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1.
Kidney Int ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32247633

RESUMO

Risk prediction models are statistical models that estimate the probability of individuals having a certain disease or clinical outcome based on a range of characteristics, and they can be used in clinical practice to stratify disease severity and characterize the risk of disease or disease prognosis. With technological advancements and the proliferation of clinical and biological data, prediction models are increasingly being developed in many areas of nephrology practice. This article guides the reader through the process of creating a prediction model, including (i) defining the clinical question and type of model, (ii) data collection and data cleaning, (iii) model building and variable selection, (iv) model performance, (v) model validation, (vi) model presentation and reporting, and (vii) impact evaluation. An example of developing a prediction model to predict mortality after intensive care unit admission for patients with end-stage kidney disease is also provided to illustrate the model development process.

2.
Clin J Am Soc Nephrol ; 15(3): 392-400, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32075809

RESUMO

BACKGROUND AND OBJECTIVES: Survival in pediatric kidney transplant recipients has improved over the past five decades, but changes in cause-specific mortality remain uncertain. The aim of this retrospective cohort study was to estimate the associations between transplant era and overall and cause-specific mortality for child and adolescent recipients of kidney transplants. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data were obtained on all children and adolescents (aged <20 years) who received their first kidney transplant from 1970 to 2015 from the Australian and New Zealand Dialysis and Transplant Registry. Mortality rates were compared across eras using Cox regression, adjusted for confounders. RESULTS: A total of 1810 recipients (median age at transplantation 14 years, 58% male, 52% living donor) were followed for a median of 13.4 years. Of these, 431 (24%) died, 174 (40%) from cardiovascular causes, 74 (17%) from infection, 50 (12%) from cancer, and 133 (31%) from other causes. Survival rates improved over time, with 5-year survival rising from 85% for those first transplanted in 1970-1985 (95% confidence interval [95% CI], 81% to 88%) to 99% in 2005-2015 (95% CI, 98% to 100%). This was primarily because of reductions in deaths from cardiovascular causes (adjusted hazard ratio [aHR], 0.25; 95% CI, 0.08 to 0.68) and infections (aHR, 0.16; 95% CI, 0.04 to 0.70; both for 2005-2015 compared with 1970-1985). Compared with patients transplanted 1970-1985, mortality risk was 72% lower among those transplanted 2005-2015 (aHR, 0.28; 95% CI, 0.18 to 0.69), after adjusting for potential confounders. CONCLUSIONS: Survival after pediatric kidney transplantation has improved considerably over the past four decades, predominantly because of marked reductions in cardiovascular- and infection-related deaths.

4.
Transpl Int ; 32(12): 1247-1258, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31408545

RESUMO

Nonadherence is an important risk factor for premature allograft failure after kidney transplantation, but outcomes after re-transplantation remain uncertain. Using data from the Australian and New Zealand Dialysis and Transplant registry, the associations between causes of first allograft failure and acute rejection-related and non-adherence-related allograft failure following re-transplantation were examined using competing risk analyses, treating the respective alternative causes of allograft failure and death with functioning graft as competing events. Fifty-nine of 2450 patients (2%) lost their first allografts from nonadherence. Patients who lost their first kidney allograft from nonadherence were younger at the time of first kidney allograft failure but waited longer for a second allograft (>5 years: 54% vs. 20%, P < 0.001) compared with other causes. Compared with patients who lost their first allograft from causes other than nonadherence, the adjusted subdistribution hazard ratio (HR and 95% CI) for acute rejection-related second allograft failure was 0.58 (0.08, 4.07; P = 0.582) for patients with allograft failure attributed to nonadherence and was 6.30 (1.34, 29.67; P = 0.020) for non-adherence-related second allograft failure. In this cohort of transplant recipients who have received second allografts, first allograft failure secondary to nonadherence was associated with a marginally greater risk of allograft failure attributed to nonadherence in subsequent transplantation.

6.
Arterioscler Thromb Vasc Biol ; 39(7): 1379-1389, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31092015

RESUMO

Objective- Investigate the impact of modulating B cell FcγRIIb (Fcγ receptor IIb) expression on atherosclerosis. Approach and Results- Western diet-induced atherosclerosis was assessed in Ldlr-/- or Apoe-/- mice with B cell-specific overexpression of FcγRIIb or with an FcγRIIb promoter mutation that alters FcγRIIb expression in germinal center (GC) B cells. In males, overexpression of FcγRIIb on B cells severely reduced activated, class switched B cell responses, as indicated by reductions in GC B cells, plasma cells, and serum IgG but not IgM antibodies. Male mice overexpressing FcγRIIb developed less atherosclerosis, suggesting a pathogenic role for GC B cell IgG responses. In support of this hypothesis, male mice with a promoter polymorphism-driven reduction in FcγRIIb on GC B cells but not plasma cells have a converse phenotype of enhanced GC responses and IgG2c antibodies and enhanced atherosclerosis. IgG2c significantly enhanced TNF (tumor necrosis factor) secretion by CD11b+ CD11c+ cells expressing the high-affinity receptor FcγRIV. In females, overexpression of FcγRIIb on B cells not only reduced GC B cell responses but also substantially reduced B-1 cells and IgM antibodies, which translated into acceleration of atherosclerosis. Promoter-driven reduction in FcγRIIb did not alter GC B cell responses in females and, therefore, had no impact on atherosclerosis. Conclusions- B cell FcγRIIb differentially alters proatherogenic adaptive GC B cell and atheroprotective innate B-1 responses in male and female mice fed a western diet. Our results highlight the importance of a better understanding and ability to selectively target B cell responses in future immunotherapeutic approaches against human cardiovascular disease. Visual Overview- An online visual overview is available for this article.


Assuntos
Aterosclerose/imunologia , Linfócitos B/imunologia , Centro Germinativo/imunologia , Receptores de IgG/fisiologia , Animais , Apolipoproteínas E/fisiologia , Feminino , Imunidade Inata , Imunoglobulina M/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/biossíntese
7.
Pediatr Nephrol ; 34(7): 1237-1245, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30788589

RESUMO

OBJECTIVE: To determine the association of socioeconomic disadvantage and parent-rated health in children with chronic kidney disease (CKD). METHODS: A total of 377 children (aged 6-18 years) with CKD stages I-V (n = 199), on dialysis (n = 43), or with a kidney transplant (n = 135) were recruited from 2012 to 2016 in Australia and New Zealand. Associations of five socioeconomic status (SES) components and the global SES index with parent-rated health of the child were examined using adjusted logistic regression. RESULTS: The median age of participants was 12.6 years (interquartile range (IQR) 8.9-15.5). In the entire cohort, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for poor parent-rated health were 1.85 (1.13-3.03) for lower household income, 1.78 (1.08-2.96) for families that did not own their own home, 2.50 (1.50-4.16) for caregivers who rated their financial status as poor, 0.84 (0.51-1.38) for lower educational attainment, and 1.68 (1.04-2.72) for children whose primary caregivers were unemployed. With reference to the highest global SES index quartile, adjusted ORs for poor parent-rated health in descending order were 1.49 (0.69-3.21), 2.11 (1.06-4.20), and 2.20 (1.09-4.46), respectively. The association between low SES and poor parent-rated health was modified by CKD stage, where lower global SES index was independently associated with poor parent-rated health in children with CKD stages I-V, but not children on dialysis or with kidney transplants (p = 0.04). CONCLUSIONS: Low SES is associated with poor parent-rated health in children with CKD stages I-V, but not children on dialysis and with kidney transplants.

8.
Arch Dis Child ; 104(2): 134-140, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30018070

RESUMO

OBJECTIVE: The aim was to compare quality of life (QoL) among children and adolescents with different stages of chronic kidney disease (CKD) and determine factors associated with changes in QoL. DESIGN: Cross-sectional. SETTING: The Kids with CKD study involved five of eight paediatric nephrology units in Australia and New Zealand. PATIENTS: There were 375 children and adolescents (aged 6-18 years) with CKD, on dialysis or transplanted, recruited between 2013 and 2016. MAIN OUTCOME MEASURES: Overall and domain-specific QoL were measured using the Health Utilities Index 3 score, with a scale from -0.36 (worse than dead) to 1 (perfect health). QoL scores were compared between CKD stages using the Mann-Whitney U test. Factors associated with changes in QoL were assessed using multivariable linear and ordinal logistic regression. RESULTS: QoL for those with CKD stages 1-2 (n=106, median 0.88, IQR 0.63-0.96) was higher than those on dialysis (n=43, median 0.67, IQR 0.39-0.91, p<0.001), and similar to those with kidney transplants (n=135, median 0.83, IQR 0.59-0.97, p=0.4) or CKD stages 3-5 (n=91, 0.85, IQR 0.60-0.98). Reductions were most frequent in the domains of cognition (50%), pain (42%) and emotion (40%). The risk factors associated with decrements in overall QoL were being on dialysis (decrement of 0.13, 95% CI 0.02 to 0.25, p=0.02), lower family income (decrement of 0.10, 95% CI 0.03 to 0.15, p=0.002) and short stature (decrement of 0.09, 95% CI 0.01 to 0.16, p=0.02). CONCLUSIONS: The overall QoL and domains such as pain and emotion are substantially worse in children on dialysis compared with earlier stage CKD and those with kidney transplants.


Assuntos
Qualidade de Vida , Insuficiência Renal Crônica/psicologia , Adolescente , Austrália , Estatura , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Renda , Masculino , Nova Zelândia , Diálise Renal/psicologia , Insuficiência Renal Crônica/classificação , Insuficiência Renal Crônica/terapia , Fatores de Risco , Inquéritos e Questionários
9.
Neurol Ther ; 8(1): 45-57, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30506485

RESUMO

Multiple sclerosis is an inflammatory neurodegenerative disease of the central nervous system (CNS) and the most frequent cause of non-traumatic disability in adults in the Western world. Currently, several drugs have been approved for the treatment of multiple sclerosis. While the newer drugs are more effective, they have less favourable safety profiles. Thus, there is a need to identify new targets for effective and safe therapies, particularly in patients with progressive disease for whom no treatments are available. One such target is granulocyte-macrophage colony-stimulating factor (GM-CSF) or its receptor. In this article we review data on the potential role of GM-CSF and GM-CSF inhibition in MS. We discuss the expression and function of GM-CSF and its receptor in the CNS, as well as data from animal studies and clinical trials in MS.

10.
Kidney Int ; 94(4): 809-817, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30173897

RESUMO

Better prognostication of graft and patient outcomes among kidney transplant recipients with post-transplant lymphoproliferative disease (PTLD) in the rituximab era is needed to inform treatment decisions. Therefore, we sought to estimate the excess risks of death and graft loss in kidney transplant recipients with PTLD, and to determine risk factors for death. Using the ANZDATA registry, the risks of mortality and graft loss among recipients with and without PTLD were estimated using survival analysis. A group of 367 patients with PTLD (69% male, 85% white, mean age 43 years) were matched 1 to 4 to 1468 controls (69% male, 88% white, mean age 43 years), and followed for a mean of 16 years. Recipients with PTLD experienced poorer 10-year patient survival (41%, 95% confidence intervals 36-47%) than controls (65%, 63-68%). Excess mortality occurred in the first 2 years post-transplant (hazard ratio 8.5, 6.7-11), but not thereafter (1.0, 0.76-1.3). Cerebral lymphoma (2.0, 1.3-3.1), bone marrow disease (2.0, 1.2-3.3) and year of diagnosis prior to 2000 (2.2, 1.4-3.5; after 2000 reference) were risk factors of death. PTLD did not confer an excess risk of graft loss (1.08, 0.69-1.70). Thus, PTLD is a risk factor for death, particularly in the first two years after diagnosis. Cerebral or bone marrow diseases were associated with increased mortality risk, but overall survival in the rituximab era (post 2000) has improved.


