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1.
Pediatr Radiol ; 52(3): 587-591, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34601621

RESUMEN

Myositis ossificans is a benign, ossifying, soft-tissue pseudotumor that most commonly occurs in men ages 30-40 years after trauma. Myositis ossificans may also occur in children, but it is extremely rare in those younger than 10 years of age. While myositis ossificans can often mimic malignant soft-tissue tumors, it has many unique findings that can aid in diagnostic differentiation. This differentiation is critical to avoid unnecessary risk with potentially harmful procedures. We present a very unusual presentation of myositis ossificans in the immediate post-birth perinatal period, as well as a review of key imaging findings.


Asunto(s)
Miositis Osificante , Sarcoma , Neoplasias de los Tejidos Blandos , Adulto , Niño , Humanos , Recién Nacido , Imagen por Resonancia Magnética , Masculino , Miositis Osificante/diagnóstico por imagen , Miositis Osificante/patología , Neoplasias de los Tejidos Blandos/patología
2.
Pediatr Cardiol ; 39(5): 1063-1065, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29736793

RESUMEN

A 16-year-old female, with a history of Williams syndrome, presented to our institution with a 2-week history of intermittent dizziness. Holter monitoring demonstrated occasional premature ventricular contractions with rare couplets and triplets as well as one short run of nonsustained ventricular tachycardia. Echocardiography revealed an abnormal and irregular left ventricular septum with multiple mobile, pedunculated muscular projections extending into the left ventricular cavity. Cardiac MR confirmed abnormally thickened trabeculations consisting of multiple parallel ridges of myocardium crossing the left ventricle. The appearance of these findings closely resembled bands of coral lining the ocean floor. As such, this finding can henceforth be known as the "coral sign." To our knowledge, no other reports of this finding in patients with Williams syndrome have been published.


Asunto(s)
Miocardio/patología , Síndrome de Williams/diagnóstico por imagen , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Ecocardiografía/métodos , Electrocardiografía Ambulatoria/métodos , Femenino , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/patología , Humanos , Imagen por Resonancia Cinemagnética/métodos , Taquicardia Ventricular/etiología , Síndrome de Williams/tratamiento farmacológico
3.
Gastroenterology ; 151(5): 902-909, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27486033

RESUMEN

BACKGROUND & AIMS: Studies are needed to determine the optimal regimen for patients with chronic hepatitis C virus (HCV) genotype 2, 3, 4, or 6 infections whose prior course of antiviral therapy has failed, and the feasibility of shortening treatment duration. We performed a phase 2 study to determine the efficacy and safety of the combination of the nucleotide polymerase inhibitor sofosbuvir, the NS5A inhibitor velpatasvir, and the NS3/4A protease inhibitor GS-9857 in these patients. METHODS: We performed a multicenter, open-label trial at 32 sites in the United States and 2 sites in New Zealand from March 3, 2015 to April 27, 2015. Our study included 128 treatment-naïve and treatment-experienced patients (1 with HCV genotype 1b; 33 with HCV genotype 2; 74 with HCV genotype 3; 17 with genotype HCV 4; and 3 with HCV genotype 6), with or without compensated cirrhosis. All patients received sofosbuvir-velpatasvir (400 mg/100 mg fixed-dose combination tablet) and GS-9857 (100 mg) once daily for 6-12 weeks. The primary end point was sustained virologic response 12 weeks after treatment (SVR12). RESULTS: After 6 weeks of treatment, SVR12s were achieved by 88% of treatment-naïve patients without cirrhosis (29 of 33; 95% confidence interval, 72%-97%). After 8 weeks of treatment, SVR12s were achieved by 93% of treatment-naïve patients with cirrhosis (28 of 30; 95% CI, 78%-99%). After 12 weeks of treatment, SVR12s were achieved by all treatment-experienced patients without cirrhosis (36 of 36; 95% CI, 90%-100%) and 97% of treatment-experienced patients with cirrhosis (28 of 29; 95% CI, 82%-100%). The most common adverse events were headache, diarrhea, fatigue, and nausea. Three patients (1%) discontinued treatment due to adverse events. CONCLUSIONS: In a phase 2 open-label trial, we found sofosbuvir-velpatasvir plus GS-9857 (8 weeks in treatment-naïve patients or 12 weeks in treatment-experienced patients) to be safe and effective for patients with HCV genotype 2, 3, 4, or 6 infections, with or without compensated cirrhosis. ClinicalTrials.gov ID: NCT02378961.


