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Multicenter Trials (multicenter + trials)
Selected AbstractsNew growth factor therapies aimed at improving intestinal adaptation in short bowel syndromeJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2006Prue M Pereira Abstract Short bowel syndrome (SBS) is used to describe a condition of malabsorption and malnutrition resulting from the loss of absorptive area following massive small bowel resection. The key to improved clinical outcome after massive small bowel resection is the ability of the residual bowel to adapt. Although still in experimental stages, a major goal in the management of SBS may be the augmented use of growth factors to promote increased adaptation. A number of growth factors have been implicated in promoting the adaptation process. The best-described growth factors are reviewed: glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF), and growth hormone (GH). This article reviews the ability of recombinant GLP-2, EGF and GH to modulate structural and functional aspects of intestinal adaptation following small bowel resection. Although these growth factors have shown promise, small sample size, inconsistent measurement parameters and uncontrolled study designs have hampered the acquisition of strong data advocating the use of growth factor treatment for SBS. Multicenter trials using well-defined outcome measures to assess clinical efficacy are needed to direct the clinical indications, timing and duration of therapy and assess potential risks associated with growth factor therapies. [source] New prospects for immunotherapy at diagnosis of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Paolo Pozzilli Immune intervention at diagnosis of type 1 diabetes (T1D) aims to prevent or reverse the disease by blocking autoimmunity, thereby preserving/restoring ,-cell mass and function. Recent clinical trials of non-specific and of antigen-specific immune therapies have demonstrated the feasibility of modulation of islet-specific autoimmunity in patients with partial prevention of loss of insulin secretion. In a series of review articles published in this issue of the journal, some of the most promising approaches of immune intervention in T1D are presented. Here we outline the rationale of such interventions and future prospects in this area. Copyright © 2009 John Wiley & Sons, Ltd. Insulin therapy in type 1 diabetes (T1D) rescues the patient from a certain death but not cure the disease. The goal of any therapeutic intervention in T1D is the preservation of insulin-secreting cells; this is achieved by the abrogation of pathogenic reactivity to beta cell autoantigens while preserving full capacity to generate a normal immune response against foreign antigens. Although several therapeutic candidates have been investigated in experimental models of T1D many of which showed promising results, a successful extrapolation of these findings to human T1D has proved to be difficult. In part, this failure results from the considerable disease heterogeneity associated with diverse genetic and non-genetic disease determinants and the spectrum of clinical phenotype at diagnosis. Thus, a younger age at onset is associated with stronger genetic susceptibility, more intense immune response to ,-cell antigens, shorter duration of symptoms, more severe metabolic derangement at diagnosis and a more rapid rate of ,-cell-destruction 1,3. Therefore, designing therapies that would be effective in all clinical settings is definitely challenging. In this issue five different approaches are discussed ranging from antigen-specific therapies [DiaPep277 and glutamic acid decarboxylase(GAD)], to non-antigen-specific immunoregulation (anti-CD3) and to anti-inflammatory (anti-IL1 receptor antagonist). These approaches are currently being tested in large international multicenter trials, and all of them use very similar outcome in terms of a beneficial effect (C-peptide secretion as evidence of a therapeutic effect on restoration of ,-cell function). The authors have been asked to follow a similar format in presenting their approaches so that the reader can easily compare them in terms of rationale and therapeutic goals. [source] The Reliability of Echocardiographic Left Ventricular Wall Motion Index to Identify High-Risk Patients for Multicenter StudiesECHOCARDIOGRAPHY, Issue 1 2006Gunnar H. Gislason M.D. Objective: To study whether the use of echocardiographic left ventricular (LV) wall motion index (WMI) is a dependable parameter for identifying patients with LV dysfunction to be enrolled in multicenter trials. Methods: Videotaped echocardiographic examinations from 200 randomly selected patients that were screened for inclusion into the DIAMOND-CHF and DIAMOND-MI trials were reevaluated by an external expert echocardiographer. WMI was calculated using the 16-segment LV model. Results: The external echocardiographer systematically found lower values of WMI than the core laboratory. The average difference in WMI was 0.18 (SD: 0.33) in the DIAMOND-CHF trial and 0.09 (SD: 0.33) in the DIAMOND-MI trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials. The cutoff value for inclusion into the DIAMOND trials was WMI , 1.2. There was an agreement on WMI dichotomized to below or above 1.2 in 82% of the patients in both trials ( , coefficient 0.66 for the DIAMOND-CHF and 0.55 for the DIAMOND-MI). Conclusions: Despite substantial interlaboratory variation in WMI in individual patients and a systematic lower WMI score by the external echocardiographer there was an acceptable overall agreement for identifying patients with severe impairment of LV function. This not only underscores the value of LV-WMI as a useful tool for selecting high-risk patients to be included in multicenter studies but also serves to warn against the use of rigid cutoff values for WMI in the treatment of individual patients. [source] National Institute of Neurological Disorders and Stroke (NINDS): Advances in understanding and treating neuropathy, 24,25 October 2006; Bethesda, MarylandJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2008Eva L. Feldman Abstract National Institute of Neurological Disorders and Stroke sponsored a meeting to explore the current status of basic and clinical research in peripheral neurobiology and clinical neuropathy. The goal of the workshop was to identify areas where additional research could lead to the development of new therapeutics in the next 5 years. Participants discussed the current understanding of disease mechanisms of axonal and demyelinating neuropathies, existing techniques in research, disease biomarkers, and assessment of neuropathy. Painful neuropathies were discussed at the basic scientific and clinical levels in relation to new insights into etiology and treatment. The meeting concluded with a discussion on therapeutic development in neuropathy and the need for a unified approach to multicenter trials. Short-term