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Recent Trials (recent + trials)
Selected AbstractsCorticosteroid Osteoporosis: Practical Implications of Recent TrialsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2000Philip N. Sambrook Abstract Corticosteroids are widely used and effective agents for control of many inflammatory diseases, but osteoporosis is a common problem associated with their long-term use. Several large double-blind controlled clinical trials in patients with corticosteroid osteoporosis recently have been published, indicating it is possible to prevent or reverse this bone loss. Ultimately, the aim of treatment is to prevent fractures, especially vertebral fractures that are the most common type of fracture associated with corticosteroid therapy, yet it remains unclear exactly which patients should receive prophylaxis. Understanding the differences between these trials is key to interpreting the results, which have important practical implications for patient management. [source] Long-Term Incidence of Malignant Ventricular Arrhythmia and Shock Therapy in Patients with Primary Defibrillator Implantation Does Not Differ from Event Rates in Patients Treated for Survived Cardiac ArrestJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 5 2005ULRICH BACKENKÖHLER M.D. Introduction: Recent trials have demonstrated benefit of prophylactic defibrillator (ICD) implantation compared to conventional treatment in high-risk patients. However, many patients have rare or no sustained arrhythmias following implantation. Our study addresses the question, whether patients with prophylactic defibrillator implantation have a lower risk for life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) compared to sudden cardiac death (SCD) survivors. Methods and Results: Over 7 years we enrolled 245 patients. Occurrence of spontaneous sustained VT/VF resulting in adequate ICD treatment was the endpoint. Incidence, type, and treatment of sustained arrhythmia in 43 previously asymptomatic ICD recipients (group B) were compared to data of 202 survivors of imminent SCD (group A). All patients had severely impaired left ventricular ejection fraction (<45%). Group B patients had long runs (>6 cycles, <30 s) of VT during Holter monitoring and inducible sustained arrhythmia. Incidence of rapid VT and VF (cycle length <240 ms/heart rate >250 bpm) after 4 years (35% in both groups, P = ns) and adequate defibrillator therapies (57% vs 55%, P = ns) were similar in both groups after univariate and multivariate analysis. Cumulative mortality tended to be lower in group B compared to group A, but the difference was not statistically significant. Conclusion: During long-term follow-up, incidence of sustained rapid ventricular arrhythmia in prophylactically treated patients is as high as that of SCD survivors. Benefit from defibrillator implantation for primary prevention (group B) appears to be comparable to that for survived cardiac arrest (group A). [source] Overcoming immunological tolerance to melanoma: Targeting CTLA-4ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2010F Stephen HODI Abstract The use of immunotherapeutics in melanoma has received much attention, and recent advances to further characterize the regulatory components of the immune system and the importance of co-stimulatory molecules have opened a new area for clinical investigation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) serves as a negative regulator of immunity. Recent trials administering fully human anti-CTLA-4 monoclonal antibodies to melanoma patients have demonstrated clinically meaningful responses. Treatment with CTLA-4 blocking antibodies, however, is not without potential toxicities. Autoimmune side-effects, the most common being colitis-associated diarrhea, are frequently associated with clinical responses. In efforts to build upon prior vaccination efforts as well as attempt to offer patients clinically meaningful immune responses with a CTLA-4 blockade but without significant toxicities, we conducted a clinical trial in patients who previously received autologous tumor cells engineered to secrete granulocyte-macrophage colony stimulating factor (GVAX; Cell Genesys, South San Francisco, CA, USA) with periodic infusions of CTLA-4 blocking antibodies. This sequential treatment resulted in clinically significant anti-tumor immunity without grade 3 or 4 toxicity in most patients. Pathological analyses following treatment of pre-existing tumors revealed a linear correlation between tumor necrosis and the ratio of intra-tumoral CD8+ effector cells to FoxP3+ regulatory cells (Tregs). Effective anti-tumor immunity and serious autoimmunity can be disassociated. Further targeting of anti-tumor Tregsin combinatorial therapy approaches may be a rich avenue of future investigation. [source] Nutrition, mood and behaviour: a reviewACTA NEUROPSYCHIATRICA, Issue 5 2009Nerissa L Soh Objective: To conduct a critical review of recent empirical research regarding mood, behaviour and nutrition factors including essential fatty acids, macronutrients, micronutrients and food additives. Method: A literature search of databases Medline, PsycInfo, CINAHL and Embase up to October 2008. The search emphasised empirical research published in the last 10 years and also included older literature. Studies in both adults and children were addressed. Results: Research into omega-3 fatty acids has been