Incidence of COVID-19 among returning travelers in quarantine facilities: A longitudinal study and lessons learned

This article is made available for unrestricted research re-use and secondary analysis in any form or be any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Introduction: The emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had resulted in an unpresented global pandemic. In the initial events, the Kingdom of Saudi Arabia implemented mandatory quarantine of returning travelers in order to contain COVID-19 cases. Materials and methods: This is a longitudinal study of the arriving travelers to Quarantine facilities and the prevalence of positive SARS-CoV-2 as detected by RT-PCR. Results: During the study period, there was a total of 1928 returning travelers with 1273 (66%) males. The age range was 28 days–69 years. Of all the travelers, 23 (1.2%) tested positive for SARS-CoV-2. Of the first swab, 14/1928 (0.7%) tested positive. The positivity rate was 0.63% and 0.92% among males and females, respectively (P = 0.57). The second swab was positive in 9 (0.5%) of the other 1914 who were initially negative with a positivity rate of 0.39% and 0.62% among males and females, respectively (P = 0.49). There was no statistical difference in the positivity rates between first and second swab (P = 0.4). Of all travelers, 40 (n = 26, 1.3%) were admitted from the quarantine facility to the hospital due to COVID-19 related positive results or development of symptoms such as fever, cough, and respiratory symptoms; and 14 (0.7%) were admitted due to non-COVID-19 related illness. Conclusion: This study showed the efforts put for facility quarantine and that such activity yielded a lower incidence of positive cases. There was a need to have a backup healthcare facility to accommodate those developing a medical need for evaluation and admission for non-COVID-19 related illnesses

WNT10B/β-catenin signalling induces HMGA2 and proliferation in metastatic triple-negative breast cancer

Wnt/β-catenin signalling has been suggested to be active in basal-like breast cancer. However, in highly aggressive metastatic triple-negative breast cancers (TNBC) the role of β-catenin and the underlying mechanism(s) for the aggressiveness of TNBC remain unknown. We illustrate that WNT10B induces transcriptionally active β-catenin in human TNBC and predicts survival-outcome of patients with both TNBC and basal-like tumours. We provide evidence that transgenic murine Wnt10b-driven tumours are devoid of ERα, PR and HER2 expression and can model human TNBC. Importantly, HMGA2 is specifically expressed during early stages of embryonic mammogenesis and absent when WNT10B expression is lost, suggesting a developmentally conserved mode of action. Mechanistically, ChIP analysis uncovered that WNT10B activates canonical β-catenin signalling leading to up-regulation of HMGA2. Treatment of mouse and human triple-negative tumour cells with two Wnt/β-catenin pathway modulators or siRNA to HMGA2 decreases HMGA2 levels and proliferation. We demonstrate that WNT10B has epistatic activity on HMGA2, which is necessary and sufficient for proliferation of TNBC cells. Furthermore, HMGA2 expression predicts relapse-free-survival and metastasis in TNBC patients

Saving and Empowering young lives in PAKistan (SEPAK): An Exploratory Cluster Randomized Controlled Trial (cRCT)

IntroductionSuicide is a leading cause of death among young people and most deaths by suicide occur in low and middle-income countries. School is the best place where we can identify and respond to youth suicide risk. School-based interventions for suicide prevention in young people have been successful across US, Europe and Australia, but require adaptations to be acceptable and feasible in Pakistan.ObjectivesTo develop and test culturally adapted preventative interventions for suicidal behaviours among pupils in secondary schools in Pakistan. The qualitative component aimed at exploring the views of students, parents, teachers and general practitioners on cultural adaptation, experience of participation, areas of improvement and suggestions for scale-up of the school-based suicide prevention program (SEPAK).MethodsA clustered randomised controlled trial. The four culturally modified interventions 1) Linking Education and Awareness of Depression and Suicide Awareness (LEADS) Training for pupils (students=260) 2) the Question, Persuade, and Refer (QPR) for teachers (students=203) 3) QPR for parents (students=445); 4) Screening by Professionals (Profscreen) (students=260) were compared against control intervention (educational posters) (students=227). Structured questionnaires were administered at baseline and 1-month post-intervention to assess suicidal behaviours, psychological well-being and quality of life. A total of 8 focus groups (FGs) were conducted at pre and post intervention stage with each stakeholders.ResultsPatient and public involvement and Engagement (PPIE) was strongly embedded in the project to ensure meaningful benefits for participants. A total of 40 schools were recruited from 8 cities across Pakistan. A total of 243 students attended LEADS intervention, 92 teachers and 304 parents completed QPR training, and 9 general practitioners were trained in ProfScreen. The retention rate at follow-up was 99% that shows feasibility of delivering intervention package in Pakistan. All participants marked SEPAK as effective in identifying risk of and preventing self-harm and suicide in young people and in improving pathways to treatment. Interventions were perceived as helpful in improving knowledge about mental health, impact of mental health difficulties on functioning, reducing stigma, equipping stakeholders to identify and signpost at-risk people. Improvement in clinical and teaching practice as well as understanding others behaviors were also reported.ConclusionsThis study suggest feasibility of integrating a suicide prevention program in existing educational system and highlights positive role of creating awareness about suicide in youth, introduction of school-based mental health programs, parental counseling and strengthening of the health system by training general practitioners in early identification of suicide risk and promoting suicide prevention strategiesDisclosure of InterestNone Declared</jats:sec

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.]

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls

Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders