Lessons learned from housing first, rapid rehousing trials with youth experiencing homelessness.

BACKGROUND: Youth, 18 to 24 years, experiencing homelessness (YEH) are recognized as having developmental challenges dissimilar to older adults. Yet, research on efforts to end homelessness and prevent or intervene in drug use and mental health problems among youth have lagged behind that of adults. The Housing First (HF) Model which underlies Permanent Supportive Housing (PSH) and Rapid Re-Housing (RRH) has become preferred over treatment-first models. METHODS AND RESULTS: We provide an overview of PSH and RRH studies to date and summarize our current understanding of their utility for use with YEH. Finally, we review our team's current and past randomized trials testing RRH with YEH, providing lessons learned and recommendations. CONCLUSION: Current research efforts to guide best practices are hampered by a lack of fidelity to HF principles, lack of randomized design, and lack of focus on youth. Lessons learned and recommendations from our work are offered to facilitate the future work of those who seek to end homelessness and address drug use and mental health problems among youth.

Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland.

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange-treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody-targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody-mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.

Corticosteroid-free Kidney Transplantation Improves Growth: 2-Year Follow-up of the TWIST Randomized Controlled Trial.

BACKGROUND: Corticosteroid withdrawal (CW) after pediatric kidney transplantation potentially improves growth while avoiding metabolic and other adverse events. We have recently reported the results of a 196 subject randomized controlled trial comparing early CW (tacrolimus, mycophenolate mofetil (MMF), daclizumab, and corticosteroids until day 4) with tacrolimus, MMF, and corticosteroid continuation (CC). At 6 months, CW subjects showed better growth with no adverse impact on acute rejection or graft survival (Am J Transplant 2010; 10: 828-836). This 2-year investigator-driven follow-up study aimed to determine whether improved growth persisted in the longer term. METHODS: Data regarding growth, graft outcomes and adverse events were collected at 1 year (113 patients) and 2 years (106 patients) after transplantation. The primary endpoint, longitudinal growth calculated as delta height standard deviation score, was analyzed using a mixed model repeated measures model. RESULTS: Corticosteroid withdrawal subjects grew better at 1 year (difference in adjusted mean change, 0.25; 95% confidence interval, 0.10, 0.40; P = 0.001). At 2 years, growth remained numerically better in CW subjects (0.20 (-0.01, 0.41); P = 0.06), and significantly better in prepubertal subjects (0.50 (0.16, 0.84); P = 0.004). Bacterial and viral infection was significantly more common in CW subjects at 1 year only. Corticosteroid withdrawal and CC subjects received similar exposure to both tacrolimus and MMF at 1 and 2 years. No significant difference in patient or graft survival, rejection, estimated glomerular filtration rate, or other adverse events was detected. CONCLUSION: Early CW effectively and safely improves growth up to 2 years after transplantation, particularly in prepubertal children.

Comparison of Kt/V and urea reduction ratio in measuring dialysis adequacy in paediatric haemodialysis in England.

BACKGROUND: The National Kidney Foundation-Dialysis Outcomes Quality Initiative (KDOQI) guidelines and the Renal Association recommend the use of either Kt/V or urea reduction ratio (URR) to measure haemodialysis adequacy. OBJECTIVES: To determine the methods used to measure paediatric haemodialysis adequacy and to assess consistency between calculations of single pool Kt/V (spKt/V) and URR. DESIGN: A service evaluation was conducted to establish current practices in measuring dialysis adequacy. A prospective longitudinal study was conducted to compare spKt/V and URR. PARTICIPANTS: Thirty-two children were recruited consisting of 13 males and 19 females in five paediatric dialysis centres. RESULTS: Inconsistencies were reported of the method of post-urea sampling with 4 of the 10 centres using the KDOQI recommended sampling method. Five dialysis centres reported using URR and five reported using spKt/V. There were substantial differences between the two measures. Using URR suggested that up to 44% of children did not receive adequate dialysis, whereas measurement by spKt/V suggested no more than 6% of the same dialysis sessions were not adequate. CONCLUSION: One standard measure should be used to assess dialysis adequacy in paediatric centres in England. KDOQI guidelines were not consistently followed in obtaining a post-urea blood sample and this procedure should be standardised.

