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Prospective Randomized Trials (prospective + randomized_trials)
Selected AbstractsShould we screen for bladder cancer in a high-risk population?CANCER, Issue 5 2006A cost per life-year saved analysis Abstract BACKGROUND. The U.S. Food and Drug Administration recently approved screening high-risk patients for bladder cancer using urine-based markers. The cost and life-years saved associated with bladder cancer screening were evaluated. METHODS. A Markov model was created to estimate cumulative cancer-related costs and efficacy of screening (vs. no screening) of a high-risk population for bladder cancer using a urine-based tumor marker over a 5-year period. Assumptions were based on literature review of survival and progression rates for patients with bladder cancer and costs associated with different bladder cancer disease states. RESULTS. Screening for bladder cancer in a population with a 4% incidence of bladder cancer resulted in a gain of 3.0 life years per 1000 subjects at a cost savings of $101,000 for the population, assuming a 50% downstaging in the screened population from muscle-invasive to nonmuscle-invasive disease. One-way sensitivity analyses found that screening is the most cost-effective strategy if cancer incidence is >1.6%, tumor marker costs <$126, marker sensitivity is >26%, marker specificity is >54%, downstaging with screening is >20%, and office cystoscopy costs <$694. Varying costs of cystectomy, transurethral resection of bladder tumor (TURBT), chemotherapy, end-of-life care, costs of metastatic disease, and a computed tomography scan over a wide range did not affect the superiority of screening. CONCLUSIONS. The model found that urine-based markers are cost-effective in a high-risk population. Prospective randomized trials in a completely asymptomatic high-risk cohort are indicated before bladder cancer screening can be recommended. Cancer 2006. © 2006 American Cancer Society. [source] Prognosis and Mechanism of Death in Treated Heart Failure: Data From the Placebo Arm of Val-HeFTCONGESTIVE HEART FAILURE, Issue 3 2006Jay N. Cohn MD The magnitude of benefit on mortality of combined angiotensin-converting enzyme inhibitor (ACEI) and ,-blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent-to-treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val-HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow-up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure-related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year. [source] Should Non-Invasive Helicobacter pylori Testing Replace Endoscopy in Investigation of Dyspepsia?HELICOBACTER, Issue S1 2000Kenneth McColl Our knowledge of Helicobacter pylori infection is now changing the way in which we investigate patients presenting with dyspepsia, with noninvasive H. pylori testing replacing endoscopy. Non-invasive H. pylori testing has been shown to be useful in predicting the underlying diagnosis in patients presenting with dyspepsia. Several studies have shown that 20,50% of dyspeptic patients with a positive H. pylori test will have evidence of underlying ulcer disease or duodenitis. In contrast, less than 5% of dyspeptic patients with a negative H. pylori test will have evidence of ulcer disease and in these subjects, the likeliest diagnosis is gastroesophageal reflux disease. This has led to many groups recommending that noninvasive H. pylori testing should be used in place of endoscopy, with all those testing positive being given anti- H. pylori therapy and those testing negative being treated symptomatically. One concern about nonendoscopic management of dyspeptic patients is the possibility of missing underlying malignancy but studies have shown that in western countries this is rare in patients less than 55 years of age presenting with dyspepsia in the absence of sinister symptoms. There is increasing evidence supporting eradication of H. pylori infection in dyspeptic patients without ulcer disease. Meta-analysis of four prospective randomized trials indicates that such treatment is superior to placebo in about 10% of subjects. H. pylori -positive dyspeptic patients are also recognized to have an increased risk of developing ulcer disease in the future which will be removed by treating the infection. Another justification for eradicating the infection in the absence of ulcer disease is the fact that H. pylori infection is now proven to be a risk factor for gastric cancer. Prospective randomized studies comparing endoscopy with noninvasive H. pylori testing in the management of dyspeptic patients indicate that managing dyspepsia by noninvasive H. pylori testing is at least as effective as endoscopic-based management in producing symptomatic resolution and saves a substantial number of endoscopic procedures. There is therefore now substantial evidence indicating that noninvasive H. pylori testing should be used in place of endoscopy to determine the management of younger dyspeptic patients without sinister symptoms and who are not taking nonsteroidal anti-inflammatory drugs. [source] Intraoperative magnetic resonance imaging in the surgical treatment of cerebral metastasesJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2010Christian Senft MD Abstract Background and Objectives To report on the value of intraoperative magnetic resonance imaging (iMRI) in the neurosurgical treatment of cerebral metastases (CM). Methods We performed a total of 204 surgical procedures with the use of a mobile ultra-low-field