Daniel J. Pambianco

Two doses of omeprazole versus placebo in symptomatic erosive esophagitis: The U.S. multicenter study

Two hundred thirty patients with reflux symptoms and endoscopically proven erosive esophagitis were enrolled from 15 U.S. centers into a randomized, double-blind, dose-ranging study comparing placebo with omeprazole, 20 or 40 mg given once daily in the morning. Esophagitis grade 2 was present in 44% of patients, grade 3 in 37% of patients, and grade 4 in 19% of patients. Endpoints, defined as complete relief of heartburn and complete esophageal mucosal healing, were assessed after 4 and 8 weeks of treatment. Both omeprazole doses were significantly superior to placebo in complete endoscopic healing. After 8 weeks of treatment, 73.5% of patients in the 20-mg omeprazole group and 74.7% in the 40-mg omeprazole group, compared with 14.0% in the placebo group, had complete healing of the esophageal mucosa. At the end of the study, complete relief of daytime heartburn was obtained in 79.5% of patients in the 20-mg omeprazole group, 81.6% in the 40-mg omeprazole group, and 37.2% in the placebo group (P less than or equal to 0.05). Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05). The median time to complete relief of daytime and nighttime heartburn occurred earlier in the 40-mg group than in the 20-mg group (9 vs. 17 days and 9 vs. 20 days, respectively); however, these differences were not statistically significant. Relief of acid regurgitation and dysphagia also occurred earlier in the 40-mg group. Omeprazole was well tolerated in this group of patients. No unexpected adverse experiences occurred. The results of this study confirm those of six multicenter, international trials in which omeprazole in doses of 20-60 mg provided a degree of esophageal mucosal healing and complete relief of reflux symptoms superior to any other medical treatment.

Computer-assisted personalized sedation for upper endoscopy and colonoscopy: a comparative, multicenter randomized study

BACKGROUND The SEDASYS System is an investigational computer-assisted personalized sedation system integrating propofol delivery with patient monitoring to enable endoscopist/nurse teams to safely administer propofol. OBJECTIVE To compare the safety and effectiveness of the SEDASYS System to the current standard of care for sedation during routine endoscopic procedures. DESIGN Nonblinded multicenter randomized comparative study. SETTING Four ambulatory surgery centers, 3 endoscopy centers, and 1 academic center in the United States. PATIENTS One thousand American Society of Anesthesiologists physical status class I to III adults undergoing routine colonoscopy or EGD. INTERVENTIONS Sedation with the SEDASYS System (SED) and sedation with each sites current standard of care (CSC; benzodiazepine/opioid combination). MAIN OUTCOME MEASUREMENTS Area under the curve of oxygen desaturation was the primary endpoint. Secondary endpoints included patient satisfaction, clinician satisfaction, level of sedation, and patient recovery time. RESULTS Four hundred ninety-six patients were randomized to SED and 504 to CSC. Area under the curve of oxygen desaturation was significantly lower for SED (23.6 s·%) than for CSC (88.0 s·%; P = .028). Patients were predominately minimally to moderately sedated in both groups. SED patients were significantly more satisfied than CSC patients (P = .007). Clinician satisfaction was greater with SED than with CSC (P < .001). SED patients recovered faster than CSC patients (P < .001). The incidence of adverse events was 5.8% in the SED group and 8.7% in the CSC group. LIMITATIONS Nonblinded. CONCLUSIONS The SEDASYS System could provide endoscopist/nurse teams a safe and effective on-label means to administer propofol to effect minimal to moderate sedation during routine colonoscopy and EGD.

The effect of ursodiol on the efficacy and safety of extracorporeal shock-wave lithotripsy of gallstones: The dornier national biliary lithotripsy study

BACKGROUND In the treatment of gallstones with extracorporeal shock-wave lithotripsy, the bile acid ursodiol is administered to dissolve the gallstone fragments. We designed our study to determine the value of administering this agent. METHODS At 10 centers, 600 symptomatic patients with three or fewer radiolucent gallstones 5 to 30 mm in diameter, as visualized by oral cholecystography, were randomly assigned to receive ursodiol or placebo for six months, starting one week before lithotripsy. RESULTS The stones were fragmented in 97 percent of all patients, and the fragments were less than or equal to 5 mm in diameter in 46.8 percent. On the basis of an intention-to-treat analysis of all 600 patients, 21 percent receiving ursodiol and 9 percent receiving placebo (P less than 0.0001) had gallbladders that were free of stones after six months. Among those with completely radiolucent solitary stones less than 20 mm in diameter, 35 percent of the patients receiving ursodiol and 18 percent of those receiving placebo (P less than 0.001) were free of stones after six months. Biliary pain, usually mild, occurred in 73 percent of all patients but in only 13 percent of those who were free of stones after three and six months (P less than 0.01). There were few adverse events. Only diarrhea occurred with a significantly different frequency in the two groups: 32.6 percent were affected in the ursodiol group, as compared with 24.7 percent in the placebo group (P less than 0.04). Severe biliary pain occurred in 1.5 percent of all patients, acute cholecystitis in 1.0 percent, and acute pancreatitis in 1.5 percent; endoscopic sphincterotomy was performed in 0.5 percent, and cholecystectomy in 2.5 percent. CONCLUSIONS Extracorporeal shock-wave lithotripsy with ursodiol was more effective than lithotripsy alone for the treatment of symptomatic gallstones, and equally safe. Treatment was more effective for solitary than multiple stones, radiolucent than slightly calcified stones, and smaller than larger stones.

