Impact of delayed adoption of novel atrial fibrillation treatments.

Objective: To examine the relationship between adoption of direct oral anticoagulants (DOACs) and health and cost outcomes for patients with nonvalvular atrial fibrillation.

Study Design: Real-world cohort study.

Methods: US adults who newly initiated treatment for nonvalvular atrial fibrillation were identified from claims data.

Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial.

Protégé was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up.

Anti-CD3 clinical trials in type 1 diabetes mellitus.

Two humanized, anti-CD3 mAbs with reduced FcR binding, teplizumab and otelixizumab, have been evaluated in over 1500 subjects, ages 7-45, with new and recently diagnosed T1D with a range of intravenous doses (3-48mg) and regimens (6-14 days, single or repeat courses). In general, studies that used adequate dosing demonstrated improvement in stimulated C-peptide responses and reduced need for exogenous insulin for two years and even longer after diagnosis. Drug treatment causes a transient reduction in circulating T cells, but the available data suggest that the mechanism of action may involve induction of regulatory mechanisms.

Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial.

Background: Findings of small studies have suggested that short treatments with anti-CD3 monoclonal antibodies that are mutated to reduce Fc receptor binding preserve β-cell function and decrease insulin needs in patients with recent-onset type 1 diabetes. In this phase 3 trial, we assessed the safety and efficacy of one such antibody, teplizumab.

Methods: In this 2-year trial, patients aged 8-35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India.

Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the Prostate Cancer Prevention Trial.

Background: The Prostate Cancer Prevention Trial (PCPT) demonstrated a 24.8% reduction in the 7-year prevalence of prostate cancer among patients treated with finasteride (5 mg daily) compared with that among patients treated with placebo; however, a 25.5% increase in the prevalence of high-Gleason grade tumors was observed, the clinical significance of which is unknown.

Pharmacokinetic considerations in determining the terminal elimination half-lives of bisphosphonates.

Background And Objective: Bisphosphonates are commonly used to treat and prevent osteoporosis. These compounds have unusual pharmacokinetic characteristics because they bind strongly to bone, and a portion becomes buried under newly formed bone. Once incorporated into bone tissue, the subsequent release during bone remodeling is probably the rate-limiting step in the terminal elimination of bisphosphonates.

Weekly oral alendronic Acid in male osteoporosis.

Objective: To evaluate the efficacy and tolerability of alendronic acid 70mg once weekly for the treatment of male osteoporosis.

Patients And Methods: This randomised, double-blind, placebo-controlled, 12-month trial compared the effect of alendronic acid 70mg once weekly or placebo (randomised 2 : 1) on bone mineral density (BMD) in 167 men with spine or hip BMD at least 2 standard deviations (SD) below the mean for young normal white males or nontraumatic fracture. All patients received calcium and vitamin D (colecalciferol).

Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men.

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the "Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95). Following an extensive review of the literature (1990-2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry.

Therapeutic equivalence of alendronate 35 milligrams once weekly and 5 milligrams daily in the prevention of postmenopausal osteoporosis.

Objective: To evaluate the efficacy and safety of alendronate 35 mg once weekly compared with alendronate 5 mg daily in the prevention of osteoporosis.

Methods: We compared the efficacy and safety of treatment with alendronate 35 mg once weekly (n = 362) and alendronate 5 mg daily (n = 361) in a 1-year, double-blind, multicenter study of postmenopausal women (6 months or greater), aged 40-70 years, with lumbar spine and femoral neck bone mineral density T-scores between -2.5 and 1.

Changes in bone mineral density following discontinuation or continuation of alendronate therapy in glucocorticoid-treated patients: a retrospective, observational study.

Objective: To evaluate the effects of discontinuing or continuing alendronate (ALN) therapy on bone mineral density (BMD) after patients on a long-term regimen of glucocorticoids (GCs) completed a 1-year treatment period with ALN.

Methods: Eligible patients were individuals with GC-induced osteoporosis who had received ALN (5 or 10 mg) for 1 year in a prior clinical trial and, at the end of the year, were still taking GCs at an average daily dose of > or =7.5 mg of prednisone or equivalent.

The upper GI safety and tolerability of oral alendronate at a dose of 70 milligrams once weekly: a placebo-controlled endoscopy study.

Objective: Alendronate (10 mg daily) has been shown in long term clinical trials to be an effective treatment for postmenopausal osteoporosis. A weekly dosing regimen of alendronate is preferred by both patients and physicians, as it has the potential to provide greater convenience and enhance compliance. In a 1-yr clinical trial, alendronate (70 mg once weekly) was equally efficacious and at least as well tolerated as the 10-mg daily dose in the treatment of postmenopausal osteoporosis, despite the higher unit dosage required.