Study protocol of a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg oral immunotherapy at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo (probiotic egg allergen oral immunotherapy for treatment of egg allergy: PEAT study)

Introduction Egg allergy is the most common food allergy in children but recent studies have shown persistence or delayed resolution into adolescence. As there is currently no effective long-term treatment, definitive treatments that improve quality of life and prevent fatalities for food allergies are required. We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut oral immunotherapy (OIT) is highly effective at inducing sustained unresponsiveness, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. In this study, we plan to extend the probiotic food OIT platform to another allergen, namely egg. We describe the protocol for a phase 2, dual-centre, randomised, controlled trial evaluating the effectiveness of probiotic and egg OIT at inducing desensitisation or sustained unresponsiveness (remission) in participants with egg allergy compared with placebo. Methods and analysis 80 participants aged 5-30 years of age with current egg allergy confirmed by double-blind placebo-controlled food challenge at study screening will be recruited from Australia and Singapore. There are two intervention arms - probiotic and egg OIT (active) or placebo. Interventions are administered once daily for 18 months. The primary outcome is the proportion of participants who attain 8-week sustained unresponsiveness in the active group versus placebo group. Ethics and dissemination This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 2019.082) and the National Healthcare Group Domain Specific Review Board (2019/00029). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences. Trial registration number ACTRN12619000480189

House dust mite sensitization, eczema, and wheeze increase risk of shellfish sensitization

Non peer reviewe

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead