Safety and Immunogenicity of Zoster Vaccine Live in Human Immunodeficiency Virus-Infected Adults With CD4+ Cell Counts >200 Cells/mL Virologically Suppressed on Antiretroviral Therapy.

Background: Herpes zoster (HZ) risk is increased in human immunodeficiency virus (HIV)-infected persons. Live attenuated zoster vaccine (ZV) reduces HZ incidence and severity in adults; safety and immunogenicity data in HIV-infected adults are limited. Methods: We conducted a randomized, double-blind, placebo-controlled trial in HIV-infected adults virally suppressed on antiretroviral therapy (ART). Participants, stratified by CD4+ count (200-349 or ≥350 cells/µL), were randomized 3:1 to receive ZV or placebo on day 0 and week 6. The primary endpoint was serious adverse event or grade 3/4 signs/symptoms within 6 weeks after each dose. Immunogenicity (varicella zoster virus [VZV]-specific glycoprotein enzyme-linked immunosorbent assay and interferon-γ enzyme-linked immunospot assay responses) was assessed at 6 and 12 weeks postvaccination. Results: Of 395 participants (296 ZV vs 99 placebo), 84% were male, 47% white, 29% black, and 22% Hispanic; median age was 49 years. Safety endpoints occurred in 15 ZV and 2 placebo recipients (5.1% [95% confidence interval {CI}, 2.9%-8.2%] vs 2.1% [95% CI, .3%-7.3%]; P = .26). Injection site reactions occurred in 42% of ZV (95% CI, 36.3%-47.9%) vs 12.4% of placebo recipients (95% CI, 6.6%-20.6%) (P < .001). Week 12 median natural log VZV antibody titer was higher for ZV (6.30 [Q1, Q3, 5.64, 6.96]) vs placebo (5.48 [Q1, Q3, 4.63, 6.44]; P < .001) overall and in the high CD4+ stratum (P = .003). VZV antibody titers were similar after 1 or 2 ZV doses. Polymerase chain reaction-confirmed HZ occurred in 2 participants (1 ZV; 1 placebo); none was vaccine strain related. Conclusions: Two doses of ZV in HIV-infected adults suppressed on ART with CD4+ counts ≥200 cells/µL were safe and immunogenic. Clinical Trials Registration: NCT00851786.

Oseltamivir, amantadine, and ribavirin combination antiviral therapy versus oseltamivir monotherapy for the treatment of influenza: a multicentre, double-blind, randomised phase 2 trial.

BACKGROUND: Influenza continues to have a substantial socioeconomic and health impact despite a long established vaccination programme and approved antivirals. Preclinical data suggest that combining antivirals might be more effective than administering oseltamivir alone in the treatment of influenza. METHODS: We did a randomised, double-blind, multicentre phase 2 trial of a combination of oseltamivir, amantadine, and ribavirin versus oseltamivir monotherapy with matching placebo for the treatment of influenza in 50 sites, consisting of academic medical centre clinics, emergency rooms, and private physician offices in the USA, Thailand, Mexico, Argentina, and Australia. Participants who were aged at least 18 years with influenza and were at increased risk of complications were randomly assigned (1:1) by an online computer-generated randomisation system to receive either oseltamivir (75 mg), amantadine (100 mg), and ribavirin (600 mg) combination therapy or oseltamivir monotherapy twice daily for 5 days, given orally, and participants were followed up for 28 days. Blinded treatment kits were used to achieve masking of patients and staff. The primary endpoint was the percentage of participants with virus detectable by PCR in nasopharyngeal swab at day 3, and was assessed in participants who were randomised, had influenza infection confirmed by the central laboratory on a baseline nasopharyngeal sample, and had received at least one dose of study drug. Safety assessment was done in all patients in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01227967. FINDINGS: Between March 1, 2011, and April 29, 2016, 633 participants were randomly assigned to receive combination antiviral therapy (n=316) or monotherapy (n=317). Seven participants were excluded from analysis: three were not properly randomised, three withdrew from the study, and one was lost to follow-up. The primary analysis included 394 participants, excluding 47 in the pilot phase, 172 without confirmed influenza, and 13 without an endpoint sample. 80 (40·0%) of 200 participants in the combination group had detectable virus at day 3 compared with 97 (50·0%) of 194 (mean difference 10·0, 95% CI 0·2-19·8, p=0·046) in the monotherapy group. The most common adverse events were gastrointestinal-related disorders, primarily nausea (65 [12%] of 556 reported adverse events in the combination group vs 63 [11%] of 585 reported adverse events in the monotherapy group), diarrhoea (56 [10%] of 556 vs 64 [11%] of 585), and vomiting (39 [7%] of 556 vs 23 [4%] of 585). There was no benefit in multiple clinical secondary endpoints, such as median duration of symptoms (4·5 days in the combination group vs 4·0 days in the monotherapy group; p=0·21). One death occurred in the study in an elderly participant in the monotherapy group who died of cardiovascular failure 13 days after randomisation, judged by the site investigator as not related to study intervention. INTERPRETATION: Although combination treatment showed a significant decrease in viral shedding at day 3 relative to monotherapy, this difference was not associated with improved clinical benefit. More work is needed to understand why there was no clinical benefit when a difference in virological outcome was identified. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA.