Asunto(s)
Antivirales/uso terapéutico , Carbamatos/uso terapéutico , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Macrocíclicos/uso terapéutico , Sofosbuvir/uso terapéutico , Sulfonamidas/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Ácidos Aminoisobutíricos , Ciclopropanos , Esquema de Medicación , Combinación de Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Genotipo , Humanos , Lactamas Macrocíclicas , Leucina/análogos & derivados , Masculino , Persona de Mediana Edad , Prolina/análogos & derivados , Quinoxalinas , Serina Proteasas , Resultado del Tratamiento , Proteínas no Estructurales Virales , Adulto Joven
4.
J Clin Gastroenterol ; 51(5): 446-453, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27779613

RESUMEN

GOALS/BACKGROUND: Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality. STUDY: Prospective 15-center US cohort of patients with cirrhosis presenting with endoscopically proven AVH, all of whom received antibiotics, vapreotide (a somatostain analog) infusion and endoscopic band ligation. Patients were enrolled between August 2006 and April 2008. Primary outcome was 6-week mortality. Secondary outcome was 5-day treatment failure. The prognostic value of Child-Turcotte-Pugh (CTP) class, Model for End-stage Liver Disease (MELD) score and a recent recalibrated MELD were compared. RESULTS: Seventy eligible patient were enrolled; 18 (26%) patients died within 6-weeks of index bleed. Demographic, clinical, and laboratory data were compared between survivors and nonsurvivors. Multivariate models showed that admission CTP or the MELD score (separately) were independent predictors of survival. The discriminative values of CTP (area under receiver operating characteristic: 0.75) and MELD (area under receiver operating characteristic: 0.79) were good and not significantly different (P=0.27). However, calibration (correlation between observed and predicted mortality) test was significantly better for CTP than for MELD, with the recently described recalibrated MELD model having the worst agreement. Predicted mortality for CTP-A was <10%, CTP-B 10% to 30%; and CTP-C >33%. CONCLUSIONS: AVH mortality of 26% in the United States is in the upper range limit compared with recent series but may be due to inclusion of patients with more advanced cirrhosis. CTP score has the best overall performance in the prediction of 6-week mortality and is best at stratifying risk.


Asunto(s)
Técnicas de Apoyo para la Decisión , Várices Esofágicas y Gástricas/diagnóstico , Hemorragia Gastrointestinal/diagnóstico , Cirrosis Hepática/diagnóstico , Progresión de la Enfermedad , Várices Esofágicas y Gástricas/mortalidad , Várices Esofágicas y Gástricas/terapia , Femenino , Hemorragia Gastrointestinal/mortalidad , Hemorragia Gastrointestinal/terapia , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Insuficiencia del Tratamiento , Estados Unidos/epidemiología
5.
Hepatology ; 61(1): 41-5, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25314116

