Comparative adherence and persistence of single- and multiple-inhaler triple therapies among patients with chronic obstructive pulmonary disease in an English real-world primary care setting.

This is the final version. Available from Dove Press via the DOI in this record. Data Sharing Statement: The data analyzed in this publication are derived from the Clinical Practice Research Datalink (www.cprd.com) and Hospital Episode Statistics database (https://digital.nhs.uk/data-and-information/data-tools-and-services/data-services/hospital-episodestatistics). Authors had access to the study data for the purposes of this work only. Data were accessed through an existing GSK license to address the prespecified research questions only. Therefore, the data cannot be broadly disclosed or made publicly available at this time. Access to each database can be requested via the respective websites.PURPOSE: Triple therapy comprising a long-acting muscarinic antagonist, long-acting β2-agonist and inhaled corticosteroid is recommended for patients with chronic obstructive pulmonary disease (COPD) who continue to experience frequent exacerbations or symptoms whilst receiving dual therapy. Adherence and persistence to multiple-inhaler triple therapy (MITT) is known to be poor. This study assessed comparative adherence to single-inhaler triple therapy (SITT) versus MITT in a real-world setting in England. PATIENTS AND METHODS: This was a retrospective cohort study using linked primary care (Clinical Practice Research Datalink Aurum) and secondary care (Hospital Episode Statistics [HES] Admitted Patient Care) data to identify patients with COPD who were newly initiated on SITT or MITT between November 2017 and June 2019. Eligible patients were aged ≥35 years and had a forced expiratory volume in 1 second/forced vital capacity 30 days between the end of a prescription and the following refill used to determine non-persistence. RESULTS: Overall, 4080 SITT and 6579 MITT users comprised the study cohort. After weighting, the baseline characteristics between the cohorts were comparable (absolute standardized mean difference <10%). SITT users had significantly higher adherence than MITT users at 6, 12, and 18 months post-initiation (p<0.001 for all comparisons). Median persistence was higher among SITT users than MITT users (5.09 months vs 0.99 months). CONCLUSION: Patients with COPD in England initiating SITT had significantly better adherence and persistence compared with MITT initiators. These improvements continued at least 18 months following treatment initiation.GlaxoSmithKlei

Ritual plants of Muslim graveyards in northern Israel

This article surveys the botanical composition of 40 Muslim graveyards in northern Israel, accompanied by an ethnobotanical study of the folkloristic traditions of the use of these plants in cemeteries. Three groups of plants were found to be repeated systematically and were also recognized for their ritual importance: aromatics herbs (especially Salvia fruticosa and Rosmarinus officinalis), white flowered plants (mainly Narcissus tazetta, Urginea maritima, Iris spp. and Pancratium spp.) and Cupressus sempervirens as the leading cemetery tree. As endemic use we can indicate the essential role of S. fruticosa as the main plant used in all human rites of passage symbolizing the human life cycle. The rosemary is of European origin while the use of basil is of Indian influence. The use of white flowers as cemeteries plants reflects an old European influence and almost the same species are used or their congeners. Most of the trees and shrubs that are planted in Muslim cemeteries in Israel have the same use in ancient as well in modern European cultures. In conclusion, our findings on the occurrence of plants in graveyards reflect the geographic situation of Israel as a crossroads in the cultural arena between Asia and Europe. Most of the traditions are common to the whole Middle East showing high relatedness to the classical world as well as to the present-day Europe

Comparative Effectiveness of Umeclidinium/Vilanterol versus Indacaterol/Glycopyrronium on Moderate-to-Severe Exacerbations in Patients with Chronic Obstructive Pulmonary Disease in Clinical Practice in England

