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1.
Pediatr Nephrol ; 35(2): 297-303, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31709464

RESUMO

BACKGROUND: While adult hemodialysis (HD) patients have increased morbidity with higher target hemoglobin levels, similar findings have not been demonstrated in pediatric patients. We evaluated changes in transfusions, anemia frequency, and erythropoietin (epo) dosing among pediatric HD patients before, during, and after implementation of federal dialysis payment policies regarding epo dosing for adult HD patients. METHODS: This is a retrospective cohort study of pediatric HD patients enrolled in NAPRTCS. We evaluated need for transfusion, anemia, median hemoglobin, and median epo dose 6 months after starting HD in 3 eras: baseline (2003-2007), implementation (2008-2011), and post implementation (2012-2016). We used multivariate logistic regression models to evaluate potential differences in transfusion across the eras. RESULTS: Six months after dialysis initiation, 12.6% of patients required transfusion pre-implementation, 17.9% during implementation, and 15.5% post implementation. Anemia occurred in 17.4% of patients pre, 23.5% during, and 23.8% post implementation, with median hemoglobin levels of 11.9 g/dL pre, 11 g/dL during, and 11 g/dL post implementation. Epo use was high across all 3 eras, but epo dosing decreased during and post implementation, despite more anemia during these periods. Odds of transfusion in implementation era compared with pre-implementation was 1.75 (95% CI 1.11-2.77) and odds of transfusion in post implementation era compared with pre was 1.19 (95% CI 0.71-1.98), controlling for age, race, gender, and prior transplant status. CONCLUSIONS: During and following implementation of adult epo dosing guidelines, transfusion and anemia frequency increased in pediatric HD patients. Ideal target hemoglobin levels for pediatric dialysis patients warrant further study.


Assuntos
Anemia/epidemiologia , Transfusão de Sangue/estatística & dados numéricos , Eritropoetina/administração & dosagem , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Adolescente , Anemia/etiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Falência Renal Crônica/complicações , Masculino , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Adulto Jovem
2.
Br J Clin Pharmacol ; 85(12): 2824-2837, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31475367

RESUMO

AIMS: To characterize the population pharmacokinetics (PK) of sildenafil and its active metabolite, N-desmethyl sildenafil (DMS), in premature infants. METHODS: We performed a multicentre, open-label trial to characterize the PK of sildenafil in infants ≤28 weeks gestation and < 365 postnatal days (cohort 1) or < 32 weeks gestation and 3-42 postnatal days (cohort 2). In cohort 1, we obtained PK samples from infants receiving sildenafil as ordered per the local standard of care (intravenous [IV] or enteral). In cohort 2, we administered a single IV dose of sildenafil and performed PK sampling. We performed a population PK analysis and dose-exposure simulations using the software NONMEM®. RESULTS: We enrolled 34 infants (cohort 1 n = 25; cohort 2 n = 9) and collected 109 plasma PK samples. Sildenafil was given enterally (0.42-2.09 mg/kg) in 24 infants in cohort 1 and via IV (0.125 or 0.25 mg/kg) in all infants in cohort 2. A 2-compartment PK model for sildenafil and 1-compartment model for DMS, with presystemic conversion of sildenafil to DMS, characterized the data well. Coadministration of fluconazole (n = 4), a CYP3A inhibitor, resulted in an estimated 59% decrease in sildenafil clearance. IV doses of 0.125, 0.5 and 1 mg/kg every 8 hours (in the absence of fluconazole) resulted in steady-state maximum sildenafil concentrations that were generally within the range of those reported to inhibit phosphodiesterase type 5 activity in vitro. CONCLUSIONS: We successfully characterized the PK of sildenafil and DMS in premature infants and applied the model to inform dosing for a follow-up, phase II study.


