carcinoma. IGF2BP1 furthermore identified ATC foci within low-grade follicular thyroid carcinoma. In conclusion, IGF2BP1 represents the most promising single-gene marker available for ATC, followed by MAGEA3, improving on current techniques. Robust markers are essential to help distinguish this high-grade malignancy from other thyroid carcinomas, to guide surgical decision making, therapy and post-resection/therapy monitoring strategies.
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Biomarcadores Tumorais/metabolismo , Proteínas de Ligação a RNA/biossíntese , Carcinoma Anaplásico da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/biossíntese , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Estudos Retrospectivos , Carcinoma Anaplásico da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Adulto JovemRESUMO
BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.
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Oxigenação por Membrana Extracorpórea/métodos , Coração Auxiliar , Vírus da Influenza A/isolamento & purificação , Influenza Humana , Respiração Artificial/métodos , Insuficiência Respiratória , Disfunção Ventricular Esquerda , Adulto , COVID-19/diagnóstico , Deterioração Clínica , Cuidados Críticos/métodos , Ecocardiografia/métodos , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/fisiopatologia , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/terapia , SARS-CoV-2 , Testes Sorológicos/métodos , Índice de Gravidade de Doença , Choque Cardiogênico/etiologia , Choque Cardiogênico/fisiopatologia , Choque Cardiogênico/terapia , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/terapiaRESUMO
Cellular stress has been considered a relevant pathogenetic factor in a variety of human diseases. Due to its primary functions by means of contractility, metabolism, and protein synthesis, the muscle cell is faced with continuous changes of cellular homeostasis that require rapid and coordinated adaptive mechanisms. Hence, a prone susceptibility to cellular stress in muscle is immanent. However, studies focusing on the cellular stress response in muscular disorders are limited. While in recent years there have been emerging indications regarding a relevant role of cellular stress in the pathophysiology of several muscular disorders, the underlying mechanisms are to a great extent incompletely understood. This review aimed to summarize the available evidence regarding a deregulation of the cellular stress response in individual muscle diseases. Potential mechanisms, as well as involved pathways are critically discussed, and respective disease models are addressed. Furthermore, relevant therapeutic approaches that aim to abrogate defects of cellular stress response in muscular disorders are outlined.
Assuntos
Doenças Musculares/patologia , Estresse Fisiológico , Animais , Estresse do Retículo Endoplasmático , Humanos , Células Musculares/patologia , Estresse Oxidativo , Resposta a Proteínas não DobradasRESUMO
OBJECTIVE: Inflammatory myopathies (IIM) include dermatomyositis (DM), sporadic inclusion body myositis (sIBM), immune-mediated necrotizing myopathy (IMNM), and overlap myositis (OLM)/antisynthetase syndrome (ASyS). There is also a rare variant termed polymyositis with mitochondrial pathology (PM-Mito), which is considered a sIBM precursor. There is no information regarding muscle MRI for this rare entity. The aim of this study was to compare MRI findings in IIM, including PM-Mito. METHODS: This retrospective analysis included 41 patients (7 PM-Mito, 11 sIBM, 11 PM/ASyS/OLM, 12 IMNM) and 20 healthy controls. Pattern of muscle involvement was assessed by semiquantitative evaluation, while Dixon method was used to quantify muscular fat fraction. RESULTS: The sIBM typical pattern affecting the lower extremities was not found in the majority of PM-Mito-patients. Intramuscular edema in sIBM and PM-Mito was limited to the lower extremities, whereas IMNM and PM/ASyS/OLM showed additional edema in the trunk. Quantitative assessment showed increased fat content in sIBM, with an intramuscular proximo-distal gradient. Similar changes were also found in a few PM-Mito- and PM/ASyS/OLM patients. In sIBM and PM-Mito, mean fat fraction of several muscles correlated with clinical involvement. INTERPRETATION: As MRI findings in patients with PM-Mito relevantly differed from sIBM, the attribution of PM-Mito as sIBM precursor should be critically discussed. Some patients in PM/ASyS/OLM and PM-Mito group showed MR-morphologic features predominantly observed in sIBM, indicative of a spectrum from PM/ASyS/OLM toward sIBM. In some IIM subtypes, MRI may serve as a biomarker of disease severity.
Assuntos
Imageamento por Ressonância Magnética , Músculo Esquelético , Miosite , Polimiosite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Miosite/diagnóstico por imagem , Miosite/patologia , Polimiosite/diagnóstico por imagem , Polimiosite/patologia , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Adulto , Idoso , Imagem Corporal Total/métodosRESUMO
Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.
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Doença de Depósito de Glicogênio Tipo II , Glicogênio , Imageamento por Ressonância Magnética , Técnicas Fotoacústicas , Humanos , Doença de Depósito de Glicogênio Tipo II/diagnóstico por imagem , Doença de Depósito de Glicogênio Tipo II/metabolismo , Doença de Depósito de Glicogênio Tipo II/patologia , Glicogênio/metabolismo , Técnicas Fotoacústicas/métodos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Estudos de Casos e Controles , Ultrassonografia/métodos , Imagens de FantasmasRESUMO
Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.
