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L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, autosomal recessive neurometabolic disease, which presents with elevated L-2-hydroxyglutarate acid. Generally, L2HGA appear as slowly progressing central nervous system function deterioration during infancy, and a rapid progression in adulthood is uncommon for the syndrome's classic phenotype.
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Oxidorreductasas de Alcohol , Encefalopatías Metabólicas Innatas , Ataxia Cerebelosa , Adulto , Humanos , Oxidorreductasas de Alcohol/genética , Encefalopatías Metabólicas/genética , Encefalopatías Metabólicas/diagnóstico , Encefalopatías Metabólicas Innatas/genética , Encefalopatías Metabólicas Innatas/diagnóstico , Ataxia Cerebelosa/genética , Pueblos del Este de Asia , Mutación del Sistema de Lectura/genéticaRESUMEN
Aim: To describe outcomes of patients with rearraned during transfection (RET) fusion-positive non-small-cell lung cancer (NSCLC) who received immune checkpoint inhibitor (ICI)-based treatments in the US. Patients & methods: Using de-identified Flatiron Health-Foundation Medicine NSCLC Clinico-Genomic and Guardant Health databases, treatment patterns and outcomes of 69 patients with advanced/metastatic RET fusion-positive NSCLC who received ICI-based treatment were described. Results: Median real-world progression-free survival and overall survival months were 4.2 (95% CI: 1.4-8.4) and 19.1 (6.9-not reached), respectively, among patients in Clinico-Genomic database (n = 17) receiving first-line ICI-based therapy. In the Guardant Health database, progression-free survival was unavailable, and the median overall survival was not reached (n = 29). Conclusion: Outcomes associated with ICI-based treatments in the first-line setting among patients with RET fusion-positive NSCLC are consistent with unselected populations reported in literature.
Lay abstract Treatment options are rapidly expanding for patients who are diagnosed with advanced/metastatic non-small-cell lung cancer. The current standard of care for patients who do not have an actionable genomic alteration includes immune checkpoint inhibitor (ICI)-based therapy. However, the role of ICI-based therapy is not well understood in patients with rearranged during transfection (RET) fusions. In this study, the survival outcomes observed in patients with RET fusion-positive non-small-cell lung cancer who received first-line ICI-based therapy were comparable with published data from patients without genomic alterations. This study is limited due to the small sample size.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-ret/genética , Adulto , Anciano , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudios de Cohortes , Femenino , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Fusión de Oncogenes , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
This retrospective observational study was designed to evaluate overall survival in a real-world patient population and to identify predictive factors associated with receipt of second-line therapy. A retrospective analysis of electronic medical records (Flatiron Health, New York) was conducted among patients initiating first-line therapy from January 1, 2013, through April 30, 2018. Eligible patients were diagnosed with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma and ≥18 years of age at the time of treatment initiation. Patients alive 45 days after discontinuation of first-line therapy were considered potentially eligible for continued therapy and were categorized into those who received and those who did not receive second-line therapy. Survival analyses were conducted using Kaplan-Meier method and log-rank test without adjusting for any baseline covariates. Factors associated with further treatment were evaluated using logistic regression. A total of 3850 patients met eligibility criteria. Among the 2516 patients available to receive second-line therapy, 1515 (60.2%) received second-line therapy and 1001 (39.8%) did not receive further therapy. Among those potentially eligible to receive second-line therapy, median survival was 15.4 months (95% confidence interval [CI]: 14.6-16.0) from initiation of first-line therapy for those who received second-line therapy and 10.0 months (95% CI: 9.3-10.7) for those who did not. Longer duration of first-line therapy (≥169 vs ≤84 days), HER2-positive tumors, initially diagnosed with stage IV disease, less weight loss during first-line therapy, and younger age were associated with receipt of second-line therapy (all P < .001). Longer survival was associated with multiple lines of therapy; however, these results should be interpreted with caution, and no causal relationship can be inferred.