Stridor in an 11-year-old child.

Stridor in older children can be due to diverse aetiology that includes infections, anaphylaxis and rarely systemic conditions leading to hypocalcaemia. We report the case of a previously asymptomatic 11-year-old girl who presented to the casualty with stridor due to hypocalcaemia. The aetiological investigations for hypocalcaemia uncovered previously undetected chronic renal failure, possibly due to a rare autosomal recessive condition called nephronophthisis. We report this case to highlight the importance of widening the diagnostic focus for children presenting with stridor, especially when they fall outside the usual age group for infections like croup, or when the history is atypical.

Bilateral progressive cystic nephroma in a 9-month-old male infant requiring renal replacement therapy.

We report the case of a 3-year-old boy who presented at 9 months of age with abdominal distension and was found to have a triad of bilateral cystic nephroma, pleuropulmonary blastoma (PPB) and juvenile intestinal polyps. There have been three previous reported cases of patients with the same associated diagnoses. Our patient is the first reported patient with PPB who received renal replacement therapy and progressed to successful renal transplantation. The potential increased risk of progression of malignancy of PPB (type 1) with immunosuppression following transplantation remains unknown.

Multicentre prospective randomised trial of tacrolimus, azathioprine and prednisolone with or without basiliximab: two-year follow-up data.

A total of 192 children and adolescents undergoing renal transplantation were randomly chosen to receive tacrolimus, azathioprine and corticosteroids (TAS, n = 93) or tacrolimus, azathioprine, corticosteroids and two doses of basiliximab (TAS + B, n = 99). Six-month outcome data have previously been reported; this manuscript reports the 2-year data. Complete 2-year data were available on 164 (85.4%) of the original 192 patients. There was a single death in the TAS arm. Kaplan-Meier estimates of survival free of graft loss at 2 years were 94.9% in the TAS + B arm and 89.6% in the TAS arm [hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.17 to 1.54, P = 0.23]. Estimates of survival free from rejection at 2 years were 75.2% in the TAS + B arm and 68.7% in the TAS arm (HR 0.81; 95% CI 0.46 to 1.40, P = 0.44). The mean estimated glomerular filtration rate (GFR) at 2 years, was 65.8 ml/min per 1.73 m(2) body surface area in the TAS arm and 66.7 ml/min per 1.73 m(2) in the TAS + B arm (P = 0.78). Blood pressure and cholesterol levels were similar in the two arms, and there was no evidence of a difference in the incidence of infection or malignancy. These data provide further evidence of a lack of benefit associated with the addition of basiliximab to a TAS regimen for European paediatric renal transplant recipients at low immunological risk.

Vascular access survival in children and young adults receiving long-term hemodialysis.

BACKGROUND: The delivery of long-term hemodialysis therapy in children is complicated by smaller vascular caliber and the potential lifelong requirement for hemodialysis access. Various factors have resulted in the increased use of cuffed central venous catheters (CVLs) in preference to autologous arteriovenous fistulae (AVFs) and arteriovenous synthetic grafts (AVGs). The aim of this study is to compare CVL, AVF, and AVG survival and determine factors affecting their survival. METHODS: A 20-year retrospective study was undertaken of pediatric patients receiving long-term hemodialysis therapy. Age, height, weight, body mass index, and sex were noted at each procedure, in addition to the presence of hypoalbuminemia, underlying diagnosis, type and site of vascular access, and effect of previous access surgery. The grade of operator also was noted. RESULTS: Three hundred four vascular access procedures were performed on 114 patients, with a median age at initial access formation of 12.0 years (range, 4 weeks to 21.9 years). The most common procedure was CVL insertion (182 procedures) and then AVF formation (107 procedures), with only 15 AVGs created. Median censored survival was 3.14 years (95% confidence interval, 1.22 to 5.06) for AVFs and 0.6 years (95% confidence interval, 0.20 to 1.00) for CVLs. Factors adversely affecting vascular access survival were younger age, trainee operator, presence of hypoalbuminemia, and type of access undertaken, with AVF better than CVL. CONCLUSION: This study shows increased survival of AVFs over CVLs and AVGs. Vascular access in children and adolescents may impact on future dialysis accessibility and should be undertaken by those most experienced in each technique.