Vestibular Stimulation for ADHD: randomized controlled trial of Comprehensive Motion Apparatus.

OBJECTIVE: This research evaluates effects of vestibular stimulation by Comprehensive Motion Apparatus (CMA) in ADHD. METHOD: Children ages 6 to 12 (48 boys, 5 girls) with ADHD were randomized to thrice-weekly 30-min treatments for 12 weeks with CMA, stimulating otoliths and semicircular canals, or a single-blind control of equal duration and intensity, each treatment followed by a 20-min typing tutorial. RESULTS: In intent-to-treat analysis (n = 50), primary outcome improved significantly in both groups (p = .0001, d = 1.09 to 1.30), but treatment difference not significant (p = .7). Control children regressed by follow-up (difference p = .034, d = 0.65), but overall difference was not significant (p = .13, d = .47). No measure showed significant treatment differences at treatment end, but one did at follow-up. Children with IQ-achievement discrepancy > or = 1 SD showed significantly more CMA advantage on three measures. CONCLUSION: This study illustrates the importance of a credible control condition of equal duration and intensity in trials of novel treatments. CMA treatment cannot be recommended for combined-type ADHD without learning disorder.

Serum zinc correlates with parent- and teacher- rated inattention in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: The aim of this study was to explore the relationship of zinc nutrition to the severity of attention-deficit/hyperactivity disorder (ADHD) symptoms in a middle-class American sample with well-diagnosed ADHD. Previous reports of zinc in ADHD, including two positive clinical trials of supplementation, have come mainly from countries and cultures with different diets and/or socioeconomic realities. METHOD: Children 5-10 years of age with DISC- and clinician-diagnosed ADHD had serum zinc determinations and parent and teacher ratings of ADHD symptoms. Zinc levels were correlated (Pearson's and multiple regression) with ADHD symptom ratings. RESULTS: Forty-eight children (37 boys, 11 girls; 33 combined type, 15 inattentive) had serum zinc levels with a median/mode at the lowest 30% of the laboratory reference range; 44 children also had parent/teacher ratings. Serum magnesium levels were normal. Nutritional intake by a parent-answered food frequency questionnaire was unremarkable. Serum zinc correlated at r = -0.45 (p = 0.004) with parent-teacher-rated inattention, even after controlling for gender, age, income, and diagnostic subtype, but only at r = -0.20 (p = 0.22) with CPT omission errors. In contrast, correlation with parent-teacher-rated hyperactivity-impulsivity was nonsignificant in the opposite direction. CONCLUSION: These findings add to accumulating evidence for a possible role of zinc in ADHD, even for middle-class Americans, and, for the first time, suggest a special relationship to inattentive symptoms. They do not establish either that zinc deficiency causes ADHD nor that ADHD should be treated with zinc. Hypothesis-testing clinical trials are needed.