Assuntos
Recém-Nascido Prematuro/sangue , Modelos Biológicos , Inibidores da Fosfodiesterase 5/farmacocinética , Citrato de Sildenafila/farmacocinética , Administração Oral , Estudos de Coortes , Citocromo P-450 CYP3A/sangue , Citocromo P-450 CYP3A/genética , Fluconazol/administração & dosagem , Fluconazol/farmacocinética , Idade Gestacional , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/tratamento farmacológico , Lactente , Recém-Nascido , Doenças do Prematuro/sangue , Doenças do Prematuro/tratamento farmacológico , Injeções Intravenosas , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/sangue , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/sangue , Citrato de Sildenafila/uso terapêutico
3.
Pediatr Transplant ; 23(5): e13469, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31169337

RESUMO

BACKGROUND: With improved outcomes for children transplanted with FSGS since previous NAPRTCS registry reports, this study re-evaluates the association of living donation, immunosuppression, and DGF on graft survival. SETTING: Patients transplanted between 2002 and 2016, comparing FSGS diagnosis vs other glomerular diseases. METHODS: Primary outcomes were allograft survival and FSGS recurrent-free graft survival. Potential risk factors were obtained at the time of transplant and up to 30 days post-transplantation. Analysis considered a priori that DGF may be a proxy for severe FSGS recurrence. Multivariable survival models for outcome were tested for sensitivity without/with DGF to determine features independent of recurrence. RESULTS: From the larger cohort of 3010 patients, 5-year graft survival in children with FSGS (n = 455) was worse (74.3%) compared with other glomerular diseases (87.1%, n = 690) (HR 1.45, P = 0.033). Modeling all glomerular diseases, survival risk was associated with deceased donor (HR 1.83, P = 0.002), re-transplantation (HR 1.58, P = 0.013), and recipient age (HR 1.06/y, P = 0.002). The living donor advantage was not confirmed in a FSGS model (HR 1.51 for deceased, P = 0.12). DGF was highly associated with graft failure (HR 4.39, P < 0.001) and independent of re-transplant history but not FSGS diagnosis. Induction agents or primary immunosuppression choices were not associated with survival. CONCLUSION: Graft survival rates have improved since the previous report. Living donor did not predict graft failure, but there remains no survival advantage. DGF was the primary independent predictor for graft loss secondary to FSGS recurrence, consistent with DGF being a proxy for severe recurrent disease.


Assuntos
Glomerulosclerose Segmentar e Focal/cirurgia , Rejeição de Enxerto , Transplante de Rim , Adolescente , Criança , Feminino , Humanos , Masculino , Sistema de Registros , Fatores de Risco
4.
Pediatr Transplant ; 23(8): e13597, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31657095

RESUMO

The NAPRTCS has collected clinical information on children undergoing renal transplantation since 1987 and now includes information on 12 920 renal transplants in 11 870 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in patient and allograft outcomes after pediatric renal transplantation in addition to identifying factors associated with both favorable and poor outcomes. The registry has served to document and influence practice patterns, clinical outcomes, and changing trends in renal transplantation and also provides historical perspective. This report highlights current practices in an era of major changes in DD kidney allocation and continuing steroid minimization. This report presents outcomes of the patients in the NAPRTCS transplant registry up to end of 2017. In particular, an increase in the cumulative incidence of late first AR has occurred in the most recent cohort, while all prior cohorts had a lower cumulative incidence of late first AR.


Assuntos
Transplante de Rim , Adolescente , Benchmarking , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/epidemiologia , Padrões de Prática Médica , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-28137820

RESUMO

Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size. The final model included TBW and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (liters/hour) = 13.8 × (TBW/70)0.75 × [PMA2.83/(39.52.83+PMA2.83)]; volume of distribution (V) was associated with TBW, albumin (ALB), and alpha-1 acid glycoprotein (AAG): V (liters) = 63.6 × (TBW/70) × (ALB/3.3)-0.83 × (AAG/2.4)-0.25 After accounting for differences in TBW, obesity status did not explain additional interindividual variability in model parameters. Our findings support TBW-based dosing for obese and nonobese children.


