ABSTRACT
UNLABELLED: Dosing regimens of oral bisphosphonates are inconvenient and contribute to poor compliance. The bone mineral density response to a once weekly delayed-release formulation of risedronate given before or following breakfast was non-inferior to traditional immediate-release risedronate given daily before breakfast. Delayed-release risedronate is a convenient regimen for oral bisphosphonate therapy. INTRODUCTION: We report the results of a randomized, controlled, clinical study assessing the efficacy and safety of a delayed-release (DR) 35 mg weekly oral formulation of risedronate that allows patients to take their weekly risedronate dose before or immediately after breakfast. METHODS: Women with postmenopausal osteoporosis were randomly assigned to receive risedronate 5 mg immediate-release (IR) daily (n = 307) at least 30 min before breakfast, or risedronate 35 mg DR weekly, either at least 30 min before breakfast (BB, n = 308) or immediately following breakfast (FB, n = 307). Bone mineral density (BMD), bone turnover markers (BTMs), fractures, and adverse events were evaluated. The primary efficacy variable was percent change from baseline in lumbar spine BMD at Endpoint. RESULTS: Two hundred fifty-seven subjects (83.7%) in the IR daily group, 252 subjects (82.1%) in the DR FB weekly group, and 258 subjects (83.8%) in the DR BB weekly group completed 1 year. Both DR weekly groups were determined to be non-inferior to the IR daily regimen. Mean percent changes in hip BMD were similar across groups. The magnitude of BTM response was similar across groups; some statistical differences were seen that were small and deemed by investigators to have no major clinical importance. The incidence of adverse events leading to withdrawal and serious adverse events were similar across treatment groups. All three regimens were well tolerated. CONCLUSIONS: Risedronate 35 mg DR weekly is similar in efficacy and safety to risedronate 5 mg IR daily, and will allow patients to take their weekly risedronate dose immediately after breakfast.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Etidronic Acid/analogs & derivatives , Osteoporosis, Postmenopausal/drug therapy , Administration, Oral , Aged , Bone Density/drug effects , Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Delayed-Action Preparations , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Etidronic Acid/administration & dosage , Etidronic Acid/adverse effects , Etidronic Acid/therapeutic use , Female , Femur/physiopathology , Humans , Lumbar Vertebrae/physiopathology , Middle Aged , Osteoporosis, Postmenopausal/physiopathology , Risedronic Acid , Tablets, Enteric-Coated , Treatment OutcomeABSTRACT
BACKGROUND: Conventional surgical wisdom is that a patient with gallstone pancreatitis should have the gallbladder removed during their initial hospitalization. However, patients are now often discharged to await operating room availability. METHODS: A retrospective review of all cases of gallstone pancreatitis at the Foothills Hospital between 1992 and 1996 was undertaken. Patients with a first attack of mild gallstone pancreatitis were studied. RESULTS: In all, 164 patients were identified: 90 patients were discharged for readmission cholecystectomy (discharged group), and 74 patients had the cholecystectomy before discharge (in-hospital group). Over the 5-year time period the proportion of patients discharged for readmission cholecystectomy increased from 27% to 67% (p<0.01). The total number of days waited for operation was greater in the discharged group versus in-hospital group: 40+/-69 days versus 8+/-10 days respectively (mean+/-SD). There was a trend towards an increased total number of days in hospital in the in-hospital group, 15.5+/-17 days versus 10.7+/-16 days. In the discharged group 20% (18 of 90) of patients experienced an adverse event requiring readmission while awaiting operation. Three had documented recurrent pancreatitis, 10 experienced recurrent pain, and 5 developed acute cholecystitis. There were no deaths in either group. DISCUSSION: Twenty percent of patients with gallstone pancreatitis who are discharged to await operating room time (average wait 40 days) will require readmission for biliary symptoms.
ABSTRACT
Patients with biliary tract obstruction have unexplained, inordinately high rates of perioperative morbidity and mortality, whereas cholestatic animals display abnormal hypothalamic responses to pyrogenic stimuli. We asked if obstructive cholestasis was associated with abnormal fever generation. Male Sprague-Dawley rats (250 g) underwent laparotomy for implantation of thermistors and either bile duct resection (BDR) or sham operation. After recovery, temperatures were recorded by telemetry and conscious, unrestrained rats in each group were injected intraperitoneally with either interleukin-1beta (IL-1beta;1 microg/kg) or Escherichia coli lipopolysaccharide (LPS; 50 microg/kg). Baseline temperatures in both groups were similar. Febrile responses after IL-1beta injection in BDR and sham groups were not significantly different. However, in response to LPS injection, BDR rats showed an initial hypothermia with a subsequently attenuated febrile response. Administration of anti-tumor necrosis factor-alpha (TNF-alpha) antibody 2 h before LPS injection blocked the LPS-induced hypothermia seen in BDR animals. However, serum levels of TNF-alpha were not significantly different between sham and BDR animals after LPS injection at any time point measured (0, 1.5, and 3 h).
