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Chinese young adults (CYA), who are at an increasing risk of developing nonalcoholic fatty liver disease (NAFLD), which in turn increases the risk of liver cancer, are an ideal target population to deliver educational interventions to improve their awareness and knowledge of NAFLD and consequently reduce their risk of developing NAFLD. The purpose of this study was to determine the efficacy of two interventions to improve awareness and knowledge of NAFLD among CYA for the prevention of liver cancer. Between May and July 2021, 1373 undergraduate students aged 18 to 25 years in one university in China completed a web-based, self-administered survey distributed through WeChat app. One week after completion of the baseline survey, all eligible participants were randomly assigned to a pamphlet, a video intervention, or no intervention (control group), with follow-up assessments immediately and 1-month post-intervention. The 7-page pamphlet or 6.5-min video had information on NAFLD. Self-assessments included NAFLD awareness, lean NAFLD awareness, and knowledge scores of NAFLD. About 26% of participants had NAFLD awareness at baseline. Compared with controls, participants in both interventions showed significant improvement of awareness of NAFLD (pamphlet, + 46.0%; video, + 44.3%; control, + 18.7%; OR [95% CI], 3.13 [2.19-4.47] and 2.84 [1.98-4.08]), awareness of lean NAFLD (pamphlet, + 41.2%; video, + 43.0%; control, + 14.5%; OR [95% CI], 2.84 [1.62-4.99] and 2.61 [1.50-4.54]), and knowledge score of NAFLD (pamphlet, + 64.2%; video, + 68.9%; control, - 1.0%; OR [95% CI], 1.62 [1.47-1.80] and 1.67 [1.50-1.86]) at immediately post-intervention. Delivering NAFLD education through a pamphlet or video intervention was effective in improving the awareness and knowledge of NAFLD among CYA.
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Conocimientos, Actitudes y Práctica en Salud , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Masculino , Femenino , Adulto Joven , Adulto , Adolescente , China , Neoplasias Hepáticas/prevención & control , Folletos , Educación en Salud , Encuestas y Cuestionarios , Estudiantes/psicología , Pueblos del Este de AsiaRESUMEN
Saturated hydrocarbon bonds are ubiquitous in organic molecules; to date, the selective functionalization of C(sp3)-H bonds continues to pose a notorious difficulty, thereby garnering significant attention from the synthetic chemistry community. During the past several decades, a wide array of powerful new methodologies has been developed to enantioselectively modify C(sp3)-H bonds that is successfully applied in asymmetric formation of diverse bonds, including C-C, C-N, and C-O bonds; nevertheless, the asymmetric C(sp3)-H alkylation is elusive and, therefore, far less explored. In this work, we report a direct and robust strategy to construct highly valuable enantioenriched unnatural α-amino acid (α-AA) cognates and peptides by a copper-catalyzed enantioselective remote C(sp3)-H alkylation of N-fluorocarboxamides and readily accessible glycine esters under ambient conditions. The key to success lies in the optically active Cu catalyst generated through the coordination of glycine derivatives to enantiopure bisphosphine/Cu(I) species, which is beneficial to the single electronic reduction of N-fluorocarboxamides and the subsequent stereodetermining alkylation. More importantly, all types (primary, secondary, tertiary, and even α-oxy) of δ-C(sp3)-H bonds could be site- and stereospecifically activated by the kinetically favored 1,5-hydrogen atom transfer (1,5-HAT) step.
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Cobre , Glicina , Cobre/química , Alquilación , Péptidos/química , CatálisisRESUMEN
PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of valid, reliable, ready-to-use survey instruments for assessing awareness and knowledge of NAFLD in this population. The aims of this study were to develop, validate, and assess the reliability of a web-based, self-administered questionnaire evaluating awareness and knowledge of NAFLD among CYA. METHODS: Based on review of relevant literature, a draft questionnaire was initially developed. Face and content validity of the questionnaire was evaluated by an expert panel of seven gastroenterologists. The construct validity was tested through item analysis based on item response theory. Reliability assessment included test-retest for stability and test for internal consistency. Two pilot tests were conducted among 60 randomly selected students at Lanzhou University, China, through WeChat App. RESULTS: The content validity and clarity indexes were both greater than 0.85. Face validity was established by concluding that questions had no issue with feasibility, readability, clarity of wording, clarity of layout, and style. Response rates for two pilot tests were 96.7% (58 out of 60) and 98.3% (59 out of 60), respectively. Results testing the construct validity showed estimated amount of information obtained by the test between -3 and +3 range of ability was 97.57%. The test-retest reliability (Pearson's r) was 0.62. The internal consistency (KR20) was 0.92. CONCLUSIONS: This newly developed questionnaire is a reliable and valid instrument for assessing awareness and knowledge of NAFLD among this sample from CYA.