RESUMEN

UNLABELLED: Historically, clinical trials of regimens to treat chronic infection with hepatitis C virus (HCV) have used, as their primary efficacy endpoint, a sustained virological response (SVR)­defined as HCV RNA levels below a designated threshold of quantification­24 weeks after the end of treatment (SVR24). More recently, regulatory authorities have begun to accept SVR at 12 weeks post-treatment (SVR12) as a valid efficacy endpoint because of its high rate of concordance with SVR24. However, the concordance between SVR12 and SVR24 has not been systematically assessed with new regimens of recently approved direct-acting antiviral agents. The aim of this study was to assess the concordance between SVR at various post-treatment time points in phase III clinical trials of sofosbuvir (SOF)-containing regimens. We conducted a retrospective analysis of five trials enrolling 863 patients infected with HCV genotypes 1-6. The concordance between SVR at 4 weeks post-treatment (SVR4) and SVR12, and between SVR12 and SVR24, were determined, as well as positive predictive values (PPVs) and negative predictive values (NPVs). Overall, 779 of 796 patients (98.0%) with an SVR4 also achieved an SVR12, making the PPV of SVR4 for SVR12 98% and the NPV 100%. Of the 779 patients with an SVR12, 777 (99.7%) also achieved an SVR24, making the PPV of SVR12 for SVR24 >99% and the NPV 100%. Of patients who relapsed post-therapy, 77.6% did so within 4 weeks of completing therapy. CONCLUSION: Data from phase III studies demonstrate that with SOF-based regimens, with or without interferon, SVR12 and SVR24 correlate closely. Thus, SVR12 can be used effectively to determine "cure" rates in trials and in clinical practice.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , ARN Viral/sangre , Uridina Monofosfato/análogos & derivados , Adulto , Femenino , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/sangre , Hepatitis C Crónica/virología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Sofosbuvir , Uridina Monofosfato/uso terapéutico
6.
N Engl J Med ; 362(12): 1071-81, 2010 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-20335583

RESUMEN

BACKGROUND: Hepatic encephalopathy is a chronically debilitating complication of hepatic cirrhosis. The efficacy of rifaximin, a minimally absorbed antibiotic, is well documented in the treatment of acute hepatic encephalopathy, but its efficacy for prevention of the disease has not been established. METHODS: In this randomized, double-blind, placebo-controlled trial, we randomly assigned 299 patients who were in remission from recurrent hepatic encephalopathy resulting from chronic liver disease to receive either rifaximin, at a dose of 550 mg twice daily (140 patients), or placebo (159 patients) for 6 months. The primary efficacy end point was the time to the first breakthrough episode of hepatic encephalopathy. The key secondary end point was the time to the first hospitalization involving hepatic encephalopathy. RESULTS: Rifaximin significantly reduced the risk of an episode of hepatic encephalopathy, as compared with placebo, over a 6-month period (hazard ratio with rifaximin, 0.42; 95% confidence interval [CI], 0.28 to 0.64; P<0.001). A breakthrough episode of hepatic encephalopathy occurred in 22.1% of patients in the rifaximin group, as compared with 45.9% of patients in the placebo group. A total of 13.6% of the patients in the rifaximin group had a hospitalization involving hepatic encephalopathy, as compared with 22.6% of patients in the placebo group, for a hazard ratio of 0.50 (95% CI, 0.29 to 0.87; P=0.01). More than 90% of patients received concomitant lactulose therapy. The incidence of adverse events reported during the study was similar in the two groups, as was the incidence of serious adverse events. CONCLUSIONS: Over a 6-month period, treatment with rifaximin maintained remission from hepatic encephalopathy more effectively than did placebo. Rifaximin treatment also significantly reduced the risk of hospitalization involving hepatic encephalopathy. (ClinicalTrials.gov number, NCT00298038.)


Asunto(s)
Antiinfecciosos/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Encefalopatía Hepática/prevención & control , Lactulosa/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Rifamicinas/uso terapéutico , Anciano , Antiinfecciosos/efectos adversos , Enfermedad Crónica , Clostridioides difficile , Infecciones por Clostridium/etiología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Rifamicinas/efectos adversos , Rifaximina , Prevención Secundaria
7.
Nucl Med Commun ; 44(9): 825-829, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37395540

