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Inhaled corticosteroids (ICS) plus long-acting β2-agonists (LABA) are recommended for maintenance-only or maintenance and reliever therapy (MART) in patients with asthma. However, real-world data on ICS/LABA as maintenance-only or MART are limited. This study characterized clinical, economic, and humanistic burdens of asthma in Canada, China, Europe, Japan, and the US, using data collected from patients and physicians via a cross-sectional survey (Asthma Disease Specific Programme). Patients were ≥18 years of age with physician-confirmed asthma and receiving fixed-dose ICS/LABA for ≥3 months. Mean physician-reported symptom-free days over the past 30 days ranged from 10.1–20.6 days, and 31.5–34.6% of ICS/LABA users self-reported not well-controlled asthma. SABA co-prescription was reported in 8.8–67.8% of patients. These findings highlight the continued disease burden among ICS/LABA users, with the high level of SABA co-prescription indicating potentially inappropriate prescribing of ICS/LABA as MART or detrimental reliance on SABA medication in addition to MART. [ABSTRACT FROM AUTHOR]

Background: Triple therapy is recommended for patients with chronic obstructive pulmonary disease (COPD) who remain symptomatic despite dual therapy. The optimal timing of triple therapy following an exacerbation of COPD is unknown. The outcomes of prompt (≤ 30 days) vs. delayed (31–180 days) initiation of single-inhaler triple therapy with fluticasone furoate, umeclidinium, and vilanterol (FF/UMEC/VI) following an exacerbation of COPD were examined. Methods: This was a retrospective cohort study of linked English primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data. Patients aged ≥ 35 years with COPD were indexed on the first and/or earliest date of exacerbation between November 15, 2017 and March 31, 2019 with subsequent FF/UMEC/VI initiation within 180 days. Patients were required to be continuously registered with a general practitioner for ≥ 12 months prior to and following index. Subsequent exacerbations, direct medical costs, and hospital readmissions were compared between prompt and delayed initiators. Inverse probability of treatment weighting was used to adjust for measured confounders between cohorts. Results: Overall, 1599 patients were included (prompt: 393, delayed: 1206). After weighting, prompt initiators had numerically lower moderate/severe exacerbations compared with delayed initiators (rate ratio: 0.87, 95% confidence interval [CI]: 0.76–1.01, p = 0.0587). Both all-cause and COPD-related 30-day hospital readmissions were significantly lower among patients with prompt initiation compared with delayed initiators (all-cause: 23.6% vs. 34.6%, odds ratio [95% CI]: 0.58 [0.36–0.95], p = 0.0293; COPD-related: 20.3% vs. 30.6%, odds ratio [95% CI]: 0.58 [0.35–0.96], p = 0.0347). Prompt initiators also had numerically lower all-cause total costs and significantly lower COPD-related costs per-person-per year compared with delayed initiators (COPD-related: £742 vs. £801, p = 0.0016). Conclusion: Prompt initiation of FF/UMEC/VI following a moderate/severe exacerbation was associated with fewer subsequent exacerbations, fewer hospital readmissions, and lower COPD-related medical costs compared with delayed initiation. Plain language summary: Triple therapy with an inhaled corticosteroid (ICS), a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) is recommended for patients with chronic obstructive pulmonary disease (COPD) who still experience symptoms while taking dual therapy (LABA/LAMA or ICS/LABA). Triple therapy can be taken using single or multiple inhalers. The best time to start triple therapy for patients who may benefit from it following a short-term worsening (flare-up) of their COPD symptoms is unknown. This study assesses the effect of starting treatment with triple therapy sooner compared with later in patients with COPD. Patients who experienced a flare-up of their COPD symptoms were split into two groups – those who started taking triple therapy (via a single inhaler) within 30 days of their symptom flare-up and those who started taking triple therapy 31–180 days following their symptom flare-up. Over the 12 months following the initial flare-up, patients who started triple therapy earlier (within 30 days) had fewer subsequent symptom flare-ups, fewer hospital admissions, and lower healthcare costs compared with patients who started triple therapy later (31–180 days). These findings suggest that doctors should consider prescribing triple therapy (via a single inhaler) to their patients with COPD straight away if they experience a flare-up of their symptoms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This correction notice addresses errors in a study published in Respiratory Research regarding the benefits of prompt initiation of a specific inhaler for patients with COPD in England. The errors were related to the costs associated with the treatment and impacted certain statements in the "Results," "Discussion," and "Conclusions" sections of the article. The corrected information indicates that prompt initiators had numerically lower all-cause total costs and similar COPD-related costs compared to delayed initiators. The authors apologize for the discrepancies and any inconvenience caused. [Extracted from the article]

