Long-term safety and efficacy of etanercept in children with polyarticular-course juvenile rheumatoid arthritis. |
Thu, Jul 22,2010 |
Methods: Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of >/=30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by >/=30%.)
Results: Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for >/=4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to /=4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit.
Conclusion: Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for >/=4 years.
|
|
Steroid Therapy for a Case of severe drug-induced cholestasis (June). |
Thu, Jul 22,2010 |
|
Case Summary: A 15-year-old girl was admitted with cholestasis probably related to treatment with clarithromycin and nimesulide for an upper respiratory tract infection. Other causes of liver disease (infections, metabolic liver disorders, genetic cholestatic syndromes, autoimmune diseases, primary biliary tract disorders) were excluded. Liver biopsy showed a severe canalicular cholestasis with bile plugs in dilated bile canaliculi, giant cell transformation, and portal and lobular infiltrate. An objective causality assessment suggested that cholestasis was probably related to clarithromycin and/or nimesulide use. No benefit was derived from a course of ursodeoxycholic acid therapy. Since the patient experienced a progressive worsening in cholestasis, prednisone was started after 20 days. This therapy was promptly followed by improvement in clinical and laboratory test results. After 2 months of prednisone treatment, the patient became symptom-free with normal liver function tests.
Discussion: The manifestations of drug-induced hepatotoxicity are highly variable, ranging from asymptomatic hypertransaminemia to fulminant hepatic failure. No specific treatment for drug-induced hepatotoxicity exists. Early recognition and drug withdrawal are the keys to management of hepatotoxicity, but in some cases, liver disease may persist despite discontinuation of the drug. Possible advantages of corticosteroid therapy have not been well demonstrated.
Conclusions: Application of the Naranjo probability scale indicates a probable relationship between cholestasis and nimesulide plus clarithromycin use. This case draws attention to a possible therapeutic option for some cases of drug-induced hepatotoxicity that show a severe course without any sign of improvement.
|
|
A combination treatment of prednisone, aspirin, folate, and progesterone in women with idiopathic recurrent miscarriage: a matched-pair study. |
Thu, Jul 22,2010 |
|
Design: Matched-pair study.
Setting: Academic research institution.
Subject(s): Women with a history of IRM, defined as three or more consecutive miscarriages before 20 weeks' gestation without associated anatomic, cytogenetic, hormonal, and infectious pathologies or antiphospholipid syndrome.
Intervention(s): Eighty of 210 eligible women consented to participate and were treated with prednisone (20 mg/d) and progesterone (20 mg/d) for the first 12 weeks of gestation, aspirin (100 mg/d) for 38 weeks of gestation, and folate (5 mg every second day) throughout their pregnancies. Fifty of 80 women became pregnant; they were compared with 52 women with IRM (matched for age and number of miscarriages), who became pregnant without treatment during the same observation period.
Maim outcome measure(s): Live birth rate, complications of pregnancy, such as preeclampsia, premature birth, and intrauterine growth restriction, and therapy-related side effects.
Result(s): The overall live birth rates of the treatment and control groups were 77% (40 of 52) and 35% (18 of 52) (P=.04). The rates of first and second trimester miscarriage among the treatment and control groups were 19% (10 of 52) and 0 (0 of 52), and 63% (33 of 52) and 2% (1 of 52), respectively (P=.09 and P=1.0, respectively). The median gestational age at birth and median birth weight did not differ between the groups. We observed two and three cases of premature birth among the treatment and control groups, respectively (P=.3) and no cases of intrauterine growth restriction and Cushing's disease. Of 80 women who started treatment, one woman had an ectopic pregnancy and one woman terminated her pregnancy due to fetal chromosome aberration (trisomy 18). Three women stopped treatment due to nausea, depression, and tachycardia.
Conclusion(s): A combination treatment of prednisone, aspirin, folate, and progesterone is associated with a higher live birth rate compared with no treatment in women with IRM.
|
|
Glucocorticoids suppress tumor angiogenesis and in vivo growth of prostate cancer cells. |
Thu, Jul 22,2010 |
|
Experimental Design: The effects of dexamethasone on VEGF and IL-8 expression and cell proliferation were examined using DU145, which expresses glucocorticoid receptor. The effects of dexamethasone on DU145 xenografts were determined by analyzing VEGF and IL-8 gene expression, microvessel density, and tumor volume.
