Consequences of Cold-Ischemia Time on Primary Nonfunction and Patient and Graft Survival in Liver Transplantation: A Meta-Analysis

Introduction: The ability to preserve organs prior to transplant is essential to the organ allocation process. Objective: The purpose of this study is to describe the functional relationship between cold-ischemia time (CIT) and primary nonfunction (PNF), patient and graft survival in liver transplant. Methods: To identify relevant articles Medline, EMBASE and the Cochrane database, including the non-English literature identified in these databases, was searched from 1966 to April 2008. Two independent reviewers screened and extracted the data. CIT was analyzed both as a continuous variable and stratified by clinically relevant intervals. Nondichotomous variables were weighted by sample size. Percent variables were weighted by the inverse of the binomial variance. Results: Twenty-six studies met criteria. Functionally, PNF%=-6.678281+0.9134701*CIT Mean+0.1250879*(CIT Mean-9.89535) 2 - 0.0067663*(CIT Mean-9.89535) 3, r2=.625, p<.0001. Mean patient survival: 93 % (1 month), 88 % (3 months), 83 % (6 months) and 83 % (12 months). Mean graft survival: 85.9 % (1 month), 80.5 % (3 months), 78.1 % (6 months) and 76.8 % (12 months). Maximum patient and graft survival occurred with CITs between 7.5-12.5 hrs at each survival interval. PNF was also significantly correlated with ICU time, % first time grafts and % immunologic mismatches. Conclusion: The results of this work imply that CIT may be the most important pre-transplant information needed in the decision to accept an organ. © 2008 Stahl et al

Greater dyspnea is associated with lower health-related quality of life among European patients with COPD

Jean-Bernard Gruenberger,1 Jeffrey Vietri,2 Dorothy L Keininger,1 Donald A Mahler3 1Health Economics and Outcomes Research, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland; 2Health Outcomes Practice, Kantar Health, Horsham, PA, 3Geisel School of Medicine at Dartmouth, Hanover, NH, USA Objective: Dyspnea is a defining symptom in the classification and treatment of chronic obstructive pulmonary disease (COPD). However, the degree of variation in burden among symptomatic COPD patients and the possible correlates of burden remain unclear. This study was conducted to characterize patients in Europe currently being treated for COPD according to the level of dyspnea in terms of sociodemographics, health-related quality of life, work productivity impairment, and health care resource use assessed by patient reports.Methods: Data were derived from the 5-EU 2013 National Health and Wellness Survey (N=62,000). Respondents aged &ge;40 years who reported currently using a prescription for COPD were grouped according to their level of dyspnea as per the Global Initiative for Chronic Obstructive Lung Disease guidelines and compared on health status (revised Short Form 36 [SF-36]v2), work impairment (Work Productivity and Activity Impairment questionnaire), and number of health care visits in the past 6 months using generalized linear models with appropriate distributions and link functions.Results: Of the 768 respondents who met the inclusion criteria, 245 (32%) were considered to have higher dyspnea (equivalent to modified Medical Research Council score &ge;2). Higher dyspnea was associated with decrements ranging from 3.9 to 8.2 points in all eight domains of the SF-36 health profile after adjustment for sociodemographics, general health characteristics, and length of COPD diagnosis; mental component summary scores and Short Form-6D health utility scores were lower by 3.5 and 0.06 points, respectively. Adjusted mean activity impairment (55% vs 37%, P&lt;0.001) and number of emergency room visits (0.61 vs 0.40, P=0.030) were higher in patients with greater dyspnea.Conclusion: Many European patients with COPD continue to experience dyspnea despite treatment and at levels associated with notable impairments in the patients&rsquo; ability to function across a multitude of domains. These patients may benefit from more intense treatment of their symptoms. Keywords: COPD, dyspnea, health-related quality of life, activity impairment, symptom

Comparative efficacy of long-acting &beta;2-agonists as monotherapy for chronic obstructive pulmonary disease: a network meta-analysis

James F Donohue,1 Keith A Betts,2 Ella Xiaoyan Du,2 Pablo Altman,3 Pankaj Goyal,4 Dorothy L Keininger,4 Jean-Bernard Gruenberger,4 James E Signorovitch5 1Department of Pulmonary Diseases and Critical Care Medicine, The University of North Carolina, Chapel Hill, NC, 2Analysis Group, Inc., Los Angeles, CA, 3Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 4Novartis Pharma AG, Basel, Switzerland; 5Analysis Group, Inc., Boston, MA, USA Purpose: Long-acting &beta;2-agonists (LABAs) have demonstrated efficacy in patients with COPD in clinical trials. The purpose of this study was to assess the comparative efficacy of all available dosages of all LABA monotherapies using a network meta-analysis.Methods: A systematic literature review identified 33 randomized controlled trials of LABA monotherapies (salmeterol 50 &micro;g twice daily [BID]; formoterol 12 &micro;g BID; indacaterol 75, 150, and 300 &micro;g once daily [OD]; olodaterol 5 and 10 &micro;g OD, and vilanterol 25 &micro;g OD). Clinical efficacy was evaluated at 12 and 24 weeks in terms of trough forced expiratory volume in 1 second (FEV1), transition dyspnea index focal score, St George&rsquo;s Respiratory Questionnaire total score, and rate of COPD exacerbations. The relative effectiveness of all LABA monotherapies was estimated by Bayesian network meta-analysis.Results: At 12 and 24 weeks, indacaterol 300 and 150 &micro;g OD were associated with statistically significant improvement in trough FEV1 compared to all other LABA monotherapies; vilanterol 25 &micro;g OD was superior to formoterol 12 &micro;g BID. At 12 weeks, indacaterol 75 &micro;g OD was associated with significant improvement in trough FEV1 compared to formoterol 12 &micro;g BID and olodaterol (5 and 10 &micro;g OD); salmeterol 50 &micro;g BID was superior to formoterol 12 &micro;g BID and olodaterol 5 &micro;g OD. Indacaterol 300 &micro;g OD was also associated with significant improvement in transition dyspnea index focal score compared to all other LABAs at 12 or 24 weeks. Indacaterol 150&nbsp;&micro;g OD had significantly better results in exacerbation rates than olodaterol 5&nbsp;&micro;g and olodaterol 10&nbsp;&micro;g OD.Conclusion: Indacaterol 300 &micro;g, followed by 150 and 75 &micro;g, were the most effective LABA monotherapies for moderate to severe COPD. Keywords: COPD, long-acting &beta;2-agonists, network meta-analysis, systematic literature review, indacatero

