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United States Food (united + states_food)
Selected AbstractsCutaneous melanoma: available therapy for metastatic diseaseDERMATOLOGIC THERAPY, Issue 1 2006Ahmad A. Tarhini ABSTRACT:, Survival of melanoma varies widely by stage, from a potentially highly curable disease when detected in early stages, to a disease with dismal prognosis when it reaches advanced inoperable stages. Stage IV melanoma defines distant metastasis and continues to comprise an ominous prognosis, with a median survival of 6,9 months. Currently, there is no therapeutic agent known to prolong survival in patients with metastatic melanoma. Therapeutic approaches studied in metastatic melanoma include chemotherapy, biochemotherapy, nonspecific immune adjuvants, cancer-specific vaccines, cytokines, monoclonal antibodies, and specific immunostimulants. Chemotherapy with single-agent dacarbazine is the only United States Food and Drug Administration (US-FDA)-approved chemotherapy agent for metastatic melanoma. Immunological approaches have yielded the only newly US-FDA-approved agent for metastatic disease in 30 years, high-dose bolus IL-2, based on durable responses in some patients with metastatic melanoma, but with associated high toxicity rate and cost. A number of novel therapeutic agents are undergoing active clinical investigation. [source] Telithromycin-associated hepatotoxicity: Clinical spectrum and causality assessment of 42 cases,HEPATOLOGY, Issue 1 2009Allen D. Brinker Telithromycin is the first of a new class of ketolide antibiotics with increased activity against penicillin-resistant and erythromycin-resistant pneumococci. This agent received approval by the United States Food and Drug Administration (FDA) in 2004 for treatment of upper and lower respiratory infections. Following market introduction, spontaneous reports of telithromycin-associated hepatotoxicity, including frank liver failure, were received. To address these reports, an ad hoc group with expertise in spontaneous adverse events reporting and experience in evaluating drug-induced liver injury was formed, including members of the FDA, other federal agencies, and academia. The primary objective of this group was to adjudicate case reports of hepatic toxicity for causal attribution to telithromycin. After an initial screening of all cases of liver injury associated with telithromycin reported to FDA as of April 2006 by one of the authors, 42 cases were comprehensively reviewed and adjudicated. Five cases included a severe outcome of either death (n = 4) or liver transplantation (n = 1); more than half were considered highly likely or probable in their causal association with telithromycin. Typical clinical features were: short latency (median, 10 days) and abrupt onset of fever, abdominal pain, and jaundice, sometimes with the presence of ascites even in cases that resolved. Concurrence in assignment of causality increased after agreement on definitions of categories and interactive discussions. Conclusion: Telithromycin is a rare cause of drug-induced liver injury that may have a distinctive clinical signature and associated high mortality rate. Consensus for attribution of liver injury to a selected drug exposure by individual experts can be aided by careful definition of terminology and discussion. (HEPATOLOGY 2009;49:250-257.) [source] Chromium Picolinate Intake and Risk of Type 2 Diabetes: An Evidence-Based Review by the United States Food and Drug AdministrationNUTRITION REVIEWS, Issue 8 2006Paula R. Trumbo PhD The labeling of both health claims that meet significant scientific agreement (SSA) and qualified health claims on conventional foods and dietary supplements requires pre-market approval by the US Food and Drug Administration (FDA). Approval by the FDA involves, in part, a thorough review of the scientific evidence to support an SSA or a qualified health claim. This article discusses FDA's evidence-based review of the scientific evidence on the role of chromium picolinate supplements in reducing the risk of type 2 diabetes. Based on this evidence-based review, FDA issued a letter of enforcement discretion for one qualified health claim on chromium picolinate and risk of insulin resistance, a surrogate endpoint for type 2 diabetes. The agency concluded that the relationship between chromium picolinate intake and insulin resistance is highly uncertain. SUMMARY In summary (Table 1), there was one intervention study that showed a beneficial effect of chromium picolinate intake on risk of insulin resistance. One other intervention study that provided chromium chloride showed no beneficial effect on insulin resistance. None of the five intervention studies showed a statistically significant beneficial effect of chromium picolinate on FBS and/or OGTT. Furthermore, none of the 10 intervention studies using other forms of chromium showed a beneficial effect of on FBS or OGTT in individuals with normal glucose tolerance. Based on FDA's evidence-based review, the agency concluded that there is very limited credible evidence for a qualified health claim for chromium picolinate and reduced risk of insulin resistance, and therefore reduced risk of type 2 diabetes. The findings of Cefalu et al. have not been replicated, and replication of scientific findings is important to substantiate results. For these reasons, FDA concluded that the existence of a relationship between chromium picolinate intake and reduced risk of either insulin resistance or type 2 diabetes is highly uncertain. On August 25, 2005, FDA issued a letter of enforcement discretion for the labeling of dietary supplements with the following qualified health claim: "One small study suggests that chromium picolinate may reduce the risk of insulin resistance, and therefore possibly may reduce the risk of type 2 diabetes. FDA concludes, however, that the existence of such a relationship between chromium picolinate and either insulin resistance or type 2 diabetes is highly uncertain." The