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Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Adulto Joven , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Reproducibilidad de los Resultados , Pueblos del Este de Asia , Conocimientos, Actitudes y Práctica en Salud , Encuestas y Cuestionarios , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/etiología , PsicometríaRESUMEN
In many clinical studies, longitudinal biomarkers are often used to monitor the progression of a disease. For example, in a kidney transplant study, the glomerular filtration rate (GFR) is used as a longitudinal biomarker to monitor the progression of the kidney function and the patient's state of survival that is characterized by multiple time-to-event outcomes, such as kidney transplant failure and death. It is known that the joint modelling of longitudinal and survival data leads to a more accurate and comprehensive estimation of the covariates' effect. While most joint models use the longitudinal outcome as a covariate for predicting survival, very few models consider the further decomposition of the variation within the longitudinal trajectories and its effect on survival. We develop a joint model that uses functional principal component analysis (FPCA) to extract useful features from the longitudinal trajectories and adopt the competing risk model to handle multiple time-to-event outcomes. The longitudinal trajectories and the multiple time-to-event outcomes are linked via the shared functional features. The application of our model on a real kidney transplant data set reveals the significance of these functional features, and a simulation study is carried out to validate the accurateness of the estimation method.
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PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of study assessing awareness and knowledge of NAFLD among them. This study aimed to assess awareness and knowledge of NAFLD, and identify the factors associated with awareness and knowledge of NAFLD among CYA. We conducted a survey to assess awareness and knowledge of NAFLD among students who enrolled in one university undergraduate program in 2018, 2019, and 2020 through a newly developed web-based, self-administered questionnaire. The outcomes included awareness of NAFLD and knowledge score of NAFLD. We conducted unadjusted and adjusted analyses of associated factors with these outcomes. A total of 1373 students participated in the survey. Of all participants, 26.2% reported that they had heard of NAFLD, 7.7% reported that they had heard of lean NAFLD, and 11.1% received ≥ 20 points in the knowledge section of NAFLD. The mean and median scores were 9.35 (Std = 7.67) and 9 (range 0-27). Factors associated with having awareness and knowledge (≥ 20 points) of NAFLD included medical background, high medical knowledge level, and family history of NAFLD. There was low NAFLD awareness and knowledge among CYA aged 18 to 25 years. Our findings point to the need to develop an educational intervention for CYA to improve their NAFLD awareness and knowledge. Further studies should include information on physical activity and dietary habits to test whether NAFLD awareness and knowledge impact those habits.
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Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Adulto Joven , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/etiología , Pueblos del Este de Asia , Pueblo Asiatico , Encuestas y Cuestionarios , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Factores de RiesgoRESUMEN
BACKGROUND: Fifteen percent of US adults have chronic kidney disease (CKD). The effect of CKD on the development of different malignancies is unknown. Understanding the effect of CKD on the risk of development of cancer could have important implications for screening and early detection of cancer in these patients. METHODS: Adult CKD patients [estimated GFR (eGFR) <60ml/min/1.73m2] between January 2001 and December 2020 were identified in this single institution study. Patients were divided into four stages of CKD by eGFR. The incidence of cancer and time to development of the first cancer were identified. Multivariable models were used to compare the overall cancer incidence while considering death as a competing risk event and adjusting for relevant covariates (sex, race, diabetes, hypertension, CAD, smoking or not, BMI, and CKD stages). Separate multivariable models of the incidence of cancers were conducted in each age group. Multivariable Cox models were used to fit the overall death adjusting for relevant covariates. Patients were censored at the conclusion of the study period (December 31, 2020). Statistical analysis was performed with SAS software (version 9.4). RESULTS: Of the 13,750 patients with a diagnosis of CKD in this cohort, 2,758 (20.1%) developed a malignancy. The median time to development of cancer following a diagnosis of CKD was 8.5 years. Factors associated with the risk of developing cancer in CKD patients included increasing age, male sex and worsening chronic kidney disease, while diabetes was associated with a lower risk of malignancy. On multivariate analysis, the factors associated with increased mortality in patients who developed cancer included increasing age, diabetes and lower eGFR. CONCLUSION: CKD is an increased risk factor for the development of various malignancies. Age appropriate cancer screening should be aggressively pursued in those with progressive CKD.
