Development of a Novel Tool to Assess the Impact of Itching in Pediatric Cholestasis.

OBJECTIVES: The aim was to develop a clinical outcome assessment (COA) for itching in children with cholestatic pruritus. METHODS: This prospective study aimed to enroll patients aged 4-30 years with Alagille syndrome (ALGS) or progressive familial intrahepatic cholestasis type 1 and caregivers of patients aged 5 months to 14 years. Eligible patients experienced itching during ≥3 of the 7 days before enrollment and had not undergone liver transplant or surgical interruption of the enterohepatic circulation. Open-ended qualitative interviews confirmed that itching was a primary concern for patients and caregivers. Diaries were modified and then evaluated by participants during cognitive debriefing. Interview results were reviewed by clinical, COA and statistical experts. Diary questions were revised following an interim analysis before finalizing the Itch Reported Outcome (ItchRO). RESULTS: Thirty-six interviews were analyzed, representing 25 families of patients with ALGS. Itching was reported spontaneously (without prompting by the interviewer) by ten of 12 patients with ALGS and 19 of 20 caregivers. Consequences of itching included skin damage (78%), mood changes (59%), and difficulties staying asleep (59%) or falling asleep (53%). Two versions of the ItchRO were developed: ItchRO(Patient) for self-completion by patients and ItchRO(Observer) for caregivers. The ItchRO diaries comprise a single scorable item to assess itch and are to be completed twice daily (morning and evening). CONCLUSIONS: Itching was the most bothersome ALGS symptom reported by study participants. We have developed the ItchRO(Patient) and ItchRO(Observer) to assess itching in children with ALGS and other cholestatic liver diseases. These diaries are being validated for use in clinical trials.

Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients.

OBJECTIVE: To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients. DESIGN: A noninferiority analysis was used to compare rates of clinically significant upper gastrointestinal bleeding in a prospective, phase 3, double-blind trial with parallel omeprazole suspension and cimetidine treatment groups. SETTING: A total of 47 intensive care units in the United States. PATIENTS: A total of 359 critically ill patients who required mechanical ventilation for > or =48 hrs, had an Acute Physiology and Chronic Health Evaluation score of > or =11 at baseline, had an intact stomach with a nasogastric or orogastric tube in place, and had at least one additional risk factor for upper gastrointestinal bleeding. INTERVENTIONS: Patients were randomized to treatment with omeprazole suspension (two 40-mg doses on day 1, via orogastric or nasogastric tube, and 40 mg each day thereafter) or intravenous cimetidine (300-mg bolus and 50 mg/hr thereafter) for up to 14 days. Gastric aspirates were sampled for bleeding and pH. Medication doses were doubled for failure of pH control (two successive aspirates with pH < or = 4). MEASUREMENTS AND MAIN RESULTS: Clinically significant upper gastrointestinal bleeding (bright red blood not clearing after 5-10 mins of lavage or persistent Gastroccult-positive "coffee-grounds" material for 8 hrs on days 1-2 or for 2-4 hrs on days 3-14 and not clearing with > or =100 mL of lavage) was the primary end point of the trial. The rate of clinically significant bleeding in the per-protocol population was 4.5% with omeprazole suspension and 6.8% with cimetidine, meeting the criteria for the noninferiority of omeprazole suspension. Median gastric pH was > or =6 on all trial days with omeprazole suspension treatment and on 50% of days with cimetidine treatment (p < .001, all trial days). In the omeprazole suspension group, median gastric pH was >4 on each trial day in 95% of patients. CONCLUSIONS: Immediate-release omeprazole suspension is effective in preventing upper gastrointestinal bleeding and more effective than intravenous cimetidine in maintaining gastric pH of >4 in critically ill patients.

LJP 394 for the prevention of renal flare in patients with systemic lupus erythematosus: results from a randomized, double-blind, placebo-controlled study.

OBJECTIVE: To determine whether LJP 394 delays or prevents renal flare in patients with systemic lupus erythematosus (SLE) and a history of renal disease. METHODS: In a 76-week, double-blind, placebo-controlled study, 230 SLE patients were randomized to receive 16 weekly doses of 100 mg of LJP 394 or placebo, followed by alternating 8-week drug holidays and 12 weekly doses of 50 mg of LJP 394 or placebo. An assay measuring the affinity of the serum IgG fraction for the DNA epitope of LJP 394 identified a high-affinity population of patients (189 of 213 patients; 89% taking LJP 394 and 90% taking placebo). Analyses were performed on both the intent-to-treat population and the high-affinity population. RESULTS: Anti-double-stranded DNA antibodies decreased and C3 levels tended to increase during treatment with LJP 394. In the intent-to-treat population, the time to renal flare was not significantly different between treatment groups, but patients taking LJP 394 had a longer time to institution of high-dose corticosteroids and/or cyclophosphamide (HDCC) and required 41% fewer treatments with HDCC. In the high-affinity population, the LJP 394 group experienced a longer time to renal flare, 67% fewer renal flares, longer time to institution of HDCC, and 62% fewer HDCC treatments compared with the placebo group. In patients with serum creatinine levels >/=1.5 mg/dl at study entry, those taking LJP 394 had 50% fewer renal flares; no renal flares were observed in the high-affinity group taking LJP 394. Serious adverse events were observed in 25 of the 114 LJP 394-treated patients (21.9%) and 34 of the 116 placebo-treated patients (29.3%). CONCLUSION: Treatment with LJP 394 in patients with high-affinity antibodies to its DNA epitope prolonged the time to renal flare, decreased the number of renal flares, and required fewer HDCC treatments compared with placebo. The study drug appeared to be well tolerated.