substantial but evidence for their potential in treating mood and behaviour is modest. In comparison, there has been much less research into carbohydrate and protein intakes and little evidence for their ability to influence mood and behaviour. Recent trials with food additives suggest their removal from the diet may benefit susceptible children with hyperactivity disorders. Micronutrient supplementation appears to improve mood only in those who were initially deficient in micronutrients. Conclusions: More stringent research designs such as longitudinal studies and the use of biologically inert placebos within randomised controlled trials are needed before supplemental use of omega-3 fatty acids to treat disorders of mood and behaviour can be recommended. Caution is advised regarding the indiscriminate use of diets free of artificial food additives in managing hyperactivity disorders, as they may place an undue burden on individuals and their families. Should omega-3 fatty acid supplementation or the elimination of certain food additives be established as effective, they may provide cost-effective, accessible and well-tolerated adjuncts to standard psychiatric treatments for mood and behavioural disturbances. [source] Botulinum toxin in the management of cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2004Rosalind J Jefferson MB BS BSc PhD DIC MRCP MRCPCH Botulinum toxin has rapidly gained wide acceptance as a treatment for focal spasticity, and is becoming more readily available. Early studies established its effectiveness, but many issues are still open for discussion. After a brief re view of the historical and scientific development of botulinum toxin as a clinical tool and an outline of previous work in the field, some important questions are discussed in the light of more recent trials. [source] Nutrition in patients with Type 2 diabetes: are low-carbohydrate diets effective, safe or desirable?DIABETIC MEDICINE, Issue 7 2005R. L. Kennedy Abstract Low-carbohydrate diets have been around for over 100 years. They have become very popular recently but the scientific basis for their use remains to be fully established. This article reviews the recent trials that have been published and also what is known about the effects of low-carbohydrate, high-protein diets on energy expenditure and body composition. Although many controversies remain, there is now mounting evidence that these diets can lead to effective weight loss and may thus be a useful intervention for patients who have, or are at risk of, diabetes. The practical aspects of using these diets as a short- to medium-term intervention are discussed. [source] Rapid infusion of a phospholipid emulsion attenuates the effects of endotoxaemia in horsesEQUINE VETERINARY JOURNAL, Issue 3 2007J. N. MOORE Summary Reasons for performing study: Endotoxaemia currently is associated with a poor prognosis in horses. The results of recent trials in other species indicate that phospholipid emulsions reduce the deleterious effects of endotoxin (LPS). However, in a previous study in horses, a 2 h infusion of emulsion caused an unacceptable degree of haemolysis. Hypothesis: Rapid administration of a lower total dose of emulsion would reduce the effects of LPS and induce less haemolysis; the emulsion would reduce inflammatory effects of LPS in vitro. Methods: Twelve healthy horses received an i.v. infusion either of saline or a phospholipid emulsion (100 mg/kg), followed immediately by E. coli O55:B5 LPS (30 ng/kg). Clinical parameters, haematological profiles, serum tumour necrosis factor (TNF) activity, serum lipid profiles, urine analyses and severity of haemolysis were monitored before and at selected times after LPS. Monocytes were also incubated in vitro with LPS in the presence or absence of emulsion, after which TNF and tissue factor activities were determined. Results: Clinical signs of endotoxaemia were reduced in horses receiving the emulsion, including clinical score, heart rate, rectal temperature, serum TNF activity, and the characteristic leucopenic response to LPS, when compared to horses not receiving the emulsion. Three horses receiving the emulsion had none, 2 had mild and one had moderate haemolysis. There were no differences in urinalysis results and creatinine concentrations, either within the groups over time or between the groups. Serum concentrations of phosphatidylcholine, bile acids and triglycerides peaked immediately after the infusion; there were no significant changes in concentrations of nonesterified fatty acids or cholesterol. Incubation of equine monocytes with emulsion prevented LPS-induced TNF and tissue factor activities. Conclusions: Rapid administration of emulsion significantly reduced inflammatory effects of LPS in vivo and caused a clinically insignificant degree of haemolysis. The results of the in vitro studies indicate that emulsion prevents not only LPS-induced synthesis of cytokines, but also expression of membrane-associated mediators (i.e. tissue factor). Potential relevance: Rapid i.v. administration of emulsions containing phospholipids that bind endotoxin may provide a clinically useful method of treating endotoxaemia in horses. [source] Positioning biologic agents in the treatment of Crohn's disease,INFLAMMATORY BOWEL DISEASES, Issue 10 2009Stephen B. Hanauer MD Abstract One decade after the emergence of biologic therapy for Crohn's disease (CD), our treatment algorithms are beginning to change. Once reserved for patients with refractory disease, disease unresponsive to conventional therapies, or those requiring multiple courses of corticosteroids, there is increasing evidence that early, aggressive interventions with immunosuppressants or biologic therapies targeting tumor necrosis factor-, or ,-4 integrins can alter the natural history of CD by reducing the transmural complications of structuring and fistulization and the nearly inevitable requisite for surgical resections. More recent trials are beginning to suggest that intervention with combination therapy for selected patients with a poor prognosis may modify the long-term course of CD. Selection of patients with features predicting a complex or progressive course and early, combined intervention is now possible. Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy. (Inflamm Bowel Dis 2009) [source] Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C , an updated Cochrane reviewALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010J. Brok Aliment Pharmacol Ther 2010; 32: 840,850 Summary Background, Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C. Aim, To meta-analyse the effect of adding ribavirin to interferon for chronic hepatitis C. Methods, The results of randomized trials were combined in cumulative meta-analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver-related morbidity plus all-cause mortality. Results, We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64,0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P -value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes. Conclusions, The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes. [source] An analysis of the placebo effect in Crohn's disease over timeALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 1 2010W. C. GALLAHAN Summary Background, Randomized, placebo controlled trials are used to assess the efficacy of therapies for Crohn's disease. The placebo response and remission rates vary among studies. Aim, To analyse how the placebo response and remission rates in Crohn's trials have changed over time in the era of parenteral biologic therapies. Methods, A search for randomized, placebo-controlled trials of parenteral biologic therapies for active Crohn's disease was conducted using online databases. The placebo response and remission rates and study week of evaluation were recorded for each trial. The placebo response and remission rates were analysed as functions of publication date and study week of evaluation. Results, The odds of a placebo-induced remission and response significantly increased as the week of evaluation increased. The placebo remission rate increased significantly with year of publication. Adjusted for week of evaluation, this increase in placebo remission rate over time was no longer significant. The increase in the placebo response over this time period was not statistically significant. Conclusion, The observed increase in placebo remission rates over time in trials of parenteral biologic therapies in Crohn's disease is explained by longer times to the primary endpoint in more recent trials. [source] Recent failures of new potential symptomatic treatments for parkinson's disease: Causes and solutionsMOVEMENT DISORDERS, Issue 7 2004Gurutz Linazasoro MD Abstract One major goal of current research in Parkinson's disease (PD) is the discovery of novel agents to improve symptomatic management. The object of these new treatments should be to provide effective symptom control throughout the course of the disease without the development of side effects such as motor and psychiatric complications. Results of several clinical trials of new treatment options reported in the past 2 years have shown negative or unsatisfactory results. Most of the drugs and surgical procedures used in these studies had been tested previously in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkeys as well as in the classic 6-hydroxydopamine,lesioned rat model. They raise several questions about the true reliability of animal studies, the adequacy of the working hypotheses and design of clinical trials, the validity of tools in current use to evaluate a specific effect, and the selectivity of the drugs used. All these factors may explain failure. This review focuses on pharmacological and surgical treatments tested to improve the management of patients with motor fluctuations and dyskinesias. Some of the recent trials and possible reasons for their lack of success are critically analysed. Finally, some suggestions to avoid further failures and improve results are proposed. © 2004 Movement Disorder Society [source] Psychiatric morbidity in psoriasis: A reviewAUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 3 2004Paul AJ Russo SUMMARY Psoriasis is a common condition, affecting 1.5,2% of the population of industrialized countries. It is important for clinicians to be aware that psoriasis can have a substantial emotional impact on an individual, which is not necessarily related to the extent of skin disease. This review examines current literature addressing the psychological and emotional aspects of psoriasis. A literature search of the MEDLINE (1966,2002) and PsycINFO (1984,2002) computer databases and bibliographies was carried out. Papers selected for the review included English language reviews and all original research relevant to the topic, in the form of randomized controlled