RESUMEN

OBJECTIVES: Determine if subspecialist second opinion review alters reporting of malignancy on 18 F-FDG PET/CT for patients with breast cancer. METHODS: This IRB-approved retrospective study compared 248 s opinion reads of 18 F-FDG PET/CT exams performed for patients with breast cancer against the original outside institution reports. Subspecialist reviews documented if malignant findings on the outside report were believed to be malignant and noted additional malignant findings not described on the outside report. Reference standard for malignancy or benignity was determined by pathology or follow-up imaging. RESULTS: Of 248 cases, 27 (11%) had discrepancies in the presence or absence of extra-axillary nodal or distant metastases. Of these 27, 14 (52%) had biopsy or imaging follow-up as a reference standard for malignancy/benignity. In cases with reference standard proof, the subspecialist second opinion review was correct in 13/14 (93%) of cases. This included eleven cases that the original report called malignant, but the subspecialist review called benign and subsequently proven to be benign; as well as two metastases called on subspecialist review, but not on the original report, and subsequently biopsy proven to be metastases. In one case, the second opinion read called a suspicious lesion that was biopsy proven to be benign. CONCLUSION: Subspecialist review improves the accuracy of diagnosis for the presence or absence of malignancy on FDG PET/CT examinations in patients with breast cancer. This demonstrates the value of performing second opinion reads of 18 F-FDG PET/CT studies in patients with breast cancer, particularly by subspecialist second opinion review reducing false positive reads.


Asunto(s)
Neoplasias de la Mama , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Fluorodesoxiglucosa F18 , Estudios Retrospectivos , Tomografía de Emisión de Positrones/métodos , Derivación y Consulta , Radiofármacos
8.
J Am Coll Radiol ; 19(9): 1052-1068, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35963282

RESUMEN

OBJECTIVE: To quantitatively assess radiologists' preferences for Maintenance of Certification (MOC) and Continuing Certification (CC) using a survey of attitudes and perceptions. METHODS: A questionnaire that assessed attitudes and perceptions and included a discrete choice or trade-off task was developed by ACR staff in conjunction with an independent market research agency and the Survey Subcommittee of the ACR Task Force on Certification in Radiology. The trade-off exercise was integrated into this methodology to better understand the underlying utilities or preferences of the components of MOC-CC among respondents and to better enable specific recommendations on how to optimize the current program. The survey was administered via e-mail to 17,305 ACR members. The demographic and practice characteristics of the 1,994 (11.5%) respondents were similar to the ACR radiologist membership and correspond to a normal distribution. At a 95% confidence level, with a margin of error 2.1%, we believe that the respondent population fairly reflects the actual population. RESULTS: Similar proportions judged the existing program as excellent or very good (36%), or fair or poor (35%), with 27% neutral. MOC-CC was perceived more often as excellent or very good by those who were grandfathered yet still participating in MOC, were in academic practice, were in an urban setting, were older, or had a role with the ABR. In contrast, MOC-CC was more often judged as fair or poor by those who were not grandfathered, were in private practice, were in a rural setting, or were younger. The current MOC-CC program is not well regarded by diplomates, with few showing preference or acceptability. The program's reception is most sensitive to the following attributes: absence or presence of a practice quality improvement requirement, Online Longitudinal Assessment content including or excluding general radiology in addition to one's specialty and inclusion or exclusion of self-assessment as part of the CME. CONCLUSION: ACR members diverged in their attitudes toward MOC, with differences among specific demographic and practice characteristics. The current package of features of MOC-CC was widely viewed as unsatisfactory, and a more optimal feature set arose from a simulation exercise.


Asunto(s)
Radiología , Consejos de Especialidades , Certificación , Competencia Clínica , Educación Médica Continua , Humanos , Radiólogos , Radiología/educación , Estados Unidos
10.
Tomography ; 4(2): 43-45, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30206543

RESUMEN

Prenatal ultrasonography in the early third trimester showed an unusual branching pattern of the right aortic arch. Echocardiography performed 4 h after birth showed the right aortic arch with mirror-image branching, patent ductus arteriosus, and patent foramen ovale. Because the location of the ductus arteriosus was unclear on echocardiography, cardiovascular magnetic resonance imaging was performed 3 days after birth. Advanced techniques including contrast-enhanced time-resolved magnetic resonance angiography and 3D time-of-flight magnetic resonance angiography allowed accurate diagnosis of a vascular ring comprising ascending and descending aorta, right aortic arch with mirror-image branching, and diverticulum of Kommerell giving rise to a left ligamentum arteriosum. The infant had hiccups, but no other symptoms. The esophagram was negative for obstruction. The infant was closely monitored; however, she developed esophageal obstruction at 7 months of age because of the vascular ring. She underwent lysis of the left ligamentum arteriosum followed by aortopexy for relief of esophageal obstruction. This report shows the utility of neonatal cardiovascular magnetic resonance imaging to evaluate complex congenital aortic arch anomalies.

