Therapeutic drug monitoring of tacrolimus (Tac) is mandatory in solid organ transplant (SOT) recipients. Finger-prick microsampling is more flexible and tolerable during the therapeutic drug ...monitoring of tacrolimus and has been shown to be applicable in adult SOT recipients. In this study, a previously validated method applying volumetric absorptive microsampling (VAMS) to measure Tac in adults was cross-validated in a pediatric population.
Patients with SOT scheduled for standard posttransplant follow-up visits were recruited. Blood samples were obtained by trained phlebotomists using standard venipuncture and capillary microsampling, before the morning dose of Tac as well as 2 and 5 hours after dosing. Tac concentrations were quantified using liquid chromatography-tandem mass spectrometry. Concordance between Tac concentrations obtained with venipuncture and VAMS was evaluated using Passing-Bablok regression, calculation of absolute and relative differences, and percentage of samples within ±20% and ±30% difference.
A total of 39 SOT patients aged 4-18 years (22 male) were included. The median (range) predose venous blood concentration was 4.8 (2.6-13.6) mcg/L, with a difference between VAMS and venous blood samples of -0.2 ± 0.7 mcg/L. The relative mean difference was -1.3% 95% confidence interval (CI), -5.9% to 3.4%. Ninety-two percent and 97% of the sample pairs demonstrated differences within ±20% and ±30%, respectively. Postdose (2 hours and/or 5 hours, n = 17) median concentration in venous blood was 7.9 (4.8-19.2) mcg/L. The difference between VAMS and venous blood samples was 0.1 ± 1.0 mcg/L, with a relative mean difference of -2.5% (95% confidence interval, -8.8% to 3.8%). Eighty-eight percent of the postdose sample pairs were within ±20% difference, and all were within ±30% difference.
Tac concentrations can be accurately measured using VAMS technology in pediatric SOT recipients. This makes home-based Tac monitoring feasible in the pediatric population.
Abstract
Background
This article summarizes the ERA-EDTA Registry’s 2016 Annual Report, by describing the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2016 ...within 36 countries.
Methods
In 2017 and 2018, the ERA-EDTA Registry received data on patients undergoing RRT for ESRD in 2016 from 52 national or regional renal registries. In all, 32 registries provided individual patient data and 20 provided aggregated data. The incidence and prevalence of RRT and the survival probabilities of these patients were determined.
Results
In 2016, the incidence of RRT for ESRD was 121 per million population (pmp), ranging from 29 pmp in Ukraine to 251 pmp in Greece. Almost two-thirds of patients were men, over half were aged ≥65 years and almost a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 84% of patients. On 31 December 2016, the prevalence of RRT was 823 pmp, ranging from 188 pmp in Ukraine to 1906 pmp in Portugal. In 2016, the transplant rate was 32 pmp, varying from 3 pmp in Ukraine to 94 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2007–11, the 5-year unadjusted patient survival probability on all RRT modalities combined was 50.5%. For 2016, the incidence and prevalence of RRT were higher among men (187 and 1381 pmp) than women (101 and 827 pmp), and men had a higher rate of kidney transplantation (59 pmp) compared with women (33 pmp). For patients starting dialysis and for patients receiving a kidney transplant during 2007–11, the adjusted patient survival probabilities appeared to be higher for women than for men.
Abstract
Background
This article summarizes the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Registry's 2015 Annual Report. It describes the epidemiology of ...renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 2015 within 36 countries.
Methods
In 2016 and 2017, the ERA-EDTA Registry received data on patients who were undergoing RRT for ESRD in 2015, from 52 national or regional renal registries. Thirty-two registries provided individual patient-level data and 20 provided aggregated-level data. The incidence, prevalence and survival probabilities of these patients were determined.