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Diabetes Mellitus , Neoplasias , Insuficiencia Renal Crónica , Adulto , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Tasa de Filtración Glomerular , Humanos , Masculino , Neoplasias/complicaciones , Neoplasias/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Factores de RiesgoRESUMEN
Patients with peripheral artery disease (PAD) have significantly reduced lower extremity muscle strength compared with healthy individuals as measured during isolated, single plane joint motion by isometric and isokinetic strength dynamometers. Alterations to the force contribution of muscles during walking caused by PAD are not well understood. Therefore, this study used simulations with PAD biomechanics data to understand lower extremity muscle functions in patients with PAD during walking and to compare that with healthy older individuals. A total of 12 patients with PAD and 10 age-matched healthy older controls walked across a 10-meter pathway with reflective markers on their lower limbs. Marker coordinates and ground reaction forces were recorded and exported to OpenSim software to perform gait simulations. Walking velocity, joint angles, muscle force, muscle power, and metabolic rate were calculated and compared between patients with PAD and healthy older controls. Our results suggest that patients with PAD walked slower with less hip extension during propulsion. Significant force and power reductions were observed in knee extensors during weight acceptance and in plantar flexors and hip flexors during propulsion in patients with PAD. The estimated metabolic rate of walking during stance was not different between patients with PAD and controls. This study is the first to analyze lower limb muscular responses during walking in patients with PAD using the OpenSim simulation software. The simulation results of this study identified important information about alterations to muscle force and power during walking in those with PAD.
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Articulación de la Cadera , Enfermedad Arterial Periférica , Fenómenos Biomecánicos , Marcha/fisiología , Humanos , Articulación de la Rodilla , Músculo Esquelético , CaminataRESUMEN
This functional joint model paper is motivated by a chronic kidney disease study post kidney transplantation. The available kidney organ is a scarce resource because millions of end-stage renal patients are on the waiting list for kidney transplantation. The life of the transplanted kidney can be extended if the progression of the chronic kidney disease stage can be slowed, and so a major research question is how to extend the transplanted kidney life to maximize the usage of the scarce organ resource. The glomerular filtration rate is the best test to monitor the progression of the kidney function, and it is a continuous longitudinal outcome with repeated measures. The patient's survival status is characterized by time-to-event outcomes including kidney transplant failure, death with kidney function, and death without kidney function. Few studies have been carried out to simultaneously investigate these multiple clinical outcomes in chronic kidney disease stage patients based on a joint model. Therefore, this paper proposes a new functional joint model from this clinical chronic kidney disease study. The proposed joint models include a longitudinal sub-model with a flexible basis function for subject-level trajectories and a competing-risks sub-model for multiple time-to event outcomes. The different association structures can be accomplished through a time-dependent function of shared random effects from the longitudinal process or the whole longitudinal history in the competing-risks sub-model. The proposed joint model that utilizes basis function and competing-risks sub-model is an extension of the standard linear joint models. The application results from the proposed joint model can supply some useful clinical references for chronic kidney disease study post kidney transplantation.
