ASCEND-8 pharmacokinetic, safety, and efficacy data for ceritinib 450 mg with food in patients with anaplastic lymphoma kinase-positive non-small cell lung Cancer: A clinical perspective.

Anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) is diagnosed in up to 126,000 patients worldwide annually. Ceritinib is a next-generation ALK-targeted tyrosine kinase inhibitor that is approved for the treatment of patients with metastatic ALK+ NSCLC. In December 2017, the US Food and Drug Administration-approved dose of ceritinib was changed from 750 mg/day under fasting conditions to 450 mg/day taken with food for the treatment of patients with ALK+ NSCLC. This change was implemented on the basis of data from studies designed to investigate ways to reduce the frequency of gastrointestinal adverse events noted in patients enrolled in several ASCEND clinical trials that evaluated a ceritinib 750-mg fasted dose as either first- or second/third-line treatment. This review highlights and discusses published findings from the ASCEND-8 food-effect trial and includes commentary from physicians regarding their own clinical cases of patients who were enrolled in the trial and treated with either the 750-mg fasted or 450-mg fed dose of ceritinib. The review also discusses the implications of using the recently approved ceritinib 450-mg dose in the clinical setting.

Pomegranate supplementation improves cognitive and functional recovery following ischemic stroke: A randomized trial.

Objectives: We tested whether supplementing with pomegranate polyphenols can enhance cognitive/functional recovery after stroke. Methods: In this parallel, block-randomized clinical trial, we administered commercially-available pomegranate polyphenol or placebo pills twice per day for one week to adult inpatients in a comprehensive rehabilitation setting starting approximately 2 weeks after stroke. Pills contained 1 g of polyphenols derived from whole pomegranate, equivalent to levels in approximately 8 oz of juice. Placebo pills were similar to the pomegranate pills except that they contained only lactose. Of the 163 patients that were screened, 22 were eligible and 16 were randomized (8 per group). We excluded one subject per group from the neuropsychological analyses since they were lost to follow-up, but we included all subjects in the analysis of functional data since outcome data were available. Clinicians and subjects were blinded to group assignment. Neuropsychological testing (primary outcome: Repeatable Battery for the Assessment of Neuropsychological Status) and functional independence scores were used to determine changes in cognitive and functional ability. Results: Pomegranate-treated subjects demonstrated more neuropsychological and functional improvement and spent less time in the hospital than placebo controls. Discussion: Pomegranate polyphenols enhanced cognitive and functional recovery after stroke, justifying pursuing larger clinical trials.

A comparison of midazolam and zolpidem as oral premedication in children, a prospective randomized double-blinded clinical trial.

BACKGROUND: Anxiety associated with pediatric surgery can be stressful. Midazolam is a well-accepted anxiolytic in this setting. However, there are cases in which this medication is not effective. Zolpidem is a short-acting nonbenzodiazepine hypnotic drug that is administered orally and has quick onset of action (~15 minutes), and 2-3 hour duration. AIMS: Based on the theory that impaired perception following oral zolpidem administration would suppress the development of anxiety, we sought to compare zolpidem to midazolam for pediatric preoperative anxiety. METHODS: This prospective randomized double-blinded clinical trial was designed to compare the effectiveness of oral midazolam and zolpidem for anxiety premedication. Eighty ASA class I-II pediatric patients between 2 and 9 years old, surgery >2 hours, and at least 23 hours postoperative admission were included in the study. Randomization was done with 0.5 mg/kg midazolam or 0.25 mg/kg zolpidem administered orally. The primary outcome measure was between group difference in patient anxiety at the time of separation using the Modified Yale Preoperative Anxiety Scale. Secondary outcomes included emergence delirium and mask acceptance at induction. RESULTS: There was no significant difference in Modified Yale Preoperative Anxiety Scale scores at separation between midazolam (median/interquartile range = 26.7/23.3-36.6) and zolpidem (median/interquartile range = 30.0/23.3-56.6) groups, difference 0.01 (95% CI -3E-5 , 3E-2 ; P = 0.07). Mask acceptance score was significantly better in the midazolam group. There was no significant difference in emergence delirium scores between groups. CONCLUSION: This study demonstrates that zolpidem, as dosed, was similar to midazolam with regard to anxiety scoring, and inferior with regard to mask acceptance scores.

Rofecoxib versus hydrocodone/acetaminophen for postoperative analgesia in functional endoscopic sinus surgery.

OBJECTIVES/HYPOTHESIS: Functional endoscopic sinus surgery (FESS) is less invasive and more tissue sparing than extirpative techniques, with an assumed benefit of diminished postoperative pain. Oral opioids are commonly prescribed after sinus surgery but are associated with adverse effects, including gastrointestinal and neurologic symptoms. Nonopioid analgesics have been suggested to offer similar pain control efficacy with fewer adverse effects. STUDY DESIGN: To investigate postoperative analgesia in FESS, a prospective randomized, double-blinded comparison of hydrocodone/acetaminophen 7.5/750 mg (an opioidderivative) with rofecoxib 50 mg (a cyclooxygenase-2 inhibitor) was performed. METHODS: Forty subjects were enrolled, of which 28 successfully completed the study. Subjects recorded peak pain levels and requirement for rescue analgesia on the day of surgery and for 4 days thereafter. On postoperative day 5, subjects completed an exit survey in which adverse effects and overall satisfaction with pain control were recorded. RESULTS: In this study, there were no statistical differences in peak pain levels between the groups at any point in the postoperative period, regardless of extent of surgery. Adverse effect profiles were also similar for the two groups. CONCLUSIONS: The use of nonopioid analgesics after FESS may provide similar pain control to oral opioids.

Ginkgo biloba and acetazolamide prophylaxis for acute mountain sickness: a randomized, placebo-controlled trial.

BACKGROUND: Acute mountain sickness (AMS) commonly occurs when unacclimatized individuals ascend to altitudes above 2000 m. Acetazolamide and Ginkgo biloba have both been recommended for AMS prophylaxis; however, there is conflicting evidence regarding the efficacy of Ginkgo biloba use. We performed a randomized, placebo-controlled trial of acetazolamide vs Ginkgo biloba for AMS prophylaxis. METHODS: We randomized unacclimatized adults to receive acetazolamide, Ginkgo biloba, or placebo in double-blind fashion and took them to an elevation of 3800 m for 24 hours. We graded AMS symptoms using the Lake Louise Acute Mountain Sickness Scoring System (LLS) and compared the incidence of AMS (defined as LLS score > or =3 and headache). RESULTS: Fifty-seven subjects completed the trial (20 received acetazolamide; 17, Ginkgo biloba, and 20, placebo). The LLS scores were significantly different between groups; the median score of the acetazolamide group was significantly lower than that of the placebo group (P=.01; effect size, 2; and 95% confidence interval [CI], 0 to 3), unlike that of the Ginkgo biloba group (P=.89; effect size, 0; and 95% CI, -2 to 2). Acute mountain sickness occurred less frequently in the acetazolamide group than in the placebo group (effect size, 30%; 95% CI, 61% to -15%), and the frequency of occurrence was similar between the Ginkgo biloba group and the placebo group (effect size, -5%; 95% CI, -37% to 28%). CONCLUSIONS: In this study, prophylactic acetazolamide therapy decreased the symptoms of AMS and trended toward reducing its incidence. We found no evidence of similar efficacy for Ginkgo biloba.