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Kai-Michael Beeh,1 Kieran J Rothnie,2 Jing Claussen,3 Fränce Hardtstock,4 Rachel K Knapp,4 Thomas Wilke,5 Alexandrosz Czira,2 Chris Compton,6 Afisi S Ismaila7,8 1Insaf Respiratory Research Institute, Wiesbaden, Germany; 2Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, UK; 3Global Medical Affairs, GSK, Munich, Germany; 4Real World & Advanced Analytics (RWAA), Cytel, Berlin, Germany; 5IPAM e.V., Institute affiliated with University of Wismar, Wismar, Germany; 6Global Medical, GSK, London, UK; 7Value Evidence and Outcomes, R&D Global Medical, GSK, Collegeville, PA, USA; 8Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Afisi S Ismaila, Value Evidence and Outcomes, GSK, 1250 South Collegeville Road, Collegeville, PA, 19426-0989, USA, Tel +1 919 315 8229, Email afisi.s.ismaila@gsk.comPurpose: To assess patient characteristics of users and new initiators of triple therapy for chronic obstructive pulmonary disease (COPD) in Germany.Patients and Methods: Retrospective cohort study of patients with COPD and ≥ 1 prescription for single-inhaler triple therapy (SITT; fluticasone furoate/umeclidinium/vilanterol [FF/UMEC/VI] or beclomethasone dipropionate/glycopyrronium bromide/formoterol [BDP/GLY/FOR]) or multiple-inhaler triple therapy (MITT), using data from the AOK PLUS German sickness fund (1 January 2015– 31 December 2019). The index date was the first date of prescription for FF/UMEC/VI or BDP/GLY/FOR (SITT users), or the first date of overlap of inhaled corticosteroid, long-acting β2-agonist, and long-acting muscarinic antagonist (MITT users). Two cohorts were defined: the prevalent cohort included all identified triple therapy users; the incident cohort included patients newly initiating triple therapy for the first time (no prior use of MITT or SITT in the last 2 years). Patient characteristics and treatment patterns were assessed on the index date and during the 24-m

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 gema.x.requena@gsk.comPurpose: 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

Alexandrosz Czira,1 Shoko Akiyama,2 Takeo Ishii,2 Robert P Wood,3 Lucinda J Camidge,3 Hannah Wallis,3 Thomas Jennison,3 Rosie AC Wild,3 Masao Yarita,2 Kenichi Hashimoto,2 Kieran J Rothnie,1 Afisi S Ismaila4,5 1Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, UK; 2Value Evidence and Outcomes, Japan Medical and Development, GSK, Tokyo, Japan; 3Real-World Evidence, Adelphi Real World, Bollington, UK; 4Value Evidence and Outcomes, R&D Global Medical, GSK, Collegeville, PA, USA; 5Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Kieran J Rothnie, Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, Middlesex, TW8 9GS, UK, Tel +44 7920 369573, Email kieran.j.rothnie@gsk.comPurpose: There is currently limited evidence for the optimal timing of triple therapy initiation in Japan, which is crucial for optimizing strategies for the effective treatment of chronic obstructive pulmonary disease (COPD). This study assessed the impact of prompt vs delayed initiation of triple therapy following a COPD exacerbation on clinical and economic outcomes in patients in Japan.Patients and Methods: Retrospective cohort study of patients in the Medical Data Vision Co., Ltd. database initiating triple therapy as single-inhaler triple therapy (fluticasone furoate/umeclidinium/vilanterol or budesonide/glycopyrronium/formoterol) or multiple-inhaler triple therapy within 180 days of a moderate-to-severe exacerbation (index). For the main analysis, patients were categorized as prompt or delayed initiators, initiating triple therapy within 0– 30 days or 31– 180 days of index, respectively. Inverse probability of treatment weighting based on propensity scores was used to adjust for measured confounders between prompt and delayed cohorts.Results: For the main analysis, 610 (60.3%) and 402 (39.7%) patients were prompt and delayed initiators, respectively. The rate of subsequent mo