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Trasplante de Riñón , Insuficiencia Renal Crónica , Tasa de Filtración Glomerular , Humanos , Riñón , Insuficiencia Renal Crónica/cirugía , Listas de EsperaRESUMEN
Kidney-alone transplant (KAT) candidates may be disadvantaged by the allocation priority given to multi-organ transplant (MOT) candidates. This study identified potential KAT candidates not receiving a given kidney offer due to its allocation for MOT. Using the Organ Procurement and Transplant Network (OPTN) database, we identified deceased donors from 2002 to 2017 who had one kidney allocated for MOT and the other kidney allocated for KAT or simultaneous pancreas-kidney transplant (SPK) (n = 7,378). Potential transplant recipient data were used to identify the "next-sequential KAT candidate" who would have received a given kidney offer had it not been allocated to a higher prioritized MOT candidate. In this analysis, next-sequential KAT candidates were younger (p < .001), more likely to be racial/ethnic minorities (p < .001), and more highly sensitized than MOT recipients (p < .001). A total of 2,113 (28.6%) next-sequential KAT candidates subsequently either died or were removed from the waiting list without receiving a transplant. In a multivariable model, despite adjacent position on the kidney match-run, mortality risk was significantly higher for next-sequential KAT candidates compared to KAT/SPK recipients (hazard ratio 1.55, 95% confidence interval 1.44, 1.66). These results highlight implications of MOT allocation prioritization, and potential consequences to KAT candidates prioritized below MOT candidates.
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Trasplante de Riñón , Trasplante de Órganos , Trasplante de Páncreas , Obtención de Tejidos y Órganos , Humanos , Donantes de Tejidos , Listas de EsperaRESUMEN
In longitudinal studies, the values of biomarkers are often informatively missing due to dropout. The conventional functional principal component analysis typically disregards the missing information and simply treats the unobserved data points as missing completely at random. As a result, the estimation of the mean function and the covariance surface might be biased, resulting in a biased estimation of the functional principal components. We propose the informatively missing functional principal component analysis (imFunPCA), which is well suited for cases where the longitudinal trajectories are subject to informative missingness. Computation of the functional principal components in our approach is based on the likelihood of the data, where information of both the observed and missing data points are incorporated. We adopt a regression-based orthogonal approximation method to decompose the latent stochastic process based on a set of orthonormal empirical basis functions. Under the case of informative missingness, we show via simulation studies that the performance of our approach is superior to that of the conventional ones. We apply our method on a longitudinal dataset of kidney glomerular filtration rates for patients post renal transplantation.
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Modelos Estadísticos , Humanos , Estudios Longitudinales , Análisis de Componente Principal , Probabilidad , Análisis de RegresiónRESUMEN
[This corrects the article DOI: 10.2196/19424.].
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BACKGROUND: Computed tomography (CT) scans are increasingly available in clinical care globally. They enable a rapid and detailed assessment of tissue and organ involvement in disease processes that are relevant to diagnosis and management, particularly in the context of the COVID-19 pandemic. OBJECTIVE: The aim of this paper is to identify differences in the CT scan findings of patients who were COVID-19 positive (confirmed via nucleic acid testing) to patients who were confirmed COVID-19 negative. METHODS: A retrospective cohort study was proposed to compare patient clinical characteristics and CT scan findings in suspected COVID-19 cases. A multivariable logistic model with LASSO (least absolute shrinkage and selection operator) selection for variables was used to identify the good predictors from all available predictors. The area under the curve (AUC) with 95% CI was calculated for each of the selected predictors and the combined selected key predictors based on receiver operating characteristic curve analysis. RESULTS: A total of 94 (56%) patients were confirmed positive for COVID-19 from the suspected 167 patients. We found that elderly people were more likely to be infected with COVID-19. Among the 94 confirmed positive patients, 2 (2%) patients were admitted to an intensive care unit. No patients died during the study period. We found that the presence, distribution, and location of CT lesions were associated with the presence of COVID-19. White blood cell count, cough, and a travel history to Wuhan were also the top predictors for COVID-19. The overall AUC of these selected predictors is 0.97 (95% CI 0.93-1.00). CONCLUSIONS: Taken together with nucleic acid testing, we found that CT scans can allow for the rapid diagnosis of COVID-19. This study suggests that chest CT scans should be more broadly adopted along with nucleic acid testing in the initial assessment of suspected COVID-19 cases, especially for patients with nonspecific symptoms.
