The Bronchiectasis Exacerbation Diary:a novel patient-reported outcome for non-cystic fibrosis bronchiectasis

Bronchiectasis is a chronic, progressive lung disease believed to result from a vicious cycle of infection and inflammation, with symptoms of chronic cough with sputum production, chronic fatigue, rhinosinusitis, chest pain, breathlessness and haemoptysis. There are currently no established instruments to monitor daily symptoms and exacerbations for use in clinical trials. Following a literature review and three expert clinician interviews, we conducted concept elicitation interviews with 20 patients with bronchiectasis to understand their personal disease experience. Findings from literature and clinician feedback were used to develop a draft version of the Bronchiectasis Exacerbation Diary (BED), which was designed to monitor key symptoms on a daily basis and during exacerbations. Patients were eligible to be interviewed if they were US residents aged ≥18 years, had a computed tomography scan–confirmed diagnosis of bronchiectasis with ≥two exacerbations in the previous 2 years and had no other uncontrolled respiratory conditions. Four waves of five patient interviews each were conducted. Patients (n=20) had a mean±SD age of 53.9±12.8 years, and most were female (85%) and white (85%). A total of 33 symptoms and 23 impacts arose from the patient concept elicitation interviews. The BED was revised and finalised based upon patient feedback. The final BED is a novel, eight-item patient-reported outcome (PRO) instrument for monitoring key exacerbation symptoms on a daily basis with content validity established through comprehensive qualitative research and direct patient insight. The BED PRO development framework will be completed following psychometric evaluations of the data from a phase 3 bronchiectasis clinical trial

An Ergonomic Study on the ‘Morningness’ and ‘Eveningness’ of Call Center Agents and Its Effect on Cognitive Performance

The increasing adaptation of shiftwork in the Philippines and its reported adverse effects had encouraged research studies among Filipino workers. This study aims to identify the circadian clock behavior of the shiftworker and its relationship together with the shift schedule against the level of performance. The subjects used in this study were call center agents. Subjects were initially asked to answer a compilation of survey from the Standard Shift work Index (SSI) and Swedish Occupational Fatigue Inventory (SOFI). During the experiment proper, three laptops with head microphones were used where each laptop contained the software and programs in measuring the speech ability, reaction time and memory of participants. Majority of the respondents belong to the morning type and only one belonged to the intermediate type. The General Health Score (SSI) of the agents was generally poor in the aspect of their psychological health. The Swedish Occupational Fatigue Inventory (SOFI) scores showed that the respondents did not experience excessive fatigue. Based on the two-way ANOVA, it was found that the three speech ability measures and reaction time were significant in terms of the performance deterioration at each schedule in relation to the body clock of the individual

Clinical Remission in Severe Asthma : A Pooled Post hoc Analysis of the Patient Journey with Benralizumab

Funding This study, the Rapid Service Fee, and the Open Access Fee were funded by AstraZeneca (Gaithersburg, MD, USA).Peer reviewedPublisher PD

A Response to : Letter to the Editor Regarding “Clinical Remission in Severe Asthma: A Pooled Post Hoc Analysis of the Patient Journey with Benralizumab”

Funding Information: No funding or sponsorship was received for the publication of this article. Medical writing support was provided by Dan Jackson, Ph.D., CMPP (CiTRUS Health Group), and was funded by AstraZeneca (Cambridge, UK) in accordance with Good Publication Practice (GPP3) guidelines. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Andrew Menzies-Gow developed the outline and content of the response letter and commented on previous versions of the manuscript. All authors read and approved the final manuscript. Andrew Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, and Teva; has received speaker fees from AstraZeneca, Novartis, Sanofi, and Teva; has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva; and has had consultancy agreements with AstraZeneca and Sanofi. Flavia L. Hoyte has attended advisory boards for AstraZeneca; has received speaker fees from AstraZeneca and GlaxoSmithKline; and has participated in research sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Teva, Sanofi, and the National Institute of Allergy and Infectious Diseases (NIAID), for which her institution has been remunerated. David B. Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Thermofisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance, and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance, and the UK National Health Service; received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, and Sanofi Genzyme; received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, and Thermofisher; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; ownership of 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; a peer reviewer role for grant committees of the UK Efficacy and Mechanism Evaluation programme and the Health Technology Assessment; and served as an expert witness for GlaxoSmithKline. David Cohen, Peter Barker, James Kreindler, Maria Jison, Chris Brooks, Peggy Papeleu, and Rohit Katial are employees of AstraZeneca. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Data sharing is not applicable to this article as no datasets were generated or analysed for this response letter. Funding Information: Andrew Menzies-Gow has attended advisory boards for AstraZeneca, GlaxoSmithKline, Novartis, Sanofi, and Teva; has received speaker fees from AstraZeneca, Novartis, Sanofi, and Teva; has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva; and has had consultancy agreements with AstraZeneca and Sanofi. Flavia L. Hoyte has attended advisory boards for AstraZeneca; has received speaker fees from AstraZeneca and GlaxoSmithKline; and has participated in research sponsored by AstraZeneca, GlaxoSmithKline, Genentech, Teva, Sanofi, and the National Institute of Allergy and Infectious Diseases (NIAID), for which her institution has been remunerated. David B. Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Thermofisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance, and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance, and the UK National Health Service; received payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, and Sanofi Genzyme; received payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, and Thermofisher; stock/stock options from AKL Research and Development Ltd, which produces phytopharmaceuticals; ownership of 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp, which develops adherence monitoring technology; a peer reviewer role for grant committees of the UK Efficacy and Mechanism Evaluation programme and the Health Technology Assessment; and served as an expert witness for GlaxoSmithKline. David Cohen, Peter Barker, James Kreindler, Maria Jison, Chris Brooks, Peggy Papeleu, and Rohit Katial are employees of AstraZeneca. Funding Information: Medical writing support was provided by Dan Jackson, Ph.D., CMPP (CiTRUS Health Group), and was funded by AstraZeneca (Cambridge, UK) in accordance with Good Publication Practice (GPP3) guidelines.Peer reviewedPublisher PD