Cystic fibrosis transmembrane conductance regulator (CFTR) has an essential role in maintaining pancreatic ductal function. Impaired CFTR function can trigger acute pancreatitis (AP) and exacerbate disease severity. We aimed to investigate the localization and expression of CFTR during AP, and determined the effects of a CFTR corrector (VX‐661) and potentiator (VX‐770) on disease severity. AP was induced in FVB/n mice by 6–10 hourly intraperitoneal injections of 50 μg/kg cerulein. Some mice were pre‐treated with five to six daily injections of 2 mg/kg VX‐661 + VX‐770. Control animals were administered physiological saline instead of cerulein and dimethyl sulfoxide instead of VX compounds. AP severity was determined by measuring laboratory and histological parameters; CFTR and CK19 expression was measured. Activity of ion transporters was followed by intracellular pH or fluid secretion measurement of isolated pancreatic intra‐/interlobular ducts. Cerulein‐induced AP severity was greatest between 12 and 24 h. CFTR mRNA expression was significantly increased 24 h after AP induction. Immunohistochemistry demonstrated disturbed staining morphology of CFTR and CK19 proteins in AP. Mislocalization of CFTR protein was observed from 6 h, while expression increased at 24 h compared to control. Ductal HCO3− transport activity was significantly increased 6 h after AP induction. AP mice pre‐treatment with VX‐661 + VX‐770 significantly reduced the extent of tissue damage by about 20–30%, but other parameters were unchanged. Interestingly, VX‐661 + VX‐770 in vitro administration significantly increased the fluid secretion of ducts derived from AP animals. This study described the course of the CFTR expression and mislocalization in cerulein‐induced AP. Our results suggest that the beneficial effects of CFTR correctors and potentiators should be further investigated in AP. Key points: Cystic fibrosis transmembrane conductance regulator (CFTR) is an important ion channel in epithelial cells. Its malfunction has several serious consequences, like developing or aggravating acute pancreatitis (AP).Here, the localization and expression of CFTR during cerulein‐induced AP in mice were investigated and the effects of CFTR corrector (VX‐661) and a potentiator (VX‐770) on disease severity were determined.CFTR mRNA expression was significantly increased and mislocalization of CFTR protein was observed in AP compared to the control group.Interestingly, pre‐treatment of AP mice with VX‐661 + VX‐770 significantly reduced the extent of pancreatic tissue damage by 20–30%.In vitro administration of VX‐661 + VX‐770 significantly increased the fluid secretion of ducts derived from AP animals.Based on these results, the utilization of CFTR correctors and potentiators should be further investigated in AP. [ABSTRACT FROM AUTHOR]

Climate change impacts determine the long term development possibilities in Hungary. Due to the different vulnerability and adaptive capacity of various regions, the impacts and problems should also be handled in a differentiated way. The key areas of climate safe planning are: water safety, food security, human health security, safety of infrastructure, energy security, natural environment. Successful adaptation to climate change is inconceivable without having a sound knowledge of the impacts of climate change. The National Adaptation Geo-information System (NAGiS) may be used by national, regional and local decision makers and stakeholders. It provides information on the climate status of the country, on the impacts of strategic risks connected to climate change and other long-term natural resource management issues and on the correspondent adaptation possibilities, based on indicators, analyses and impact studies. Data layers of NAGiS were elaborated by the Geological and Geophysical Institute of Hungary and partner projects funded by the Adaptation to Climate Change programme of the EEA Grants. The main parts of the NAGiS are a map-visualization system with 650 data layers; a database containing the calculation results based on modeling (GeoDat with 910 data layers) and a meta-database to help finding relevant data. NAGiS can be a useful tool for climate safe planning, analyzing, decision-support activities in governmental strategic planning; or for municipalities in spatial planning, settlement planning, organizing public services. It can be used in climate policy, energy policy planning, transport and energy infrastructure design and numerous other fields. The further development of NAGiS is financed by the Environmental and Energy Efficiency Operative Programme. Between 2016 and 2018, the project will elaborate a decision support toolbox for underpinning policy and municipal adaptation measures, based on the development of the databases, methodologies and evaluation modules