Effectiveness of Computerized Cognitive Training on Working Memory in Pediatric Cancer Survivors: A Systematic Review and Meta-analysis.

BACKGROUND: Interactive features of computerized cognitive training (CCT) may enhance adherence to training, providing a relatively low-cost intervention. A robust systematic review on the effectiveness of CCT for improving working memory (WM) among pediatric survivors with cancer is lacking. OBJECTIVE: To summarize the available evidence and determine the effectiveness of CCT for WM among pediatric survivors with cancer. INTERVENTIONS/METHODS: Five databases were searched. The Effective Public Health Practice Project was used to assess the study quality. ReviewerManager was used. The primary outcome was WM performance. Secondary outcomes included processing speed, attention, intervention adherence, and number of adverse events. RESULTS: Six studies were included. Regarding overall quality, 1 study was weak, and 5 studies were moderate. Five studies reported a significant improvement of WM postintervention (P < .05). The meta-analysis of Cogmed interventions on symbolic WM revealed a significant difference between groups (vs placebo), with an overall pooled effect size of 0.71 (95% confidence interval, 0.02-1.41; P = .04). Two and 4 studies investigated the effects of CCT on processing speed and attention, respectively, with conflicting results. Four studies reported adherence of 80% or greater. Two studies reported no adverse events. CONCLUSIONS: Computerized cognitive training using Cogmed has a significant positive effect on WM. The effects of CCT on processing speed and attention remain inconclusive. IMPLICATIONS FOR PRACTICE: More rigorous trials should be conducted to elucidate the cognitive effects of CCT, particularly processing speed and attention, in the pediatric population with cancer. Further studies should consider combining CCT with other existing interventions to strengthen their effectiveness.

Association of vitamin D-binding protein polymorphisms and serum 25(OH)D concentration varies among Chinese healthy infants of different VDR-FokI genotypes: A multi-centre cross-sectional study.

Hypovitaminosis D during infancy is associated with the development of chronic diseases and poor health later in life. While the effect of environmental factors on vitamin D concentration has been extensively explored, this study aimed to explore the effect of genetic factors on vitamin D concentration among Chinese infants. We conducted a multi-centre cross-sectional study in Hong Kong from July 2019 to May 2021. A candidate genetic approach was adopted to study four selected genetic variants of the vitamin D-binding protein (DBP) and vitamin D receptor (VDR) (rs4588, rs7041, rs2282679 and rs2228570) to examine their associations with measured serum 25(OH)D concentration. A total of 378 Chinese infants aged 2-12 months were recruited in this study. Peripheral blood samples were collected from the infants to measure serum 25(OH)D concentration and extract DNA. Results showed that rs7041T and rs2282679C were significantly associated with lower serum 25(OH)D concentration. Further analysis of the DBP variants revealed that the GC1F allele was significantly associated with lower 25(OH)D concentration and identified as the risk DBP isoform in infants. While our results revealed that there is no direct association between VDR-FokI genotype and serum 25(OH)D concentration, a VDR-FokI genotype-specific pattern was observed in the association between DBP isoforms and serum 25(OH)D concentration. Specifically, significant associations were observed in the DBP genotypes GC1F/F, GC1F/2 and GC1S/2 among VDR-FokI TT/TC carriers, but not in VDR-FokI CC carriers. Our findings lay down the basis for the potential of genetic screening to identify high risk of hypovitaminosis D in Chinese infants.

Genome-Wide DNA Methylation Profiling as Frontline Diagnostics for Central Nervous System Embryonal Tumors in Hong Kong.

This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research.

Current Challenges of Asian National Children's Cancer Study Groups on Behalf of Asian Pediatric Hematology and Oncology Group.

In Asia, a few countries have a long and established history of collaborative clinical trials successfully formed national children's cancer study groups, but many still do not have such groups. The process of forming national children's cancer groups is fraught with many hurdles, which varies among the countries. One of the basic requirements for running clinical trials is an affordable health care system in which most of the children with cancer can receive the proposed treatment. The health insurance coverage for children with cancer varies from <20% to as high as 100% among Asian countries, and the operation of clinical trials must also be adjusted accordingly. Shortage of research personnel is common, including medical, nursing, research coordinators, and data managers. The establishment of the Asian Pediatric Hematology and Oncology Group aims to provide a good platform for promotion of international clinical trials in the Asian countries.

Significant healthcare burden and life cost of spinal muscular atrophy: real-world data.