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

An ergonomic study on the \u27morningness\u27 and \u27eveningness\u27 of call center agents and its effect on cognitive performance

The increasing adaptation of shiftwork in the Philippines and its reported adverse effects had encouraged research studies among Filipino workers. This study aims to identify the circadian clock behavior of the shiftworker and its relationship together with the shift schedule against the level of performance. The subjects used in this study were call center agents. Subjects were initially asked to answer a compilation of survey from the Standard Shift work Index (SSI) and Swedish Occupational Fatigue Inventory (SOFI). During the experiment proper, three laptops with head microphones were used where each laptop contained the software and programs in measuring the speech ability, reaction time and memory of participants. Majority of the respondents belong to the morning type and only one belonged to the intermediate type. The General Health Score (SSI) of the agents was generally poor in the aspect of their psychological health. The Swedish Occupational Fatigue Inventory (SOFI) scores showed that the respondents did not experience excessive fatigue. Based on the two-way ANOVA, it was found that the three speech ability measures and reaction time were significant in terms of the performance deterioration at each schedule in relation to the body clock of the individual. © 2017 IJTech

Predicting response to benralizumab in chronic obstructive pulmonary disease: analyses of GALATHEA and TERRANOVA studies

Benralizumab did not significantly reduce exacerbations compared with placebo in the phase 3 GALATHEA and TERRANOVA trials of benralizumab for patients with chronic obstructive pulmonary disease (COPD). We aimed to identify clinical and physiological characteristics of patients with COPD that could help to identify people who are likely to have the greatest treatment effect with benralizumab

Efficacy and safety of benralizumab in chronic rhinosinusitis with nasal polyps : a randomized, placebo-controlled trial

Background: Eosinophilic inflammation has been implicated in the pathogenesis, severity, and treatment responsiveness of chronic rhinosinusitis with nasal polyps (CRSwNP). Objective: We sought to assess the efficacy and safety of benralizumab-mediated eosinophil depletion for treating CRSwNP. Methods: The phase 3 OSTRO study enrolled patients with severe CRSwNP who were symptomatic despite treatment with intranasal corticosteroids and who had a history of systemic corticosteroid (SCS) use and/or surgery for nasal polyps (NP). Patients were randomized 1:1 to treatment with benralizumab 30 mg or placebo every 4 weeks for the first 3 doses and every 8 weeks thereafter. Coprimary end points were change from baseline to week 40 in NP score (NPS) and patient-reported mean nasal blockage score reported once every 2 weeks. Results: The study population comprised 413 randomized patients (207 in the benralizumab group and 206 in the placebo group). Benralizumab significantly improved NPS and nasal blockage score compared to placebo at week 40 (P <= .005). Improvements in Sinonasal Outcome Test 22 score at week 40, time to first NP surgery and/or SCS use for NP, and time to first NP surgery were not statistically significant between treatment groups. Nominal significance was obtained for improvement in difficulty in sense of smell score at week 40 (P = .003). Subgroup analyses suggested influences of comorbid asthma, number of NP surgeries, sex, body mass index, and baseline blood eosinophil count on treatment effects. Benralizumab was safe and well tolerated. Conclusion: Benralizumab, when added to standard-of-care therapy, reduced NPS, decreased nasal blockage, and reduced difficulty with sense of smell compared to placebo in patients with CRSwNP