Assuntos
Antibacterianos/farmacocinética , Clindamicina/farmacocinética , Modelos Estatísticos , Obesidade/metabolismo , Adolescente , Antibacterianos/sangue , Área Sob a Curva , Teorema de Bayes , Disponibilidade Biológica , Índice de Massa Corporal , Peso Corporal , Criança , Clindamicina/sangue , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Injeções Intravenosas , Masculino , Obesidade/fisiopatologia , Orosomucoide/metabolismo , Albumina Sérica/metabolismo
6.
Pediatr Nephrol ; 32(12): 2319-2330, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28762101

RESUMO

BACKGROUND: The 2011 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry comprises data on 6482 dialysis patients over the past 20 years of the registry. METHODS: The study compared clinical parameters and patient survival in the first 10 years of the registry (1992-2001) with the last decade of the registry (2002-2011). RESULTS: There was a significant increase in hemodialysis as the initiating dialysis modality in the most recent cohort (42% vs. 36%, p < 0.001). Patients in the later cohort were less likely to have a hemoglobin <10 g/dl [odds ratio (OR) 0.68; confidence interval (CI) 0.58-0.81; p < 0.001] and height z-score <2 standard deviations (SD) below average (OR 0.68, CI 0.59-0.78, p < 0.0001). They were also more likely to have a parathyroid hormone (PTH) level two times above the upper limits of normal (OR 1.39, CI 1.21-1.60, p < 0.0001). Although hypertension was common regardless of era, patients in the 2002-2011 group were less likely to have blood pressure >90th percentile (OR 1.39, CI 1.21-1.60, p < 0.0001), and a significant improvement in survival at 36 months after dialysis initiation was observed in the 2002-2011 cohort compared with the 1992-2001 cohort (95% vs. 90%, respectively). Cardiopulmonary causes were the most common cause of death in both cohorts. Young age, growth deficit, and black race were poor predictors of survival. CONCLUSIONS: The survival of pediatric patients on chronic dialysis has improved over two decades of dialysis registry data, specifically for children <1year.


Assuntos
Falência Renal Crônica/terapia , Diálise Renal/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Falência Renal Crônica/mortalidade , Masculino , América do Norte , Sistema de Registros , Diálise Renal/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento
7.
J Pediatr ; 165(1): 65-72.e2, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24801243

RESUMO

OBJECTIVE: To determine the evolution of cognitive and academic deficits and risk factors in children after liver transplantation. STUDY DESIGN: Patients ≥2 years after liver transplantation were recruited through Studies of Pediatric Liver Transplantation. Participants age 5-6 years at Time 1 completed the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition, Wide Range Achievement Test, 4th edition, and Behavior Rating Inventory of Executive Function (BRIEF). Participants were retested at age 7-9 years, Time 2 (T2), by use of the Wechsler Intelligence Scales for Children, 4th edition, Wide Range Achievement Test, 4th edition, and BRIEF. Medical and demographic variables significant at P ≤ .10 in univariate analysis were fitted to repeated measures modeling predicting Full Scale IQ (FSIQ). RESULTS: Of 144 patients tested at time 1, 93 (65%) completed T2; returning patients did not differ on medical or demographic variables. At T2, more participants than expected had below-average FSIQ, Verbal Comprehension, Working Memory, and Math Computation, as well as increased executive deficits on teacher BRIEF. Processing Speed approached significance. At T2, 29% (14% expected) had FSIQ = 71-85, and 7% (2% expected) had FSIQ ≤70 (P = .0001). A total of 42% received special education. Paired comparisons revealed that, over time, cognitive and math deficits persisted; only reading improved. Modeling identified household status (P < .002), parent education (P < .01), weight z-score at liver transplantation (P < .03), and transfusion volume during liver transplantation (P < .0001) as predictors of FSIQ. CONCLUSIONS: More young liver transplantation recipients than expected are at increased risk for lasting cognitive and academic deficits. Pretransplant markers of nutritional status and operative complications predicted intellectual outcome.