Gema Requena,1 Alexandrosz Czira,1 Victoria Banks,2 Robert Wood,2 Theo Tritton,2 Catherine Castillo,2 Jie Yeap,2 Rosie Wild,2 Chris Compton,1 Kieran J Rothnie,1 Felix JF Herth,3 Jennifer K Quint,4 Afisi S Ismaila5,6 1GSK, R&D Global Medical, Brentford, Middlesex, UK; 2Real-World Evidence, Adelphi Real World, Bollington, Cheshire, UK; 3Department of Pneumology and Critical Care Medicine, Thoraxklinik, University of Heidelberg and Translational Lung Research Center Heidelberg, Heidelberg, Germany; 4National Heart and Lung Institute, Imperial College London, London, UK; 5Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 6Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Gema Requena, Epidemiology, Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, UK, Tel +44 20 80476893, Email [email protected]: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with significant morbidity and mortality and increased economic healthcare burden for patients with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) dual therapy is recommended for patients receiving mono-bronchodilator therapy who experience exacerbations or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), on moderate-to-severe exacerbation rates in patients with COPD in England.Patients and Methods: This retrospective cohort study used linked primary care electronic health record data (Clinical Practice Research Datalink-Aurum) and secondary care data (Hospital Episode Statistics) to assess outcomes for patients with COPD who had a first prescription for single-inhaler UMEC/VI or IND/GLY (index date) between 1 January 2015 and 30 September 2019 (indexing period). Analyses compared UMEC/VI and IND/GLY on moderate-to-severe, moderate, and severe exacerbations, healthcare resource utilization (HCRU), and direct costs at 6, 12, 18, and 24 months, and time-to-first on-treatment exacerbation up to 24 months post-index date. Following inverse probability of treatment weighting (IPTW), non-inferiority and superiority of UMEC/VI versus IND/GLY were assessed.Results: In total, 12,031 patients were included, of whom 8753 (72.8%) were prescribed UMEC/VI and 3278 (27.2%) IND/GLY. After IPTW, for moderate-to-severe exacerbations, weighted rate ratios were < 1 at 6, 12, and 18 months and equal to 1 at 24 months for UMEC/VI; around the null value for moderate exacerbations and < 1 at all timepoints for severe exacerbations. UMEC/VI showed lower HCRU incidence rates than IND/GLY for all-cause Accident and Emergency visits and COPD-related inpatient stays and associated all-cause costs at 6 months post-indexing. Time-to-triple therapy was similar for both treatments.Conclusion: UMEC/VI demonstrated non-inferiority to IND/GLY in moderate-to-severe exacerbation reduction at 6, 12 and 18 months. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY on reduction of moderate-to-severe exacerbations.Plain Language Summary: Sudden exacerbations, or flare-ups, of chronic obstructive pulmonary disease (COPD) are linked with worsening health and increased risk of death, as well as increased healthcare costs for people with COPD. Long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) dual therapy is recommended for patients with COPD who take LAMA or LABA monotherapy but continue to experience flare-ups or ongoing breathlessness. This study compared two single-inhaler LAMA/LABA dual therapies, umeclidinium/vilanterol (UMEC/VI) and indacaterol/glycopyrronium (IND/GLY), in terms of flare-ups in patients with COPD in England.We used two linked databases of de-identified medical records from general practitioners and hospitals for patients with COPD who had a first prescription for UMEC/VI or IND/GLY between 1 January 2015 and 30 September 2019. We compared the two treatments on COPD flare-ups, healthcare resource utilization and related costs, and changes in medication over the 2 years following starting treatment.We found that the treatments were comparable for moderate-to-severe flare-ups. Patients taking UMEC/VI had less Accident and Emergency (A&E) visits in total and less inpatient stays related to their COPD, and had a lower overall cost of healthcare for A&E visits and inpatient stays than patients taking IND/GLY. Changes to treatment and time before their first flare-up were similar for all patients, regardless of their prescribed treatment.This study showed that UMEC/VI is as effective as IND/GLY at preventing moderate-to-severe flare-ups. These results support previous findings demonstrating similarity between UMEC/VI and IND/GLY in reducing the rate of moderate-to-severe exacerbations after starting treatment.Keywords: COPD dual therapy, LABA/LAMA new users, healthcare resource utilization, exacerbations, comparative effectiveness, single-inhaler dual therap

