Siah Kim

Diagnosis, Monitoring, and Treatment of Systemic Lupus Erythematosus: A Systematic Review of Clinical Practice Guidelines

Management of systemic lupus erythematosus (SLE) is complex and variability in practices exists. Guidelines have been developed to help improve the management of SLE patients, but there has been no formal evaluation of these guidelines. This study aims to compare the scope, quality, and consistency of clinical practice guidelines on the diagnosis, monitoring, and treatment of patients with SLE.

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.

Steroid-sensitive nephrotic syndrome: An evidence-based update of immunosuppressive treatment in children

Nephrotic syndrome is one of the most common paediatric glomerular diseases, with an incidence of around two per 100 000 children per year. Corticosteroids are the mainstay of treatment, with 85%–90% of children going into remission with an 8-week course of treatment. Unfortunately, nephrotic syndrome follows a relapsing and remitting course in the majority, with 90% relapsing at least once. About half will progress to frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Different initial steroid regimens have been evaluated since the first trials in Europe and America in the 1960s. Most trials have been designed to evaluate the optimal duration of the initial therapy, rather than different cumulative doses of corticosteroid, or the management of relapses. Until recently, these data suggested that an initial treatment duration of up to 6 months reduced the number of children developing a relapse, without evidence of increased steroid toxicity. Recently, three large, well-designed randomised control trials were published, which demonstrated no significant reduction in risk of relapse or of developing FRNS by extended treatment compared with 2 or 3 months. While there are few trial data to guide the treatment of individual relapses in steroid-sensitive nephrotic syndrome (SSNS), there is some evidence that a short course of corticosteroid therapy during upper respiratory tract infection may prevent relapse. In patients with FRNS or SDNS who continue to relapse despite low-dose alternate-day steroids a number of non-corticosteroid, steroid-sparing immunosuppressive agents (cyclophosphamide, ciclosporin, tacrolimus, mycophenolate mofetil, levamisole, rituximab) have been shown to reduce the risk of relapse and of FRNS. However, there are limited head-to-head data to inform which agent should be preferred. In this article, we review recent data from randomised trials to update paediatricians on the current evidence supporting interventions in SSNS.

Toward Establishing Core Outcome Domains For Trials in Kidney Transplantation: Report of the Standardized Outcomes in Nephrology-Kidney Transplantation Consensus Workshops

Background Treatment decisions in kidney transplantation requires patients and clinicians to weigh the benefits and harms of a broad range of medical and surgical interventions, but the heterogeneity and lack of patient-relevant outcomes across trials in transplantation makes these trade-offs uncertain, thus, the need for a core outcome set that reflects stakeholder priorities. Methods We convened 2 international Standardized Outcomes in Nephrology-Kidney Transplantation stakeholder consensus workshops in Boston (17 patients/caregivers; 52 health professionals) and Hong Kong (10 patients/caregivers; 45 health professionals). In facilitated breakout groups, participants discussed the development and implementation of core outcome domains for trials in kidney transplantation. Results Seven themes were identified. Reinforcing the paramount importance of graft outcomes encompassed the prevailing dread of dialysis, distilling the meaning of graft function, and acknowledging the terrifying and ambiguous terminology of rejection. Reflecting critical trade-offs between graft health and medical comorbidities was fundamental. Contextualizing mortality explained discrepancies in the prioritization of death among stakeholders—inevitability of death (patients), preventing premature death (clinicians), and ensuring safety (regulators). Imperative to capture patient-reported outcomes was driven by making explicit patient priorities, fulfilling regulatory requirements, and addressing life participation. Specificity to transplant; feasibility and pragmatism (long-term impacts and responsiveness to interventions); and recognizing gradients of severity within outcome domains were raised as considerations. Conclusions Stakeholders support the inclusion of graft health, mortality, cardiovascular disease, infection, cancer, and patient-reported outcomes (ie, life participation) in a core outcomes set. Addressing ambiguous terminology and feasibility is needed in establishing these core outcome domains for trials in kidney transplantation.

The long-term outcomes of atypical haemolytic uraemic syndrome: a national surveillance study

Background Atypical haemolytic uraemic syndrome (aHUS) accounts for ∼10% of all cases of HUS and is often due to complement dysregulation. The short-term outcomes for this disease are established, but there are limited long-term data. The long-term outcomes of a comprehensive nationwide cohort of children with aHUS are presented here. Methods The Australian Paediatric Surveillance Unit prospectively collected data on all cases of HUS in children seen by paediatricians between 1994 and 2001. Patients with aHUS were followed-up with a written questionnaire to the treating clinician at 1 year and again before transition to adult services or at last known follow-up. Results There were 146 reported cases of HUS, of which 14 were aHUS. Ten children required dialysis at first presentation, including two who died and three who did not recover renal function. The disease was relapsing in all but one who survived the presenting episode, with most relapses occurring in the first 12 months. At 1 year, one child was lost to follow-up. Nine of the remaining 11 patients were dialysis dependent. Thirteen kidneys were transplanted into eight children. There was disease recurrence in eight kidneys, which resulted in graft loss in seven. There were three further deaths 1.7, 6.7 and 16.1 years after the initial presentation. Five children developed neurological complications and two had cardiac complications, largely at the time of onset of the disease. Conclusions aHUS is a rare but devastating disease with very high mortality and morbidity that extends beyond the initial presentation period.

Current trends in immunosuppression following organ transplantation in children.

Purpose of reviewTo highlight the current trends in immunosuppression and their application to paediatric transplantation informed by the systematic reviews and randomized controlled trials: new induction agents, steroid avoidance, calcineurin minimization and desensitization protocols. Recent findingsNewer induction agents, belatacept and alemtuzumab, are associated with serious side-effects, and interleukin-2 receptor antagonists remain the preferred agents in children. Steroid-free regimens may improve growth and, compared with steroid-containing regimens, have similar short to medium term graft survival, although long-term outcomes are uncertain. Mammalian target of rapamycin inhibitors, sirolimus and everolimus, when used in recipients as primary immunosuppression to avoid calcineurin exposure, results in poorer graft survival. Although desensitization is being performed more frequently, the relative benefits and harms of regimens used are uncertain. SummaryThere is growing evidence for the use of steroid-free immunosuppression regimens in children to maximize growth. Further trials with a focus on long-term graft survival are needed to establish the role of desensitization protocols in organ transplantation in children.

Obesity and hypertension in Australian young people: Results from the Australian Health Survey 2011 to 2012

Few studies have focused on the prevalence of obesity and hypertension among young people (ages 15–24).

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.