11.
Cureus ; 9(3): e1113, 2017 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-28446992

RESUMEN

Secondary tumoral calcinosis (STC) refers to periarticular calcified masses associated with an identifiable condition. The most common of these identifiable conditions is a chronic renal failure. We present a unique case in which massive periarticular masses in a patient with calcinosis of chronic renal failure (CCRF) are demonstrated in the shoulder and hip on sonography, radiography and computed tomography (CT).

12.
Am J Clin Nutr ; 83(5): 1097-105, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16685052

RESUMEN

BACKGROUND: Grapefruit juice (GFJ) enhances the systemic exposure of numerous CYP3A4 drug substrates, including felodipine, by inhibiting intestinal (but not hepatic) first-pass metabolism. Furanocoumarins have been identified as major CYP3A4 inhibitors contained in the juice, but their contribution to the GFJ effect in vivo remains unclear. OBJECTIVE: To ascertain whether furanocoumarins mediate the GFJ-felodipine interaction, a furanocoumarin-free GFJ was created and tested against orange juice and the original GFJ with respect to the oral pharmacokinetics of felodipine. DESIGN: With the use of food-grade solvents and absorption resins, furanocoumarins were removed (approximately 99%) from whole GFJ, whereas other major ingredients (flavonoids) were retained. In an open, 3-way, randomized crossover design, 18 healthy volunteers ingested felodipine (10 mg) with 1 of the 3 juices (240 mL). Blood was collected over 24 h. At least 1 wk elapsed between juice treatments. RESULTS: The median and range of the area under the curve and the maximum concentration of felodipine were significantly (P < 0.001) greater with consumption of GFJ [110 (range: 58-270) nmol . h/L and 21 (7.6-50) nmol/L, respectively] than with that of orange juice [54 (29-150) nmol . h/L and 7.6 (3.4-13.9) nmol/L, respectively] or furanocoumarin-free GFJ [48 (23-120) nmol . h/L and 8.3 (3.0-16.6) nmol/L, respectively]. GFJ, orange juice, and furanocoumarin-free GFJ did not differ significantly (P > 0.09) in median time to reach maximum plasma concentration [2.5 (1.5-6), 2.8 (1.5-4), and 2.5 (2-6) h, respectively] or terminal half-life [6.6 (4.2-13.6), 7.8 (4.4-13.2), and 6.8 (2.6-14.4) h, respectively]. CONCLUSION: Furanocoumarins are the active ingredients in GFJ responsible for enhancing the systemic exposure of felodipine and probably other CYP3A4 substrates that undergo extensive intestinal first-pass metabolism.


Asunto(s)
Bebidas/análisis , Citrus paradisi/química , Felodipino/farmacocinética , Frutas/química , Furocumarinas/análisis , Furocumarinas/farmacología , Adulto , Células CACO-2 , Citocromo P-450 CYP3A , Inhibidores Enzimáticos del Citocromo P-450 , Interacciones Farmacológicas , Inhibidores Enzimáticos , Felodipino/sangre , Femenino , Furocumarinas/química , Humanos , Intestinos/ultraestructura , Masculino , Microsomas/enzimología
13.
Case Rep Infect Dis ; 2016: 6151570, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27313921