Assuntos
Doenças da Medula Óssea/mortalidade , Neoplasias Encefálicas/mortalidade , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/mortalidade , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Linfoma/mortalidade , Masculino , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
11.
Pediatr Transplant ; 22(7): e13265, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29992708

RESUMO

BACKGROUND: Understanding the relationship between the factors that influence long-term kidney transplant survival remains a key priority for pediatric nephrologists. We assessed the relative impact of donor/recipient age difference and HLA matching on long-term graft outcomes. METHODS: We conducted a retrospective cohort study of pediatric and adolescent recipients who received a primary kidney transplant in Australia and New Zealand between January 1, 1990, and December 31, 2015. The primary outcome was graft survival analyzed by Kaplan-Meier method. RESULTS: During the 26-year period, 1134 primary (395 DD and 739 LD) kidney transplants were performed in recipients less than 20 years of age. The median follow-up time was 10.2 years. Overall, 405 patients (35.7%) lost their transplant with graft survival 93.8% at 1 year, 82.5% at 5 years, 65.8% at 10 years, and 49.9% at 15 years post-transplant. There was consistently higher graft loss of DD kidneys as compared to LD kidneys at each time point. Both increasing donor/recipient age difference (aHR 1.11 per 10 years; 95% CI, 1.02-1.20; P = 0.009) and increasing HLA mismatch (aHR 1.20 per mismatch; 95% CI, 1.10-1.30; P < 0.001) were associated with decreased graft survival. CONCLUSIONS: Donor/recipient age difference and HLA matching are important factors influencing long-term graft outcomes in pediatric kidney transplantation. HLA mismatch remains a strong predictor of graft loss. For patients without the option of a LD, we suggest that the degree of HLA mismatch should not be discounted as part of the decision-making process of organ allocation.


Assuntos
Sobrevivência de Enxerto , Transplante de Rim/métodos , Adolescente , Fatores Etários , Criança , Pré-Escolar , Função Retardada do Enxerto/etiologia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
13.
Pediatr Transplant ; 22(5): e13185, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29676031

RESUMO

Disease recurrence affects around a third of renal transplants for children with FSGS and is associated with poor graft outcomes. Unfortunately, there are no large trials guiding treatment for recurrent FSGS. We aimed to describe current therapies and treatment response for recurrent FSGS in 4 centres in Australia and New Zealand. Data were collected on children (age <18 years) with recurrent FSGS (1990-2015). We reviewed patient charts to obtain clinical information. Ethics approval was obtained from the relevant boards. Complete records were available on 24 patients (62% female, 54% Caucasian). Median time to first recurrence was 4 days (IQR 2-5 days). There were 14 separate treatment regimens, involving an average of 2 agents. The most common therapies were plasma exchange (20/24 patients, 83%), cyclosporin (15/24, 63%), and methylprednisolone (9/24, 38%). Full remission was achieved in 15 (63%), partial remission in 2 (8%), and no remission in 7 (29%) patients. Of the patients with no remission, 5 lost their graft to recurrent disease and 1 to concurrent acute vascular rejection. The plethora of different treatment regimens reflects the poor evidence guiding management for recurrent FSGS. More research is needed to improve outcomes.