A Brief Outline of the Israel–Palestinian Conflict

Before we can explore the use of management science, game theory, cognitive science and artificial intelligence to attempt to resolve (or just manage) the Israel–Palestinian dispute, we need some sort of mutual understanding about the conflict. Given such a long and multi-faceted history rife with multiple conflicting claims, interpretations and emphases, all fraught with moral and political implications, it is unlikely that any account will be acceptable to all parties as authoritative.Nevertheless, we must search for some common ground. Our examination of history commences with the life of Abraham, the father of the three great monotheistic religions: Judaism, Christianity, and Islam and continues through to a discussion of Zionism and Arab nationalism. This leads to the creation of the State of Israel on May 14, 1948; celebrated as Yom Ha’atzmaut (Independence Day) and commemorated as ‘al-Nakhba (the catastrophe), according to one’s background. Whilst our discussion concludes with recent events, including the spring 2011 protests and demonstrations spread throughout the Middle East, there is no doubt that during the time between which this article is written and it appears in a journal, momentous events will have occurred

Comparative Effectiveness of Umeclidinium/Vilanterol versus Inhaled Corticosteroid/Long-Acting &beta;2-Agonist in Patients with Chronic Obstructive Pulmonary Disease in a Primary Care Setting in England

Alexandrosz Czira,1 Gema Requena,1 Victoria Banks,2 Robert Wood,2 Theo Tritton,2 Catherine M Castillo,2 Jie Yeap,2 Rosie Wild,2 Chris Compton,1 Kieran J Rothnie,1 Felix Herth,3,4 Jennifer K Quint,5 Afisi S Ismaila6,7 1R&D Global Medical, GSK, Brentford, Middlesex, UK; 2Real-World Evidence, Adelphi Real World, Bollington, Cheshire, UK; 3Department of Pulmonology and Respiratory Care Medicine, Thoraxklinik at the University of Heidelberg, Heidelberg, Germany; 4Translational Lung Research Center Heidelberg, Member of the German Center for Lung Research DZL, Heidelberg, Germany; 5National Heart and Lung Institute, Imperial College London, London, UK; 6Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Alexandrosz Czira, Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, UK, Tel +44 7788 351610, Email [email protected]: To compare adherence to once-daily umeclidinium/vilanterol (UMEC/VI), a long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA), and twice-daily inhaled corticosteroids (ICS)/LABA single-inhaler dual therapy in patients with chronic obstructive pulmonary disease (COPD) in a primary care cohort in England.Patients and Methods: Active comparator, new-user, retrospective cohort study using CPRD-Aurum primary care data and linked Hospital Episode Statistics secondary care administrative data. Patients without exacerbations in the previous year were indexed on first/earliest prescription date of once-daily UMEC/VI or twice-daily ICS/LABA as initial maintenance therapy between July 2014-September 2019. Primary outcome: medication adherence at 12 months post-index, defined as proportion of days covered (PDC) ≥ 80%. PDC represented proportion of time over the treatment duration that the patient was theoretically in possession of the medication. Secondary outcomes: adherence at 6, 18, and 24 months post-index, time-to-triple therapy, time-to-first on-treatment COPD exacerbation, COPD-related and all-cause healthcare resource utilization (HCRU), and direct health-care costs. A propensity score was generated and inverse probability of treatment weighting (IPTW) was used to balance potential confounders. Superiority was defined as > 0% difference between treatment groups.Results: In total, 6815 eligible patients were included (UMEC/VI:1623; ICS/LABA:5192). At 12 months post-index, weighted odds of a patient being adherent were significantly greater with UMEC/VI versus ICS/LABA (odds ratio [95% CI]: 1.71 [1.09, 2.66]; p=0.0185), demonstrating superiority of UMEC/VI. Patients taking UMEC/VI were statistically significantly more adherent than those taking ICS/LABA at 6, 18, and 24 months post-index (p< 0.05). Differences in time-to-triple therapy, time-to-moderate COPD exacerbations, HCRU, and direct medical costs were not statistically significant between treatments after IPTW was applied.Conclusion: At 12 months post-treatment initiation, once-daily UMEC/VI was superior to twice-daily ICS/LABA in medication adherence among patients with COPD without exacerbations in the previous year, newly initiating dual maintenance therapy in England. The finding was consistent at 6, 18, and 24 months.Keywords: adherence, comparative effectiveness, chronic obstructive pulmonary disease (COPD) treatment, inhaled corticosteroid/long-actingβ2-agonist (ICS/LABA) dual therapy, long-acting muscarinic antagonist (LAMA)/LABA dual therap