Current Transition Practice for Primary Immunodeficiencies and Autoinflammatory Diseases in Europe: a RITA-ERN Survey.

BACKGROUND: Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. Effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term outcomes. It is currently not known what transition services are available for young people with IEI in Europe. OBJECTIVE: To understand the prevalence and practice of transition services in Europe for young people with IEI, encompassing both primary immunodeficiencies (PID) and systemic autoinflammatory disorders (AID). METHODS: A survey was generated by the European Reference Network on immunodeficiency, autoinflammatory, and autoimmune diseases Transition Working Group and electronically circulated, through professional networks, to pediatric centers across Europe looking after children with IEI. RESULTS: Seventy-six responses were received from 52 centers, in 45 cities across 17 different countries. All services transitioned patients to adult services, mainly to specialist PID or AID centers, typically transferring up to ten patients to adult care each year. The transition process started at a median age of 16-18 years with transfer to the adult center occurring at a median age of 18-20 years. 75% of PID and 68% of AID centers held at least one joint appointment with pediatric and adult services prior to the transfer of care. Approximately 75% of PID and AID services reported having a defined transition process, but few centers reported national disease-specific transition guidelines to refer to. CONCLUSIONS: Transition services for children with IEI in Europe are available in many countries but lack standardized guidelines to promote best practice.

Quality of Life and Social and Psychological Outcomes in Adulthood Following Allogeneic HSCT in Childhood for Inborn Errors of Immunity.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) is well established as a corrective treatment for many inborn errors of immunity (IEIs) presenting in childhood. Due to improved techniques, more transplants are undertaken and patients are living longer. However, long-term complications can significantly affect future health and quality of life. Previous research has focused on short-term medical outcomes and little is known about health or psychosocial outcomes in adulthood. OBJECTIVE: This project aimed to ascertain the long-term social and psychological outcomes for adults who underwent HSCT for IEI during childhood. METHODS: Adult patients, who had all undergone HSCT for IEI during childhood at two specialist immunology services at least 5 years previously, were invited to participate in the study. Questionnaires and practical tasks assessed their current functioning and circumstances. Information was also gathered from medical notes. Data was compared with population norms and a control group of participant-nominated siblings or friends. RESULTS: Eighty-three patients and 46 matched controls participated in the study. Patients reported significantly better physical health-related quality of life than the general population norm, but significantly worse than matched controls. Patient's self-reported physical health status and the perceived impact of their physical health on everyday life were worse than matched controls and patients reported higher levels of anxiety and lower mood than the general population. For those where their IEI diagnosis was not associated with a learning disability, cognitive function was generally within the normal range. CONCLUSIONS: Patients who have had a HSCT in childhood report mixed psychosocial outcomes in adulthood. More research is needed to establish screening protocols and targeted interventions to maximize holistic outcomes. CLINICAL IMPLICATIONS: Screening for holistic needs and common mental health difficulties should be part of routine follow-up. Information should be provided to patients and families in order to support decision-making regarding progression to transplant and the early identification of any difficulties.

Retrospective, Landmark Analysis of Long-term Adult Morbidity Following Allogeneic HSCT for Inborn Errors of Immunity in Infancy and Childhood.

PURPOSE: Allogeneic hematopoietic stem cell transplant (HSCT) remains the treatment of choice for patients with inborn errors of immunity (IEI). There is little published medical outcome data assessing late medical complications following transition to adult care. We sought to document event-free survival (EFS) in transplanted IEI patients reaching adulthood and describe common late-onset medical complications and factors influencing EFS. METHODS: In this landmark analysis, 83 adults surviving 5 years or more following prior HSCT in childhood for IEI were recruited. The primary endpoint was event-free survival, defined as time post-first HSCT to graft failure, graft rejection, chronic infection, life-threatening or recurrent infections, malignancy, significant autoimmune disease, moderate to severe GVHD or major organ dysfunction. All events occurring less than 5 years post-HSCT were excluded. RESULTS: EFS was 51% for the whole cohort at a median of 20 years post HSCT. Multivariable analysis identified age at transplant and whole blood chimerism as independent predictors of long-term EFS. Year of HSCT, donor, conditioning intensity and underlying diagnosis had no significant impact on EFS. 59 events occurring beyond 5 years post-HSCT were documented in 37 patients (45% cohort). A total of 25 patients (30% cohort) experienced ongoing significant complications requiring active medical intervention at last follow-up. CONCLUSION: Although most patients achieved excellent, durable immune reconstitution with infrequent transplant-related complications, very late complications are common and associated with mixed chimerism post-HSCT. Early intervention to correct mixed chimerism may improve long-term outcomes and adult health following HSCT for IEI in childhood.