agency concluded that there was no credible evidence to suggest that chromium picolinate intake may reduce the risk of elevated blood glucose levels. [source] Long-Term Structural Failure of Coaxial Polyurethane Implantable Cardioverter Defibrillator LeadsPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 6 2002ROBERT G. HAUSER HAUSER, R.G., et al.: Long-Term Structural Failure of Coaxial Polyurethane Implantable Cardioverter Defibrillator Leads. Transvene models 6936/6966, a coaxial polyurethane ICD lead, may be prone to structural failure. These models comprise 54% of ICD lead failures in the authors' Multicenter Registry database. Because ICD leads perform a vital function, the clinical features, causes, and probability of Transvene 6936/6966 lead failure were determined. The Registry and United States Food and Drug Administration databases were queried for the clinical features and structural causes of the Transvene 6936/6966 lead failure, and a five-center substudy estimated the survival probability for 521 Transvene 6936/6966 implants. The mean time to failure was 4.8 ± 2.1 years, and the estimated survival at 60 and 84 months after implant were 92% and 84%, respectively. Oversensing was the most common sign of failure (76%), and 24 patients experienced inappropriate shocks. The manufacturer's reports indicated that high voltage coil fracture and 80A polyurethane defects were the predominant causes of lead failure. Transvene models 6936 and 6966 coaxial polyurethane ICD leads are prone to failure over time. Patients who have these leads should be evaluated frequently. Additional studies are needed to identify safe management strategies. [source] The Brief Pain Inventory and Its "Pain At Its Worst in the Last 24 Hours" Item: Clinical Trial Endpoint ConsiderationsPAIN MEDICINE, Issue 3 2010Thomas M. Atkinson PhD Abstract Context., In 2006, the United States Food and Drug Administration (FDA) released a draft Guidance for Industry on the use of patient-reported outcomes (PRO) Measures in Medical Product Development to Support Labeling Claims. This draft guidance outlines psychometric aspects that should be considered when designing a PRO measure, including conceptual framework, content validity, construct validity, reliability, and the ability to detect clinically meaningful score changes. When finalized, it may provide a blueprint for evaluations of PRO measures that can be considered by sponsors and investigators involved in PRO research and drug registration trials. Objective., In this review we examine the short form of the Brief Pain Inventory (BPI) and particularly the "pain at its worst in the last 24 hours" item in the context of the FDA draft guidance, to assess its utility in clinical trials that include pain as a PRO endpoint. Results and Conclusions., After a systematic evaluation of the psychometric aspects of the BPI, we conclude that the BPI and its "pain at its worst in the last 24 hours" item generically satisfy most key recommendations outlined in the draft guidance for assessing a pain-reduction treatment effect. Nonetheless, when the BPI is being considered for assessment of pain endpoints in a registration trial, sponsors and investigators should consult with the appropriate FDA division early during research design to discuss whether there is sufficient precedent to use the instrument in the population of interest or whether additional evaluations of measurement properties are advisable. [source] FDA report: Ferumoxytol for intravenous iron therapy in adult patients with chronic kidney disease,,§AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Min Lu On June 30, 2009, the United States Food and Drug Administration (FDA) approved ferumoxytol (FerahemeÔ injection, AMAG Pharmaceuticals), an iron-containing product for intravenous (IV) administration, for the treatment of iron deficiency anemia in adult patients with chronic kidney disease (CKD). The safety and efficacy of ferumoxytol were assessed in three randomized, open-label, controlled clinical trials. Two trials evaluated patients with nondialysis dependent CKD and a third trial assessed patients undergoing hemodialysis. Randomization was either to ferumoxytol or oral iron. Ferumoxytol was administered as two 510 mg IV injections, separated by 3,8 days. Oral iron, Ferro-Sequels®, was administered at a dose of 100 mg twice daily for 21 days. In all three clinical trials, ferumoxytol administration increased the mean blood hemoglobin (Hgb) concentrations by ,1.0 g/dL over the 35 day period, a mean increase that was greater than what was observed in patients receiving oral iron. Patients receiving ferumoxytol also had increases in blood transferrin saturation (TSAT) and ferritin values. For the proposed ferumoxytol dosing regimen, 4.9% of patients had serum ferritin ,800 ng/mL and TSAT ,50% post-treatment. The most important ferumoxytol safety concerns were hypersensitivity reactions and/or hypotension. Anaphylaxis or anaphylactoid reactions were reported in 0.2% of subjects, and other adverse reactions potentially associated with hypersensitivity (e.g., pruritus, rash, urticaria, or wheezing) were reported in 3.7%. Hypotension was observed in 1.9%, including three patients with serious hypotensive reactions. Ferumoxytol administration may transiently affect the diagnostic ability of magnetic resonance imaging and the drug label provides further information regarding this effect. Am. J. Hematol. 