RESUMEN

Eradication of chronic hepatitis C virus (HCV) infection is now possible with all oral antiviral medications, including the combination of ombitasvir, paritaprevir, dasabuvir, and ritonavir (PrOD) with or without ribavirin. While high rates of sustained virologic response (SVR) can be achieved, a small subset of patients experience on-treatment liver enzyme elevations, in particular women using concurrent estradiol-containing oral contraceptive medications (OCPs). Herein, we describe four cases of liver enzyme elevations within 2-3 weeks of PrOD initiation in African-American men infected with HCV genotype 1a or 1b. Three patients with varying degrees of hepatic fibrosis received a full treatment course without medication modification, achieved SVR, and experienced resolution of liver enzyme abnormalities. One patient with cirrhosis was switched mid-treatment to an alternate HCV regimen, experienced subsequent resolution of liver enzyme abnormalities, and achieved SVR. In summary, these cases suggest that all HCV patients treated with PrOD, independent of gender or concurrent medications, should have laboratory monitoring for liver enzyme elevations, with a particular emphasis on early monitoring in cirrhotic patients.

16.
Hepatol Int ; 8(1): 83-93, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26202409

RESUMEN

PURPOSE: Advanced liver fibrosis is a negative predictor of virologic response in genotype 1 chronic hepatitis C (CHC) patients. Biopsy, however, is invasive, costly, and carries some risk of complications. METHODS: Using data from the prospective, international cohort study PROPHESYS, we assessed two alternative noninvasive measures of fibrosis, the FIB-4 and AST-to-platelet ratio index (APRI), to predict virologic response in CHC patients. RESULTS: CHC genotype 1, monoinfected, treatment-naive patients prescribed peginterferon alfa-2a (40 KD)/ribavirin in accordance with country-specific legal and regulatory requirements and who had baseline METAVIR, FIB-4, and APRI scores (N = 1,592) were included in this analysis. Patients were stratified according to the baseline METAVIR, FIB-4, or APRI score to assess virologic response [hepatitis C virus (HCV) RNA <50 IU/mL] by week 4 of treatment (rapid virologic response) and 24 weeks after untreated follow-up ]sustained virologic response (SVR)]. Baseline predictors of SVR were explored by multiple logistic regression, and the strength of the association between each fibrosis measure and SVR was evaluated. Both FIB-4 and APRI scores increased with increasing levels of biopsy-assessed fibrosis. The association between FIB-4 and SVR (p < 0.1 × 10(-30)) was stronger than that between METAVIR (p = 3.86 × 10(-13)) or APRI (p = 5.48 × 10(-6)) and SVR. Baseline factors significantly associated with SVR included male gender, lower HCV RNA, lower FIB-4 score, no steatosis, and higher alanine aminotransferase ratio. CONCLUSION: The FIB-4 index provides a valuable, noninvasive measure of fibrosis and can be used to predict virologic response in patients treated with peginterferon alfa-2a (40  KD)/ribavirin.

17.
Patient Prefer Adherence ; 5: 587-99, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22163158

RESUMEN

BACKGROUND: Peginterferon alfa-2a (40 kDa) is currently administered using a prefilled syringe. The peginterferon alfa-2a disposable autoinjector is a new safety-engineered device designed to facilitate injection and reduce the risk of needlestick injuries. The analysis of two open-label Phase I trials evaluated the pharmacokinetics, successful administration, and tolerability of peginterferon alfa-2a when using the autoinjector. The studies were performed to support the filing and registration of the autoinjector device. METHODS: In trial 1, 50 healthy adult subjects received one 180 µg dose of peginterferon alfa-2a via the autoinjector. Serial blood samples were collected predose, up to 336 hours following drug administration, and at follow-up (28 ± 3 days post-dosing) for noncompartmental pharmacokinetic analysis. Trial 2 randomized 60 adult patients with chronic hepatitis C to 180 µg peginterferon alfa-2a once weekly by the autoinjector or prefilled syringe for 3 weeks followed by the alternative device (prefilled syringe or autoinjector, respectively) for 3 weeks. Patients also received ribavirin. Administration by the devices was evaluated under direct observation by a study staff member and by patient subjective assessment. RESULTS: In trial 1, following a single dose of peginterferon alfa-2a, the maximum plasma concentration was 16.1 ± 5.3 ng/mL (mean ± standard deviation), and area under the concentration time curve (0-168 hours) was 1996 ± 613 ng · hour/mL, similar to that reported using a vial/syringe or prefilled syringe. In trial 2, few patients showed handling difficulties with either device. Generally, patients were observed to be more satisfied and confident, followed instructions better, and successfully initiated injection with the autoinjector versus the prefilled syringe. Patients reported the autoinjector to be more convenient and easier to use. No pain or discomfort was experienced using the autoinjector. The autoinjector safety profile was consistent with that known for peginterferon alfa-2a/ribavirin. CONCLUSION: These results indicate that peginterferon alfa-2a can be successfully and safely delivered via the autoinjector and that the device is easy to handle.