Gema Requena,1 Alexandrosz Czira,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 1GSK, R&D Global Medical, 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: Gema Requena, GSK, R&D Global Medical, Brentford, Middlesex, UK, Tel +44 20 80476893, Email gema.x.requena@gsk.comPurpose: Routinely collected healthcare data on the comparative effectiveness of the long-acting muscarinic antagonist/long-acting β2-agonist combination umeclidinium/vilanterol (UMEC/VI) versus tiotropium bromide/olodaterol (TIO/OLO) for chronic obstructive pulmonary disease (COPD) is limited. This study compared rescue medication prescriptions in patients with COPD in England receiving UMEC/VI versus TIO/OLO.Patients and Methods: This retrospective cohort study used primary care data from the Clinical Practice Research Datalink Aurum database linked with secondary care administrative data from Hospital Episode Statistics. Patients with a COPD diagnosis at age ≥ 35 years were included (indexed) following initiation of single-inhaler UMEC/VI or TIO/OLO between July 1, 2015, and September 30, 2019. Outcomes included the number of rescue medication prescriptions at 12-months (primary), and at 6-, 18- and 24-months (secondary), adherence at 6-, 12-, 18- and 24-months post-index, defined as proportion of days covered ≥ 80% (second

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 alexandrosz.x.czira@gsk.comBackground: 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)

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 alexandrosz.x.czira@gsk.comPurpose: 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

Gema Requena,1 Victoria Banks,2,* Alexandrosz Czira,1 Robert Wood,2 Theo Tritton,2 Rosie Wild,2 Chris Compton,1 Afisi S Ismaila3,4 1Value Evidence and Outcomes, GSK, R&D Global Medical, Brentford, Middlesex, UK; 2Real-World Evidence, Adelphi Real World, Bollington, Cheshire, UK; 3Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 4Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada*At the time of the studyCorrespondence: Gema Requena, Epidemiology, Value Evidence and Outcomes, R&D Global Medical, GSK, Middlesex, UK, Tel +44 20 80476893, Email gema.x.requena@gsk.comPurpose: Selection of treatments for patients with chronic obstructive pulmonary disease (COPD) may impact clinical outcomes, healthcare resource use (HCRU) and direct healthcare costs. We aimed to characterize these outcomes along with treatment patterns, for patients with COPD following initiation of single-inhaler long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual therapy in the primary care setting in England.Patients and Methods: This retrospective cohort study used linked primary care electronic medical record data (Clinical Practice Research Datalink-Aurum) and secondary care administrative data (Hospital Episode Statistics) in England to assess outcomes for patients with COPD who had a prescription for one of four single-inhaler LAMA/LABA dual therapies between 1st June 2015– 31st December 2018 (indexing period). Outcomes were assessed during a 12-month follow-up period from the index date (date of earliest prescription of a single-inhaler LAMA/LABA within the indexing period). Incident users were those without previous LAMA/LABA dual therapy prescriptions prior to index; this manuscript focuses on a subset of incident users: non-triple therapy users (patients without concomitant inhaled corticosteroid use at index).Results: Of 10,991 incident users included, 9888 (90.0%) were non-triple therap

Gema Requena,1 Victoria Banks,2 Alexandrosz Czira,1 Robert Wood,2 Theo Tritton,2 Rosie Wild,2 Chris Compton,1 Maria Duarte,1 Afisi S Ismaila3,4 1Value Evidence and Outcomes, Epidemiology, GSK, R&D Global Medical, Brentford, Middlesex, UK; 2Real-world Evidence, Adelphi Real World, Bollington, Cheshire, UK; 3Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 4Department 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 gema.x.requena@gsk.comPurpose: Treatment pathways of patients with chronic obstructive pulmonary disease (COPD) receiving single-inhaler dual therapies remain unclear. We aimed to describe characteristics, prescribed treatments, healthcare resource use (HCRU) and costs of patients with COPD who initiated single-inhaler long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) dual therapy in primary care in England.Patients and Methods: Retrospective study using linked data from Clinical Practice Research Datalink Aurum and Hospital Episode Statistics datasets. Patients with COPD with ≥ 1 single-inhaler LAMA/LABA prescription between June 2015 and December 2018 (index) were included. Demographic and clinical characteristics, prescribed treatments, HCRU and costs were evaluated in the 12 months pre-index. Data are presented for patients not receiving concomitant inhaled corticosteroids at index (non-triple users).Results: Of 10,991 patients initiating LAMA/LABA, 9888 were non-triple users, of whom 21.3% (n=2109) received aclidinium bromide/formoterol, 18.1% (n=1785) received indacaterol/glycopyrronium, 12.0% (n=1189) received tiotropium bromide/olodaterol and 48.6% (n=4805) received umeclidinium/vilanterol. Demographic and clinical characteristics were similar across indexed therapies. LAMA monotherapy was the most frequently prescribed re