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Técnicas de Laboratorio Clínico/métodos , Tórax/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Prueba de COVID-19 , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Reproducibilidad de los Resultados , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Administrative data are commonly used to study clinical outcomes in renal disease. Race is an important determinant of renal health delivery and outcomes in Canada but is not validated in most administrative data, and the correlation with census-based definitions of race is unknown. OBJECTIVES: Validation of self-reported race (SRR) in a Canadian provincial renal administrative database (Patient Records and Outcome Management Information System [PROMIS]) and comparison with the Canadian census categories of race. DESIGN: Prospective patient survey study to validate SRR in PROMIS. SETTING: British Columbia, Canada. PATIENTS: Adult patients registered in PROMIS. MEASUREMENTS: Survey SRR was used as gold standard to validate SRR in PROMIS. Self-reported race in PROMIS was compared with census race categories. METHODS: This is a cross-sectional telephone survey of a random sample of all adults in PROMIS conducted between February 2016 and November 2016. Responders selected a race category from PROMIS and from the Canadian census. Sensitivity (Sn) and specificity (Sp) were calculated with 95% confidence intervals (CIs). RESULTS: A total of 21 039 patients met inclusion criteria, 1677 were selected for the survey and 637 participated (38% response rate). There were no differences between the PROMIS, sampled, and responder populations. PROMIS SRR had an accuracy of 95.3% (95% CI: 94.2%-97.0%) when validated against the survey SRR with Sn and Sp ≥90% in all race groups except in Aboriginals (Sn 87.5%). The positive and negative predictive values were ≥95%, except in very low and high-prevalence groups, respectively. The Canadian census had an accuracy of 95.7% (95% CI: 94.4%-97.6%) when validated against PROMIS SRR with Sn and Sp ≥90%. The results did not differ in subgroups based on age, sex, birth outside Canada, or renal group (glomerulonephritis, chronic kidney disease, hemodialysis, peritoneal dialysis, transplant recipients, or live donors). LIMITATIONS: Analysis of minority groups and lower prevalence groups is limited by sample size. Results may not be generalizable to other administrative databases. CONCLUSIONS: We have shown high accuracy of PROMIS SRR that validates its use in the secondary analysis of administrative data for research. There is high correlation between PROMIS and census race categories which allows linkage with other data sources that use census-based definitions of race.
CONTEXTE: Les données administratives sont fréquemment utilisées pour étudier les issues cliniques en néphrologie. L'origine ethnique (OE) du patient est un déterminant important de la prestation de soins et des résultats en santé rénale au Canada, mais n'est pas validée dans la plupart des données administratives et la corrélation avec les définitions d'ethnies fondées sur le recensement demeure inconnue. OBJECTIFS: L'étude visait à valider l'origine ethnique autodéclarée (OEAD) dans une base de données administrative provinciale relative à la santé rénale (PROMIS), et à la comparer à l'origine ethnique inscrite au recensement canadien. TYPE D'ÉTUDE: Une étude prospective menée sous forme de sondage auprès de patients pour valider l'OEAD dans PROMIS. CADRE: Colombie-Britannique, Canada. SUJETS: Des patients adultes inscrits dans PROMIS. MESURES: L'OE mentionnée dans le sondage a servi d'étalon-or pour valider l'OEAD dans PROMIS, et cette dernière a été comparée à l'OE rapportée par le recensement. MÉTHODOLOGIE: Une enquête transversale conduite par téléphone entre février et novembre 2016 auprès d'un échantillon aléatoire d'adultes inscrits dans PROMIS. Les répondants devaient choisir une OE dans PROMIS et dans les catégories du recensement canadien. La sensibilité (Sn) et la spécificité (Sp) ont été calculées avec un intervalle de confiance à 95 % (IC 95 %). RÉSULTATS: Des 21 039 patients qui satisfaisaient les critères d'inclusion, 1 677 ont été sélectionnés pour le sondage et 637 ont participé (taux de réponse: 38 %). Aucune différence n'a été observée entre les populations de PROMIS, de l'échantillon et de répondants. L'OEAD dans PROMIS était exacte dans 95,3 % des cas (IC 95 %: 94,2-97,0 %), lorsque validée contre l'OEAD dans le sondage, avec une Sn et une Sp d'au moins 90 % pour tous les groupes ethniques, à l'exception des Autochtones (Sn: 87,5 %). Les valeurs prédictives positive et négative étaient d'au moins 95 %, sauf dans les groupes à très faible et à forte prévalence, respectivement. Le recensement canadien a montré une précision de 95,7 % (IC 95 %: 94,4-97,6 %) lorsque validé contre l'OEAD dans PROMIS avec une Sn et une Sp d'au moins 90 %. Les résultats n'ont pas varié dans les sous-groupes selon l'âge, le sexe, la naissance hors Canada ou le groupe de néphrologie (glomérulonéphrite, insuffisance rénale chronique, hémodialyse, dialyse péritonéale, receveurs d'une greffe ou donneurs vivants). LIMITES: L'analyse des groupes minoritaires et des groupes à faible prévalence est limitée par la taille de l'échantillon. Les résultats pourraient ne pas être généralisables à d'autres bases de données administratives. CONCLUSION: Nous avons montré la grande précision de l'OEAD dans PROMIS, ce qui valide son utilisation pour l'analyse secondaire de données administratives à des fins de recherche. Une forte corrélation existe entre les définitions de l'OE dans PROMIS et le recensement, ce qui permet d'établir des liens avec d'autres sources de données qui utilisent les mêmes définitions que le recensement.