Results
In 2015, 81 373 individuals commenced RRT for ESRD, equating to an overall unadjusted incidence rate of 119 per million population (pmp). The incidence ranged by 10-fold, from 24 pmp in Ukraine to 232 pmp in the Czech Republic. Of the patients commencing RRT, almost two-thirds were men, over half were aged ≥65 years and a quarter had diabetes mellitus as their primary renal diagnosis. Treatment modality at the start of RRT was haemodialysis for 85% of the patients, peritoneal dialysis for 11% and a kidney transplant for 4%. By Day 91 of commencing RRT, 82% of patients were receiving haemodialysis, 13% peritoneal dialysis and 5% had a kidney transplant. On 31 December 2015, 546 783 individuals were receiving RRT for ESRD, corresponding to an unadjusted prevalence of 801 pmp. This ranged throughout Europe by more than 10-fold, from 178 pmp in Ukraine to 1824 pmp in Portugal. In 2015, 21 056 kidney transplantations were performed, equating to an overall unadjusted transplant rate of 31 pmp. This varied from 2 pmp in Ukraine to 94 pmp in the Spanish region of Cantabria. For patients commencing RRT during 2006-10, the 5-year unadjusted patient survival probabilities on all RRT modalities combined was 50.0% (95% confidence interval 49.9-50.1).
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Due to a high inter-individual variability in its pharmacokinetics, tacrolimus dose individualization is mandatory. Even though the expert opinion has defined the area under the curve ...(AUC) as the best marker to use when performing dose adjustment of tacrolimus, most centres only use trough levels. Multiple targets have been proposed for this parameter and physicians rely largely on their personal experience when making a decision about dose adjustment. Several population pharmacokinetics models (POPPK) allowing AUC determination have been developed, but only a few are actually used in routine practice for dose individualization. These POPPK models can also be used to perform Monte Carlo simulations that help to establish different dosing rules or to anticipate the pharmacokinetics of tacrolimus in particular populations, without conducting clinical trials. Various available applications of POPPK models to assist the prescriber in choosing the best tacrolimus dose are discussed in this paper as well as the difficulties in introducing them into routine therapeutic drug monitoring.
Aims
The aim of this population-based historical cohort study was to investigate the influence of lifestyle factors on the risk of developing migraine or tension-type headache (TTH).
Methods
Data ...from the Nord-Trøndelag Health Study performed in 1995–1997 and 2006–2008 was used. A total of 15,276 participants without headache at baseline were included. A Poisson regression was used to evaluate the associations between lifestyle factors and risk ratios (RRs) of migraine and TTH 11 years later. Precision of the estimates was assessed by 95% confidence interval (CIs).
Results
Increased risk of migraine (RR 1.30, 95% CI 1.11–1.52) was found in smokers (past or current) compared to those who had never smoked. Hard physical exercise 1–2 hours per week reduced the risk of migraine (OR 0.71, 95% CI 0.54–0.94) compared to inactivity, and the risk of migraine was also lower among those who consumed alcohol (RR 0.73, 95% CI 0.57–0.94) compared to abstainers. No association was found between smoking, physical activity, alcohol use and risk of TTH.
Conclusions
The main finding was that current and previous smoking was associated with increased risk of migraine, but not of TTH.
Introduction Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive ...strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx. Methods We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses. Results In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01). Conclusion Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients.
The impact of chronic musculoskeletal complaints (CMSC) and chronic widespread chronic musculoskeletal complaints (CWMSC) on mortality is controversial. The aim of this study was to investigate the ...relationship between these conditions and mortality. In this prospective population-based cohort study from Norway, baseline data from the second Nord-Trøndelag Health Survey (HUNT2, performed 1995-1997) were linked to the comprehensive National Cause of Death Registry in Norway with follow-up through the year 2011. A total of 65,026 individuals (70%) participated and were categorized based on their response to CMSC questions in HUNT2 (no CMSC, CMSC, or CWMSC). Hazard ratios (HRs) of mortality during a mean of 14.1 years of follow-up were estimated using Cox regression. During the follow-up period, 12,521 subjects died, 5162 from cardiovascular diseases, 3478 from cancer, and 3881 from all other causes. In the multivariate-adjusted analyses, there was no difference in all-cause mortality between individuals with or without CMSC (HR 1.01, confidence interval, 0.97-1.05) and CWMSC (HR 1.01, confidence interval, 0.96-1.05). Similarly, there was no association between CMSC or CWMSC and cardiovascular mortality, mortality from cancer, or mortality from all other causes. Therefore, from this study, we conclude that there is no evidence for a higher mortality rate among individuals with CMSC or CWMSC.
Background
The primary aim of this cross-sectional population-based study was to evaluate the 1-year prevalence of common headache disorders by a face-to-face interview.
Methods
The fourth wave of ...Nord-Trøndelag Health Survey (HUNT4) started in September 2017. The study was undertaken as part of a project mainly focusing on sleep disorders, where a total of 232 (19.3%) out of 1200 invited HUNT4 participants underwent a face-to-face headache interview.