Human sphincter of Oddi motility and cholecystokinin response following liver transplantation

The reported incidence of sphincter of Oddi dysfunction following orthotopic liver transplantation has ranged from 3% to 7%. If sphincteric dysfunction is unrecognized, therapy may be inappropriate; when recognized, extensive surgery may be required. To prospectively identify patients with sphincteric dysfunction, we performed sphincter of Oddi motility studies through the t-tube tract three months after transplantation. Baseline sphincter motility and response to intravenous cholecystokinin were evaluated. The results of 10 subjects are reported; nine had normal basal sphincter pressure (16±5.8 mm Hg), and all had normal frequency (3.6±1/min), amplitude (86±31 mm Hg), and duration (4.5±1 sec) of phasic contractions. One subject had an elevated basal pressure (47 mm Hg). All, including the subject with elevated basal pressure, demonstrated a normal response to intravenous cholecystokinin with significant inhibition of phasic contraction frequency and amplitude. We demonstrate that simultaneous studies of the sphincter and duodenum can be obtained via the t-tube tract, providing the opportunity for prospective evaluation of sphincteric function. We conclude that sphincter of Oddi function usually remains normal following liver transplantation with choledochocholedochostomy.

Intragastric balloon as an adjunct to lifestyle intervention: a randomized controlled trial

Background/objectives:This trial evaluated the safety and effectiveness of the Orbera Intragastric Balloon as an adjunct to lifestyle intervention.Subjects/methods:In this multicenter, randomized, open-label clinical trial, 255 adults with a body mass index of 30–40 kg m−2 were treated and outcomes were assessed up to 12 months. Participants were randomized to endoscopic placement of an intragastric balloon plus lifestyle or lifestyle intervention alone. Balloons were removed at 6 months and lifestyle intervention continued for both groups through 12 months. At 9 months, coprimary end points were two measures of weight loss.Results:At 6 months, weight loss was −3.3% of total body weight (−3.2 kg) in the lifestyle arm vs −10.2% (−9.9 kg) in the balloon plus lifestyle arm (P<0.001); at 9 months (3 months postballoon removal), weight loss was −3.4% (−3.2 kg) vs −9.1% (−8.8 kg, P⩽0.001); and at 12 months, −3.1% (−2.9 kg) vs −7.6% (−7.4 kg, P⩽0.001). For the primary end points, at 9 months, mean percent loss of weight in excess of ideal body weight (s.d.) at 9 months was 26.5% (20.7) (P=0.32) and 9.7% (15.1) in the balloon and control groups, respectively. Also, 45.6% (36.7, 54.8) of the subjects randomized to the balloon achieved at least 15% loss of weight in excess of ideal body weight greater than the control group (P<0.001). The majority of balloon subjects experienced adverse events; 86.9% nausea, 75.6% vomiting, 57.5% abdominal pain and 18.8% had their device removed before 6 months because of an adverse event or subject request. Five subjects (3.1%) in the balloon group had a gastric abnormality at the time of device removal, and no ulcers were found.Conclusions and relevance:Intragastric balloon achieved greater short-term weight loss at 3 and 6 months postballoon removal than lifestyle intervention alone. Adverse gastrointestinal events were common.

A phase IIb study comparing the safety and efficacy of remimazolam and midazolam in patients undergoing colonoscopy

BACKGROUND AND AIMS Remimazolam is an ultra-short-acting benzodiazepine currently being developed for procedural sedation and for induction and maintenance of anesthesia. This trial was the fourth study for procedural sedation. The aim was to compare the safety and efficacy profile of remimazolam and to refine suitable doses for subsequent phase III studies in this indication. METHODS This was a randomized, double-blind, parallel group, active controlled clinical trial with 162 male and female patients, aged 18 to 70, scheduled to undergo a routine colonoscopy. Patients were randomized to receive 1 of 3 remimazolam doses or midazolam for sedation. Supplemental oxygen and 100 μg of fentanyl was given before procedures were started, and the colonoscopy commenced as soon as suitable sedation had been achieved (Modified Observers Assessment of Alertness/Sedation score ≤3). Top-up doses of the study drug and/or fentanyl were allowed to maintain suitable sedation and/or analgesia. Response was defined as sufficient sedation, no rescue sedative, and no ventilation required. RESULTS This study showed that a single dose of remimazolam or midazolam, followed by top-up doses to maintain suitable sedation, provided adequate sedation with a high success rate (>92%) for the remimazolam groups, compared with 75% for the midazolam group (P = .007). There was no requirement for mechanical ventilation in any group, and procedure failures were all due to use of rescue sedative. CONCLUSIONS The high success rates and good safety profile of remimazolam observed in this study warrants further investigation and confirmation in phase III trials. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01145222.).