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Recurrent glomerulonephritis (GN) is a common cause of graft loss after kidney transplantation. Steroids are critical to GN management before transplantation, but it is unclear if early steroid withdrawal after transplantation increases the risk of graft loss in patients with GN. Here USRDS data were used to examine the association of early steroid withdrawal with death censored graft loss and all cause graft loss in GN and non-GN adult, non-diabetic, non-sensitized first kidney-only transplant recipients from 1998-2012. A 2-stage propensity score-based matching algorithm was used to match early steroid withdrawal to steroid-maintained patients in the GN and non-GN groups. Multivariate Cox models using a robust variance estimator to account for matched pairs were used to examine the association of early steroid withdrawal with death censored or all cause graft loss in patients with (6388 patients each in early steroid withdrawal and steroid groups) or without GN (6590 each in early steroid withdrawal and steroid groups). Early steroid withdrawal was not associated with an increased risk of death censored or all cause graft loss in patients with or without GN. These findings were consistent across GN types and after accounting for transplant center. Thus, our findings support consideration of early steroid withdrawal in patients with GN at high risk of the adverse consequences of prolonged steroid exposure.
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Glomerulonefritis/tratamiento farmacológico , Glucocorticoides/administración & dosificación , Rechazo de Injerto/prevención & control , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/prevención & control , Adulto , Esquema de Medicación , Femenino , Estudios de Seguimiento , Glomerulonefritis/etiología , Glomerulonefritis/mortalidad , Glucocorticoides/efectos adversos , Rechazo de Injerto/etiología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Humanos , Inmunosupresores/efectos adversos , Estimación de Kaplan-Meier , Fallo Renal Crónico/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/mortalidad , Puntaje de Propensión , Recurrencia , Prevención Secundaria/métodos , Factores de TiempoRESUMEN
This article is motivated by jointly modelling longitudinal and time-to-event clinical data of patients with diabetes and end-stage renal disease. All patients are on the waiting list for the pancreas transplant after kidney transplant, and some of them have a pancreas transplant before kidney transplant failure or death. Scant literature has studied the dynamical joint relationship of the estimated glomerular filtration rates trajectory, the effect of pancreas transplant, and time-to-event outcomes, although it remains an important clinical question. In an attempt to describe the association in the multiple outcomes, we propose a new joint model with a longitudinal submodel and an accelerated failure time submodel, which are linked by some latent variables. The accelerated failure time submodel is used to determine the relationship of the time-to-event outcome with all predictors. In addition, the piecewise linear function in the survival submodel is used to calculate the dynamic hazard ratio curve of a time-dependent side event, because the effect of the side event on the time-to-event outcome is non-proportional. The model parameters are estimated with a Monte Carlo EM algorithm. The finite sample performance of the proposed method is investigated in simulation studies. Our method is demonstrated by fitting the joint model for the clinical data of 13,635 patients with diabetes and the end-stage renal disease.