18.
Am J Clin Nutr ; 87(4): 863-71, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18400708

RESUMEN

BACKGROUND: We previously established furanocoumarins as mediators of the interaction between grapefruit juice (GFJ) and the model CYP3A4 substrate felodipine in healthy volunteers using a GFJ devoid of furanocoumarins. It remains unclear whether furanocoumarins mediate drug-GFJ interactions involving CYP3A4 substrates that are also P-glycoprotein substrates. OBJECTIVE: The effects of furanocoumarin-free GFJ on drug disposition were further characterized by using the dual CYP3A4/P-glycoprotein substrate cyclosporine. DESIGN: By randomized crossover design, 18 healthy volunteers received cyclosporine (5 mg/kg) with 240 mL orange juice (control), GFJ, or furanocoumarin-free GFJ. Blood was collected over 24 h. Juice treatments were separated by > or = 1 wk. The effects of diluted extracts of each juice and of purified furanocoumarins on [3H]cyclosporine translocation in Caco-2 cells were then compared. RESULTS: The median (range) dose-corrected cyclosporine area under the curve and the maximum concentration with GFJ (P < or = 0.007), but not with furanocoumarin-free GFJ (P > or = 0.50), were significantly higher than those with orange juice [15.6 (6.7-33.5) compared with 11.3 (4.8-22.0) x 10(-3) h/L and 3.0 (1.6-5.8) compared with 2.4 (1.1-3.1) mL(-1), respectively]. The median time to reach maximum concentration and terminal elimination half-life were not significantly different between the juices (2-3 and 7-8 h, respectively; P > or = 0.08). Relative to vehicle, the GFJ extract, orange juice extract, and purified furanocoumarins partially increased apical-to-basolateral and decreased basolateral-to-apical [3H]cyclosporine translocation in Caco-2 cells, whereas the furanocoumarin-free GFJ extract had negligible effects. Reanalysis of the clinical juices identified polymethoxyflavones as candidate P-glycoprotein inhibitors in orange juice but not in GFJ. CONCLUSIONS: Furanocoumarins mediate, at least partially, the cyclosporine-GFJ interaction in vivo. A plausible mechanism involves the combined inhibition of enteric CYP3A4 and P-glycoprotein.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Citrus paradisi/química , Ciclosporina/farmacocinética , Inhibidores del Citocromo P-450 CYP3A , Inhibidores Enzimáticos/farmacocinética , Furocumarinas/farmacología , Adulto , Área Bajo la Curva , Bebidas/análisis , Células CACO-2 , Citrus/química , Estudios Cruzados , Citocromo P-450 CYP3A/metabolismo , Inhibidores Enzimáticos del Citocromo P-450 , Sistema Enzimático del Citocromo P-450/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Interacciones Alimento-Droga , Frutas/química , Humanos , Masculino , Persona de Mediana Edad
19.
J Clin Gastroenterol ; 40(3): 220-4, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16633123

