Madeleine Didsbury

Exercise Training in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis

Background Exercise training is effective in improving the cardiovascular risk profiles of nontransplanted patients, but the health benefits and potential harms of routine exercise training after solid organ transplantation are unclear. This study aims to assess the health benefits and harms of supervised exercise training programs in solid organ recipients. Methods We systematically reviewed all randomized controlled trials (RCTs) comparing the outcomes of exercise training programs in solid organ recipients against standard care. MEDLINE, EMBASE, the Transplant Library from the Centre for Evidence in Transplantation, and the Cochrane Central Register of Controlled Trials were searched to June 2012. Results In total, 15 eligible RCTs involving 643 patients (9 cardiac transplants [n=250 patients], 2 kidney transplants [n=164 patients], 3 lung transplants [n=110 patients], and 1 liver transplant [n=119 patients]) were included. Cardiac transplant recipients who engaged in an exercise program after transplantation showed significant improvement in maximal oxygen uptake (standardized mean difference, 0.77; 95% confidence interval, 0.10–1.45) but no improvement in the overall serum lipid profile, blood pressure, and glycemic control compared with standard care. Among other solid organ transplant recipients, no significant improvements in exercise capacity or cardiovascular risk factors such as incidence of new-onset diabetes after transplantation were observed, but all effect estimates were very imprecise. Conclusions Exercise training is a promising but unproven intervention for improving the cardiovascular outcomes of solid organ transplant recipients. Existing trials are small, of relatively short duration, and focused on surrogate outcomes. Large-scale RCTs are urgently required if resources are to be directed toward exercise programs.

Socio‐economic status and quality of life in children with chronic disease: A systematic review

Reduced quality of life (QoL) is a known consequence of chronic disease in children, and this association may be more evident in those who are socio‐economically disadvantaged. The aims of this systematic review were to assess the association between socio‐economic disadvantage and QoL among children with chronic disease, and to identify the specific socio‐economic factors that are most influential. MEDLINE, Embase and PsycINFO were searched to March 2015. Observational studies that reported the association between at least one measure of social disadvantage in caregivers and at least one QoL measure in children and young people (age 2–21 years) with a debilitating non‐communicable childhood disease (asthma, chronic kidney disease, type 1 diabetes mellitus and epilepsy) were eligible. A total of 30 studies involving 6957 patients were included (asthma (six studies, n = 576), chronic kidney disease (four studies, n = 796), epilepsy (14 studies, n = 2121), type 1 diabetes mellitus (six studies, n = 3464)). A total of 22 (73%) studies reported a statistically significant association between at least one socio‐economic determinant and QoL. Parental education, occupation, marital status, income and health insurance coverage were associated with reduced QoL in children with chronic disease. The quality of the included studies varied widely and there was a high risk of reporting bias. Children with chronic disease from lower socio‐economic backgrounds experience reduced QoL compared with their wealthier counterparts. Initiatives to improve access to and usage of medical and psychological services by children and their families who are socio‐economically disadvantaged may help to mitigate the disparities and improve outcomes in children with chronic illnesses.

A systematic review of acute kidney injury in pediatric allogeneic hematopoietic stem cell recipients

The process of allogeneic HSCT in children is associated with frequent AKI and mortality, but the epidemiology is not widely reported. The aim of this review was to summarize the available evidence on incidence, risk factors, timing, and prognosis of AKI in children following HSCT. We systematically reviewed all observational studies reporting incidence and outcomes of AKI in pediatric allogenic HSCT recipients. The minimum criteria for AKI were defined as an increase in sCr ≥ x1.5 or urine output ≤0.5 mL/kg/min over six h. Medline and Embase were searched until March 2014. From 993 electronic records, five were eligible for inclusion (n = 571 patients). The average incidence of AKI within the first 100 days following HSCT was 21.7% (range 11–42%), and the average time of onset was 4–6 wk post‐transplant. Risk factors for AKI included cyclosporine toxicity, amphotericin B and foscarnet, SOS, and having a mismatched donor. There were conflicting reports on whether AKI was associated with the development of CKD. AKI is a common and potentially life‐threatening complication following HSCT in children. Further quality observational studies are needed to accurately determine the epidemiology and prognosis of AKI in this population.

Treatment of recurrent focal segmental glomerulosclerosis post-kidney transplantation in Australian and New Zealand children: A retrospective cohort study

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.

Neurocognitive and Educational Outcomes in Children and Adolescents with CKD A Systematic Review and Meta-Analysis

BACKGROUND AND OBJECTIVES Poor cognition can affect educational attainment, but the extent of neurocognitive impairment in children with CKD is not well understood. This systematic review assessed global and domain-specific cognition and academic skills in children with CKD and whether these outcomes varied with CKD stage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Electronic databases were searched for observational studies of children with CKD ages 21 years old or younger that assessed neurocognitive or educational outcomes. Risk of bias was assessed using a modified Newcastle-Ottawa scale. We used random effects models and expressed the estimates as mean differences with 95% confidence intervals stratified by CKD stage. RESULTS Thirty-four studies (25 cross-sectional, n=2095; nine cohort, n=991) were included. The overall risk of bias was high because of selection and measurement biases. The global cognition (full-scale intelligence quotient) of children with CKD was classified as low average. Compared with the general population, the mean differences (95% confidence intervals) in full-scale intelligence quotient were -10.5 (95% confidence interval, -13.2 to -7.72; all CKD stages, n=758), -9.39 (95% confidence interval, -12.6 to -6.18; mild to moderate stage CKD, n=582), -16.2 (95% confidence interval, -33.2 to 0.86; dialysis, n=23), and -11.2 (95% confidence interval, -17.8 to -4.50; transplant, n=153). Direct comparisons showed that children with mild to moderate stage CKD and kidney transplants scored 11.2 (95% confidence interval, 2.98 to 19.4) and 10.1 (95% confidence interval, -1.81 to 22.0) full-scale intelligence quotient points higher than children on dialysis. Children with CKD also had lower scores than the general population in executive function and memory (verbal and visual) domains. Compared with children without CKD, the mean differences in academic skills (n=518) ranged from -15.7 to -1.22 for mathematics, from -9.04 to -0.17 for reading, and from -14.2 to 2.53 for spelling. CONCLUSIONS Children with CKD may have low-average cognition compared with the general population, with mild deficits observed across academic skills, executive function, and visual and verbal memory. Limited evidence suggests that children on dialysis may be at greatest risk compared with children with mild to moderate stage CKD and transplant recipients.

Quality of life of children and adolescents with chronic kidney disease: a cross-sectional study

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.