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Diabetes Mellitus/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Método de Montecarlo , Análisis de Supervivencia , Diabetes Mellitus/mortalidad , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Estudios Longitudinales , Masculino , Trasplante de Páncreas/mortalidad , Factores de Riesgo , Listas de EsperaRESUMEN
This article is motivated by some longitudinal clinical data of kidney transplant recipients, where kidney function progression is recorded as the estimated glomerular filtration rates at multiple time points post kidney transplantation. We propose to use the functional principal component analysis method to explore the major source of variations of glomerular filtration rate curves. We find that the estimated functional principal component scores can be used to cluster glomerular filtration rate curves. Ordering functional principal component scores can detect abnormal glomerular filtration rate curves. Finally, functional principal component analysis can effectively estimate missing glomerular filtration rate values and predict future glomerular filtration rate values.
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Tasa de Filtración Glomerular , Trasplante de Riñón , Análisis de Componente Principal , Humanos , Evaluación de Resultado en la Atención de SaludRESUMEN
Concern about the long-term impact of delayed graft function (DGF) may limit the use of high-risk organs for kidney transplantation. To understand this better, we analyzed 29,598 mate kidney transplants from the same deceased donor where only 1 transplant developed DGF. The DGF associated risk of graft failure was greatest in the first posttransplant year, and in patients with concomitant acute rejection (hazard ratio: 8.22, 95% confidence interval: 4.76-14.21). In contrast, the DGF-associated risk of graft failure after the first posttransplant year in patients without acute rejection was far lower (hazard ratio: 1.15, 95% confidence interval: 1.02-1.29). In subsequent analysis, recipients of transplants complicated by DGF still derived a survival benefit when compared with patients who received treatment with dialysis irrespective of donor quality as measured by the Kidney Donor Profile Index (KDPI). The difference in the time required to derive a survival benefit was longer in transplants with DGF than in transplants without DGF, and this difference was greatest in recipients of lower quality kidneys (difference: 250-279 days for KDPI 20%-60% vs. 809 days for the KDPI over 80%). Thus, the association of DGF with graft failure is primarily limited to the first posttransplant year. Transplants complicated by DGF provide a survival benefit compared to treatment with dialysis, but the survival benefit is lower in kidney transplants with lower KDPI. This information may increase acceptance of kidneys at high risk for DGF and inform strategies to minimize the risk of death in the setting of DGF.
Asunto(s)
Aloinjertos/patología , Funcionamiento Retardado del Injerto/complicaciones , Rechazo de Injerto/mortalidad , Supervivencia de Injerto , Fallo Renal Crónico/terapia , Trasplante de Riñón/mortalidad , Funcionamiento Retardado del Injerto/mortalidad , Femenino , Humanos , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Diálisis Renal/mortalidad , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/mortalidadRESUMEN
BACKGROUND: Identification of risk factors for BK polyoma virus (BKPyV) without confounding by donor factors and era effects in paired analysis may inform strategies to prevent BKPyV. METHODS: In this analysis of 21,575 mate kidney pairs in the Scientific Registry of Transplant Recipients between 2004 and 2010, the presence of a treatment code for BKPyV virus in follow-up forms was used to identify pairs in which 1 of 2 mate kidneys was treated (discordant treatment) or both mate kidneys were treated (concordant treatment). RESULTS: Among 1975 discordant pairs, younger than 18 years or 60 years or older, male sex, HLA mismatch or 4 greater, acute rejection, and depleting antibody induction had a higher odds of treatment, whereas diabetes and sirolimus had a lower odds of treatment, and treatment was associated with a higher risk of allograft failure (hazards ratio, 2.01; 95% confidence interval, 1.63-2.48). The rate of concordant treatment (0.81%) was 2.8 times higher than expected. Concordant treatment was associated with nonwhite donor ethnicity, donation after circulatory death, transplantation after 2008, and transplantation of mate kidneys in the same center. CONCLUSIONS: This analysis of kidneys from the same donor in which only 1 transplant was treated for BKPyV identifies specific risk factors (age <18 or ≥ 60 years, male sex, depleting antibody, HLA mismatch ≥ 4) for BKPyV and provides an estimate of the BKPyV-associated risk of allograft failure (hazards ratio = 2.01) without confounding by donor factors or era effects. The higher than expected rate of concordant treatment suggests the importance of donor factors in BKPyV pathogenesis and warrants further study.
