A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for ≥6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchRO™) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchRO™ weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC

Analysis of cardiac symptoms preceding cardiac arrest

Prodromal symptoms and cardiac history were examined in 227 patients with coronary artery disease who were successfully resuscitated after out-of-hospital cardiac arrest. Cardiac arrest was sudden--with either no symptoms or symptoms for less than 1 hour--in 71% of the patients. Nonsudden death--death occurring after more than 1 hour of symptoms--occurred in 29% of the patients. A history of cardiovascular disease was present in 85% of patients with sudden cardiac arrest and in 83% with nonsudden arrest. Cardiac arrest occurred without symptoms in 38% of the patients with sudden cardiac arrest and was the first expression of coronary artery disease in 4% of the entire study group. This study indicates that cardiac arrest usually occurs with symptoms and almost always in the setting of a history of cardiovascular disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25967/1/0000033.pd

The effect of bystander CPR on survival of out-of-hospital cardiac arrest victims

The effect of bystander cardiopulmonary resuscitation (CPR) was studied in 2142 emergency medical service (EMS) cardiac arrest runs. When bystander CPR was administered to cardiac arrest victims, 22.9% of the victims survived until they were admitted to the hospital and 11.9% were discharged alive. In comparison, the statistics for cardiac arrest victims who did not receive bystander CPR were 14.6% and 4.7%, respectively (p < 0.001). A critical factor in patient survival was the amount of time that elapsed before the EMS personnel arrived and administered CPR. Patients who received bystander CPR were more likely to have ventricular fibrillation when the EMS arrived. Other factors relating to patient survival were the location of the victim at the time of the cardiac arrest and the age of the victim. Understanding these factors is important in developing community strategies to treat patients with cardiac arrest out of hospital.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25928/1/0000491.pd

Effect of empiric antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims with coronary artery disease

The effect of empiric antiarrhythmic therapy with quindine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), qiinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p &lt; 0.05), and for sudden death was 69, 69 and 89% (p &lt; 0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28573/1/0000376.pd