Assuntos
Ciclosporina/uso terapêutico , Glomerulosclerose Segmentar e Focal/terapia , Imunossupressores/uso terapêutico , Transplante de Rim , Metilprednisolona/uso terapêutico , Troca Plasmática , Adolescente , Austrália , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Nova Zelândia , Recidiva , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento
14.
Nephrol Dial Transplant ; 33(5): 881-889, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29342279

RESUMO

Background: Differences in the epidemiology of post-transplant lymphoproliferative disease (PTLD) between adult and paediatric kidney transplant recipients remain unclear. Methods: Using the Australian and New Zealand Dialysis and Transplant Registry (1963-2015), the cumulative incidences of PTLD in children (age <20 years) and adults were calculated using a competing risk of death model and compared with age-matched population-based data using standardized incidence ratios (SIRs). Risk factors for PTLD were assessed using Cox proportional hazards regression. Results: Among 23 477 patients (92% adult, 60% male), 505 developed PTLD, with 50 (10%) occurring in childhood recipients. The 25-year cumulative incidence of PTLD was 3.3% [95% confidence interval (CI) 2.9-3.6] for adult recipients and 3.6% (95% CI 2.7-4.8) for childhood recipients. Childhood recipients had a 30-fold increased risk of lymphoma compared with the age-matched general population [SIR 29.5 (95% CI 21.9-38.8)], higher than adult recipients [SIR 8.4 (95% CI 7.7-9.2)]. Epstein-Barr virus (EBV)-negative recipient serology [adjusted hazard ratio (aHR) 3.33 (95% CI 2.21-5.01), P < 0.001], year of transplantation [aHR 0.93 for each year after the year 2000 (95% CI 0.88-0.99), P = 0.02], induction with an agent other than anti-CD25 monoclonal antibody [aHR 2.07 (95% CI 1.16-3.70), P = 0.01] and having diabetes [aHR 3.49 (95% CI 2.26-5.38), P < 0.001] were independently associated with PTLD. Conclusions: Lymphoma occurs at similar rates in adult and paediatric recipients, but has been decreasing since the year 2000. EBV-negative patients and those with diabetes or induction agent other than anti-CD25 monoclonal antibody are at substantially increased risk of PTLD.


Assuntos
Transplante de Rim/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Transtornos Linfoproliferativos/epidemiologia , Complicações Pós-Operatórias , Sistema de Registros/estatística & dados numéricos , Adolescente , Adulto , Austrália/epidemiologia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Transtornos Linfoproliferativos/etiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Transplantados , Adulto Jovem
15.
Pediatr Nephrol ; 33(6): 973-983, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-28707039

RESUMO

Advances in the care of children mean that adolescents with chronic kidney disease (CKD) are surviving to adulthood and requiring transition to adult care. The transition phase is well-recognised to be associated with considerable excess morbidity and graft loss, but these outcomes may be avoidable through a structured transition programme. This review will discuss the (1) challenges encountered by patients with CKD, caregivers and clinicians during transition; (2) predictors and outcomes of transition; (3) current guidelines on transition from paediatric to adult renal services; (4) interventions and research directions that may help to improve the care and outcomes for young people with CKD in transition. In spite of the substantial improvement in health gains required for this disadvantaged population, there is to date only limited evidence on the effects of current transition programmes.


Assuntos
Insuficiência Renal Crônica/terapia , Transição para Assistência do Adulto , Adolescente , Adulto , Criança , Humanos , Transplante de Rim/métodos , Guias de Prática Clínica como Assunto
16.
Phys Occup Ther Pediatr ; 37(2): 155-169, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27282190