Results
The mean age of the 232 participants was 58.4 years (range 22–89). There were 71.6% (95% CI 65.7–77.4) who reported headache during the last year, and 18.5% (95% CI 13.5–23.6) had suffered from headache in the same period. The 1-year prevalence of tension-type headache (TTH) was 43.1% (95% CI 36.7–49.5), of idiopathic stabbing headache 34.1% (27.9–40.2), and of definite migraine 18.1% (95% CI 13.1–23.1). A total of 7.6% (95% CI 4.0–10.7%) had migraine with coexisting TTH. Lifetime prevalence of migraine was 32.8% (95% CI 26.7–38.8). Headache yesterday was reported by 12.1% (95% CI 7.9–16.3), and 5.6% (95% CI 2.6–8.6) had headache during the interview.
Conclusion
In this population-based cross-sectional headache study performed by a face-to-face interview, the 1-year prevalence of TTH was 43.1% and of idiopathic stabbing headache 34.1%. A total of 18.1% had active migraine (18.1%), whereas the lifetime prevalence of migraine was 32.8%.
Abstract
Background
The European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) Registry collects data on kidney replacement therapy (KRT) via national and regional renal ...registries in Europe and countries bordering the Mediterranean Sea. This article summarizes the 2018 ERA-EDTA Registry Annual Report, and describes the epidemiology of KRT for kidney failure in 34 countries.
Methods
Individual patient data on patients undergoing KRT in 2018 were provided by 34 national or regional renal registries and aggregated data by 17 registries. The incidence and prevalence of KRT, the kidney transplantation activity and the survival probabilities of these patients were calculated.
Results
In 2018, the ERA-EDTA Registry covered a general population of 636 million people. Overall, the incidence of KRT for kidney failure was 129 per million population (p.m.p.), 62% of patients were men, 51% were ≥65 years of age and 20% had diabetes mellitus as cause of kidney failure. Treatment modality at the onset of KRT was haemodialysis (HD) for 84%, peritoneal dialysis (PD) for 11% and pre-emptive kidney transplantation for 5% of patients. On 31 December 2018, the prevalence of KRT was 897 p.m.p., with 57% of patients on HD, 5% on PD and 38% living with a kidney transplant. The transplant rate in 2018 was 35 p.m.p.: 68% received a kidney from a deceased donor, 30% from a living donor and for 2% the donor source was unknown. For patients commencing dialysis during 2009–13, the unadjusted 5-year survival probability was 42.6%. For patients receiving a kidney transplant within this period, the unadjusted 5-year survival probability was 86.6% for recipients of deceased donor grafts and 93.9% for recipients of living donor grafts.
Background
Questionnaire-based headache diagnoses should be validated against diagnoses made by the gold standard, which is personal interview by a headache expert. The diagnostic algorithm with the ...best diagnostic accuracy should be used when later analysing the data.
Methods
The Nord-Trøndelag Health Study (HUNT4) was performed between 2017 and 2019. Among HUNT4 participants, a total of 232 (19.3%) out of 1201 randomly invited were interviewed by a headache expert to assess the sensitivity, specificity and kappa value of the questionnaire-based headache diagnoses.
Results
The median interval between answering the headache questions and the validation interview was 60 days (95% CI 56–62 days). The best agreements were found for self-reported lifetime migraine (sensitivity of 59%, specificity of 99%, and a kappa statistic of 0.65, 95% CI 0.55–0.75), self-reported active migraine (sensitivity of 50%, specificity of 97%, and a kappa statistic of 0.55, 95% 0.39–0.71), liberal criteria of migraine (sensitivity of 64%, specificity of 93%, and a kappa statistic of 0.58, 95% CI 0.43–0.73) and ICDH3-based migraine ≥1 days/month (sensitivity of 50%, specificity of 94%, and a kappa statistic of 0.49, 95% CI 0.30–0.68). For headache suffering ≥1 days/month a sensitivity of 90%, specificity 80%, and a kappa statistic of 0.55, 95% CI 0.41–0-69 were found. For tension-type headache (TTH) ≥ 1 days/month the agreement was 0.33 (95% CI 0.17–0.49).
Conclusion
The HUNT4 questionnaire is a valid tool for identifying persons with lifetime migraine, self-reported active migraine and active migraine applying liberal modified criteria. The agreement for TTH was fair.
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