OBJECTIVES: The aim of this study is to quantify the mortality rate, direct healthcare costs, and cumulative life costs of pediatric patients with spinal muscular atrophy (SMA) type 1, type 2, and type 3 born in Hong Kong. METHODS: Data were collected from genetically confirmed SMA patients born in or after 2000 from the Hospital Authority medical database. Patients were followed up from birth until they died, left Hong Kong, reached 18 years, or initiated disease-modifying treatment. Study outcomes included incidence risks of mortality, cumulative direct medical costs-attendances of special outpatient clinics, emergency department, allied health services, and mean length of stay in hospitals over time. Total direct medical costs were calculated as unit costs multiplied by utilization frequencies of corresponding healthcare services at each age. RESULTS: Seventy-one patients with SMA were included. Over a median follow-up period of 6 years, the overall incidence rate of death was 5.422/100 person-years (95%CI 3.542-7.945/100 person-years). 67.7% and 11% of deaths occurred in SMA1 and SMA2 groups, respectively. The median age of death was 0.8 years in SMA1 and 10.9 years in SMA2. The mean cumulative direct medical costs in overall SMA, SMA1, SMA2 and SMA3 groups per patient were US$935,570, US$2,393,250, US$413,165, and US$40,735, respectively. INTERPRETATION: Our results confirmed a significantly raised mortality and extremely high healthcare burden for patients with SMA especially SMA type 1 and 2 without disease-modifying treatment. Study evaluating health and economic impact of newborn screening and early treatment is needed.

DICER1 -Altered Extraovarian Moderately Differentiated Sertoli-Leydig Cell Tumor: Report of a Rare Case.

We report an unusual case of a pelvic extraovarian moderately differentiated Sertoli-Leydig cell tumor arising in a 4-yr-old female. The tumor contained a DICER1 pathogenic variant which was absent in the germline ruling out DICER1 syndrome. In reporting this case, we discuss the differential diagnosis and possible histogenesis and review reported cases of extraovarian Sertoli-Leydig cell tumor.

Functional outcomes at PICU discharge in hemato-oncology children at a tertiary oncology center in Hong Kong.

BACKGROUND: Advancements in cancer treatment have resulted in longer survival but often at the expense of new therapy-associated morbidities. The aim of this study is to evaluate functional outcomes of hemato-oncology patients at PICU discharge, and to identify associated risk factors. METHODS: A single-center retrospective observational study. All children (< 19 years) with a hemato-oncology diagnosis admitted to the Hong Kong Children's Hospital PICU over a 2-year period were included. Functional status upon admission and discharge were compared. Univariable and multi-variable analyses were employed to identify risk factors associated with new morbidities. RESULTS: Out of 288 PICU admissions, there were 277 live discharges (mortality 4%), of which 52 (18.8%) developed new morbidities. Emergency admission, severity of illness at admission, organ dysfunction and support were associated with new morbidities (OR 1.08-11.96; p < 0.05). Adjusting for confounding factors, higher Pediatric Logistic Organ Dysfunction 2 score at admission was significantly associated with development of new morbidities (OR 1.34; 95% CI 1.18-1.54; p < 0.001). CONCLUSION: Critically ill children with hemato-oncological diseases had a higher rate of developing new morbidities (18.8%) compared with the general PICU population (4-8%). This was associated with severity of illness at admission. Further work is warranted to understand the lasting effects of these new morbidities and mitigating interventions.

Family Financial Pressure in Childhood and Telomere Length in Early Adolescence: A Prospective Study.

Much research on children in high-risk environments has focused on the biological consequences of maltreatment, adversity, and trauma. Whether other early-life stress sources such as family financial hardship are implicated in the cellular mechanism of disease development remains unclear. This study investigated the long-term effect of childhood exposure to family financial pressure on telomere length. It involved two waves of data collection occurring when participants reached Grade 3 (W1) and 7 (W2), respectively. In W1, parents reported family demographics and perceived financial stressors and pressure. In W2, participants provided buccal swab samples for measurement of their telomere length. Data from 92 participants (Mage in W2 = 13.2 years; 56.5% male) were analyzed. The main type of stressors reported by parents who perceived high family financial pressure in W1 were child-level stressors including affordability of their medical and educational expenses. Participants exposed to high parent-perceived family financial pressure in W1 had shorter telomeres in W2 when compared to those exposed to low parent-perceived family financial pressure (ß = -0.61, p = 0.042). Subgroup analyses revealed stronger associations in girls than boys. These findings reveal an important spillover effect between parental financial perceptions and stress and children's health at the cellular level.