RESUMO

BACKGROUND: Handwriting speed is an important component of students' ability to adequately express their ideas, knowledge and creativity in a timely and effective manner. AIMS: Psychometric properties of the Handwriting Speed Test (HST) and Detailed Assessment of Speed of Handwriting (DASH) and accuracy of the norms for identifying current Australian students with handwriting speed difficulties were examined. METHODS: An exploratory, cross-sectional study was conducted involving students, with and without handwriting difficulties, in Years 3-12 (mean age: 12.0 yrs, SD = 3.0 yrs; range = 7 to 18 yrs) in New South Wales (NSW; Australia). Participants were recruited through occupational therapists and schools. Students completed the HST and all DASH subtests. RESULTS: Thirty-two students with, and 139 students without, handwriting difficulties participated. Intra-rater and inter-rater reliability were found to be excellent; sensitivity was low and specificity high for the HST and DASH. No significant differences were found between test scores and normative data for students without handwriting difficulties (year/age groups with n > 10). CONCLUSIONS: The HST and DASH are reliable assessments of handwriting speed. Further research is required into discriminant validity of the HST and DASH and need for updated norms.


Assuntos
Escrita Manual , Destreza Motora , Análise e Desempenho de Tarefas , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Psicometria , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fatores de Tempo
17.
Clin J Am Soc Nephrol ; 11(11): 2041-2046, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27797890

RESUMO

BACKGROUND AND OBJECTIVES: FSGS can recur after kidney transplantation and is associated with poor graft outcomes. We aimed to assess the incidence of FSGS recurrence post-transplant and determine the effect of graft source on recurrence and graft survival in patients with biopsy-proven FSGS. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the Australian and New Zealand Dialysis and Transplant Registry, we assessed incidence of FSGS, the influence of donor type on the risk of FSGS recurrence, and graft loss in recipients with ESRD caused by primary FSGS using Kaplan-Meier and logistic regression analyses. RESULTS: Between 1992 and 2011, 736 first kidney transplants were performed in 666 adults and 70 children (≤20 years old) with biopsy-proven primary FSGS. FSGS recurred in 76 (10.3%) patients. Younger age (P<0.001), nonwhite ethnicity (P=0.02), and having a live donor (P=0.02) were independent risk factors associated with recurrence. Median graft survival was significantly better for live donor compared with deceased donor grafts (14.8 versus 12.1 years; P<0.01). Disease recurrence predicted poor graft outcomes, with 52% (95% confidence interval, 40% to 63%) 5-year graft survival in the recurrence group compared with 83% (95% confidence interval, 79% to 86%) in the group without recurrent disease (P<0.001). CONCLUSIONS: FSGS recurrence after kidney transplantation was more common in live donor kidneys. Despite this, graft survival in live donor recipients was significantly better for both children and adults with FSGS. We propose that live donor transplantation should not be avoided in patients with FSGS.


Assuntos
Glomerulosclerose Segmentar e Focal/complicações , Sobrevivência de Enxerto , Falência Renal Crônica/cirurgia , Transplante de Rim , Adolescente , Adulto , Fatores Etários , Austrália , Criança , Grupos Étnicos/estatística & dados numéricos , Feminino , Glomerulosclerose Segmentar e Focal/etnologia , Humanos , Falência Renal Crônica/etiologia , Doadores Vivos/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Recidiva , Sistema de Registros , Fatores de Tempo , Adulto Jovem
18.
Pediatr Nephrol ; 31(6): 1011-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26692022

RESUMO

BACKGROUND: Low socioeconomic status (SES) and geographic disparity have been associated with worse outcomes and poorer access to pre-emptive transplantation in the adult end-stage kidney disease (ESKD) population, but little is known about their impact in children with ESKD. The aim of our study was to determine whether access to pre-emptive transplantation and transplant outcomes differ according to SES and geographic remoteness in Australia. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry (1993-2012), we compared access to pre-emptive transplantation, the risk of acute rejection and graft failure, based on SES and geographic remoteness among Australian children with ESKD (≤ 18 years), using adjusted logistic and Cox proportional hazard modelling. RESULTS: Of the 768 children who commenced renal replacement therapy, 389 (50.5%) received living donor kidney transplants and 28.5% of these (111/389) were pre-emptive. There was no significant association between SES quintiles and access to pre-emptive transplantation, acute rejection or allograft failure. Children residing in regional or remote areas were 35% less likely to receive a pre-emptive transplant compared to those living in major cities [adjusted odds ratio (OR) 0.65, 95% confidence interval (CI) 0.45-1.0]. There was no significant association between geographic disparity and acute rejection (adjusted OR 1.03, 95% CI 0.68-1.57) or graft loss (adjusted hazard ratio 1.05, 95% CI 0.74-1.41). CONCLUSIONS: In Australia, children from regional or remote regions are much less likely to receive pre-emptive kidney transplantation. Strategies such as improved access to nephrology services through expanding the scope of outreach clinics, and support for regional paediatricians to promote early referral may ameliorate this inequity.