goals of the workshop were to form a working group for neuropathy, the Peripheral Neuropathy Study Group, and to translate new scientific findings into therapies and complete clinical trials. [source] Could Prolonged Air Travel Be Causally Associated with Subclavian Vein Thromboembolism?JOURNAL OF TRAVEL MEDICINE, Issue 1 2002Theodore Teruya Background: Air travel associated with venous thromboembolism has recently achieved public awareness due to intense media coverage. The interest has focused on deep vein thrombosis (DVT) of the lower limbs with pulmonary embolism. The World Health Organization (WHO) is planning several international multicenter trials to study the problem and, if it exists, try to find a means for prevention. Methods: This is a case presentation of acute venous thromboembolism of the upper limbs associated with long-haul flights. Five patients were admitted to Straub Hospital in Honolulu after 5 to 10 hours' flight. Results: Patient 1 had a previous shoulder injury with DVT; patient 2 had chronic atrial fibrillation; patients 3 and 5 had clavicular fractures; and patient 4 had a subclavian vein compression. Conclusion: It is not possible to draw any conclusions about the association between air flights and subclavian vein thrombosis from this small retrospective case study. Our objective was to indicate the possibility of such a relationship. [source] Banff '09 Meeting Report: Antibody Mediated Graft Deterioration and Implementation of Banff Working GroupsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010B. Sis The 10th Banff Conference on Allograft Pathology was held in Banff, Canada from August 9 to 14, 2009. A total of 263 transplant clinicians, pathologists, surgeons, immunologists and researchers discussed several aspects of solid organ transplants with a special focus on antibody mediated graft injury. The willingness of the Banff process to adapt continuously in response to new research and improve potential weaknesses, led to the implementation of six working groups on the following areas: isolated v-lesion, fibrosis scoring, glomerular lesions, molecular pathology, polyomavirus nephropathy and quality assurance. Banff working groups will conduct multicenter trials to evaluate the clinical relevance, practical feasibility and reproducibility of potential changes to the Banff classification. There were also sessions on quality improvement in biopsy reading and utilization of virtual microscopy for maintaining competence in transplant biopsy interpretation. In addition, compelling molecular research data led to the discussion of incorporation of omics-technologies and discovery of new tissue markers with the goal of combining histopathology and molecular parameters within the Banff working classification in the near future. [source] Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: A combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trialsCANCER, Issue 6 2009By the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR), the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO) Abstract BACKGROUND: Primary surgery followed by platinum-taxane based chemotherapy has been the standard therapy in advanced ovarian cancer. However, the prognostic role of complete and so-called optimal and suboptimal debulking and its interaction with biological factors has not been not fully defined. METHODS: Exploratory analysis was conducted of 3 prospective randomized trials (AGO-OVAR 3, 5, and 7) investigating platinum-taxane based chemotherapy regimens in advanced ovarian cancer conducted between 1995 and 2002. RESULTS: A total of 3126 patients were analyzed. Approximately one-third each fulfilled criteria for complete resection (group A), small residual tumor burden of 1-10 mm (group B), or macroscopic residual disease exceeding 1 cm in diameter (group C). Multivariate analysis showed improved progression-free and overall survival for group A with complete resection compared with groups B or C (P < .0001). The impact of so-called optimal debulking as in group B showed a smaller prognostic impact compared with group C. Further independent prognostic factors for overall survival were age, performance status, grade, FIGO stage, and histology, namely the mucinous subtype. An interaction between residual tumor and some biologic factors was demonstrated. CONCLUSIONS: The goal of primary surgery should be complete resection. The prognostic impact of tumor biology seemed to be partially overruled by residual tumor and further evaluation of biologic factors should stratify for residual tumor. Cancer 2009. © 2009 American Cancer Society. [source] Cancer chronotherapy: Principles, applications, and perspectivesCANCER, Issue 1 2003Marie-Christine Mormont Ph.D. Abstract BACKGROUND Cell physiology is regulated along the 24-hour timescale by a circadian clock, which is comprised of interconnected molecular loops involving at least nine genes. The cellular clocks are coordinated by the suprachiasmatic nucleus, a hypothalamic pacemaker that also helps the organism adjust to environmental cycles. The rest-activity rhythm is a reliable marker of the circadian system function in both rodents and humans. This circadian organization is responsible for predictable changes in the tolerability and efficacy of anticancer agents, and possibly also may be involved in tumor promotion or growth. METHODS Expected least toxic times of chemotherapy were extrapolated from experimental models to human subjects with reference to the rest-activity cycle. The clinical relevance of the chronotherapy principle (i.e., treatment administration as a function of rhythms) has been investigated previously in randomized multicenter trials. RESULTS In the current study, chronotherapeutic schedules were used to safely document activity of the combination of oxaliplatin, 5-fluorouracil, and leucovorin against metastatic colorectal carcinoma and to establish new medicosurgical management for this disease, and were reported to result in unprecedented long-term survival. CONCLUSIONS Chronotherapy concepts appear to offer further potential to improve current cancer treatment options as well as to optimize the development of new anticancer or supportive agents. Cancer 2003;97:155,69. © 2003 American Cancer Society. DOI 10.1002/cncr.11040 [source] Which place for surgery for macular edema due to diabetic retinopathy ?ACTA OPHTHALMOLOGICA, Issue 2009JB JONAS Purpose To present treatment options for macular edema Methods The various types of macular edema will briefly be discussed and available and potentially future treatment strategies will be presented. Results The results of the current multicenter trials as well as the findings of previous studies using different medical agents for the treatment of diabetic macular edema will be compared. Conclusion It may still be unclear which treatment strategy appears to be the best for which type of diabetic macular edema. Commercial interest [source] | ||||||||||