Successful haploidentical hematopoietic stem cell transplantation (HSCT) and durable engraftment by repeated donor lymphocyte infusions for a Chinese patient with transfusion-dependent hemoglobin (Hb) Hammersmith and massive splenomegaly.

BACKGROUND: Hemoglobin (Hb) Hammersmith is a rare form of unstable ß-chain hemoglobinopathy causing hemolytic anemia. This rare event led to a more serious transfusion-dependent phenotype in a patient. It was successfully cured by haploidentical hematopoietic stem cell transplantation (HSCT). METHODS AND RESULTS: A 9-year-old mainland Chinese male with a history of neonatal unconjugated hyperbilirubinemia was diagnosed to have hemoglobin (Hb) Hammersmith. He required regular blood transfusion but was unable to be transfused to desired parameters for 8 years prior to transplant due to social and geographical reasons. He subsequently developed marrow hyperplasia and progressive splenomegaly (down to umbilicus level), suggestive of extramedullary hematopoiesis. Eventually, the family came to Hong Kong and complied to a more intensive transfusion regimen and preconditioning chemotherapy 3 months prior to transplant. He underwent haploidentical HSCT using paternal TCRαß/CD45RA-depleted graft but suffered from graft rejection, despite splenic irradiation for massive splenomegaly. It was successfully salvaged with second HSCT with unmanipulated graft from the same donor with additional serotherapy and donor lymphocyte infusions. CONCLUSION: Allogenic haploidentical HSCT for hemoglobin Hammersmith is feasible but adequate immunosuppression during conditioning is crucial. Precise adoptive cell therapy can promote durable engraftment.

Sleep disruption and its contributing factors in Chinese survivors of childhood cancer: A cross-sectional study.

OBJECTIVES: This study provided information about sleep disruption, particularly its prevalence and severity among Hong Kong Chinese childhood cancer survivors. Additionally, we identified the factors influencing sleep disruption and explored how fatigue, depressive symptoms and physical activity (PA) affect sleep disruption. METHODS: Four hundred two survivors 6-18 years old and 50 age- and gender-matched healthy counterparts were assessed for depressive symptoms, fatigue, PA and subjective sleep quality. Demographic and clinical information were collected. Multiple logistic regression analyses were conducted to identify any factors contributing to poor sleep. RESULTS: Mean scores of depressive symptoms, fatigue for children and that for adolescents, and PA in survivors were 16.1 (SD = 11.1), 24.6 (SD = 10.3), 27.7 (SD = 7.8), and 3.08 (SD = 2.9), respectively. 44.8% of the survivors were poor sleepers, which was more that in healthy counterparts. The three most common sleep problem were prolonged sleep latency (31.9%), daytime dysfunction (23.4%), and sleep disturbance (22.9%). The time since last treatment (children: AOR = 0.54, 95% CI = 0.30-0.96, p = 0.04; adolescents: AOR = 0.80, 95% CI = 0.70-0.92, p < 0.01) and PA levels (children: AOR = 0.46, 95% CI = 0.260-0.82, p = 0.01; adolescents: AOR = 0.70, 95% CI = 0.49-0.98, p = 0.04) were negatively associated with sleep disruption, while depressive symptoms (children: AOR = 1.31, 95% CI = 1.04-1.64, p = 0.02; adolescents: AOR = 1.07, 95% CI = 1.01-1.13, p = 0.03), fatigue (children: AOR = 1.15, 95% CI = 1.00-1.31, p = 0.04; adolescents: AOR = 1.08, 95% CI = 1.02-1.15, p = 0.01), number of treatment received (children: AOR = 16.56, 95% CI = 1.27-216.82, p = 0.03; adolescents: AOR = 7.30, 95% CI = 2.36-22.56, p < 0.01), and co-sleeping (children: AOR = 29.19, 95% CI = 1.65-511.57, p = 0.02; adolescents: AOR = 4.63, 95% CI = 1.22-17.61, p = 0.02) were positively associated with sleep disruption. CONCLUSION: Physical activity made the largest contribution to reduce sleep disruption. It is crucial to advocate for the adoption and maintenance of PA in survivorship.

Mental health & maltreatment risk of children with special educational needs during COVID-19.