Assuntos
Acesso aos Serviços de Saúde , Disparidades em Assistência à Saúde/economia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Serviços de Saúde Rural , Classe Social , Adolescente , Austrália/epidemiologia , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Lactente , Recém-Nascido , Transplante de Rim/economia , Doadores Vivos , Masculino , Sistema de Registros , Diálise Renal , Fatores de Tempo , Resultado do Tratamento
19.
Artigo em Inglês | MEDLINE | ID: mdl-26167189

RESUMO

Infection is a major cause of morbidity and mortality at all stages of chronic kidney disease (CKD). Multiresistant organisms are becoming increasingly common, particularly in the CKD population. Unfortunately, the rapid evolution of antibiotic resistance has not been mirrored by innovation in new antibiotic agents. Novel treatments are therefore urgently needed. Honey has garnered much interest due to its broad-spectrum antibacterial properties based on extensive experimental data. Unlike conventional antibiotics, honey has an added advantage as it appears to avoid inducing antimicrobial resistance in bacteria. This review discusses the potential mechanisms of action and role of honey in infection management in the general population, epidemiology and special challenges of infections in CKD populations, and the clinical trial evidence pertaining to the safety and efficacy of honey for the prevention and treatment of infections in CKD population.

20.
Behav Neurosci ; 129(4): 491-501, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26214215

RESUMO

We investigated the role of the septo-hippocampal cholinergic projection in anxiety, spatial novelty preference, and differential reward for low rates of responding (DRL) performance. Cholinergic neurons of the rat medial septum (MS) and the vertical limb of the diagonal band of Broca (VDB) were lesioned using the selective immunotoxin, 192 IgG-saporin. Rats were then tested on several behavioral tests previously shown to be sensitive to either (a) hippocampal lesions or (b) nonselective MS/VDB lesions which target both cholinergic and γ-aminobutyric acid (GABA)-ergic projections, or both. Saporin lesions substantially reduced hippocampal cholinergic innervation, resulting in an absence of acetyl cholinesterase staining and markedly reduced choline acetyltransferase activity (mean reduction: 80 ± 5%; range: 50-97%). However, the saporin-lesioned rats did not differ from control rats in any of the behavioral tests. Thus we found no evidence from these lesion studies that the septo-hippocampal cholinergic projection plays an essential role in anxiety, spatial novelty preference, or DRL.


Assuntos
Acetilcolina/fisiologia , Ansiedade/fisiopatologia , Feixe Diagonal de Broca/fisiologia , Comportamento Exploratório/fisiologia , Hipocampo/fisiologia , Recompensa , Núcleos Septais/fisiologia , Acetilcolina/metabolismo , Acetilcolinesterase/metabolismo , Animais , Colina O-Acetiltransferase/metabolismo , Neurônios Colinérgicos/efeitos dos fármacos , Neurônios Colinérgicos/fisiologia , Feixe Diagonal de Broca/citologia , Feixe Diagonal de Broca/efeitos dos fármacos , Hipocampo/química , Hipocampo/enzimologia , Masculino , Atividade Motora , Vias Neurais/fisiologia , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Proteínas Inativadoras de Ribossomos Tipo 1/farmacologia , Saporinas , Núcleos Septais/citologia , Núcleos Septais/efeitos dos fármacos
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