RESUMEN
BACKGROUND: In US hospitals, the liquid embolic systems (LESs) n-butyl cyanoacrylate (n-BCA) and ethylene vinyl alcohol copolymer (EVOH) are used for brain arteriovenous malformation (bAVM) embolization to achieve presurgical devascularization. The aim of this study was to perform an economic analysis comparing four techniques for bAVM embolization based on LES, ancillary device, and angiography suite time costs. METHODS: An economic model was developed comparing the embolization costs for n-BCA, EVOH with the plug and push technique, EVOH with detachable-tip microcatheters, and EVOH with balloon microcatheters. Per procedure costs were calculated for bAVMs with one to four pedicles. Annual cohort analyses were performed to evaluate the potential impact for low and high-volume centers. Sensitivity analyses were performed to determine cost drivers. RESULTS: The analyses showed that the n-BCA technique was the least costly of the four techniques. Total per procedure costs for one to four embolized pedicles ranged from $5941 to $10,074 for the n-BCA technique, $8428 to $30,345 for the EVOH balloon microcatheter technique, $12,711 to $47,477 for the EVOH plug and push technique, and $13,900 to $52,233 for the EVOH detachable-tip microcatheter technique. Cohort analyses costs for 52 annual cases ranged from $308,953 to $523,838 with the n-BCA technique and from $722,816 to $2,716,096 with the EVOH detachable-tip microcatheter technique. CONCLUSIONS: Procedure costs associated with n-BCA are lower than those with each of the three EVOH techniques examined. Future cost analyses should compare the costs of new LES products once available.
Asunto(s)
Embolización Terapéutica , Enbucrilato , Malformaciones Arteriovenosas Intracraneales , Humanos , Enbucrilato/uso terapéutico , Resultado del Tratamiento , Malformaciones Arteriovenosas Intracraneales/cirugía , Polivinilos/uso terapéutico , Embolización Terapéutica/métodos , EncéfaloRESUMEN
AIMS: Endovascular coiling is a common modality for treating intracranial aneurysms; however, recanalization occurs in approximately 1 in 5 cases, with downstream consequences of regrowth and rupture. Aneurysm packing density >24% reduces recanalization risk; packing density can be increased by inserting additional coils or by using coils with larger volumetric filling. Coil volume depends on length and primary wind diameter (PWD). This study evaluated the influence of PWD on packing density and total case costs. MATERIALS AND METHODS: Two hypothetical scenarios and one case study were analyzed. In scenario one, the number of coils required to achieve packing density >24% in a hypothetical aneurysm was determined for 0.012â³ vs. 0.010â³ PWD coils. In scenario two, the total length of 0.010â³ vs. 0.012â³ PWD coils required to achieve a packing density >24% was analyzed relative to aneurysm volume. In the case study, packing densities with one 0.012â³ PWD coil (actual scenario) and one 0.010â³ PWD coil (theoretical scenario) were compared. RESULTS: In scenario one, cost savings would be realized by using four 0.012â³ PWD coils vs. seven 0.010â³ PWD coils to achieve packing density >24%. In scenario two, greater volumetric filling of 0.012â³ vs. 0.010â³ PWD coils was correlated with lower total length of coil required. In the case study, a 0.012â³ PWD coil achieved packing density >24%, whereas an equivalent length 0.010â³ PWD coil would not. LIMITATIONS: Theoretical modeling was used to explore the impact of coil PWD on aneurysm packing density. In clinical practice, packing density depends not only on PWD but on its length, shape, distribution within an aneurysm, and other recanalization risk factors. CONCLUSIONS: Coil PWD influences packing density, the number of coils required to achieve a specific packing density, and total case costs. Using 0.012â³ PWD coils may provide cost and procedural efficiencies.
Asunto(s)
Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Resultado del Tratamiento , VientoRESUMEN
BACKGROUND: First-pass effect (FPE), restoring complete or near complete reperfusion (modified Thrombolysis in Cerebral Infarction (mTICI) 2c-3) in a single pass, is an independent predictor for good functional outcomes in the endovascular treatment of acute ischemic stroke. The economic implications of achieving FPE have not been assessed. OBJECTIVE: To assess the economic impact of achieving complete or near complete reperfusion after the first pass. METHODS: Post hoc analyses were conducted using ARISE II study data. The target population consisted of patients in whom mTICI 2c-3 was achieved, stratified into two groups: (1) mTICI 2c-3 achieved after the first pass (FPE group) or (2) after multiple passes (non-FPE group). Baseline characteristics, clinical outcomes, and healthcare resource use were compared between groups. Costs from peer-reviewed literature were applied to assess cost consequences from the perspectives of the United States (USA), France, Germany, Italy, Spain, Sweden, and United Kingdom (UK). RESULTS: Among patients who achieved mTICI 2c-3 (n=172), FPE was achieved in 53% (n=91). A higher proportion of patients in the FPE group reached good functional outcomes (90-day modified Rankin Scale score 0-2 80.46% vs 61.04%, p<0.01). The patients in the FPE group had a shorter mean length of stay (6.10 vs 9.48 days, p<0.01) and required only a single stent retriever, whereas 35% of patients in the non-FPE group required at least one additional device. Driven by improvement in clinical outcomes, the FPE group had lower procedural/hospitalization-related (24-33% reduction) and annual care (11-27% reduction) costs across all countries. CONCLUSIONS: FPE resulted in improved clinical outcomes, translating into lower healthcare resource use and lower estimated costs.
Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Humanos , Estudios Retrospectivos , Stents , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/cirugía , Trombectomía , Resultado del Tratamiento , Estados UnidosRESUMEN
Breast cancer is the most common cancer in Western women and while its precise etiology is unknown, environmental factors are thought to play a role. The organochlorine pesticide dieldrin is a persistent environmental toxicant thought to increase the risk of breast cancer and reduce survival in the human population. The objective of this study was to define the effect of developmental exposure to environmentally relevant concentrations of dieldrin, on mammary tumor development in the offspring. Sexually mature FVB-MMTV/neu female mice were treated with vehicle (corn oil), or dieldrin (0.45, 2.25, and 4.5 microg/g body weight) daily by gavage for 5 days prior to mating and then once weekly throughout gestation and lactation until weaning. Dieldrin concentrations were selected to produce serum levels representative of human background body burdens, occupational exposure, and overt toxicity. Treatment had no effect on litter size, birth weight or the number of pups surviving to weaning. The highest dose of dieldrin significantly increased the total tumor burden and the volume and number of tumors found in the thoracic mammary glands. Increased mRNA and protein expression of the neurotrophin BDNF and its receptor TrkB was increased in tumors from the offspring of dieldrin treated dams. This study indicates that developmental exposure to the environmental contaminant dieldrin causes increased tumor burden in genetically predisposed mice. Dieldrin exposure also altered the expression of BNDF and TrkB, novel modulators of cancer pathogenesis.
Asunto(s)
Dieldrín/administración & dosificación , Dieldrín/toxicidad , Lactancia , Neoplasias Mamarias Experimentales/patología , Exposición Materna , Receptor ErbB-2/metabolismo , Animales , Peso Corporal/efectos de los fármacos , Factor Neurotrófico Derivado del Encéfalo/genética , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Lactancia/efectos de los fármacos , Neoplasias Mamarias Experimentales/genética , Ratones , Ratones Transgénicos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor trkB/genética , Receptor trkB/metabolismoRESUMEN
Epidemiological evidence suggests that exposure to the pesticide dieldrin, is associated with increased risk of breast cancer and mortality. We hypothesize that dieldrin promotes breast cancer by increasing survival of breast cancer cells. The aims of this study were to measure the effect of dieldrin on survival of breast cancer cells and the expression of tyrosine kinase B (TrkB), a suppressor of anoikis (apoptosis triggered by inappropriate anchorage). The human breast cancer cell line MDA-MB-231 was treated with dieldrin and proliferation, viability and resistance to anoikis were measured. TrkB expression was measured by Western blot in lysates and by immunohistochemistry in human tissue specimens. Dieldrin increased resistance to anoikis and TrkB expression. TrkB was expressed in a subset of high-grade breast carcinoma specimens. Our results demonstrate that dieldrin increases resistance to anoikis and expression of TrkB and show for the first time TrkB protein expression in human breast cancer.
Asunto(s)
Anoicis/efectos de los fármacos , Neoplasias de la Mama/inducido químicamente , Dieldrín/toxicidad , Insecticidas/toxicidad , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Receptor trkB/análisis , Receptor trkB/fisiologíaRESUMEN
Stress-induced intestinal barrier dysfunction may be involved in chronic intestinal disorders. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic growth hormone that can rapidly improve intestinal epithelial barrier function. Here, we investigated whether mouse intestine is responsive to chronic psychological stress and whether pretreatment with GLP-2 can ameliorate stress-induced changes. Mice were subjected to water avoidance stress (WAS; 1 h/day for 10 days) with GLP-2 or saline administered 4 h before each WAS session. After the final stress period, the intestine was removed for assessment of physiological/morphological changes. Compared with controls (sham-stressed mice), stressed mice demonstrated enhanced ion secretion and permeability in the jejunum, ileum, and colon. In addition, increased numbers of bacteria were observed adhering to and/or penetrating the epithelium, associated with infiltration of mononuclear cells into the mucosa. GLP-2 treatment improved intestinal barrier function in stressed mice and ameliorated other aspects of impaired host defense. Our study extends previous findings in rats of stress-induced intestinal dysfunction and provides insights into potential novel therapeutics.
Asunto(s)
Intestinos/fisiopatología , Péptidos/farmacología , Estrés Psicológico/fisiopatología , Animales , Infecciones Bacterianas/inmunología , Peso Corporal/efectos de los fármacos , Colon/patología , Cámaras de Difusión de Cultivos , Epitelio/efectos de los fármacos , Epitelio/fisiología , Péptido 2 Similar al Glucagón , Péptidos Similares al Glucagón , Peroxidasa de Rábano Silvestre/metabolismo , Inflamación/patología , Intestinos/efectos de los fármacos , Intestinos/ultraestructura , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica , Péptidos/uso terapéutico , Estrés Psicológico/tratamiento farmacológicoRESUMEN
Penetration of the gut epithelial barrier by intact luminal antigen is necessary for immunologically mediated pathophysiology in the context of food allergy. We investigated if glucagon-like peptide-2 (GLP-2) could affect immediate hypersensitivity and late-phase allergic inflammation in a murine model. Mice were sensitized to horseradish peroxidase (HRP); studies were conducted 14 days later. Mice were treated with 5 microg GLP-2 subcutaneously 4 h before antigen challenge. For immediate hypersensitivity, jejunal segments in Ussing chambers were challenged by luminal HRP antigen. GLP-2 treatment reduced the uptake of HRP and the antigen-induced secretory response after luminal challenge. GLP-2 appears to reduce macromolecular uptake independent of the CD23-mediated enhanced antigen uptake pathway. For the late phase, mice were gavaged with antigen, and 48 h later the function and histology of the jejunum were examined. GLP-2 prevented the usual prolonged permeability defect and reduced the number of inflammatory cells in the mucosa. Our studies demonstrate that a single treatment of sensitized mice with GLP diminishes both immediate and late-phase hypersensitivity reactions characteristic of food allergy by inhibiting transepithelial uptake of antigen.