BACKGROUND: Children with special educational needs (SEN) are more vulnerable during the COVID-19 pandemic with risk of poor mental wellbeing and child maltreatment. OBJECTIVE: To examine the impact of COVID-19 on the mental health of children with SEN and their maltreatment risk. PARTICIPANTS AND SETTING: 417 children with SEN studying at special schools and 25,427 children with typical development (TD) studying at mainstream schools completed an online survey in April 2020 in Hong Kong during school closures due to COVID-19. METHOD: Emotional/behavioural difficulties, quality of life and parental stress of children with SEN were compared with typically developed children using mixed effect model. Linear regression analyses were performed to explore factors associated with child emotional/behavioural difficulties and parental stress during the pandemic. Chi-square test was performed to detect the differences in maltreatment risk before and during COVID-19. RESULTS: Children with SEN had significantly poorer overall quality of life (68.05 vs 80.65, p < 0.01). 23.5% of children had at least one episode of severe physical assault and 1.9% experienced very severe physical assault during COVID-19. Rates of physical assault increased significantly (59.8% vs. 71.2% p < 0.001) while children with mental disorders had increased risk of severe physical assault comparing to those without mental disorders (RR = 1.58, ꭓ2 = 5.19 p = 0.023). CONCLUSION: Children with SEN had poorer mental health than typically developed children during the COVID-19 pandemic. Maltreatment risk for children with SEN is higher in comparison to pre-COVID-19 era. Surveillance of child maltreatment, continuity of medical and rehabilitation care to support children with SEN are essential during a disease pandemic.

Vulnerability and resilience in children during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is having a profound impact on the health and development of children worldwide. There is limited evidence on the impact of COVID-19 and its related school closures and disease-containment measures on the psychosocial wellbeing of children; little research has been done on the characteristics of vulnerable groups and factors that promote resilience. METHODS: We conducted a large-scale cross-sectional population study of Hong Kong families with children aged 2-12 years. Parents completed an online survey on family demographics, child psychosocial wellbeing, functioning and lifestyle habits, parent-child interactions, and parental stress during school closures due to COVID-19. We used simple and multiple linear regression analyses to explore factors associated with child psychosocial problems and parental stress during the pandemic. RESULTS: The study included 29,202 individual families; of which 12,163 had children aged 2-5 years and 17,029 had children aged 6-12 years. The risk of child psychosocial problems was higher in children with special educational needs, and/or acute or chronic disease, mothers with mental illness, single-parent families, and low-income families. Delayed bedtime and/or inadequate sleep or exercise duration, extended use of electronic devices were associated with significantly higher parental stress and more psychosocial problems among pre-schoolers. CONCLUSIONS: This study identifies vulnerable groups of children and highlights the importance of strengthening family coherence, adequate sleep and exercise, and responsible use of electronic devices in promoting psychosocial wellbeing during the COVID-19 pandemic.

Multilevel Factors Affecting Healthcare Workers' Perceived Stress and Risk of Infection During COVID-19 Pandemic.

Objectives: This study aimed to identify key factors affecting Healthcare workers (HCWs) perceived stress and risk of contracting COVID-19 among themselves and their family members during the pandemic. Methods: A cross-sectional online questionnaire study was conducted between 19 March and April 5, 2020 in Hong Kong. HCWs from public hospitals and private dentists, and their family members participated. Results: A total of 747 HCWs and 245 family members participated. Higher perceived stress in HCWs was associated with more negative changes in family relationship (p = 0.025). The HCWs' perceived stress, however, was positively associated with family cohesion (p = 0.033) and stress levels of family members (p < 0.001). The level of HCWs' satisfaction toward the hospital policies in response to the COVID-19 outbreak was associated with lower levels of perceived stress and risk of themselves or their family members contracting COVID-19. HCWs' previous frontline experience of SARS was significantly associated with less perceived risk of themselves or their family members contracting COVID-19. Conclusion: Hospital policies addressing HCWs' needs, frontline experience of SARS, and family relationship influenced psychological wellbeing of HCWs during the COVID-19 outbreak.

Psychometric properties of the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) among Hong Kong Chinese childhood cancer survivors.

