Fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy compared with other therapies for the treatment of COPD: A network meta-analysis.

This is the final version. Available from Springer via the DOI in this record. Data Availability: The datasets analyzed during the current study are available from the corresponding author on reasonable request.INTRODUCTION: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting β2-agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD. METHODS: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an ICS/LABA/LAMA combination with any dual therapy (ICS/LABA or LAMA/LABA). Outcomes of interest included forced expiratory volume in 1 s (FEV1), annualized rate of combined moderate and severe exacerbations, St George's Respiratory Questionnaire (SGRQ) total score and SGRQ responders, transition dyspnea index focal score, and rescue medication use (RMU). Analyses were conducted at 24 weeks (primary endpoint), and 12 and 52 weeks (if feasible). RESULTS: The NMA was informed by five trials reporting FEV1 at 24 weeks. FF/UMEC/VI was statistically significantly more effective at increasing trough FEV1 (based on change from baseline) than all triple comparators in the network apart from UMEC + FF/VI. The NMA was informed by 17 trials reporting moderate or severe exacerbation endpoints. FF/UMEC/VI demonstrated statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus single-inhaler budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR). At 24 weeks, the NMA was informed by five trials. FF/UMEC/VI showed statistically significant improvements in annualized rate of combined moderate or severe exacerbations versus UMEC + FF/VI and BUD/GLY/FOR. FF/UMEC/VI also demonstrated improvements in mean SGRQ score versus other triple therapy comparators at 24 weeks, and a significant reduction in RMU compared with BUD/GLY/FOR (160/18/9.6). CONCLUSION: The findings of this NMA suggest favorable efficacy with single-inhaler triple therapy comprising FF/UMEC/VI. Further analysis is required as additional evidence becomes available.GlaxoSmithKlei

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

Comparative efficacy of Umeclidinium/Vilanterol versus other bronchodilators for the treatment of chronic obstructive pulmonary disease: A network meta-analysis.

This is the final version. Available from Springer via the DOI in this record. Data Availability: Anonymised individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com. Extracted data summaries are available upon request to the authors.INTRODUCTION: Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD. METHODS: A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV1), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented. RESULTS: The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV1 versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation. CONCLUSION: UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV1 at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.GlaxoSmithKlei

Correction to: Comparative efficacy of Umeclidinium/Vilanterol versus other bronchodilators for the treatment of chronic obstructive pulmonary disease: A network meta-analysis.

This is the final version. Available from Springer via the DOI in this record. The authors regret to inform readers that the labels for the ‘treatment favour’ arrows were incorrectly labelled in Fig. 4. The ‘Favours UMEC/VI 62.5/25’ and ‘Favours comparator’ labels were appended to the wrong arrows and the corrected Fig. 4 is shown below. Please note that the data have not changed between versions

Neuropsychological performance in a sample of 13-25 year olds with a history of non-psychotic major depressive disorder

BackgroundThere is evidence for neuropsychological dysfunction in depression among adult and elderly participants but little research has been conducted on the neuropsychological functioning of youth with depression. The aim of the present study was to investigate the neuropsychological functioning of outpatient young participants with depression.MethodsComputerised neuropsychological tests requiring executive functioning, working memory, attention, verbal memory and learning, planning, and visuospatial skills were carried out in a sample of 13-25year-olds with a lifetime history of non-psychotic major depression (n=32) and in healthy age balanced controls (n=65). Psychiatric diagnoses were ascertained using the MINI International Neuropsychiatric Interview.ResultsParticipants with current or previous major depressive disorder demonstrated impairments in executive function tasks requiring conceptual skills and set-shifting, attention and working memory. However, planning skills were found to be largely intact. Positive affect was associated to better attention, working memory and verbal learning in depressed participants, independently from gender and education.LimitationsThe results may be affected by the small sample size and heterogeneity of the sample.ConclusionThe findings from this study indicate, and are one of the first to identify, that young subjects aged between 13 and 25, with a lifetime history of depression, have impaired executive and working memory functioning.Bernhard T. Baune, Maria E. Czira, Annie L. Smith, David Mitchell, Grant Sinnamo

Burden of Disease in Patients with Mild or Mild-to-Moderate Chronic Obstructive Pulmonary Disease (Global Initiative for Chronic Obstructive Lung Disease Group A or B): A Systematic Literature Review