Asunto(s)
Antivirales/uso terapéutico , Virus BK/efectos de los fármacos , Enfermedades Renales/tratamiento farmacológico , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Infecciones Oportunistas/tratamiento farmacológico , Infecciones por Polyomavirus/tratamiento farmacológico , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Virus BK/patogenicidad , Femenino , Antígenos HLA/inmunología , Histocompatibilidad , Humanos , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Estimación de Kaplan-Meier , Enfermedades Renales/diagnóstico , Enfermedades Renales/inmunología , Enfermedades Renales/virología , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/inmunología , Infecciones Oportunistas/mortalidad , Infecciones Oportunistas/virología , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/inmunología , Infecciones por Polyomavirus/mortalidad , Modelos de Riesgos Proporcionales , Sistema de Registros , Ajuste de Riesgo , Factores de Riesgo , Factores Sexuales , Factores de Tiempo , Donantes de Tejidos , Insuficiencia del Tratamiento , Infecciones Tumorales por Virus/diagnóstico , Infecciones Tumorales por Virus/inmunología , Infecciones Tumorales por Virus/mortalidad , Infecciones Tumorales por Virus/virología , Carga Viral , Adulto JovenRESUMEN
BACKGROUND: Participation of compatible living donors and recipients in kidney paired donation (KPD) could double the number of KPD transplants. We determined the willingness of previous directed donors and their recipients to participate in KPD and identified the association of various factors, including financial incentives, with willingness to participate. METHODS: Survey of previous directed living kidney donors and their recipients in a single Canadian center between 2001 and 2009. RESULTS: Among 207 of 222 eligible living donors contacted, 86 (42%) completed the anonymous survey: 93% (78/86) of donors indicated willingness to participate in KPD if this option had been provided at the time of donation. An increased willingness to participate was reported among the majority of respondents if reimbursements for lost wages and travel expenses were provided; however, cash payments between $5 000 and $50 000 had little impact on willingness. Willingness was also increased with an advantage to the recipient (younger donor or better human leukocyte antigen match), whereas delays beyond 3 months and donor travel were associated with reduced willingness to participate. Among 38 recipients approached during routine clinical follow-up visits over a 3-month period, 100% completed the survey, and 36 of 38 (92%) reported they would have been willing to participate in KPD. CONCLUSIONS: Over 90% of directed donors and recipients were willing to participate in KPD. Reimbursement for the costs of participation and improved efficiency of KPD (i.e., eliminating travel and reducing transplant times), but not cash payments, may increase participation of compatible donors and recipients in KPD.
Asunto(s)
Donación Directa de Tejido , Conocimientos, Actitudes y Práctica en Salud , Trasplante de Riñón/psicología , Donadores Vivos/psicología , Motivación , Participación del Paciente , Receptores de Trasplantes/psicología , Adulto , Altruismo , Colombia Británica , Compensación y Reparación , Donación Directa de Tejido/economía , Femenino , Donaciones , Humanos , Renta , Trasplante de Riñón/economía , Trasplante de Riñón/métodos , Donadores Vivos/provisión & distribución , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Transportes/economíaRESUMEN
Living kidney donation is declining in the United States. We examined longitudinal trends in living donation as a function of median household income and donor relation to assess the effect of financial barriers on donation in a changing economic environment. The zip code-level median household income of all 71,882 living donors was determined by linkage to the 2000 US Census. Longitudinal changes in the rate of donation were determined in income quintiles between 1999 and 2004, when donations were increasing, and between 2005 and 2010, when donations were declining. Rates were adjusted for population differences in age, sex, race, and ESRD rate using multilevel linear regression models. Between 1999 and 2004, the rate of growth in living donation per million population was directly related to income, increasing progressively from the lowest to highest income quintile, with annualized changes of 0.55 (95% confidence interval [95% CI], 0.14 to 1.05) for Q1 and 1.77 (95% CI, 0.66 to 2.77) for Q5 (P<0.05). Between 2005 and 2010, donation declined in Q1, Q2, and Q3; was stable in Q4; and continued to grow in Q5. Longitudinal changes varied by donor relationship, and the association of income with longitudinal changes also varied by donor relationship. In conclusion, changes in living donation in the past decade varied by median household income, resulting in increased disparities in donation between low- and high-income populations. These findings may inform public policies to support living donation during periods of economic volatility.