RESUMEN

GOAL: Our aim was to assess stigmatization by evaluating the impact of hepatitis C virus (HCV) on social interactions, feelings of rejection, internalized shame, and financial insecurity, and behavior. BACKGROUND: HCV patients suffer from slowly progressive disease. Although much research has improved the long-term prognosis of chronic HCV, quality of life may be affected by perceived social stigmatization. STUDY: In a cross-sectional study, HCV patients without cirrhosis or significant comorbidities were recruited from the University of North Carolina viral hepatitis clinic. Subjects completed a questionnaire administered by a trained interviewer that assessed changes in sexual behavior, personal hygiene habits, social function, and interactions. Additionally, subjects completed validated, standardized questionnaires, the Health Status Questionnaire, and the SCL-90-R. Frequencies were calculated for the prevalence of stigmatization and altered social interaction. Correlations between education and behavior changes were assessed. A series of multivariate analyses controlling for age, sex, and education were performed to assess the association between HCV acquisition risk and stigmatization. RESULTS: One hundred seventy-five of 217 potential subjects (81%) participated in the survey. The average age was 45.2+/-7.7 years. Fifty-five percent were men and 53% were single. Twenty-nine percent had some college education. Risk factors for HCV acquisition included transfusion (21%) and injection drug use (29%), whereas 32% had an unknown mode of infection. Among common activities, 47% were less likely to share drinking glasses, 14% were less likely to prepare food, and one-third of subjects were less likely to share a towel. Thirty-five percent of respondents reported changes in their sexual practices. Decreased frequency of kissing and sexual intercourse was reported in 20% and 27% of individuals, respectively. Almost half of the single subjects reported increased use of condoms compared with only 20% among married couples. The majority of subjects perceived financial insecurity, internalized shame, and social rejection. Only 39% reported health impairment. Education level did not influence behavior change. CONCLUSION: The majority of HCV subjects alter common behaviors and report financial insecurity, internalized shame, and social rejection, regardless of the method of HCV acquisition or socioeconomic status. These findings indicate that all HCV individuals be counseled and encouraged to participate in educational programs at the time of diagnosis to reduce unnecessary behavioral changes and stigmatization perceptions to improve quality of life.


Asunto(s)
Hepatitis C Crónica/psicología , Prejuicio , Calidad de Vida/psicología , Estudios Transversales , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Perfil de Impacto de Enfermedad , Encuestas y Cuestionarios
20.
Radiology ; 226(3): 675-85, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12616016

RESUMEN

PURPOSE: To evaluate the spectrum of magnetic resonance (MR) imaging appearances of the liver in primary sclerosing cholangitis (PSC) and to examine their correlation with clinical stage of disease. MATERIALS AND METHODS: Fifty-two patients (25 female, 27 male; mean age, 43 years; age range, 11-87 years) with PSC underwent nonenhanced and gadolinium-enhanced MR imaging. Two abdominal radiologists retrospectively reviewed all images (independently and then in consensus) for the imaging pattern of the liver parenchyma, presence and grade of intrahepatic biliary ductal dilatation, and presence of areas of parenchymal atrophy or abnormal signal intensity and/or gadolinium enhancement. Imaging findings were correlated with Child class, Child-Turcotte-Pugh score, and Mayo end-stage liver disease (MELD) score. Statistical analyses (kappa scoring for interobserver agreement, McNemar test, Mann-Whitney U test, multiple regression analysis, Spearman correlation) were performed. RESULTS: Of 52 patients, seven (13%) had no imaging findings of cirrhosis, 17 (33%) had a diffuse pattern of cirrhosis, and 28 (54%) had a large macronodular pattern (with nodules >or=3 cm) (kappa = 0.84). Intrahepatic biliary ductal dilatation was observed in 44 (85%) patients and was general in 18 (35%) and segmental in 26 (50%). Peripheral wedge-shaped areas of parenchyma were observed with atrophy in 23 (44%) and 25 (48%) patients by the two readers (kappa = 0.76) and without atrophy in 18 (35%) patients by both readers (kappa = 1.00). No correlation was found between imaging findings and clinical scores (P >.05, multiple regression analysis; P =.25-.75, Mann-Whitney U test; Spearman correlation coefficients between -0.33 and 0.33). CONCLUSION: The spectrum of MR imaging appearances of PSC is diverse and comprises distinct patterns that do not appear to correlate with severity of disease. Large regenerative nodules are a frequent finding and may help to establish the diagnosis.


Asunto(s)
Colangitis Esclerosante/patología , Cirrosis Hepática/patología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Niño , Medios de Contraste/administración & dosificación , Femenino , Gadolinio DTPA/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas
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