Alexandrosz Czira,1 Sneha Purushotham,2 Ike Iheanacho,2 Kieran J Rothnie,1 Chris Compton,3 Afisi S Ismaila4,5 1Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, UK; 2Evidera, London, UK; 3Global Medical, GSK, London, UK; 4Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Alexandrosz Czira, Value Evidence and Outcomes, R&D Global Medical, GSK, 980 Great West Road, Brentford, Middlesex, TW8 9GS, UK, Tel +44 7788 351610, Email [email protected]: Patients with mild or mild-to-moderate chronic obstructive pulmonary disease (COPD), defined as Global Initiative for Chronic Obstructive Lung Disease (GOLD) group A/B, are regarded as having a lower risk of experiencing multiple or severe exacerbations compared with patients classified as GOLD group C/D. Current guidelines suggest that patients in GOLD A/B should commence treatment with a bronchodilator; however, some patients within this population who have a higher disease burden may benefit from earlier introduction of dual bronchodilator or inhaled corticosteroid-containing therapies. This study aimed to provide research-based insights into the burden of disease experienced by patients classified as GOLD A/B, and to identify characteristics associated with poorer outcomes.Methods: A systematic literature review (SLR) was conducted to identify evidence (burden of disease and prevalence data) relating to the population of interest (patients with COPD classified as GOLD A/B).Results: A total of 79 full-text publications and four conference abstracts were included. In general, the rates of moderate and severe exacerbations were higher among patients in GOLD group B than among those in group A. Among patients classified as GOLD A/B, the risk of exacerbation was higher in those with more symptoms (modified Medical Research Council or COPD Assessment Test scales) and more severe airflow limitation (forced expiratory volume in 1 second % predicted).Conclusion: Data from this SLR provide clear evidence of a heavier burden of disease for patients in GOLD B, compared with those in GOLD A, and highlight factors associated with worse outcomes for patients in GOLD A/B.Keywords: COPD Assessment Test, COPD, disease burden, GOLD A/B, modified Medical Research Council, systematic revie

Temperature dependences of ion currents of alcohol clusters under low-temperature secondary ion mass spectrometric conditions

The dependences of ion currents on temperature (ion thermograms) obtained by monitoring the abundance of different types of ions during the thawing of frozen samples of methanol and ethanol in low-temperature secondary ion mass spectrometry revealed special features in the temperature behaviour of the samples. Correlations between the changes in ion production and phase transitions (melting, boiling, evaporation) in the sample with temperature increase were revealed

Association between neurological disorders, functioning, and mortality in the elderly

Abstract not availableM. E. Czira, B. T. Baune, A. Roesler, K. Pfadenhauer, C. Trenkwalder, K. Berge

Body mass index, waist circumference and mortality in kidney transplant recipients.

Higher body mass index (BMI) appears paradoxically associated with better outcomes in patients with chronic kidney disease. Whereas higher BMI reflects both increased visceral and subcutaneous fat and/or muscle mass, a combined assessment of BMI and waist circumference may enable differentiation of visceral adiposity from muscle and/or nonvisceral fat mass. We examined the association of BMI and waist circumference with all-cause mortality in a prospective cohort of 993 kidney transplant recipients. Associations were examined in Cox models with adjustment for demographic and comorbid conditions and for inflammatory markers. Unadjusted death hazard ratios (95%CI) associated with one standard deviation higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20 (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p &lt; 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p &lt; 0.001). The associations of waist circumference with mortality remained significant after additional multivariable adjustments. Higher BMI and waist circumference display opposite associations with mortality in kidney transplant recipients. Waist circumference appears to be a better prognostic marker for obesity than BMI

Body mass index, waist circumference and mortality in kidney transplant recipients.

Higher body mass index (BMI) appears paradoxically associated with better outcomes in patients with chronic kidney disease. Whereas higher BMI reflects both increased visceral and subcutaneous fat and/or muscle mass, a combined assessment of BMI and waist circumference may enable differentiation of visceral adiposity from muscle and/or nonvisceral fat mass. We examined the association of BMI and waist circumference with all-cause mortality in a prospective cohort of 993 kidney transplant recipients. Associations were examined in Cox models with adjustment for demographic and comorbid conditions and for inflammatory markers. Unadjusted death hazard ratios (95%CI) associated with one standard deviation higher BMI and waist circumference were 0.94 (0.78, 1.13), p = 0.5 and 1.20 (1.00, 1.45), p = 0.05, respectively. Higher BMI was associated with lower mortality after adjustment for waist circumference (0.48 [0.34, 0.69], p &lt; 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p &lt; 0.001). The associations of waist circumference with mortality remained significant after additional multivariable adjustments. Higher BMI and waist circumference display opposite associations with mortality in kidney transplant recipients. Waist circumference appears to be a better prognostic marker for obesity than BMI