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Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/mortalidad , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Anciano , Unión Esofagogástrica/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Objectives: Soft-tissue sarcoma (STS) is a heterogeneous group of rare solid tumors that arise from various soft tissues in the body, such as muscle, fat, nerves, and blood vessels. Current International Classification of Diseases (ICD) coding systems include a set of nonspecific codes for malignancies of connective and soft tissue (ICD-9-CM code 171 and ICD-10-CM code C49). The goal of this study was to evaluate the use of these codes for health services research involving patients with a diagnosis of this rare malignancy. Methods: Two databases were utilized to explore ICD coding for STS: claims data from Truven MarketScan and electronic medical records (EMRs) from Flatiron Health. Eligible patients from claims data were those with at least two ICD-9-CM codes of 171.x on two different days between July 1, 2004, and March 30, 2014. The treatment patterns of these cases were evaluated for consistency with known therapeutic approaches for STS. Eligible patients from the Flatiron EMR system were those who received olaratumab (a drug indicated only for use in patients diagnosed with STS) after its US Food and Drug Administration approval in October 2016 through the end of the data set (November 2017). ICD-10-CM codes were evaluated for this known STS cohort. Results: In claims data, 4,159 patients were eligible for inclusion. Although national treatment guidelines include only a limited number of drugs used to treat STS, 98 unique anticancer drugs were identified as being used to treat patients in a claims data cohort. Only 7.7 percent of patients had claims for doxorubicin-based therapy and 3.8 percent had claims for ifosfamide-based therapy as initial treatment for STS, despite these being a standard of care. In the EMR data, 350 patients were eligible; only 170 patients (48.6 percent) had any evidence in the database of a connective or soft-tissue ICD-10-CM malignancy code within 60 days before or after initiation of olaratumab. Conclusions: ICD coding for STS using the "Malignant neoplasm of connective and soft tissue" code is not reliable as a method to identify patients diagnosed with STS. Although codes reflecting the primary site of disease may have clinical relevance, lack of consistency in ICD coding for the diagnosis and treatment of this disease is a limiting factor in the ability to conduct real-world observational research of this rare disease. In the absence of consistent use of this code, an algorithm needs to be developed and validated to accurately identify patients with STS in these databases.
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Antineoplásicos/uso terapéutico , Recolección de Datos/normas , Investigación sobre Servicios de Salud/organización & administración , Clasificación Internacional de Enfermedades/normas , Sarcoma/tratamiento farmacológico , Adulto , Anciano , Bases de Datos Factuales/normas , Registros Electrónicos de Salud/normas , Femenino , Investigación sobre Servicios de Salud/normas , Humanos , Revisión de Utilización de Seguros/normas , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estados UnidosRESUMEN
Objective To evaluate the feasibility of dual microcatheter "cross-regional" embolization technique in treating intracranial irregular aneurysms. Methods The clinical data of 19 patients with intracranial irregular aneurysms, who were treated with "cross-regional" embolization technique at authors' hospital during the period from May 2016 to May 2017, were retrospectively analyzed. The embolization strategy formulation, selection of embolization materials, surgical process and embolization effect were summarized. Results Successful treatment of intracranial irregular aneurysm was accomplished in all the 19 patients. In one patient, during the embolization process of the neck of aneurysm the steel coil was over-protruded into the parent artery, and stent implantation had to be carried out to rescue the therapy, and finally successful treatment was achieved. The technical success rate of "cross-regional" embolization was 95%. Complete embolization was obtained in 15 patients and subtotal embolization in 3 patients. Conclusion For the treatment of some specified intracranial irregular aneurysms, dual microcatheter "cross - regional" embolization technique is technically simple, and it is a safe and effective treatment option. (J Intervent Radiol, 2018, 27: 199-202)