of NAGiS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives In aging populations, the prevalence of neurological disorders increases, which imposes high population burden in terms of mortality, disability, and impaired quality of life. The aim of this study was to assess the prevalence of common neurological disorders and signs and their association with functioning and mortality in an elderly general population. Materials and methods We used data from the Memory and Morbidity in Augsburg Elderly ( MEMO) project, a population-based study of 385 individuals aged ≥65. The prevalence of neurological disorders and signs was assessed by physical examination and medical interview. The basic and instrumental activities of daily living were assessed ( ADL, IADL). We assessed the association of neurological disorders and signs with everyday functioning and prospectively analyzed their relationship with mortality. Results We observed considerably impaired functioning for cases with stroke, TIA, PD, and mild motor parkinsonian signs ( MMPS). All-cause mortality was significantly increased in participants with stroke and MMPS, even after adjusting for co-variables ( HR = 2.71 and 1.80, respectively). Conclusions We found that not only specific neurological disorders, but also earlier symptoms are related to impaired functioning and predict mortality in the elderly. These findings have potential clinical relevance for screening and early detection of individuals at risk. [ABSTRACT FROM AUTHOR]

Angiopoietin 2 ( Angpt2) impairs endothelial function by preventing angiopoietin 1 from binding to their common endothelial-specific receptor Tie2. Here, we examined whether circulating Angpt2 predicts outcome in kidney transplant recipients. For this case-cohort study, we selected 130 kidney transplant recipients who had died or returned to dialysis within the first 2 years of follow-up of our cohort study, as well as 130 age- and gender-matched kidney transplant recipients without an event (controls) from a total of 993 kidney transplant recipients. The total of 260 selected patients were followed in median 4 years. Serum Angpt2 at baseline was measured using an in-house immunoluminometric assay. Median Angpt2 concentrations were significantly higher in patients who died [median (interquartile range - IQR) 3.6 (2.8-5.9) ng/ml] as compared to patients who did not die during the study period [2.8 (2.1-4.1) ng/ml; P < 0.001]. Ln (natural log) Angpt2 levels correlated positively with C-reactive protein levels ( r = 0.315, P < 0.001) and the Charlson Comorbidity Index ( r = 0.188, P = 0.002) and were inversely associated with e GFR ( r = −0.301, P < 0.001) hemoglobin ( r = −0.269, P < 0.001), and serum albumin concentrations ( r = -0.382, P < 0.001). On multivariate analyses, baseline Angpt2 levels independently predicted all-cause mortality (multivariable-adjusted hazard ratio associated with one natural log unit higher Angpt2 level: 1.70 (95% confidence interval: 1.10-2.61)). In our analysis, circulating Angpt2 was an independent predictor of all-cause mortality in stable, prevalent kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Red cell distribution width (RDW), a parameter routinely reported as part of the complete blood count, is associated with increased morbidity and mortality risk in different patient populations. No published data are available about the association between RDW and mortality in kidney transplant recipients. Methods: We collected socio-demographic, clinical parameters, medical and transplant history and laboratory data at baseline in 723 prevalent kidney transplant recipients between June and October 2008 [mean age 51 ± 13 (SD) years, 56 % men, 21 % diabetics]. Associations between baseline RDW values and all-cause mortality over 3 years were examined in unadjusted and adjusted models. Results: Increasing RDW was associated with increased mortality in both unadjusted [(HR = 1.63; 95 % CI 1.41-1.89) and (HR = 2.74; 95 % CI 1.68-4.48)] and fully adjusted models [(HR = 1.60; 95 % CI 1.27-1.89) and (HR = 1.33; 95 % CI 0.76-2.35)]. In reclassification analyses, RDW improved the predictive value of all-cause mortality prediction models [the net reclassification improvement (NRI) was 0.189; p < 0.001]. Conclusions: RDW, a cheap and readily available but largely neglected parameter independently, predicts mortality in prevalent kidney transplant recipients and could potentially been used in everyday risk assessment of kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Red cell distribution width (RDW), a measure of heterogeneity in the size of circulating erythrocytes, reportedly predicts mortality. Similarly to RDW, impaired renal function is also associated with inflammation and protein-energy wasting. This study assessed if renal function is associated with RDW independent of relevant confounders in stable kidney transplant recipients. We examined the association between RDW and estimated glomerular filtration rate ( eGFR) in a cohort of 723 prevalent kidney transplanted recipients who were not receiving erythropoietin-stimulating