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Background In a previously reported Co FAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy ( eOIT). Active treatment induced desensitization in most and sustained unresponsiveness ( SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects. Methods Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white ( EW)-, ovalbumin ( OVA)-, and ovomucoid ( OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using Immuno CAP ®. Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders. Results No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE- OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE- EW ( P = 0.038), IgE- OVM ( P = 0.032), and a higher IgG4/IgE- OVM ratio ( P = 0.013) were associated with clinical response. Relative increases in IgG4- EW, IgA- EW, and IgA2- EW were observed in responders ( P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders ( P = 0.004, 0.009, 0.028, and 0.008, respectively). Conclusions Increased IgG4- EW, IgA- EW, and IgA2- EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE- EW and IgE- OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers. [ABSTRACT FROM AUTHOR]

This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), covering the years 1987–96 (January 15, 1997), analyzed data on 4898 patients who received 5362 transplants. Over the 10 yr of the study, 21.3% of the patients were under the age of 6 yr. Of the disorders that lead to end‐stage renal disease (ESRD), structural and developmental anomalies of aplasia, dysplasia, and obstructive uropathy accounted for over 1500 patients. Despite the potential therapies for focal segmental glomerulosclerosis (FSGS), there has been little change in its incidence and this lesion continues to be the most common cause of renal failure and transplantation among acquired diseases. Eighty‐nine per cent of patients with a functioning graft continue to receive cyclosporin A (CsA) 5 yr post‐transplantation, and 84% of patients continue to receive azathioprine (AZA), whereas 26% of patients receive alternate‐day steroid therapy at 4 yr post‐transplant. Thirty‐seven per cent of the living donor (LD) recipients and 47% of cadaver donor (CD) recipients were treated with the polyclonal T‐cell antibody ATG/ALG for induction, and the monoclonal T‐cell antibody, OKT3, was utilized for induction in 12% of LD patients and in 19% of CD patients. Twenty‐five per cent of the 5362 transplants (1333) have failed over the 10‐yr period. Graft survival is 90% at 1 yr and 74% at 6 yr for LD kidneys, and is 80% at 1 yr and 58% at 6 yr for CD patients. The most common cause for graft failure (30%) is chronic rejection. For recipients of LD grafts, relative risk (RR) factors for graft survival are African–American race (RR = 2.1, p<0.001) and greater than five prior transfusions (RR = 1.6, p<0.001). Prophylactic anti‐T‐cell antibody reduces the risk of graft failure (RR = 0.76, p=0.009). For recipients of cadaver kidneys, risk factors are: recipient age < 2 yr (RR = 2, p<0.001),... [ABSTRACT FROM AUTHOR]

The purpose of this randomized, double-blind study was to test the safety and immunogenicity of an HIV-1LAI recombinant gp160 (rgp160) vaccine in healthy, uninfected volunteers using accelerated dosing schedules. Thirty volunteers were randomly assigned to receive 50-μg doses of rgp 160 in one of two immunization schedules. Group 1 received rgp160 at times 0, 1, 2 and 5 months; and group 2 received rgp160 at times 0, 1, 2, 3 and 4 months. The vaccine was safe and stimulated high levels of HIV-1 envelope-specific binding antibody and T cell memory. There was a trend (P < 0.10) suggesting neutralizing antibodies were better induced by the regimen incorporating a rest period before the final immunization in group 1 volunteers. Both accelerated immunization schedules induced immune responses at levels similar to or better than those achieved by four rgp160 vaccine injections given over 12 - 18 months in other studies. [ABSTRACT FROM AUTHOR]

An abstract of the conference paper "Antibodies to the envelope protein protect macaques from SIVmac251 acquisition in an immunization regimen that mimics the RV-144 Thai trial," by G. Franchini and colleagues is presented.

Background: Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX., Methods: We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433., Findings: Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group)., Interpretation: In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications., Funding: NIDA Clinical Trials Network., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: For opioid-dependent patients in the US and elsewhere, detoxification and counseling-only aftercare are treatment mainstays. Long-term abstinence is rarely achieved; many patients relapse and overdose after detoxification. Methadone, buprenorphine-naloxone (BUP-NX) and extended-release naltrexone (XR-NTX) can prevent opioid relapse but are underutilized. This study is intended to develop an evidence-base to help patients and providers make informed choices and to foster wider adoption of relapse-prevention pharmacotherapies., Methods: The National Institute on Drug Abuse's Clinical Trials Network (CTN) study CTN-0051, X:BOT, is a comparative effectiveness study of treatment for 24weeks with XR-NTX, an opioid antagonist, versus BUP-NX, a high affinity partial opioid agonist, for opioid dependent patients initiating treatment at 8 short-term residential (detoxification) units and continuing care as outpatients. Up to 600 participants are randomized (1:1) to XR-NTX or BUP-NX., Results: The primary outcome is time to opioid relapse (i.e., loss of persistent abstinence) across the 24-week treatment phase. Differences between arms in the distribution of time-to-relapse will be compared (construction of the asymptotic 95% CI for the hazard ratio of the difference between arms). Secondary outcomes include proportions retained in treatment, rates of opioid abstinence, adverse events, cigarette, alcohol, and other drug use, and HIV risk behaviors; opioid cravings, quality of life, cognitive function, genetic moderators, and cost effectiveness., Conclusions: XR-NTX and BUP-NX differ considerably in their characteristics and clinical management; no studies to date have compared XR-NTX with buprenorphine maintenance. Study design choices and compromises inherent to a comparative effectiveness trial of distinct treatment regimens are reviewed., Clinical Trial Registration: NCT02032433., (Copyright © 2016 Elsevier Inc. All rights reserved.)