Assuntos
Atrofia Muscular Espinal , Proteína 2 de Sobrevivência do Neurônio Motor , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Idade de Início , Áustria/epidemiologia , Progressão da Doença , Alemanha , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/diagnóstico , Triagem Neonatal , Sistema de Registros , Estudos Retrospectivos , Proteína 2 de Sobrevivência do Neurônio Motor/genética , SuíçaRESUMO
Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites. Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded. Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified. Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA. Funding: Financial support for the registry from Biogen, Novartis and Roche.
RESUMO
GFPT1-related congenital myasthenic syndrome (CMS) is characterized by progressive limb girdle weakness, and less prominent involvement of facial, bulbar, or respiratory muscles. While tubular aggregates in muscle biopsy are considered highly indicative in GFPT1-associated CMS, excessive glycogen storage has not been described. Here, we report on three affected siblings with limb-girdle myasthenia due to biallelic pathogenic variants in GFPT1: the previously reported missense variant c.41Gâ>âA (p.Arg14Gln) and the novel truncating variant c.1265_1268del (p.Phe422TrpfsTer26). Patients showed progressive proximal atrophic muscular weakness with respiratory involvement, and a lethal disease course in adulthood. In the diagnostic workup at that time, muscle biopsy suggested a glycogen storage disease. Initially, Pompe disease was suspected. However, enzymatic activity of acid alpha-glucosidase was normal, and gene panel analysis including 38 genes associated with limb-girdle weakness (GAA included) remained unevocative. Hence, a non-specified glycogen storage myopathy was diagnosed. A decade later, the diagnosis of GFPT1-related CMS was established by genome sequencing. Myopathological reexamination showed pronounced glycogen accumulations, that were exclusively found in denervated muscle fibers. Only single fibers showed very small tubular aggregates, identified in evaluation of serial sections. This family demonstrates how diagnostic pitfalls can be addressed by an integrative approach including broad genetic analysis and re-evaluation of clinical as well as myopathological findings.
Assuntos
Doença de Depósito de Glicogênio Tipo II , Síndromes Miastênicas Congênitas , Adulto , Diagnóstico Diferencial , Testes Genéticos , Glutamina-Frutose-6-Fosfato Transaminase (Isomerizante)/genética , Glicogênio , Doença de Depósito de Glicogênio Tipo II/diagnóstico , Doença de Depósito de Glicogênio Tipo II/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Debilidade Muscular/genética , Síndromes Miastênicas Congênitas/diagnóstico , Síndromes Miastênicas Congênitas/genéticaRESUMO
OBJECTIVE: MATR3-associated distal myopathy is a rare distal myopathy predominantly affecting lower legs as well as wrist- and finger extensors. Whilst most distal myopathies are clinically and genetically well characterized, diagnosis often remains challenging. Pattern-based magnetic resonance imaging (MRI) approaches offer valuable additional information. However, a consistent pattern of muscular affection is missing for most distal myopathies. Thus, the aim of the present study was to establish a disease-specific pattern of muscular involvement in MATR3-associated distal myopathy using whole-body MRI. METHODS: 15 patients (25-79 years of age, 7 female) with MATR3-associated distal myopathy were subjected to whole-body MRI. The grade of fatty involution for individual muscles was determined using Fischer-Grading. Results were compared to established MRI-patterns of other distal myopathies. RESULTS: There was a predominant affection of the distal lower extremities. Lower legs showed a severe fatty infiltration, prominently affecting gastrocnemius and soleus muscle. In thighs, a preferential involvement of semimembranous and biceps femoris muscle was observed. Severe affection of gluteus minimus muscle as well as axial musculature, mainly affecting the thoracic segments, was seen. A sufficient discrimination to other forms of distal myopathy based solely on MRI-findings of the lower extremities was not possible. However, the inclusion of additional body parts seemed to yield specificity. INTERPRETATION: Muscle MRI of patients with MATR3-associated distal myopathy revealed a distinct pattern of muscular involvement. The usage of whole-body muscle MRI provided valuable additional findings as compared to regular MRI of the lower extremities to improve distinction from other disease entities.