Assuntos
Transtornos Cognitivos/etiologia , Deficiências da Aprendizagem/etiologia , Transplante de Fígado/efeitos adversos , Criança , Pré-Escolar , Escolaridade , Função Executiva , Feminino , Seguimentos , Humanos , Testes de Inteligência , Estudos Longitudinais , Masculino , Sistema de Registros , Fatores de Risco , Resultado do Tratamento
8.
Pediatr Nephrol ; 29(9): 1477-84, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25055994

RESUMO

The Standardizing Care to Improve Outcomes in Pediatric End Stage Renal Disease (SCOPE) Collaborative is a North American multi-center quality transformation effort whose primary aim is to minimize exit-site infection and peritonitis rates among pediatric chronic peritoneal dialysis patients. The project, developed by the quality improvement faculty and staff at the Children's Hospital Association's Quality Transformation Network (QTN) and content experts in pediatric nephrology and pediatric infectious diseases, is modeled after the QTN's highly successful Pediatric Intensive Care Unit and Hematology-Oncology central line-associated blood-stream infection (CLABSI) Collaboratives. Like the Association's other QTN efforts, the SCOPE Collaborative is part of a broader effort to assist pediatric nephrology teams in learning about and using quality improvement methods to develop and implement evidence-based practices. In addition, the design of this project allows for targeted research that builds on high-quality, ongoing data collection. Finally, the project, while focused on reducing peritoneal dialysis catheter-associated infections, will also serve as a model for future pediatric nephrology projects that could further improve the quality of care provided to children with end stage renal disease.


Assuntos
Infecções Relacionadas a Cateter/prevenção & controle , Pediatria/normas , Diálise Peritoneal/efeitos adversos , Melhoria de Qualidade/normas , Criança , Comportamento Cooperativo , Humanos , Falência Renal Crônica/terapia
9.
Pediatr Transplant ; 17(2): 149-57, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23281637

RESUMO

The NAPRTCS transplant registry has collected clinical information on children undergoing kidney transplantation since 1987 and now includes information on 11 603 kidney transplants in 10 632 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in outcome after kidney transplantation in addition to identifying factors associated with both favorable and poor outcomes. Patient demographics have changed over the course of the registry with a decrease in the percentage of white recipients from a high of 72% in 1987 to less than 43% in 2007. The percentage of living donors decreased to its lowest point in 2007 at 37%. Acute rejection rates continue to decline with improvements in short- and long-term graft survival. Recently, NAPRTCS data have been used as a source of benchmark data for pediatric kidney transplant centers.


Assuntos
Benchmarking , Transplante de Rim/tendências , Avaliação de Resultados em Cuidados de Saúde , Padrões de Prática Médica/tendências , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão/métodos , Terapia de Imunossupressão/normas , Terapia de Imunossupressão/estatística & dados numéricos , Terapia de Imunossupressão/tendências , Lactente , Recém-Nascido , Transplante de Rim/etnologia , Transplante de Rim/normas , Transplante de Rim/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , América do Norte , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , Doadores de Tecidos/estatística & dados numéricos , Adulto Jovem
10.
Pediatr Transplant ; 17(8): 726-30, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24164825

RESUMO

Kidney transplant recipients have an increased risk of cancer. Data on non-LPD malignancies (solid tumors) in pediatric renal transplant recipients are limited. We performed a cohort study using the NAPRTCS transplant registry to describe the incidence of non-LPD malignancy compared with the general pediatric population. The observed incidence rate of non-LPD malignancy in the NAPRTCS transplant registry was 72.1 per 100,000 person-years (SIR 6.7; 95% CI, 5.3, 8.5); a 6.7-fold increased risk compared with the general pediatric population (10.7 cases per 100,000 person-years). Non-LPD malignancy was diagnosed in 35 subjects at a median of 726 days post-transplant. The most common type of malignancy was renal cell carcinoma. The increased risk of non-LPD malignancy was seen in all patients regardless of age, gender, race, etiology of end-stage kidney disease, and transplant era. The specific type of immunosuppression was not identified as a risk factor. In this first large-scale study of North American pediatric renal transplant recipients, we observed a 6.7-fold increased risk of non-LPD malignancy compared with the general pediatric population. Further examination of this unique patient population may provide greater insight into the impact of transplant and immunosuppression on malignancy risk.