agents. Associations were examined in regression models adjusted for age, sex, comorbidity, blood haemoglobin, iron indices, markers of nutritional status and inflammation, markers of bone and mineral metabolism and the use of immune suppressants. Lower eGFR was significantly associated with higher RDW ( r = −0·382, P < 0·001). This association remained highly significant even after multivariate adjustments where 10 ml/min decrease in the eGFR was significantly associated with an increase of the RDW values ( B10 ml/min decrease = 0·078; 95% confidence interval: 0·044-0·111). The results were consistent in subgroups of patients with different levels of haemoglobin, chronic kidney disease status and various markers of inflammation and iron status. Lower eGFR is associated with higher RDW, independent of comorbidity, iron deficiency, inflammation and nutritional status in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

A large number of studies have examined associations between brain-derived neurotrophic factor (BDNF) gene polymorphisms and depressive symptoms. However, results still remain controversial. Recent studies suggested a significant age and gender effect on the heritability of depression. The potential neurobiological pathways that could possibly mediate this relationship have not been examined so far. Since BDNF is involved in the regulation of neurotransmitter production, a mediating role of neurotransmitters seems plausible. The present study aims to examine the association between three common BDNF single-nucleotid polymorphisms (SNPs; rs7103411, rs7124442, and rs6265) and depressive symptoms in a community-based elderly population taking into account the serum levels of four neurotransmitters, serotonin, dopamine, adrenalin, and noradrenalin, as potential mediating factors. We also examined whether age and gender had a modifying effect on this association. We collected and analyzed the genetic and laboratory data as well as Center for Epidemiologic Studies-Depression scores of 350 community-dwelling elderly individuals (aged 65+ years). We found that the BDNF rs6265 polymorphism was related to the severity of depressive symptoms, and that this association was independent of neurotransmitter levels. Stratified analyses showed that this association was restricted to older individuals (≥74 years) and men. The associations of SNPs rs7103411 or rs7124442 SNP with depressive symptoms were not statistically significant. This study importantly adds to the existing literature by affirming previous assumptions on an age and gender difference in the relation between BDNF genotype and depression. We moreover first-time report a missing mediating role of neurotransmitters in this association. [ABSTRACT FROM AUTHOR]

Purpose: Chronic kidney disease has profound effects on the health-related quality of life (HRQoL) of patients, with serious physiological, psychological and socio-economic implications. The co-occurrence of protein-energy wasting and inflammation in end-stage renal disease patients is associated with worse HRQoL and increased mortality. We designed this study to examine the relationship between nutritional and inflammatory status and HRQoL in kidney transplant recipients. Methods: Data from 100 randomly selected kidney transplant patients were analyzed in a cross-sectional survey. Socio-demographic parameters, laboratory results, transplantation-related data, comorbidities, medication and malnutrition-inflammation score (MIS) (Kalantar Score) were tabulated at baseline. Patients completed the Kidney Disease Quality of Life-SF (KDQoL-SF™) self-administered questionnaire. Results: Mean age was 51 ± 13 years, median (interquartile range, IQR) time since transplantation 66 (83) months, 57% were men, and 19% had diabetes. The median (IQR) MIS was 3 (3). The MIS significantly and negatively correlated with almost all HRQoL domains analyzed, and this association remained significant in multivariate linear regression analysis for the log-transformed scores on energy/fatigue (β = −0.059 P < 0.001), bodily pain (β = −0.056 P = 0.004), physical functioning (β = −0.029, P = 0.022) and symptoms/problems (β = −0.023 P = 0.005) domains after statistical correction for age, gender, eGFR, dialysis vintage, Charlson Comorbidity Index and occupational status. Additionally, cubic spline analyses revealed linearly increasing, 'dose-response' relationship between almost all domains of KDQoL-SF™ and the MIS. Conclusions: Malnutrition-inflammation score is independently associated with different dimensions of HRQoL in kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Background: Racial 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. Methods: In 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. Results:: During 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. Conclusions: Roma 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. [ABSTRACT FROM AUTHOR]