Assuntos
Miopatias Distais , Doenças Musculares , Criança , Miopatias Distais/diagnóstico por imagem , Miopatias Distais/genética , Feminino , Corpo Humano , Humanos , Imageamento por Ressonância Magnética , Músculo Esquelético/diagnóstico por imagem , Doenças Musculares/diagnóstico por imagem , Proteínas Associadas à Matriz Nuclear , Proteínas de Ligação a RNARESUMO
BACKGROUND: Concerns have been raised about the use of clinical data in cost-effectiveness models. The aim of this analysis was to evaluate the appropriate use of data on clinical effectiveness in cost-effectiveness modeling studies that were published between 2001 and 2015. METHODS: Assessors rated 72 modeling studies obtained from three therapeutic areas by applying criteria defined by the Grading of Recommendations Assessment, Development and Evaluation group for assessing the quality of clinical evidence: selection of clinical data (publication bias), imprecision, indirectness, inconsistency (i.e., heterogeneity), and study limitations (risk of bias). For all parameters included in the analyses, potential changes over time were assessed. RESULTS: Although three out of four modeling studies relied on randomized controlled trials, more than 60% of the modeling studies were based on clinical data with a high or unclear risk of bias, in more than 80%, a risk of publication bias was found, and in about 30%, evidence was based on indirect clinical evidence, having significantly increased over the years. Study limitations were inadequately described in more than one third of the studies. However, less than 10% of clinical studies showed inconsistency or imprecision in study results. CONCLUSION: Despite the fact that the majority of economic evaluations are based on precise and consistent randomized controlled trials, their results are often affected by limitations arising from methodological shortcomings in the underlying data on clinical efficacy. Modelers and assessors should be more aware of aspects surrounding the quality of clinical evidence as considered by the Grading of Recommendations Assessment, Development and Evaluation group.
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Análise Custo-Benefício/métodos , Análise Custo-Benefício/normas , Modelos Econômicos , Garantia da Qualidade dos Cuidados de Saúde/estatística & dados numéricos , Viés , HumanosRESUMO
The cost-effectiveness of rituximab in combination with fludarabine/cyclophosphamide (R-FC) for the first line treatment of chronic lymphocytic leukemia (CLL) was evaluated. Based on long-term clinical data (follow-up of 5.9 years) from the CLL8-trial, a Markov-model with three health states (Free from disease progression, Progressive disease, Death) was used to evaluate the cost per quality-adjusted life-year (QALY) and cost per life years gained (LYG) of R-FC from the perspective of the German statutory health insurance (SHI). The addition of rituximab to FC chemotherapy results in a gain of 1.1 quality-adjusted life-years. The incremental cost-effectiveness ratio (ICER) of R-FC compared with FC was 17,979 per QALY (15,773 per LYG). Results were robust in deterministic and probabilistic sensitivity analyses. From the German SHI perspective, rituximab in combination with FC chemotherapy represents good value for first-line treatment of patients with CLL and compares favorably with chemotherapy alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise Custo-Benefício , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Anos de Vida Ajustados por Qualidade de Vida , Rituximab/administração & dosagem , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivadosRESUMO
OBJECTIVE: The aim of this study was to assess the cost effectiveness of the novel fixed-dose anticoagulant rivaroxaban compared with the current standard of care, warfarin, for the prevention of stroke in patients with atrial fibrillation (AF). METHODS: A Markov model was constructed to model the costs and health outcomes of both treatments, potential adverse events, and resulting health states over 35 years. Analyses were based on a hypothetical cohort of 65-year-old patients with non-valvular AF at moderate to high risk of stroke. The main outcome measure was cost per quality-adjusted life-year (QALY) gained over the lifetime, and was assessed from the German Statutory Health Insurance (SHI) perspective. Costs and utility data were drawn from public data and the literature, while event probabilities were derived from both the literature and rivaroxaban's pivotal ROCKET AF trial. RESULTS: Stroke prophylaxis with rivaroxaban offers health improvements over warfarin treatment at additional cost. From the SHI perspective, at baseline the incremental cost-effectiveness ratio of rivaroxaban was
Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Rivaroxabana/uso terapêutico , Acidente Vascular Cerebral/prevenção & controle , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/economia , Fibrilação Atrial/complicações , Fibrilação Atrial/economia , Análise Custo-Benefício , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/economia , Inibidores do Fator Xa/uso terapêutico , Alemanha , Hemorragia/economia , Hemorragia/epidemiologia , Humanos , Cadeias de Markov , Anos de Vida Ajustados por Qualidade de Vida , Fatores de Risco , Rivaroxabana/administração & dosagem , Rivaroxabana/economia , Acidente Vascular Cerebral/economia , Acidente Vascular Cerebral/etiologia , Varfarina/administração & dosagem , Varfarina/economia , Varfarina/uso terapêuticoRESUMO
For many years, the legal situation within the statutory health insurance (SHI) system in Germany has allowed for health economic evaluations. There are various reasons why health economic evaluations have played virtually no role in decision making until now: to begin with, a method for the evaluation of the relation between benefits and costs which needed to be in accordance with the legal requirements had to be developed, the outcome of which was the efficiency frontier approach. Subsequent health care reforms have led to changing objectives and strategies. Currently, price negotiations of newly launched drugs are based on an early benefit assessment of dossiers submitted by pharmaceutical manufacturers. Other reasons might be the presently very comfortable financial situation of the statutory health insurance system as well as a historically grown societal fear and discomfort towards what is perceived to be a rationing of medicinal products. For the time being, it remains open how long the German health care system can afford to continue neglecting the benefits of health economic evaluations for drug and non-drug interventions, and when it will be time to wake this sleeping beauty.