Assuntos
Carcinoma de Células Renais/etiologia , Falência Renal Crônica/complicações , Transplante de Rim/efeitos adversos , Neoplasias/etiologia , Criança , Feminino , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Masculino , Neoplasias/epidemiologia , América do Norte , Pediatria , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Programa de SEER
11.
Pediatr Transplant ; 17(7): 605-11, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23902630

RESUMO

Data from 997 pediatric LT recipients were used to model demographic and medical variables as predictors of lower levels of HRQOL. Data were collected through SPLIT FOG project. Patients were between 2 and 18 yr of age and survived LT by at least 12 months. Parents and children (age ≥ 8 yr) completed PedsQL™ 4.0 Generic Core and CF Scales at one time point. Demographic and medical variables were obtained from SPLIT. HRQOL scores were categorized as "poor" based on lower 25% of scores for each measure. Logistic regression models were generated. Single-parent households (OR 1.94, CI 1.13-3.33, p = 0.017), anti-seizure medications (OR 3.99, CI 1.26-12.70, p = 0.019), and number of days hospitalized (OR 1.03, CI 1.01-1.06, p = 0.0067) were associated with lower self-reported HRQOL. Parent data identified increasing age at transplant, age 5-12 yr at survey, hospitalization >21 days at LT, re-operations, diabetes, and growth failure at LT as additional predictors of generic HRQOL. Male gender, single-parent households, higher bilirubin levels at LT, and use of anti-seizure medication predicted lower cognitive function scores. HRQOL following pediatric LT is related to medical and demographic variables.


Assuntos
Falência Hepática/terapia , Transplante de Fígado/psicologia , Qualidade de Vida , Adolescente , Anticonvulsivantes/química , Criança , Pré-Escolar , Transtornos Cognitivos/etiologia , Estudos de Coortes , Estudos Transversais , Etnicidade , Feminino , Seguimentos , Hospitalização , Humanos , Tempo de Internação , Falência Hepática/etnologia , Masculino , Razão de Chances , Pais , Complicações Pós-Operatórias , Classe Social , Inquéritos e Questionários , Resultado do Tratamento
12.
Clin Infect Dis ; 55(11): 1495-502, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22955430

RESUMO

BACKGROUND: Intra-abdominal infections are common in young infants and lead to significant morbidity and mortality. Meropenem is a broad-spectrum antimicrobial with excellent activity against pathogens associated with intra-abdominal infections. The purpose of this study was to determine the safety and effectiveness of meropenem in young infants with suspected or complicated intra-abdominal infections. METHODS: Preterm and term infants <91 days of age with suspected or confirmed intra-abdominal infections hospitalized in 24 neonatal intensive care units were studied in an open-label, multiple-dose study. Adverse events and serious adverse events were collected through 3 and 30 days following the last meropenem dose, respectively. Effectiveness was assessed by 3 criteria: death, bacterial cultures, and presumptive clinical cure score. RESULTS: Of 200 subjects enrolled in the study, 99 (50%) experienced an adverse event, and 34 (17%) had serious adverse events; no adverse events were probably or definitely related to meropenem. The most commonly reported adverse events were sepsis (6%), seizures (5%), elevated conjugated bilirubin (5%), and hypokalemia (5%). Only 2 of the serious adverse events were determined to be possibly related to meropenem (isolated ileal perforation and an episode of fungal sepsis). Effectiveness was evaluable in 192 (96%) subjects, and overall treatment success was 84%. CONCLUSIONS: Meropenem was well tolerated in this cohort of critically ill infants, and the majority of infants treated with meropenem met the definition of therapeutic success. CLINICAL TRIALS REGISTRATION: NCT00621192.