BACKGROUND: Sleep disruption is a prevalent symptom reported by survivors of childhood cancer. However, there is no validated instrument for assessing this symptom in this population group. To bridge the literature gap, this study translated and adapted the Pittsburgh Sleep Quality Index (PSQI) for Hong Kong Chinese cancer survivors and examined its psychometric properties and factor structure. METHODS: A convenience sample of 402 Hong Kong Chinese childhood cancer survivors aged 6-18 years were asked to complete the Chinese version of the PSQI, Center for Epidemiologic Studies Depression Scale for Children (CES-DC), Fatigue Scale-Child (FS-C)/Fatigue Scale-Adolescent (FS-A), and Pediatric Quality of Life Inventory (PedsQL). To assess known-group validity, 50 pediatric cancer patients and 50 healthy counterparts were recruited. A sample of 40 children were invited to respond by phone to the PSQI 2 weeks later to assess test-retest reliability. A cutoff score for the translated PSQI used with the survivors was determined using receiver operating characteristic analysis. RESULTS: The Chinese version of the PSQI had a Cronbach alpha of 0.71, with an intraclass correlation coefficient of 0.90. Childhood cancer survivors showed significantly lower mean PSQI scores than children with cancer, and significantly higher mean scores than healthy counterparts. This reflected that childhood cancer survivors had a better sleep quality than children with cancer, but a poorer sleep quality than healthy counterparts. We observed positive correlations between PSQI and CES-DC scores and between PSQI and FS-A/FS-C scores, but a negative correlation between PSQI and PedsQL scores. The results supported that the Chinese version of the PSQI showed convergent validity. Confirmatory factor analysis showed that the translated PSQI data best fit a three-factor model. The best cutoff score to detect insomnia was 5, with a sensitivity of 0.81 and specificity of 0.70. CONCLUSION: The Chinese version of the PSQI is a reliable and valid instrument to assess subjective sleep quality among Hong Kong Chinese childhood cancer survivors. The validated PSQI could be used in clinical settings to provide early assessments for sleep disruption. Appropriate interventions can therefore be provided to minimize its associated long-term healthcare cost. Trial registration This study was registered in ClinicalTrials.gov with the reference number NCT03858218.

Randomized Trial of Two Induction Therapy Regimens for High-Risk Neuroblastoma: HR-NBL1.5 International Society of Pediatric Oncology European Neuroblastoma Group Study.

PURPOSE: Induction therapy is a critical component of the therapy of high-risk neuroblastoma. We aimed to assess if the Memorial Sloan Kettering Cancer Center (MSKCC) N5 induction regimen (MSKCC-N5) would improve metastatic complete response (mCR) rate and 3-year event-free survival (EFS) compared with rapid COJEC (rCOJEC; cisplatin [C], vincristine [O], carboplatin [J], etoposide [E], and cyclophosphamide [C]). PATIENTS AND METHODS: Patients (age 1-20 years) with stage 4 neuroblastoma or stage 4/4s aged < 1 year with MYCN amplification were eligible for random assignment to rCOJEC or MSKCC-N5. Random assignment was stratified according to national group and metastatic sites. Following induction, therapy comprised primary tumor resection, high-dose busulfan and melphalan, radiotherapy to the primary tumor site, and isotretinoin with ch14.18/CHO (dinutuximab beta) antibody with or without interleukin-2 immunotherapy. The primary end points were mCR rate and 3-year EFS. RESULTS: A total of six hundred thirty patients were randomly assigned to receive rCOJEC (n = 313) or MSKCC-N5 (n = 317). Median age at diagnosis was 3.2 years (range, 1 month to 20 years), and 16 were younger than 1 year of age with MYCN amplification. mCR rate following rCOJEC induction (32%, 86/272 evaluable patients) was not significantly different from 35% (99/281) with MSKCC-N5 (P = .368), and 3-year EFS was 44% ± 3% for rCOJEC compared with 47% ± 3% for MSKCC-N5 (P = .527). Three-year overall survival was 60% ± 3% for rCOJEC compared with 65% ± 3% for MSKCC-N5 (P = .379). Toxic death rates with both regimens were 1%. However, nonhematologic CTC grade 3 and 4 toxicities were higher with MSKCC-N5: 68% (193/283) versus 48% (129/268) (P < .001); infection 35% versus 25% (P = .011); stomatitis 25% versus 3% (P < .001); nausea and vomiting 17% versus 7% (P < .001); and diarrhea 7% versus 3% (P = .011). CONCLUSION: No difference in outcome was observed between rCOJEC and MSKCC-N5; however, acute toxicity was less with rCOJEC, and therefore rCOJEC is the preferred induction regimen for International Society of Pediatric Oncology European Neuroblastoma Group.