Periodic limb movements in sleep (PLMS) is prevalent among dialysed patients and is associated with increased risk of mortality. Our study aimed to determine the prevalence of this disease in a sample of transplanted and waiting-list haemodialysed patients. One hundred transplanted and 50 waiting-list patients underwent polysomnography. Moderate and severe diseases were defined as periodic limb movements in sleep index (PLMSI) higher than 15 and 25 events h−1, respectively. The 10-year coronary heart disease risk was estimated for all patients using the Framingham Score. Moreover, the 10-year estimated risk of stroke was calculated according to the modified version of the Framingham Stroke Risk Profile. PLMS was present in 27% of the transplanted and 42% of the waiting-list group ( P = 0.094); the proportion of severe disease was twice as high in waiting-list versus transplanted patients (32 versus 16%, P = 0.024). Patients with severe disease had a higher 10-year estimated risk of stroke in the transplanted group [10 (7-17) versus 5 (4-10); P = 0.002] and a higher 10-year coronary heart disease risk in both the transplanted [18 (8-22) versus 7 (4-14); P = 0.002], and the waiting-list groups [11 (5-18) versus 4 (1-9); P = 0.032]. In multivariable linear regression models the PLMSI was associated independently with the Framingham cardiovascular and cerebrovascular scores after adjusting for important covariables. Higher PLMSI is an independent predictor of higher cardiovascular and cerebrovascular risk score in patients with chronic kidney disease. Severe PLMS is less frequent in kidney transplant recipients compared to waiting-list dialysis patients. [ABSTRACT FROM AUTHOR]

Purpose: In patients on dialysis, the results of studies examining the association between sleep disorders and inflammation are controversial. We assessed the association between inflammatory markers and different sleep disorders in a large sample of kidney transplant recipients. Methods: Cross-sectional study of 100 randomly selected kidney transplant patients who underwent one-night polysomnography ('sleep disorders evaluation in patients after kidney transplantation study') to diagnose obstructive sleep apnea (OSA) and periodic limb movements in sleep (PLMS). Athens Insomnia Scale (AIS) was utilized to assess the prevalence of insomnia. Sociodemographic information and data about medication, comorbidity and laboratory parameters were collected. Levels of inflammatory markers, such as C-reactive protein, serum albumin, white blood cell count, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were measured. Results: The mean age was 51 ± 13 years, 43% were women, and the prevalence of diabetes was 19%. We found no significant difference in the levels of inflammatory markers between patients with versus without OSA and PLMS. Apnea-hypopnea index showed a significant association with white blood cell count (ρ = 0.23), and weak (ρ < |0.15|), non-significant correlation with the other inflammatory markers. PLM index showed weak (ρ < |0.15|), non-significant correlation with all markers of inflammation. The serum IL-6 level was significantly higher in patients with insomnia (AIS ≥ 10) than in non-insomniacs [median (IQR): 3.2(2.6-5.1) vs. 1.7(1.2-2.9) ng/l; P = 0.009]. The levels of other inflammatory markers were similar between insomniacs and non-insomniacs. Conclusions: We did not find any association between the presence of objectively assessed sleep disorders and inflammatory markers in kidney transplant patients. [ABSTRACT FROM AUTHOR]

Background. Post-transplant anaemia (PTA) is common and is associated with adverse consequences. The protein-energy wasting (PEW) syndrome is associated with erythropoietin resistance in patients on maintenance dialysis. We assessed the association between PEW and PTA in a large prevalent cohort of stable kidney-transplanted patients.Methods. Data from 942 prevalent kidney-transplanted patients were analysed. Socio-demographic parameters, laboratory results, transplantation-related data and medication were obtained from the charts. Biomarkers reflecting nutritional status and inflammation [serum leptin, albumin, interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and C-reactive protein] were measured. Anthropometric measures and the malnutrition-inflammation score (MIS) were also tabulated. Anaemia was defined according to the guidelines of the American Society of Transplantation.Results. Mean age was 51 ± 13 years, 57% were males and 22% had diabetes. The prevalence of PTA was 33%. The haemoglobin (Hb) level significantly and negatively correlated with the MIS (rho = − 0.316), marginally with serum TNF-α (rho = − 0.079) and serum IL-6 (rho = − 0.075) and positively with serum transferrin (r = 0.298), serum albumin (r = 0.274), abdominal circumference (r = 0.254) and serum leptin (rho = − 0.152), P < 0.05 for all. In a multivariable linear regression model, MIS was independently associated with Hb (beta = − 0.118, P = 0.004) in patients with estimated glomerular filtration rate (eGFR) lower than or equal to 60 mL/min/1.73 m2, but not in patients with higher eGFR.Conclusions. The MIS is independently associated with PTA in the kidney-transplanted population with eGFR