Withdrawal of HF therapy in recovered AF-mediated cardiomyopathy: clarifying trial designs.

Bone mineral content, cortical thickness and fracture rate in osteoporotic women after withdrawal of treatment with nandrolone decanoate, 1-alpha hydroxyvitamin D 3, or intermittent calcium infusions

Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [International Normalized Ratio (INR) 2–3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample sizerequired will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of ‘withdrawal of therapy’, and a 1% rate of ‘lost to follow-up’. Conduct of Trial: Patients with TIA or nondisabling stroke caused by ≧50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients.

Initiation, Continuation, Switching, and Withdrawal of Heart Failure Medical Therapies During Hospitalization

ABSTRACTObjectives: To determine whether hormones derived from the adrenal gland affected the progression of androgen‐independent (AI) prostate cancer for patients already receiving treatment with high‐dose bicalutamide. This was accomplished by using a sequential trial design in which medically or surgically castrated patients with AI prostate cancer whose cancers were progressing while receiving bicalutamide were treated with adrenolytic therapy in the form of aminoglutethimide (AM) and hydrocortisone (HC).Materials and Methods: Sixteen patients with AI prostate cancer were enrolled into this trial. All patients had metastatic disease in the bone, and two patients had additional metastases at other sites. Using prostate specific antigen (PSA) level as an indicator of disease activity, patients initially received bicalutamide therapy, then AM and HC were added to the regimen, and then bicalutamide therapy was discontinued, with each documented PSA level increase (see Figure 1). Clinical Trial Study Design: Patients were treated with sequential hormonal interventions according to the scheme depicted above. imageResults: Four (25%) patients demonstrated PSA level reductions of at least 50% after the initiation of bicalutamide, 150 mg/day. No patient demonstrated a PSA or obvious clinical response to the addition of AM and HC to the regimen. This includes the four patients who were initially sensitive to bicalutamide. Therapy with AM and HC was associated with fatigue and skin rashes. These side effects persisted after the withdrawal of bicalutamide therapy and were therefore attributed to AM and HC therapy.Conclusions: Bicalutamide at high doses seems to effectively block the androgen receptor (AR) from the growth stimulation derived from adrenal hormones. Therefore, the inhibition of adrenal hormone production by AM is not a useful therapeutic maneuver in this setting and is associated with moderate side effects. The activation of the AR pathway in these patients may occur by a mechanism other than stimulation by the androgens derived from the testes or adrenal gland.

Analysis of the Results of Phase III Controlled Clinical Trials with Recombinant Human Thyrotropin: Developing a Clinical Guide

British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy.

Trial of Nonpharmacologic Intervention in the Elderly (TONE): Design and rationale of a blood pressure control trial

Pleural effusions are common in adult intensive care unit (ICU) patients with respiratory failure. Ultrasonography-guided therapeutic pleural drainage is widely used and associated with improved oxygenation and ventilatory parameters, but no randomised clinical trial data exist. This paper outlines the protocol and detailed statistical analysis plan for the Drainage Of Pleural Effusions in the ICU (DOPE-ICU) feasibility trial. This is an investigator-initiated, pragmatic, multicentre, open-label, randomised, parallel-group feasibility trial. Adults acutely admitted to the ICU with pleural effusion ≥ 2 cm and respiratory failure will be screened for inclusion. We will exclude patients with existing pleural or mediastinal drain, suspected or confirmed haemothorax, pneumothorax, empyema or pleural malignancy, coagulation deficiency or antithrombotic therapy incompatible with drainage, clinical indication for therapeutic pleural drainage and predefined severe hypoxaemic or hypercapnic respiratory failure, expected ICU stay < 24 h, pregnancy, imminent withdrawal of active therapy, or patients previously randomised in the trial. A total of 88 eligible patients will be allocated 1:1 to ultrasonography-guided therapeutic pleural drainage with small-bore catheter, with repeated drainage of repeated pleural effusions during ICU stay including readmissions within 90 days versus no therapeutic pleural drainage during ICU stay within 90 days unless pre-specified escape criteria apply. The primary outcome is a feasibility outcome assessing group separation, i.e., proportion of patients receiving pleural drainage in ICU within 90 days. Secondary clinical outcomes include all-cause 90-day mortality, number of patients with one or more serious adverse events within 90 days, and absolute number of days alive without life support and out of hospital, respectively, in 90 days. Additional secondary feasibility and process outcomes will also be investigated. Data will be compared in the intension-to-treat population using generalised linear models adjusted for the stratification variable trial site. ClinicalTrials.gov identifier: NCT06709456. The DOPE-ICU feasibility trial will assess whether randomised allocation to ultrasonography-guided therapeutic pleural drainage or not in adult ICU patients with respiratory failure and pleural effusion is feasible. This will inform the design of a future large randomised clinical trial evaluating the clinical effects and safety of pleural drainage in this population.

Reply to the letter “About sorafenib in castration-resistant prostate cancer” by G. Colloca, F. Checcaglini and A. Venturino

Routine Unloading in Patients Treated With Extracorporeal Membrane Oxygenation for Cardiogenic Shock: Mixed Outcomes Set the Stage for Future Trials.

Absence of rebound from diltiazem therapy in Prinzmetal's variant angina

Obstructive sleep apnea (OSA) is heterogeneous in terms of contributing pathophysiological mechanisms, clinical presentation, and consequences. Different study models from animal models of intermittent hypoxia over case-control, cohort, and population-based observational studies to uncontrolled interventional and randomized controlled interventional trials have contributed to the knowledge base. Controversial findings on underlying mechanisms and consequences of untreated OSA have challenged the field and resulted in uncertainty in treatment recommendations. The heterogeneity of OSA in pathogenesis and clinical outcomes and strengths and limitations of different study models and designs used for studying OSA pathophysiology and cardiovascular consequences are discussed on the background of controversial findings on cardiovascular outcomes in OSA. In addition, recent findings from randomized controlled continuous positive airway pressure therapy withdrawal trials, an efficient and controlled study model, are highlighted. Novel designs for clinical trials on long-term outcomes in the highly prevalent patient group with OSA addressing the heterogeneity in underlying mechanisms, different phenotypes in terms of cardiovascular risk, and new treatment concepts are needed to improve clinical practice standards.

This is the second of two review articles evaluating peri-operative statin therapy. In surgical patients, the utility of peri-operative statin therapy is strongly suggested by retrospective studies, although it is probably overestimated, as important confounding factors have not been controlled for and hence the literature is considered to be currently inconclusive. This review examines the potential mechanisms and indications for peri-operative statin protection, the efficacy of acute peri-operative beta-blockade in addition to statin therapy, the effect of peri-operative statin therapy withdrawal and the implications of comorbidities associated with peri-operative cardiovascular risk on statin therapy. Recommendations concerning appropriate dosing, duration, therapeutic targets and necessary investigations when prescribing peri-operative statins are made. Peri-operative study design recommendations are suggested, so that future meta-analyses may be more informative. Recommendations are made regarding retrospective reporting of statin studies to minimise the bias inherent in a number of the current retrospective studies on this subject.