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BACKGROUND: In lung cancer, there is an increasing number of oral agents available for patients; however, little is known about the factors associated with adherence to and treatment duration on oral medications in non-small cell lung cancer (NSCLC). OBJECTIVE: To evaluate the clinical and demographic factors associated with adherence and treatment discontinuation, respectively, to oral oncolytics among patients with NSCLC. METHODS: A retrospective, claims-based analysis of the Humana Research Database supplemented with medical chart review was conducted among patients with NSCLC who started an oral oncolytic between January 1, 2008, and June 30, 2013. Patients were required to be enrolled at least 1 year before the start of oral oncolytics and have no evidence of any oral oncolytic use during this period. Logistic regression models and Cox proportional hazard models were used to identify predictors associated with medication adherence and treatment duration, respectively. RESULTS: Among all oral oncolytics, only the cohort starting on erlotinib had sufficient sample size (n = 1,452). A wide variety of factors were found to be associated with adherence. Low-income subsidy status, previous use of intravenous chemotherapy, and lower total baseline health care costs were significantly related to decreasing adherence (each P < 0.05). Additionally, increasing patient out-of-pocket cost was associated with decreasing adherence to erlotinib (P < 0.0001). Factors significantly related to longer treatment duration included low-income subsidy status (P < 0.001) and having Medicare insurance, (P = 0.0004), dual eligibility (Medicare and Medicaid, P = 0.007), and higher erlotinib out-of-pocket costs (P < 0.0001). CONCLUSIONS: There is a need for mechanisms to be in place to identify and address barriers to care. Future research should focus on evaluating and reducing any potential risk to patient outcomes that may be associated with low adherence to or shorter treatment duration on oral chemotherapy. DISCLOSURES: This study was supported by funding from Eli Lilly and Company to Comprehensive Health Insights, a Humana company, as a collaborative research project involving employees of both companies. Hess, Winfree, Zhu, and Oton are employees of Eli Lilly and Company. Louder and Nair are employees of Comprehensive Health Insights, which received funding to complete this research. Study concept and design were contributed by Hess, Zhu, Winfree, and Oton. Nair and Louder collected the data, and data interpretation was performed by all the authors. The manuscript was written primarily by Hess, along with Nair, and revised by Hess, Nair, Louder, and Winfree, with assistance from Zhu and Louder.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/economía , Clorhidrato de Erlotinib/economía , Clorhidrato de Erlotinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/economía , Cumplimiento de la Medicación/estadística & datos numéricos , Anciano , Femenino , Costos de la Atención en Salud , Gastos en Salud , Humanos , Revisión de Utilización de Seguros/economía , Estudios Longitudinales , Masculino , Medicaid/economía , Medicare/economía , Estudios Retrospectivos , Estados UnidosRESUMEN
BACKGROUND: After myocardial infarction (MI) treated with percutaneous coronary intervention (PCI), guidelines recommend dual antiplatelet therapy (DAPT) with aspirin and an ADP receptor inhibitor (ADPri) for at least 1year. However, whether real-world Canadian practice patterns reflect this recommendation is unknown. METHODS: We studied 2175 MI patients treated with PCI and discharged from 26 Canadian hospitals between 12/2011 and 05/2013 in the Canadian Observational Antiplatelet sTudy (COAPT). Hierarchical Cox proportional hazard regression modeling was used to determine baseline demographic and clinical factors associated with duration of ADPri therapy post-discharge. RESULTS: At index-hospitalization discharge, 1597 (73%) patients were treated with clopidogrel, 220 (10%) with prasugrel, and 358 (17%) with ticagrelor. ADPri was discontinued prior to 1year in 474 (21.8%) patients; discontinuation rates were lowest for patients discharged on prasugrel (17.7%), compared with clopidogrel (22.5%) or ticagrelor (21.0%), (log rank test, p=0.03). In addition to regional variability, factors associated with shorter ADPri duration included older age, low body weight, Killip III/IV heart failure, atrial fibrillation, ticagrelor on discharge, and bare metal stent use, while longer ADPri duration was associated with history of prior MI. CONCLUSIONS: One in five PCI-treated MI patients did not complete Canadian guideline-recommended 1-year course of ADPri treatment. Premature ADPri discontinuation was most strongly associated with factors that increase the risk of bleeding. Further study is required to assess the clinical implications of premature ADPri discontinuation on patient outcomes.