David MG Halpin,1 Kieran J Rothnie,2 Victoria Banks,3 Alexandrosz Czira,2 Chris Compton,4 Robert Wood,3 Theo Tritton,3 Olivia Massey,3 Rosie Wild,3 Neil Snowise,5 Kirill Nikitin,2 Raj Sharma,4 Afisi S Ismaila,6,7 Claus F Vogelmeier8 1University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, UK; 2Value Evidence and Outcomes, R&D Global Medical, GSK, Brentford, UK; 3Real-World Evidence, Adelphi Real World, Bollington, UK; 4Global Medical, GSK, London, UK; 5Institute of Pharmaceutical Science, Faculty of Life Sciences and Medicine, King’s College, London, UK; 6Value Evidence and Outcomes, GSK, Collegeville, PA, USA; 7Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada; 8Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Center for Lung Research (DZL), Marburg, GermanyCorrespondence: David MG Halpin, University of Exeter Medical School, College of Medicine and Health, University of Exeter, Exeter, EX1 2LU, UK, Tel +44 (0)1392 201178, Email d.halpin@nhs.netPurpose: 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

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.

Background and objectivesAdiponectin (ADPN), an adipose tissue-derived hormone, has protective properties with respect to atherogenesis, inflammation, and energy homeostasis. Its beneficial role has not been consistent in patients with CKD or those undergoing dialysis.Design, setting, participants, & measurementsThis study examined the association of plasma ADPN levels in 987 prevalent kidney transplant recipients (mean age ± SD, 51.0±12.8 years; estimated GFR, 52.8±21.9 ml/min per 1.73 m(2); median time since transplant, 78 months) on all-cause mortality and death-censored graft failure. Patients were enrolled between February and August 2007 and were followed for a median of 51 months (interquartile range, 49-53 months). Using Cox proportional hazard models, the association of log-transformed plasma adiponectin was studied, with and without adjustment for demographic variables, baseline GFR, markers of inflammation, and cardiovascular risk factors.ResultsAt baseline, patients in the lowest ADPN tertile were significantly more likely to be male; to be smokers; to have a higher baseline GFR, lower systolic BP, and lower HDL cholesterol level; and to have higher body mass index, abdominal circumference, C-reactive protein level, and total cholesterol level. The adjusted hazard ratio for death with elevated plasma ADPN (per natural log) was 1.44, and there was no significant interaction with any relevant cardiovascular risk subgroups (i.e., advanced age; diabetes; or elevated body mass index, waist circumference, C-reactive protein, or Framingham risk score). The hazard for death-censored graft failure was nonsignificant at 1.03.ConclusionElevated ADPN levels are associated with higher risk for death but not allograft failure in prevalent kidney transplant recipients.

Background and objectivesAdiponectin (ADPN), an adipose tissue-derived hormone, has protective properties with respect to atherogenesis, inflammation, and energy homeostasis. Its beneficial role has not been consistent in patients with CKD or those undergoing dialysis.Design, setting, participants, & measurementsThis study examined the association of plasma ADPN levels in 987 prevalent kidney transplant recipients (mean age ± SD, 51.0±12.8 years; estimated GFR, 52.8±21.9 ml/min per 1.73 m(2); median time since transplant, 78 months) on all-cause mortality and death-censored graft failure. Patients were enrolled between February and August 2007 and were followed for a median of 51 months (interquartile range, 49-53 months). Using Cox proportional hazard models, the association of log-transformed plasma adiponectin was studied, with and without adjustment for demographic variables, baseline GFR, markers of inflammation, and cardiovascular risk factors.ResultsAt baseline, patients in the lowest ADPN tertile were significantly more likely to be male; to be smokers; to have a higher baseline GFR, lower systolic BP, and lower HDL cholesterol level; and to have higher body mass index, abdominal circumference, C-reactive protein level, and total cholesterol level. The adjusted hazard ratio for death with elevated plasma ADPN (per natural log) was 1.44, and there was no significant interaction with any relevant cardiovascular risk subgroups (i.e., advanced age; diabetes; or elevated body mass index, waist circumference, C-reactive protein, or Framingham risk score). The hazard for death-censored graft failure was nonsignificant at 1.03.ConclusionElevated ADPN levels are associated with higher risk for death but not allograft failure in prevalent kidney transplant recipients.