trials, cohort studies, case,control studies, cross-over and uncontrolled clinical trials, patient surveys, quality-of-life studies, case series and case reports. Despite significant shortcomings, the available prevalence studies showed uniformly high rates of psychopathology among psoriasis sufferers. The few intervention studies available are summarized and critically discussed. Psoriasis is associated with a variety of psychological problems, including poor self esteem, sexual dysfunction, anxiety, depression and suicidal ideation. The clinical severity of the psoriasis may not reflect the degree of emotional impact of the disease. A number of psychological interventions have shown promise in recent trials. It is important that clinicians consider the psychosocial aspects of this illness. [source] The Treatment of Cognitive Impairment Associated with Parkinson's DiseaseBRAIN PATHOLOGY, Issue 3 2010David J. Burn FRCP Abstract Cognitive impairment and dementia associated with Parkinson's disease (PD) are common and often have devastating effects upon the patient and their family. Early cognitive impairment in PD is frequent, and the functional impact may be underestimated. Optimal management will rely upon better identification of the predominant symptoms and greater knowledge of their pathophysiological basis. The management of dementia in PD (PD-D) also has to consider the significant neuropsychiatric burden that frequently accompanies the cognitive decline, as well as fluctuations in attention. Atypical anti-psychotics have a limited role at present in treating PD-D, although new drugs are under development. The mainstay of drug management for people with PD-D is cholinesterase inhibitors, although recent trials have suggested that the N-methyl-D aspartate antagonist memantine may also have some benefit. Disease modification remains the ultimate goal for preventing the inexorable decline in PD-D, although effective interventions are still some way off. Limited benefit may, however, be possible through exercise programmes and so-called "medical foods", although randomised trials are required to confirm largely anecdotal observations. [source] Either interleukin-12 or interferon-, can correct the dendritic cell defect induced by transforming growth factor ,1 in patients with myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2004Ross Brown Summary The poor response to immunotherapy in patients with multiple myeloma (MM) indicates that a better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed. Recently we reported that high potency (CMRF44+) dendritic cells (DC) in the peripheral blood of patients with MM failed to significantly up-regulate the expression of the B7 co-stimulatory molecules, CD80 and CD86, in response to an appropriate signal from soluble trimeric human CD40 ligand. This defect was caused by transforming growth factor ,1 (TGF,1) and interleukin (IL)-10, produced by malignant plasma cells, and the defect was neutralized in vitro with anti-TGF,1. As this defect could impact on immunotherapeutic strategies and may be a major cause of the failure of recent trials, it was important to identify a more clinically useful agent that could correct the defect in vivo. In this study of 59 MM patients, the relative and absolute numbers of blood DC were only significantly decreased in patients with stage III disease and CD80 up-regulation was reduced in both stage I and stage III. It was demonstrated that both IL-12 and interferon- , neutralized the failure to stimulate CD80 up-regulation by huCD40LT in vitro. IL-12 did not cause a change in the distribution of DC subsets that were predominantly myeloid (CD11c+ and CDw123,) suggesting that there would be a predominantly T-helper cell type response. The addition of IL-12 or interferon- , to future immunotherapy trials involving these patients should be considered. [source] The impact of retroviral suicide gene transduction procedures on T cellsBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2003Waseem Qasim Summary., Retroviral vectors encoding the herpes simplex thymidine kinase gene have been used to render T cells sensitive to the prodrug ganciclovir. Such genetically modified T cells have been used in clinical trials for their graft-versus-leukaemia effects following allogeneic haematopoietic stem cell transplantation. In the event of graft-versus-host disease (GVHD) the cells were susceptible to elimination through exposure to ganciclovir. We have investigated the impact of T-cell activation, required for successful retrovirus-mediated gene transfer, on T-cell receptor repertoire profile, subset distribution and antiviral potential. Using a combination of antibodies against CD3 and CD28, T cells were transduced at high efficiency when exposed to retrovirus between 48 and 72 h later. Lymphocytes had undergone up to seven cycles of cell division by the end of the procedure. Although the T-cell receptor V, repertoire was not altered after retroviral transduction, there were notable shifts in subset profiles with an increased proportion of CD45RO cells in transduced populations. T cells continued to proliferate for several days after transduction and were difficult to sustain under the extended culture conditions required to generate virus-specific T cells. These observations may explain the lower than expected levels of GVHD and poor antiviral immunity reported in recent trials. [source] | ||||||||||