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

Clinical outcomes in patients with severe asthma who had or had not initiated biologic therapy : results from the CLEAR study

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Clinical outcomes and emergency healthcare utilization in patients with severe asthma who continued, switched or stopped biologic therapy : results from the CLEAR study

Funding This study was funded by AstraZeneca. The International Severe Asthma Registry is jointly funded by Optimum Patient Care Global and AstraZeneca. Acknowledgments Medical writing support was provided by Madeleine Wynn, MRes, of PharmaGenesis London, London, UK, with funding from AstraZeneca.Peer reviewe

The prevalence of pelvic organ prolapse symptoms and signs and their relation with bladder and bowel disorders in a general female population

Contains fulltext : 81191.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: In selected populations, pelvic organ prolapse (POP) was associated with bladder/bowel symptoms, but data on the general female population are lacking. Our aim was to obtain normative data on the prevalence of POP and pelvic floor dysfunction (PFD) symptoms and signs and to identify associations. METHODS: Validated questionnaires on POP and PFD (urogenital distress inventory, (UDI) and defaecation distress inventory (DDI)) were sent to a general population of 2,979 women (aged 45-85 years). Data were analysed using the Kruskal-Wallis test, chi square test and Spearman's rank correlation coefficient. RESULTS: Response rate was 62.7%. Associations between POP stage and parity (0.002) and vaginal bulging (<0.001) are significant. Anatomical locations of POP and PFD symptoms correlated significantly with incontinence of flatus, feeling anal prolapse, manual evacuation of stool, vaginal bulging, constipation and pain during faecal urge (p < or = 0.005). CONCLUSIONS: Strategies should be developed to alleviate obstructive bowel disorders associated with POP

Perineal descent and patients’ symptoms of anorectal dysfunction, pelvic organ prolapse, and urinary incontinence

Contains fulltext : 89793.pdf (publisher's version ) (Closed access)INTRODUCTION AND HYPOTHESIS: The aim of this dynamic magnetic resonance (MR) imaging study was to assess the relation between the position and mobility of the perineum and patients' symptoms of pelvic floor dysfunction. METHODS: Patients' symptoms were measured with the use of validated questionnaires. Univariate logistic regression analyses were used to study the relationship between the questionnaires domain scores and the perineal position on dynamic MR imaging, as well as baseline characteristics (age, body mass index, and parity). RESULTS: Sixty-nine women were included in the analysis. Only the domain score genital prolapse was associated with the perineal position on dynamic MR imaging. This association was strongest at rest. CONCLUSIONS: Pelvic organ prolapse symptoms were associated with the degree of descent of the perineum on dynamic MR imaging. Perineal descent was not related to anorectal and/or urinary incontinence symptoms.1 juni 201

Functional Anatomy of the Female Pelvic Floor

The anatomic structures in the female that prevent incontinence and genital organ prolapse on increases in abdominal pressure during daily activities include sphincteric and supportive systems. In the urethra, the action of the vesical neck and urethral sphincteric mechanisms maintains urethral closure pressure above bladder pressure. Decreases in the number of striated muscle fibers of the sphincter occur with age and parity. A supportive hammock under the urethra and vesical neck provides a firm backstop against which the urethra is compressed during increases in abdominal pressure to maintain urethral closure pressures above the rapidly increasing bladder pressure. This supporting layer consists of the anterior vaginal wall and the connective tissue that attaches it to the pelvic bones through the pubovaginal portion of the levator ani muscle, and the uterosacral and cardinal ligaments comprising the tendinous arch of the pelvic fascia. At rest the levator ani maintains closure of the urogenital hiatus. They are additionally recruited to maintain hiatal closure in the face of inertial loads related to visceral accelerations as well as abdominal pressurization in daily activities involving recruitment of the abdominal wall musculature and diaphragm. Vaginal birth is associated with an increased risk of levator ani defects, as well as genital organ prolapse and urinary incontinence. Computer models indicate that vaginal birth places the levator ani under tissue stretch ratios of up to 3.3 and the pudendal nerve under strains of up to 33%, respectively. Research is needed to better identify the pathomechanics of these conditions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72597/1/annals.1389.034.pd

Comparative effectiveness of Anti-IL5 and Anti-IgE biologic classes in patients with severe asthma eligible for both.

BACKGROUND: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. METHODS: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. RESULTS: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). CONCLUSIONS: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use