2010. Published 2010 Wiley-Liss, Inc. [source] Quality assurance implications for computerized systems following the Able Laboratories FDA InspectionQUALITY ASSURANCE JOURNAL, Issue 1 2006R. D. McDowall Abstract The quality assurance implications for hybrid systems (electronic records with handwritten signatures on the paper copies) following an inspection of a computerized system by the United States Food and Drug Administration (FDA) are explored. The major compliance problem occurred because the paper copies differed, sometime radically, from the electronic records contained within a chromatography data system. These non-compliances ultimately caused the inspected company to go bankrupt. Copyright © 2006 John Wiley & Sons, Ltd. [source] Epigenetic changes in cancer,APMIS, Issue 10 2007KIRSTEN GRØNBÆK A cancer develops when a cell acquires specific growth advantages through the stepwise accumulation of heritable changes in gene function. Basically, this process is directed by changes in two different classes of genes: Tumor suppressor genes that inhibit cell growth and survival and oncogenes that promote cell growth and survival. Since several alterations are usually required for a cancer to fully develop, the malignant phenotype is determined by the compound status of tumor suppressor genes and oncogenes. Cancer genes may be changed by several mechanisms, which potentially alter the protein encoding nucleotide template, change the copy number of genes, or lead to increased gene transcription. Epigenetic alterations, which, by definition, comprise mitotically and meiotically heritable changes in gene expression that are not caused by changes in the primary DNA sequence, are increasingly being recognized for their roles in carcinogenesis. These epigenetic alterations may involve covalent modifications of amino acid residues in the histones around which the DNA is wrapped, and changes in the methylation status of cytosine bases (C) in the context of CpG dinucleotides within the DNA itself. Methylation of clusters of CpGs called "CpG-islands" in the promoters of genes has been associated with heritable gene silencing. The present review will focus on how disruption of the epigenome can contribute to cancer. In contrast to genetic alterations, gene silencing by epigenetic modifications is potentially reversible. Treatment by agents that inhibit cytosine methylation and histone deacetylation can initiate chromatin decondensation, demethylation and reestablishment of gene transcription. Accordingly, in the clinical setting, DNA methylation and histone modifications are very attractive targets for the development and implementation of new therapeutic approaches. Many clinical trials are ongoing, and epigenetic therapy has recently been approved by the United States Food and Drug Administration (US FDA) for use in the treatment of myelodysplastic syndrome (MDS) and primary cutaneous T-cell lymphoma (CTCL). [source] Bioprocess optimization using design-of-experiments methodologyBIOTECHNOLOGY PROGRESS, Issue 6 2008Carl-Fredrik Mandenius Abstract This review surveys recent applications of design-of-experiments (DoE) methodology in the development of biotechnological processes. Methods such as factorial design, response surface methodology, and (DoE) provide powerful and efficient ways to optimize cultivations and other unit operations and procedures using a reduced number of experiments. The multitude of interdependent parameters involved within a unit operation or between units in a bioprocess sequence may be substantially refined and improved by the use of such methods. Other bioprocess-related applications include strain screening evaluation and cultivation media balancing. In view of the emerging regulatory demands on pharmaceutical manufacturing processes, exemplified by the process analytical technology (PAT) initiative of the United States Food and Drug Administration, the use of experimental design approaches to improve process development for safer and more reproducible production is becoming increasingly important. Here, these options are highlighted and discussed with a few selected examples from antibiotic fermentation, expanded bed optimization, virus vector transfection of insect cell cultivation, feed profile adaptation, embryonic stem cell expansion protocols, and mammalian cell harvesting. [source] Inhaled tiotropium bromide and risk of strokeBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2009Anthony Grosso WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Conflicting studies have raised uncertainty over the vascular effects of the long-acting anticholinergic, tiotropium bromide. WHAT THIS STUDY ADDS , Our results show no increased risk of stroke with tiotropium bromide, or with inhaled anticholinergics in general. AIMS A recent communication from the United States Food and Drug Administration highlighted a possible increased risk of stroke associated with use of the relatively new inhaled anticholinergic drug, tiotropium bromide. Using the United Kingdom General Practice Research Database, we set out to assess the risk of stroke in individuals exposed to inhaled tiotropium bromide and two other inhaled treatments for airways disease. METHODS We used the self-controlled case-series that reduces confounding and minimizes the potential for biases in the quantification of risk estimates. RESULTS Of 1043 people with a diagnosis of incident stroke who had had at least one prescription for tiotropium bromide, 980 satisfied inclusion criteria. The age-adjusted incidence rate ratio for all-cause stoke in individuals exposed to tiotropium bromide (n= 980), ipratropium bromide (n= 4181) and fluticasone propionate/salmeterol xinafoate (n= 1000) was 1.1 [95% confidence interval (CI) 0.9, 1.3], 0.8 (95% CI 0.7, 0.9) and 1.0 (95% CI 0.9, 1.2), respectively. CONCLUSIONS We found no evidence of an increased risk of all-cause stroke for individuals exposed to commonly prescribed inhaled treatments for chronic obstructive pulmonary disease. [source] Growth hormone therapy,established uses in short childrenACTA PAEDIATRICA, Issue 2006W. Frederick Schwenk II Abstract Since the first reported efficacious use of human growth hormone in 1958, numerous children have been treated with this hormone. This review discusses the five indications for use of human growth hormone in children that have been approved to date by the United States Food and Drug Administration. Conclusion: Further, long-term studies will be needed to address the optimal use of this hormone in each of these conditions. [source] | ||||||||||