Governance of community health worker programs in a decentralized health system: a qualitative study in the Philippines.

BACKGROUND: Community health worker (CHW) programs are an important resource in the implementation of universal health coverage (UHC) in many low- and middle-income countries (LMICs). However, in countries with decentralized health systems like the Philippines, the quality and effectiveness of CHW programs may differ across settings due to variations in resource allocation and local politics. In the context of health system decentralization and the push toward UHC in the Philippines, the objective of this study was to explore how the experiences of CHWs across different settings were shaped by the governance and administration of CHW programs. METHODS: We conducted 85 semi-structured interviews with CHWs (n = 74) and CHW administrators (n = 11) in six cities across two provinces (Negros Occidental and Negros Oriental) in the Philippines. Thematic analysis was used to analyze the qualitative data with specific attention to how the experiences of participants differed within and across geographic settings. RESULTS: Health system decentralization contributed to a number of variations across settings including differences in the quality of human resources and the amount of financial resources allocated to CHW programs. In addition, the quality and provider of CHW training differed across settings, with implications for the capacity of CHWs to address specific health needs in their community. Local politics influenced the governance of CHW programs, with CHWs often feeling pressure to align themselves politically with local leaders in order to maintain their employment. CONCLUSIONS: The functioning of CHW programs can be challenged by health system decentralization through the uneven operationalization of national health priorities at the local level. Building capacity within local governments to adequately resource CHWs and CHW programs will enhance the potential of these programs to act as a bridge between the local health needs of communities and the public health system.

Improving number abilities in low achieving preschoolers: Symbolic versus non-symbolic training programs.

BACKGROUND: Although previous correlational studies have shown that both symbolic and non-symbolic abilities relate to mathematical abilities, correlational studies cannot show the cause and effect of these abilities for mathematical success. AIMS: The current study examined the effect of a non-symbolic training program, called PLUS and a symbolic training program, called DIGIT, to provide further insight into the causal nature of domain specific factors that contribute to mathematical abilities. METHODS: and Procedures: Forty-nine preschool children who had low mathematical abilities were recruited and randomly allocated to the DIGIT and PLUS training programs. Performance on a number of mathematical tasks was compared to 20 preschoolers with no mathematical difficulties. OUTCOMES AND RESULTS: Performance in both training programs improved on the Test of Early Mathematical Abilities as well as on a non-symbolic Approximate Number Sense task, counting tasks, and digit recognition tasks, immediately after five weeks of training and this improvement remained six months later. CONCLUSIONS AND IMPLICATIONS: This study provides further evidence that symbolic and non-symbolic abilities bi-directionally impact on each other and that ordinality knowledge is an important factor of mathematical development.

Emotional and behavioral problems in children and adolescents with neurofibromatosis type 1.

To assess emotional and behavioral problems in children and adolescents with neurofibromatosis type 1,parents of 183 individuals aged 10.8 ± 3.1 years (range 6-17) completed the Child Behavior Checklist (CBCL). Also, 173 teachers completed the Teacher's Report Form (TRF), and 88 adolescents (children from 11 to 17 years) completed the Youth Self-Report (YSR). According to parental ratings, 32% scored in the clinical range (above the 90th percentile). This percentage was much lower when rated by teachers or adolescents themselves. Scores from all informants on scales for Somatic complaints, Social problems, and Attention problems were significantly different from normative scores. Attentional problems were associated with lower verbal IQ, male gender, younger age, and ADHD-symptoms. Disease-related factors did not predict behavioral problems scores. Substantial emotional and behavioral problems were reported by parents, teachers, and to a lesser extent by adolescents with NF1 themselves. Possibly, a positive illusory bias affects the observation of behavioral problems by adolescents with NF1.