BackgroundRacial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients.MethodsIn a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft.ResultsDuring the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively.ConclusionsRoma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

BackgroundRacial and ethnic disparities among North American patients with chronic kidney disease have received significant attention. In contrast, little is known about health-related outcomes of patients with end-stage renal disease among the Roma minority, also known as gypsies, compared to Caucasian individuals. We prospectively assessed the association between Roma ethnicity and long-term clinical outcomes in kidney transplant recipients.MethodsIn a prevalent cohort of renal transplant recipients, followed up over a median of 94 months, we prospectively collected socio-demographic, medical (and transplant related) characteristics and laboratory data at baseline from 60 Roma and 1,003 Caucasian patients (mean age 45 (SD = 11) and 49 (SD = 13) years, 33 and 41% women, 18 and 17% with diabetes mellitus, respectively). Survival analyses examined the associations between Roma ethnicity and all-cause mortality and death-censored graft loss or death with functioning renal allograft.ResultsDuring the follow-up period, 341 patients (32%) died. Two-hundred eighty (26%) patients died with a functioning graft and 201 patients (19%) returned to dialysis. After multivariable adjustments, Roma ethnicity was associated with 77% higher risk of all-cause mortality (Hazard Ratio (HR): 1.77; 95% confidence interval (CI): 1.02, 3.07), two times higher risk of mortality with functioning graft (2.04 [1.17-3.55]) and 77% higher risk of graft loss (1.77 [1.01-3.13]), respectively.ConclusionsRoma ethnicity is independently associated with increased mortality risk and worse graft outcome in kidney transplant recipients. Further studies should identify the factors contributing to worse outcomes among Roma patients.

Background and objectivesPosttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients.Design, setting, participants, & measurementsWe collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 ± 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk.ResultsDuring the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 ± 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P = 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR(1SD increase) 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR(1SD increase) 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups.ConclusionsIn this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.

Background and objectivesPosttransplant anemia is frequently reported in kidney transplant recipients and is associated with worsened patient survival. Similar to high erythropoiesis-stimulating agent requirements, resistance to endogenous erythropoietin may be associated with worse clinical outcomes in patients with ESRD. We examined the association between serum erythropoietin levels and mortality among kidney transplant recipients.Design, setting, participants, & measurementsWe collected sociodemographic, clinical, medical, and transplant history and laboratory data at baseline in 886 prevalent kidney transplant recipients (mean age 51 ± 13 [SD] years, 60% men, 21% diabetics). A solid-phase chemiluminescent immunometric assay was used to measure serum erythropoietin. Cox proportional hazards regression was used to model the association between baseline serum erythropoietin levels and all-cause mortality risk.ResultsDuring the median 39-month follow-up, 99 subjects died. The median serum erythropoietin level was 10.85 U/L and hemoglobin was 137 ± 16 g/L. Mortality rates were significantly higher in patients with higher erythropoietin levels (crude mortality rates in the highest to lowest erythropoietin tertiles were 51.7, 35.5, and 24.0 per 1000 patient-years, respectively [P = 0.008]). In unadjusted and also in adjusted Cox models each SD higher serum erythropoietin level significantly predicted all-cause mortality: HR(1SD increase) 1.22 and 1.28, respectively. In adjusted Cox models each SD higher serum erythropoietin/blood hemoglobin ratio also significantly predicted all-cause mortality: HR(1SD increase) 1.32. Serum erythropoietin predicted mortality in all analyzed subgroups.ConclusionsIn this sample of prevalent kidney transplant recipients, higher serum erythropoietin levels were associated with increased mortality.