COPD uncovered: a cross-sectional study to assess the socioeconomic burden of COPD in Japan

Ataru Igarashi,1 Yoshinosuke Fukuchi,2 Kazuto Hirata,3 Masakazu Ichinose,4 Atsushi Nagai,5 Masaharu Nishimura,6 Hajime Yoshisue,7 Kenichi Ohara,8 Jean-Bernard Gruenberger9 1Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan; 2Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan; 3Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan; 4Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; 5Research Institute for Respiratory Diseases, Shin-Yurigaoka General Hospital, Kawasaki City, Japan; 6Department of Pulmonary Medicine, Faculty School of Medicine, Hokkaido University, Hokkaido, Japan; 7Medical Division, Novartis Pharma K.K., Tokyo, Japan; 8Market Access Division, Novartis Pharma K.K., Tokyo, Japan; 9Market Access Division, Novartis Pharma AG, Basel, Switzerland Background: COPD remains a major health problem in Japan. Patients with COPD experience a reduced quality of life (QoL) and have a higher chance of work impairment and productivity loss. However, there is a lack of data on the impact of COPD in terms of QoL and work activity impairment in Japan. This study assessed the socioeconomic burden of COPD in Japan and the impact it may have on the working age population. Patients and methods: This was a 2-year retrospective chart review in COPD patients aged &ge;40&nbsp;years, with at least one health care visit to clinic or hospital in the previous 12&nbsp;months. Patients were required to have available medical charts for at least the previous 24&nbsp;months. Symptoms were assessed using COPD assessment test score; EuroQoL Group 5 Dimension (EQ-5D-5L) and work productivity and activity impairment general health questionnaires were used to evaluate health-related QoL and work productivity, and health care resource utilization data were obtained from clinical charts. Results: In total, 71 patients aged &lt;65&nbsp;years, and 151 patients aged &ge;65&nbsp;years were included; the majority of patients had moderate or severe airflow limitation. Exacerbations (moderate or severe) were reported by ~35% of patients in both age groups; 52.1% and 62.9% of patients in the &lt;65-year and &ge;65-year age groups had COPD assessment test scores &ge;10. EQ-5D-5L index scores in the &lt;65-year and &ge;65-year age groups were 0.79 and 0.77, respectively. Work productivity and activity impairment scores were higher in &lt;65-year age group. Annual costs of health care resource use per patient in the &lt;65-year and &ge;65-year age groups were &yen;438,975 (US4,389) and ¥467,871 (US4,678), respectively. Costs due to productivity loss were estimated to be &yen;5,287,024 (US52,870) in the <65-year age group and ¥3,018,974 (US30,187) in the &ge;65-year age group. Conclusion: COPD represents a significant socioeconomic burden in Japan. Patients with COPD report significant use of health care resources. Higher impact on work impairment and productivity loss was observed frequently in the working age population. Keywords: health-realted quality of life, chart review, EQ-5D-5L questionnaire, health care resource utilization, productivity loss, work impairment WPAI-G

Economic burden of COPD in a Swedish cohort: the ARCTIC study

Karin Lisspers,1 Kjell Larsson,2 Gunnar Johansson,1 Christer Janson,3 Madlaina Costa-Scharplatz,4 Jean-Bernard Gruenberger,5 Milica Uhde,6 Leif Jorgensen,7 Florian S Gutzwiller,5 Bj&ouml;rn St&auml;llberg1 1Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, 2Department of&nbsp;Work Environment Toxicology, The&nbsp;National Institute of Environmental Medicine, Karolinska Institute, Solna, 3Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, 4Novartis AB, T&auml;by, Sweden; 5Novartis, Basel, Switzerland; 6IQVIA, Solna, Sweden; 7IQVIA, Copenhagen, Denmark Background: We assessed direct and indirect costs associated with COPD in Sweden and examined how these costs vary across time, age, and disease stage in a cohort of patients with COPD and matched controls in a real-world, primary care (PC) setting.Patients and methods: Data from electronic medical records linked to the mandatory national health registers were collected for COPD patients and a matched reference population in 52&nbsp;PC centers from 2000 to 2014. Direct health care costs (drug, outpatient or inpatient, PC, both COPD related and not COPD related) and indirect health care costs (loss of income, absenteeism, loss of productivity) were assessed.Results: A total of 17,479 patients with COPD and 84,514 reference controls were analyzed. During 2013, direct costs were considerably higher among the COPD patient population (&euro;13,179) versus the reference population (&euro;2,716), largely due to hospital nights unrelated to COPD. Direct costs increased with increasing disease severity and increasing age and were driven by higher respiratory drug costs and non-COPD-related hospital nights. Indirect costs (~&euro;28,000 per patient) were the largest economic burden in COPD patients of working age during 2013.Conclusion: As non-COPD-related hospital nights represent the largest direct cost, management of comorbidities in COPD would offer clinical benefits and relieve the financial burden of disease. Keywords: COPD, direct cost, indirect cost, burden, Swede