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Infarto del Miocardio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Antagonistas del Receptor Purinérgico P2/administración & dosificación , Adenosina/administración & dosificación , Adenosina/análogos & derivados , Anciano , Canadá , Clopidogrel , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea , Clorhidrato de Prasugrel/administración & dosificación , Estudios Retrospectivos , Ticagrelor , Ticlopidina/administración & dosificación , Ticlopidina/análogos & derivados , Resultado del TratamientoRESUMEN
OBJECTIVE: Our objective was to compare 1-year real-world healthcare resource utilization (HRU), associated charges, and antiplatelet treatment patterns among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with ticagrelor or prasugrel. METHODS: Using the ProMetis-Lx database, adult ACS-PCI patients treated with ticagrelor or prasugrel post-discharge were identified between 1 August 2011 and 31 May 2013 and propensity matched to adjust for baseline differences. RESULTS: Before matching, ticagrelor-treated patients (n = 2991) were older with increased baseline ischemic and bleeding risks compared with prasugrel-treated patients (n = 12,797). After matching, ticagrelor patients had higher all-cause HRU (2.5 vs. 2.4 per patient per month; P = 0.012) and cardiovascular (CV) HRU (0.4 vs. 0.3 per patient per month; P = 0.026), with the difference in CV rehospitalizations (17.7 vs. 15.7 %; P = 0.011) primarily driven by congestive heart failure (CHF) (4.9 vs. 3.8 %; P = 0.02). All-cause charges within 1 year did not significantly differ between groups ($US5456 vs. 4844 per patient per month; P = 0.37), but dyspnea-related total charges were significantly higher with ticagrelor ($US139 vs. 95 per patient per month; P = 0.005). Although infrequent, switching was slightly higher with ticagrelor (8.3 vs. 6.0 %; P < 0.001) at 1 year, and mean persistence was slightly longer with prasugrel (150 vs. 159 days; P = 0.002), with no significant difference in mean adherence (61 vs. 63 %; P = 0.17). CONCLUSION: Overall monthly HRU was slightly lower with prasugrel than with ticagrelor, with no significant difference in bleeding HRU. Prasugrel was associated with slightly higher pharmacy charges, but lower dyspnea charges, resulting in no significant difference in total charges. Patients receiving prasugrel tended to use it for longer than those receiving ticagrelor as less switching occurred. These findings may aid decision making, but must be tempered due to inherent study limitations.
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Síndrome Coronario Agudo/terapia , Adenosina/análogos & derivados , Anticoagulantes/uso terapéutico , Servicios de Salud/estadística & datos numéricos , Intervención Coronaria Percutánea/métodos , Clorhidrato de Prasugrel/uso terapéutico , Adenosina/administración & dosificación , Adenosina/efectos adversos , Adenosina/economía , Adenosina/uso terapéutico , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Comorbilidad , Femenino , Servicios de Salud/economía , Hemorragia/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Clorhidrato de Prasugrel/administración & dosificación , Clorhidrato de Prasugrel/efectos adversos , Clorhidrato de Prasugrel/economía , Estudios Retrospectivos , TicagrelorRESUMEN
INTRODUCTION: Serial alterations in protein C levels appear to correlate with disease severity in patients with severe sepsis, and it may be possible to tailor severe sepsis therapy with the use of this biomarker. The purpose of this study was to evaluate the dose and duration of drotrecogin alfa (activated) treatment using serial measurements of protein C compared to standard therapy in patients with severe sepsis. METHODS: This was a phase 2 multicenter, randomized, double-blind, controlled study. Adult patients with two or more sepsis-induced organ dysfunctions were enrolled. Protein C deficient patients were randomized to standard therapy (24 µg/kg/hr infusion for 96 hours) or alternative therapy (higher dose and/or variable duration; 24/30/36 µg/kg/hr for 48 to 168 hours). The primary outcome was a change in protein C level in the alternative therapy group, between study Day 1 and Day 7, compared to standard therapy. RESULTS: Of 557 patients enrolled, 433 patients received randomized therapy; 206 alternative, and 227 standard. Baseline characteristics of the groups were largely similar. The difference in absolute change in protein C from Day 1 to Day 7 between the two therapy groups was 7% (P = 0.011). Higher doses and longer infusions were associated with a more pronounced increase in protein C level, with no serious bleeding events. The same doses and longer infusions were associated with a larger increase in protein C level; higher rates of serious bleeding when groups received the same treatment; but no clear increased risk of bleeding during the longer infusion. This group also experienced a higher mortality rate; however, there was no clear link to infusion duration. CONCLUSIONS: The study met its primary objective of increased protein C levels in patients receiving alternative therapy demonstrating that variable doses and/or duration of drotrecogin alfa (activated) can improve protein C levels, and also provides valuable information for incorporation into potential future studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00386425.