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 < 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p < 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.

BackgroundChronic protein-energy wasting, termed malnutrition-inflammation complex syndrome, is frequent in patients with chronic kidney disease and is associated with anemia, morbidity, and mortality in patients on maintenance dialysis therapy. The Malnutrition-Inflammation Score (MIS) recently has been developed and validated in dialysis patients.Study designObservational cross-sectional study.Setting & participants993 prevalent kidney transplant recipients.PredictorMIS computed from change in body weight, dietary intake, gastrointestinal symptoms, functional capacity, comorbid conditions, decreased fat store/Systemic Global Assessment, signs of muscle wasting/Systemic Global Assessment, body mass index, serum albumin level, and serum transferrin level.OutcomesMarkers of inflammation and malnutrition, including serum C-reactive protein, interleukin 6, tumor necrosis factor alpha, serum leptin, prealbumin, body mass index, and abdominal circumference. The relationship was modeled by using structural equation models.ResultsMean age was 51 +/- 13 years, 57% were men, and 21% had diabetes. Median time from transplant was 72 months. MIS significantly correlated with abdominal circumference (r = -0.144), serum C-reactive protein level (r = 0.094), serum interleukin 6 level (r = 0.231), and serum tumor necrosis factor alpha level (r = 0.102; P < 0.01 for all). A structural equation model with 2 latent variables (malnutrition and inflammation factor) showed good fit to the observed data.LimitationsSingle-center study, lack of information about vascular access, presence of nonfunctioning kidney transplant, relatively high refusal rate.ConclusionsOur results confirm that MIS reflects both energy-protein wasting and inflammation in kidney transplant recipients. This simple instrument appears to be a useful tool to assess the presence of protein-energy wasting in this patient population.

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 < 0.001), and higher waist circumference was more strongly associated with higher mortality after adjustment for BMI (2.18 [1.55-3.08], p < 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.

BackgroundChronic protein-energy wasting, termed malnutrition-inflammation complex syndrome, is frequent in patients with chronic kidney disease and is associated with anemia, morbidity, and mortality in patients on maintenance dialysis therapy. The Malnutrition-Inflammation Score (MIS) recently has been developed and validated in dialysis patients.Study designObservational cross-sectional study.Setting & participants993 prevalent kidney transplant recipients.PredictorMIS computed from change in body weight, dietary intake, gastrointestinal symptoms, functional capacity, comorbid conditions, decreased fat store/Systemic Global Assessment, signs of muscle wasting/Systemic Global Assessment, body mass index, serum albumin level, and serum transferrin level.OutcomesMarkers of inflammation and malnutrition, including serum C-reactive protein, interleukin 6, tumor necrosis factor alpha, serum leptin, prealbumin, body mass index, and abdominal circumference. The relationship was modeled by using structural equation models.ResultsMean age was 51 +/- 13 years, 57% were men, and 21% had diabetes. Median time from transplant was 72 months. MIS significantly correlated with abdominal circumference (r = -0.144), serum C-reactive protein level (r = 0.094), serum interleukin 6 level (r = 0.231), and serum tumor necrosis factor alpha level (r = 0.102; P < 0.01 for all). A structural equation model with 2 latent variables (malnutrition and inflammation factor) showed good fit to the observed data.LimitationsSingle-center study, lack of information about vascular access, presence of nonfunctioning kidney transplant, relatively high refusal rate.ConclusionsOur results confirm that MIS reflects both energy-protein wasting and inflammation in kidney transplant recipients. This simple instrument appears to be a useful tool to assess the presence of protein-energy wasting in this patient population.

The ion-fragmentation behaviour of hydrogenated fullerenes has been investigated by tandem mass spectrometry applying sector instrumentation. In addition to the expected loss of hydrogen, unimolecular decay reactions are observed featuring cage rupture by the loss of hydrocarbon moieties. The findings are discussed in comparison with the behaviour of other fullerene derivatives. The gas-phase coalescence reactivity of C60H36 has been studied utilising laser desorption/ionization time-of-flight mass spectrometry. In contrast to pure fullerenes and certain organic fullerene derivatives, hydrogenated fullerenes do not readily undergo laser-induced fusion reactions.