Assuntos
Antibacterianos/uso terapêutico , Infecções Intra-Abdominais/tratamento farmacológico , Tienamicinas/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Lactente , Recém-Nascido , Infecções Intra-Abdominais/patologia , Masculino , Meropeném , Tienamicinas/administração & dosagem , Tienamicinas/efeitos adversos , Tienamicinas/farmacocinética
13.
J Pediatr ; 160(4): 621-625.e1, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22056352

RESUMO

OBJECTIVE: To evaluate and characterize the degree of blood pressure (BP) control in children on chronic dialysis and to identify significant predictors of hypertension and BP control in these patients. STUDY DESIGN: Linear and logistic regression models were used to examine trends in BP and BP control in a cross-sectional sample of patients on chronic dialysis aged 1-21 years enrolled in the North American Pediatric Renal Trials and Collaborative Studies registry from 1992-2008. RESULTS: At 6 months after dialysis initiation, 67.9% of patients had uncontrolled or untreated hypertension, and 57.8% were prescribed antihypertensive medications. More recent year of dialysis initiation was associated with a higher use of antihypertensive medication and lower systolic BP and diastolic BP z scores (P < .001) measured over time from 6 months to 3 years post dialysis initiation. Other factors associated with higher BP included black race, glomerular disease, younger age, hemodialysis (systolic BP only), and antihypertensive use. There were significant differences in BP control by dialysis modality and disease etiology, with patients on hemodialysis or those with glomerular diseases having the highest percentage of uncontrolled hypertension. CONCLUSIONS: Despite widespread antihypertensive use, many pediatric patients on dialysis are at risk for untreated or uncontrolled hypertension. Additional efforts are needed to improve management of hypertension in these children.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Diálise Renal , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/prevenção & controle , Lactente , Masculino
14.
Nephrol Dial Transplant ; 27(4): 1682-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21810763

RESUMO

BACKGROUND: Studies show that adult dialysis patients with allograft failure have increased mortality and morbidity on dialysis compared to transplant naïve patients. We previously showed comparable mortality risk in pediatric dialysis patients after allograft failure compared to transplant naïve patients; the impact on morbidity is less clear. Specifically, the effect of allograft failure on school attendance in pediatric patients has not previously been studied. METHODS: Using the North American Pediatric Renal Trials and Collaborative Studies database, we compared school attendance between transplant naïve and allograft failure patients from 1 January 1992 to 31 December 2007. School attendance was compared between the two groups at 6 and 12 months after dialysis initiation using a chi-square test. Factors which can potentially impact on school attendance data were evaluated using a multivariate logistic regression analysis. RESULTS: There were 2783 patients who had a follow-up at least 6 months after dialysis initiation and were capable of attending school during the study period. Patients were categorized by transplant history: previous allograft failure (n=576) and transplant naïve (n=2207). At 6 months, full-time school attendance was 67.2% in the allograft failure group and 72.3% in the transplant naïve group (P=0.0164). At 12 months, attendance was 68.6% in the allograft failure group and 72.5% in the transplant naïve group (P=0.103). After covariate adjustment, transplant failure did not impact school attendance at either 6 or 12 months follow-up [hazard ratio (HR) 1.12, confidence interval (CI) 0.91-1.39; HR 0.99, CI 0.78-1.27, respectively]. CONCLUSIONS: Children with failed allografts who return to dialysis have comparable school attendance compared to their transplant naïve dialysis counterparts. These results suggest that transplant failure is not an adverse prognostic factor for quality of life as measured by full-time school attendance.