iMRI-unit. Of these, there were 12 craniotomies and 2 minimal-invasive procedures for CM, and 63 craniotomies for glioblastoma (GBM). Results On intraoperative imaging, all tumors could be localized and targeted with the help of the integrated neuronavigation system. Intraoperative imaging resulted in continued tumor resection due to unexpected residual tumor tissue in 13 patients harboring GBM (20.6%), but no patient with a CM (0%). In two patients with cystic CM, iMRI helped to achieve complete collapse of cysts by means of stereotactic aspiration, relieving mass effect and allowing for adjuvant radiotherapy. All patients subsequently received adjuvant treatment according to clinical protocols. Conclusion Surgical resection represents one of several treatment modalities in metastatic brain disease. iMRI is useful for neuronavigation and resection control and as an adjunct in minimal-invasive procedures in patients with CM; however, its exact value is yet to be determined by prospective randomized trials. J. Surg. Oncol. 2010; 101:436,441. © 2010 Wiley-Liss, Inc. [source] Defibrillation Threshold Testing: Tradition or Necessity?PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2009CHRISTOF KOLB M.D. Implantable cardioverter defibrillators (ICDs) have become an essential tool for primary and secondary prevention of sudden cardiac death. Traditionally, defibrillation threshold (DFT) testing is part of the "lege artis" ICD implantation. Taking into consideration that the absolute mortality reduction in primary prevention trials is estimated around 8% and in secondary prevention trials around 7%, it is only in these patients that an acceptable DFT is expected to affect survival. Using a high-energy ICD, the likelihood of obtaining an inadequate DFT is about 2.5%. Thus, the number of patients needed to be subjected to DFT testing in order to avert one potential death is about 500. Application of antitachycardia pacing for rapid ventricular tachycardias further reduces the percentage of patients dependent on reliable ICD defibrillation capability. Thus, the mortality rate that can be prevented by DFT testing is below 0.2%. This contrasts a 0.4% risk of life-threatening complications and a low but not negligible mortality risk owed to the procedure. Although in light of these data the balance between DFT-related risk and benefit seems to tilt toward the former, insights gained from prospective randomized trials will clarify whether the abandonment of routine DFT testing can be claimed on a rightful basis. [source] PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myelomaBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2005Heather E. Oakervee Summary Bortezomib (formerly PS-341) has significant activity in patients with relapsed multiple myeloma (MM), its efficacy is increased with the addition of dexamethasone and it demonstrates synergy with doxorubicin, thus providing the rationale for combination therapy with bortezomib, doxorubicin and dexamethasone (PAD). Patients with untreated MM received four 21-d cycles of PAD, comprising bortezomib 1·3 mg/m2 on days 1, 4, 8 and 11, along with dexamethasone 40 mg on days 1,4, 8,11 and 15,18 during cycle 1 and days 1,4 during cycles 2,4. During days 1,4, patients also received 0, 4·5 or 9 mg/m2 of doxorubicin at dose levels 1, 2, and 3 respectively. Following peripheral blood stem cell (PBSC) collection, patients received high-dose melphalan (MEL200) with PBSC transplantation (PBSCT). After PAD induction alone, 20 of 21 patients (95%) achieved at least a partial response (PR), including complete response (CR) in five patients (24%). Twenty of 21 had PBSC mobilized, and 18 of 20 received MEL200/PBSCT. In an intention-to-treat analysis, response rates were: CR 43%, near CR 14%, very good PR 24%, PR 14% and stable disease 5%. PAD was effective, did not prejudice subsequent PBSC collection, and should be further evaluated in prospective randomized trials. [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] Haematopoietic stem cell transplantation in the treatment of severe autoimmune disease: results from phase I/II studies, prospective randomized trials and future directionsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 1 2005A. Tyndall Summary Around 700 patients have received an autologous haematopoietic stem cell transplant (HSCT) as treatment for a severe autoimmune disease (AD). The majority of these have been within the context of phase I/II clinical trials and following international guidelines proposed 7 years ago. In general, a positive benefit/risk ratio has led to phase III prospective randomized controlled trials in multiple sclerosis (MS), systemic sclerosis (SSc) and rheumatoid arthritis (RA) in Europe. In the US, similar trials are being planned for SSc, MS and systemic lupus erythematosus (SLE). Transplant related mortality (TRM) has fallen in all disease subgroups since the inception due to more appropriate patient selection, and so far a clear advantage of the more intense myeloablative regimens in terms of remission induction and relapse rate has not emerged. Although each AD has a different profile, over a third of patients have sustained a durable remission, often with no further need for immunosuppressive drugs. In those who relapsed, many responded to agents which pre transplant had been ineffective. The study of immune reconstitution and gene expression pre and post HSCT is being undertaken to further understand the mechanism of autoimmunity. [source] | ||||||||||||||||||||||