lower than or equal to 60 mL/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background/Aims: Elevated parathyroid hormone (PTH) is used to diagnose high turnover bone disease in chronic kidney disease (CKD). The diagnostic accuracy of PTH in kidney transplant recipients with CKD is unknown. Methods: We examined kidney transplant recipients with CKD stages 3 (n = 498) and 4 (n = 141) to determine the sensitivity and specificity of the Kidney/Dialysis Outcome Quality Initiative (K/DOQI)-recommended PTH levels in detecting elevated serum β-CrossLaps (CTX) or osteocalcin (OC) levels. We performed receiver-operator curve analyses to determine CKD stage-specific PTH levels that provide optimal diagnostic accuracy. Results: PTH below the lower limits of the K/DOQI ranges (35 and 70 pg/ml in CKD stages 3 and 4, respectively) showed sensitivity of >90% in diagnosing increases in biochemical markers. The upper limits (70 and 110 pg/ml), however, showed poor specificity. A specificity of >90% for detecting increased biochemical markers was seen with PTH of >140 and >240 pg/ml in CKD stages 3 and 4, respectively. Conclusion: Currently applied cutoffs for PTH in kidney transplant recipients with CKD stages 3 and 4 do not appear to adequately detect increased biochemical markers of bone turnover. Diagnostic uncertainty exists in patients with CKD stage 3 and PTH between 35 and 140 pg/ml, and CKD stage 4 and PTH between 70 and 240 pg/ml. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Elevated parathyroid hormone (PTH) is used to diagnose high turnover bone disease in chronic kidney disease (CKD). The diagnostic accuracy of PTH in kidney transplant recipients with CKD is unknown. Methods: We examined kidney transplant recipients with CKD stages 3 (n = 498) and 4 (n = 141) to determine the sensitivity and specificity of the Kidney/Dialysis Outcome Quality Initiative (K/DOQI)-recommended PTH levels in detecting elevated serum β-CrossLaps (CTX) or osteocalcin (OC) levels. We performed receiver-operator curve analyses to determine CKD stage-specific PTH levels that provide optimal diagnostic accuracy. Results: PTH below the lower limits of the K/DOQI ranges (35 and 70 pg/ml in CKD stages 3 and 4, respectively) showed sensitivity of >90% in diagnosing increases in biochemical markers. The upper limits (70 and 110 pg/ml), however, showed poor specificity. A specificity of >90% for detecting increased biochemical markers was seen with PTH of >140 and >240 pg/ml in CKD stages 3 and 4, respectively. Conclusion: Currently applied cutoffs for PTH in kidney transplant recipients with CKD stages 3 and 4 do not appear to adequately detect increased biochemical markers of bone turnover. Diagnostic uncertainty exists in patients with CKD stage 3 and PTH between 35 and 140 pg/ml, and CKD stage 4 and PTH between 70 and 240 pg/ml. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Impaired kidney function is common in kidney-transplanted patients and complications of chronic kidney disease (CKD), such as mineral and bone disorders (MBD) are also prevalent in this population. Similarly to other stages of CKD, increasing evidence supports the association between MBD and cardiovascular risk after kidney transplantation as well. Still, little is known about the prevalence, clinical correlates of MBD and its management in transplanted patients. In this study, we aimed to examine the characteristics of MBD and its associations with clinical parameters in a large prevalent cohort of patients after kidney transplantation. Nine hundred and ninety stable patients followed at a single kidney transplant outpatient clinic were included in the study. Detailed medical history, demographic data and routine laboratory results, including Ca, P and intact PTH were collected. Estimated GFR was calculated using the abbreviated MDRD formula, patients were stratified into three groups based on eGFR. Target levels for Ca, P and iPTH were based on CKD stages according to the NKF-K/DOQI guidelines. Standard statistical procedures, binomial and multinomial regressions were used in the analysis. The mean age was 51 years, 57% were males and 21% were diabetic, with 72 months (median) post-transplantation. Most of the patients were in CKD stage 3. Serum phosphorus showed strong negative correlation with graft function in CKD stages 4–5 ( r = −0.633, P < 0.001). Hyperphosphatemia was independently associated with the time spent on dialysis before transplantation, serum iPTH and CKD stages 4–5. iPTH showed negative correlation with eGFR in CKD stages 3–5 (rho = −0.289, P < 0.001) and weak positive correlation with time spent on dialysis prior to transplant (rho = 0.114, P < 0.001). Both hyperparathyroidism (42%) and relative hypoparathyroidism (15%) were frequent. The prescription of P-binders (6%) and vitamin D analogs (33%) was sporadic. Disturbances of bone and mineral metabolism after transplantation are prevalent and are strongly correlated with the kidney function, similarly to non-transplanted CKD patients. MBD in this population is not adequately managed. [ABSTRACT FROM AUTHOR]