Assuntos
Absenteísmo , Falência Renal Crônica/complicações , Transplante de Rim/efeitos adversos , Qualidade de Vida , Diálise Renal/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Sistema de Registros , Fatores de Risco , Transplante Homólogo
15.
Contemp Clin Trials Commun ; 30: 101025, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36345347

RESUMO

Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to alveolar simplification, impaired alveolar-capillary development, interstitial fibrosis, and often pulmonary hypertension. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. Sildenafil reduces lung injury and preserves normal vasculature in preclinical models, and improves outcomes in children with pulmonary hypertension, and thus is a promising candidate for BPD. Following phase I studies, we developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD. SIL02 is a randomized, double-blind, placebo-controlled, 3-cohort, sequential dose-escalating trial of enteral or intravenous (IV) sildenafil dosed every 8 h for up to 34 days. The target IV doses were 0.125, 0.5 and 1 mg/kg/dose in cohorts 1, 2 and 3, respectively; while the enteral doses will be double the IV doses. Eligible infants must be < 29 weeks' gestation at birth and requiring respiratory support at 7-28 days' postnatal age. Adverse events and preliminary effectiveness will be compared by treatment group. Using the final population PK model, empirical Bayesian estimates will be generated for each patient. Preliminary effectiveness will be measured by the incidence of moderate to severe BPD or death at 36 weeks and change in the BPD risk estimation.

16.
J Perinatol ; 42(1): 31-36, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741102

RESUMO

OBJECTIVE: To characterize the safety of sildenafil in premature infants. STUDY DESIGN: A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring. RESULTS: Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases. CONCLUSION: Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants. CLINICAL TRIAL: ClinicalTrials.gov Identifier: NCT01670136.


Assuntos
Hipotensão , Doenças do Prematuro , Humanos , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Lactente Extremamente Prematuro , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/tratamento farmacológico , Citrato de Sildenafila/efeitos adversos
17.
Ann Surg ; 254(1): 145-54, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21606838

RESUMO

OBJECTIVE: The purpose of this study was to identify significant, independent factors that predicted 6 month patient and graft survival after pediatric liver transplantation. SUMMARY BACKGROUND DATA: The Studies of Pediatric Liver Transplantation (SPLIT) is a multicenter database established in 1995, of currently more than 4000 US and Canadian children undergoing liver transplantation. Previous published analyses from this data have examined specific factors influencing outcome. This study analyzes a comprehensive range of factors that may influence outcome from the time of listing through the peri- and postoperative period. METHODS: A total of 42 pre-, peri- and posttransplant variables evaluated in 2982 pediatric recipients of a first liver transplant registered in SPLIT significant at the univariate level were included in multivariate models. RESULTS: In the final model combining all baseline and posttransplant events, posttransplant complications had the highest relative risk of death or graft loss. Reoperation for any cause increased the risk for both patient and graft loss by 11 fold and reoperation exclusive of specific complications by 4 fold. Vascular thromboses, bowel perforation, septicemia, and retransplantation, each independently increased the risk of patient and graft loss by 3 to 4 fold. The only baseline factor with a similarly high relative risk for patient and graft loss was recipient in the intensive care unit (ICU) intubated at transplant. A significant center effect was also found but did not change the impact of the highly significant factors already identified. CONCLUSIONS: We conclude that the most significant factors predicting patient and graft loss at 6 months in children listed for transplant are posttransplant surgical complications.


Assuntos
Transplante de Fígado/mortalidade , Período Perioperatório , Adolescente , Criança , Pré-Escolar , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Análise Multivariada , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
18.
Pediatr Transplant ; 15(4): 376-83, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21466638

RESUMO

Kidney transplantation is the treatment of choice for the majority of pediatric patients with end-stage kidney disease. Previous studies demonstrating racial or gender disparities in access to the deceased donor transplant list could not evaluate the impact of medical concerns or patient preference on waitlist status. We undertook a retrospective cohort study using the NAPRTCS registry to begin to determine barriers to wait list registration for kidney transplantation among pediatric dialysis patients. Clinical and demographic factors were compared in listed vs. non-listed patients. Reasons cited for not listing patients were examined by clinical and demographic factors. At dialysis initiation, 88.7% of pediatric dialysis patients were not on the renal transplant wait list. Twelve months after dialysis initiation, 67.1% of pediatric dialysis patients were not on the wait list. The groups least likely to be on the wait list were infants (adjusted OR 0.23, 95% CI 0.16, 0.32) and girls (adjusted OR 0.78, 95% CI 0.67, 0.90) after adjusting for multiple confounders. The reason most often cited for not listing was medical reason for young infants and that the transplant workup was pending for girls. Further study is needed to identify barriers to wait list registration.