Results: Dexamethasone significantly down-regulated VEGF and IL-8 gene expression by 50% (P < 0.001) and 89% (P < 0.001), respectively, and decreased VEGF and IL-8 protein production by 55% (P < 0.001) and 74% (P < 0.001), respectively, under normoxic condition. Similarly, hydrocortisone down-regulated VEGF and IL-8 gene expression. The effects of dexamethasone were completely reversed by the glucocorticoid receptor antagonist RU486. Even under hypoxia-like conditions, dexamethasone inhibited VEGF and IL-8 expression. In DU145 xenografts, dexamethasone significantly decreased tumor volume and microvessel density and down-regulated VEGF and IL-8 gene expression, whereas dexamethasone did not affect the in vitro proliferation of the cells.
Conclusion: Glucocorticoids suppressed androgen-independent prostate cancer growth possibly due to the inhibition of tumor-associated angiogenesis by decreasing VEGF and IL-8 production directly through glucocorticoid receptor in vivo.
|
|
Organizing pneumonia in patients with hematologic malignancies: A steroid-responsive lesion. |
Thu, Jul 22,2010 |
|
Study objectives: To examine the association of OP with hematologic malignancies and to assess the clinical course of affected patients. Design: A retrospective review of our institutional experience of unexplained OP developing in patients with hematologic malignancies.
Setting: Tertiary care, referral medical center.
Patients: We identified 6 patients with a verified histopathologic diagnosis of OP and antecedent or concomitant diagnosis of a hematologic malignancy from the Mayo Clinic database (1995-2003). Clinical, radiologic, and outcome data were abstracted from records.
Results: Underlying hematologic disorders included lymphoma (2), acute leukemia (2), cutaneous T-cell lymphoma (1), and myelodysplastic syndrome (1). OP was diagnosed by surgical lung biopsy in 4 and bronchoscopic biopsy in 2. Four of the 6 patients had previously been exposed to chemotherapeutic agents, two had not. Three of the 6 patients had bone marrow transplantation prior to development of OP. Five patients were treated with prednisone and all experienced symptomatic improvement with documented radiologic resolution in 4. One patient experienced symptomatic and radiologic resolution with observation alone. Three patients ultimately died from complications of their underlying hematologic disorder and 1 patient died of unknown causes. Two patients were alive without respiratory complaints more than 1 year after lung biopsy.
Conclusions: OP occurs in patients with underlying hematologic malignancies who may or may not have been treated with chemotherapy and responds favorably to corticosteroid therapy.
|
|
The Follicular Lymphoma International Prognostic Index (FLIPI) separates high risk from intermediate or low risk patients |
Thu, Jul 22,2010 |
|
The Follicular Lymphoma International Prognostic Index (FLIPI) was developed to predict prognosis of patients with follicular lymphoma (FL). However, it was based on different protocols, none of which included Rituximab. The current analysis aimed at evaluating the predictive value of the FLIPI for treatment outcome in 362 patients with advanced stage FL treated front-line with Rituximab/CHOP in a prospective trial of the German Low Grade Lymphoma Study Group. According to the FLIPI, 14% of the patients were classified as low risk, 41% as intermediate risk and 45% as high risk patients. With a 2-year time to treatment failure (TTF) of 67%, high risk patients had a significantly shorter TTF as compared to low or intermediate risk patients (2-year TTF of 92% and 90%, respectively; p = 0.0002). Our data demonstrate that the FLIPI is able to identify high risk patients with advanced stage FL after first-line treatment with Rituximab/chemotherapy.
|
|
Nocardia brain abscesses in a male patient with SLE: successful outcome despite delay in diagnosis. |
Thu, Jul 22,2010 |
|
He had been treated intermittently from May 2001 to November 2004 with intravenously (i.v.) administered cyclophosphamide and high doses of prednisone due to unrelenting proteinuria. In November 2004, he was admitted to the hospital because of deterioration of renal function and massive proteinuria (21 g dl(-1) 24 h(-1)) and treated with pulses of methylprednisolone and two courses of i.v. administered cyclophosphamide. His hospital course was complicated by cellulitis and bacteremia with Pseudomonas spp. and Streptococcus bovis. He was discharged on prednisone 60 mg daily, ciprofloxacin, augmentin, and hemodialysis. He was readmitted a week later with new onset of seizure activity, slurred speech, and left-sided hemiparesis. Magnetic resonance imaging of the brain revealed multiple ringlike enhancing foci in the frontal and occipital lobes. Brain biopsy was performed, and Gram stain and initial cultures were negative. Empiric tobramycin, cefepime, and metronidazole were administered. Diagnosis was delayed for several months, but culture eventually grew Nocardia asteroides. Trimethoprim-sulfomethoxazole and linezolid therapy was begun. This was followed by slow, but steady, clinical improvement. Risk factors, diagnostic clues, and treatment are reviewed.
|
|
Complete anterior pituitary failure and postpartum cardiomyopathy. |
Thu, Jul 22,2010 |
|
OBJECTIVE: To present a case of presumed autoimmune hypophysitis that occurred concurrently with severe postpartum cardiomyopathy and pneumonitis. METHODS: We describe the clinical, laboratory, and imaging findings in a young postpartum woman who presented with decompensated heart failure. RESULTS: Two weeks after childbirth, a 37-year-old previously healthy woman required urgent pericardiocentesis and inotropic support because of new-onset left ventricular systolic dysfunction, pericardial effusions, and hypotension. Analysis of pericardial fluid was negative for malignant cells and culture, and no cardiac tamponade or thrombus was evident. Results of a rheumatologic serology survey were negative, as was an assessment for antithyroid antibodies. Chest radiography revealed bilateral pleural effusions. Magnetic resonance imaging of the pituitary showed a homogeneously enlarged gland, consistent with the postpartum state, but no discrete pituitary lesions. Laboratory results included low levels of thyrotropin, free triiodothyronine, free thyroxine, and cortisol and a high erythrocyte sedimentation rate. The patient's symptoms responded to prednisone therapy (60 mg/day) as well as an angiotensin-converting enzyme inhibitor and a b -adrenergic blocking agent. Follow-up magnetic resonance images showed an atrophic pituitary with an empty sella turcica. CONCLUSION: To our knowledge, this is the first reported case of concomitant presumed autoimmune hypophysitis, complete anterior pituitary failure, postpartum cardiomyopathy, and pneumonitis.
|
|
A phase II trial of rituximab as adjuvant to intensive sequential chemotherapy in patients under 60 years with untreated poor-prognosis diffuse large B-cell lymphoma. |
Thu, Jul 22,2010 |
|
The potential benefit of rituximab as adjuvant to high-dose therapy (HDT) has been investigated in patients under 60 years with poor-risk (age-adjusted international prognostic index at 2-3) CD20+ diffuse large B-cell lymphoma (DLBCL). The treatment consisted of four cycles of high-dose CEOP (cyclophosphamide, epirubicin, vincristine, prednisone), plus etoposide and cisplatin during the two last cycles. Peripheral blood stem cells were collected after cycle 1, and reinfused after cycles 3 and 4. Four weekly rituximab infusions were subsequently delivered. Among the 36 patients included, 30 could complete chemotherapy schedule, and 24/36 received rituximab. A complete response occured in 26/36 patients (72%). With a median follow-up of 30 months, the estimated 5-year overall survival (OS) and event-free survival (EFS) rates (mean +/- s.d.) were 65 +/- 16 and 63 +/- 15%, respectively. For the 24 patients who received both chemotherapy and rituximab, the estimated 5-year OS and EFS rates were 86 +/- 14 and 82 +/- 15%. These data suggest that rituximab after HDT is feasible. Both complete remission rate and survival curves compare favorably with the poor outcome usually observed in high-risk DLBCL patients managed with HDT without rituximab.
|
|
Sensitivity analysis of cost factors for various therapy options in the treatment of follicular lymphoma. |
Thu, Jul 22,2010 |
|
BACKGROUND: In Germany, patients with relapsed follicular non-Hodgkin's lymphoma do not all receive the same treatment. In this study, 3 therapy regimens were analyzed which were considered to be similar. With the goal of determining the treatment option with the lowest direct costs whilst maintaining the same degree of effectiveness, a cost analysis model was established and applied by way of example to the existing illness constellation. METHODS: The German doctors' fee scale (Einheitlicher Bewertungsmassstab, EBM) valid until 2005 served as the basis for the calculation of medical services within the scope of the present statutory health insurance guidelines. A virtual standard patient was constructed for the cost model and treated with the different therapy regimens. The incidences of individual adverse events described in literature served as the basis for the characterization of the average toxicity of the respective treatment methods. RESULT: The overall costs result from the sum of the treatment costs and the toxicity-related costs. The effect of additional interventions on the overall cost was also examined. CONCLUSION: Whereas the accompanying documentation of costs in clinical studies is organizationally complex and very tedious, the model applied here offers a reliable method of quantifying the costs of the different therapy regimens. It permits the comparison of different treatment alternatives, and it enables, by means of a cost variance analysis, the identification of cost drivers and less expensive measures within a therapy method.
|
|
|
