Definitions, End Points, and Clinical Trial Designs for Bladder Cancer: Recommendations From the Society for Immunotherapy of Cancer and the International Bladder Cancer Group.

Purpose: There is a significant unmet need for new and efficacious therapies in urothelial cancer (UC). To provide recommendations on appropriate clinical trial designs across disease settings in UC, the Society for Immunotherapy of Cancer (SITC) and the International Bladder Cancer Group (IBCG) convened a multidisciplinary, international consensus panel.

Methods: Through open communication and scientific debate in small- and whole-group settings, surveying, and responses to clinical questionnaires, the consensus panel developed recommendations on optimal definitions of the disease state, end points, trial design, evaluations, sample size calculations, and pathology considerations for definitive studies in low- and intermediate-risk nonmuscle-invasive bladder cancer (NMIBC), high-risk NMIBC, muscle-invasive bladder cancer in the neoadjuvant and adjuvant settings, and metastatic UC.

Spinal astrocyte glutamate receptor 1 overexpression after ischemic insult facilitates behavioral signs of spasticity and rigidity.

Using a rat model of ischemic paraplegia, we examined the expression of spinal AMPA receptors and their role in mediating spasticity and rigidity. Spinal ischemia was induced by transient occlusion of the descending aorta combined with systemic hypotension. Spasticity/rigidity were identified by simultaneous measurements of peripheral muscle resistance (PMR) and electromyography (EMG) before and during ankle flexion.

Limitations of Levothyroxine Bioequivalence Evaluation: Analysis of An Attempted Study.

The relative bioavailability and therapeutic comparability of four levothyroxine products (two proprietary and two nonbranded) were determined in an open-label, block-randomized, four-way crossover trial with no washout periods in 24 presumed hypothyroid ambulatory care patients who were considered euthyroid while on 100 &mgr;g or 150 &mgr;g of oral levothyroxine daily for at least 3 months. Patients randomly received each of the four levothyroxine products for 6 weeks at the same dosage as their prestudy regimen. Area under the serum concentration versus time curve (AUC), maximum change in serum concentration (C(max)), and time to peak serum concentration (T(max)) were calculated for total thyroxine (TT(4)), total triiodothyronine (TT(3)), free thyroxine index (FT(4)I), and thyrotropin (TSH) for each product, with and without baseline correction and normalization for tablet potency differences.