Assuntos
Falência Renal Crônica/terapia , Diálise Renal/estatística & dados numéricos , Listas de Espera , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Intervalos de Confiança , Feminino , Seguimentos , Humanos , Lactente , Falência Renal Crônica/diagnóstico , Transplante de Rim/estatística & dados numéricos , Modelos Logísticos , Masculino , América do Norte , Razão de Chances , Sistema de Registros , Diálise Renal/métodos , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo
19.
Pediatr Transplant ; 15(2): 167-71, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21199208

RESUMO

NAPRTCS data were analyzed to assess outcome of TX recipients from YDs (<5 yr) in comparison with IDs (6-35 yr) and ODs (36-55 yr). Of 9854 TX in NAPRTCS (1987-2003), 469 were YD. Patient survival (PS) and graft survival (GS) were compared between DD TX after 1995; 81YD, 1324 ID, and 429 OD and eGFR were compared among functioning grafts (YD 31, ID 439, OD 174) at three yr. PS was comparable in all groups; GS at one, two, and three yr in TX of YD (91.1%, 83.8%, 79.7%), ID (93.5%, 89.7%, 83.6%), and OD (92.2%, 87.2%, 82.4%) was comparable. The eGFR in YD was comparable to ID but better than OD (86.5 vs. 79.7 vs. 67.2 mL/min/1.73 m2, p 0.139 and<0.0003). Primary graft non-function was more frequent in TX from YD than ID and OD (3.7% vs. 0.3 and 0.7%, p=0.004); the incidence of vascular thrombosis was similar. The aforementioned data show that pediatric recipients of YD had equivalent patient and graft survival. Although primary graft non-function was higher, eGFR of functioning grafts was comparable to ID. With further improvements in care, kidneys from YD may present a viable option for transplantation.


Assuntos
Transplante de Rim/métodos , Doadores de Tecidos , Adolescente , Adulto , Fatores Etários , Distribuição de Qui-Quadrado , Criança , Intervalo Livre de Doença , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Testes de Função Renal , Transplante de Rim/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Pediatria , Cuidados Pós-Operatórios/métodos , Sistema de Registros , Estudos Retrospectivos , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos , Adulto Jovem
20.
Pediatr Transplant ; 15(3): 245-53, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21199214

RESUMO

This cross-sectional, multicenter cohort study compares the level of HRQOL of pediatric LT recipients to children with other chronic health conditions. LT sample included 873 children who survived at least 12 months following LT. Six chronic disease samples were compiled from numerous studies, including over 800 patients with JRA, type 1 diabetes, cancer in remission, cardiac disease, end-stage renal disease, and inflammatory bowel disease. Generic HRQOL was measured from both the parental and patient perspective using the PedsQL™ 4.0 Generic Core Scales. Pediatric LT patients reported better physical health than children with JRA. According to parents, pediatric LT recipients had better HRQOL than children on renal dialysis on all domains except school functioning. Across all domains but emotional functioning, pediatric LT recipients reported significantly lower HRQOL than children with type 1 diabetes. Overall, pediatric LT patients reported HRQOL comparable to that of children who had undergone renal transplantation and patients with cancer in remission. Pediatric LT patients manifested impaired HRQOL similar to that of children with chronic diseases and these data suggest that they face ongoing challenges that warrant monitoring and indicate a need for interventions to improve their HRQOL.


Assuntos
Falência Hepática/psicologia , Falência Hepática/terapia , Transplante de Fígado/métodos , Adolescente , Criança , Doença Crônica , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 1/terapia , Feminino , Nível de Saúde , Humanos , Falência Renal Crônica/terapia , Falência Hepática/cirurgia , Masculino , Pediatria/métodos , Qualidade de Vida , Indução de Remissão
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