An intervention module for caregivers of children with acute lymphoblastic leukemia (ALL).

INTRODUCTION: Childhood cancer caregivers report psychological distress and unmet psychosocial needs, affecting outcomes for their children. An experimental study was carried out to measure the effectiveness of an intervention in addressing traumatic stress, depression and anxiety. METHODS: Caregivers (n = 59) of children with ALL were allocated to both groups (intervention, n = 29; TAU control, n = 30) via the SNOSE method. The intervention is a physical copy of a 2-week psychosocial self-help guidebook. Scores on the PCL-5, BDI and BAI were recorded at baseline, post-intervention and 1-month follow-up. RESULTS: There was a statistically significant difference in traumatic stress symptoms post intervention (F(1, 57) = 5.760, p = .020, np2 = 0.093) in favor of the intervention group. No statistical significance was found for its effect at one-month follow-up, overall depression and anxiety. CONCLUSION: A psychosocial module developed for caregivers of children with ALL was found to be effective in reducing symptoms of traumatic stress and potentially depression. However, the maintenance of its effectiveness and the effectiveness on anxiety requires further study.

Population pharmacokinetic modelling of intravenous immunoglobulin in patients with predominantly antibody deficiencies.

AIMS: There is considerable interpatient variability in the pharmacokinetics (PK) of intravenous immunoglobulin G (IVIG), causing difficulty in optimizing individual dosage regimen. This study aims to estimate the population PK parameters of IVIG and to investigate the impact of genetic polymorphism of the FcRn gene and clinical variability on the PK of IVIG in patients with predominantly antibody deficiencies. METHODS: Patients were recruited from four hospitals. Clinical data were recorded and blood samples were taken for PK and genetic studies. Population PK parameters were estimated by nonlinear mixed-effects modelling in Monolix®. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive check and bootstrap analysis. Monte Carlo simulation was conducted to evaluate different dosing regimens for IVIG. RESULTS: A total of 30 blood samples were analysed from 10 patients. The immunoglobulin G concentration data were best described by a one-compartment model with linear elimination. The final model included both volume of distribution (Vd) and clearance (CL) based on patient's individual weight. Goodness-of-fit plots indicated that the model fit the data adequately, with minor model mis-specification. Genetic polymorphism of the FcRn gene and the presence of bronchiectasis did not affect the PK of IVIG. Simulation showed that 3-4-weekly dosing intervals were sufficient to maintain IgG levels of 5 g L-1 , with more frequent intervals needed to achieve higher trough levels. CONCLUSIONS: Body weight significantly affects the PK parameters of IVIG. Genetic and other clinical factors investigated did not affect the disposition of IVIG.

A Systematic Review and Meta-regression Analysis on the Impact of Increasing IgG Trough Level on Infection Rates in Primary Immunodeficiency Patients on Intravenous IgG Therapy.

PURPOSE: We conducted a systematic review and meta-regression analysis to evaluate the impact of increasing immunoglobulin G (IgG) trough levels on the clinical outcomes in patients with PID receiving intravenous immunoglobulin G (IVIG) treatment. METHODS: Systematic search was conducted in PubMed and Cochrane. Other relevant articles were searched by reviewing the references of the reviewed article. All clinical trials with documented IgG trough levels and clinical outcome of interest in patients receiving IVIG treatment were eligible to be included in this review. Meta-regression analysis was conducted using Comprehensive Meta-analysis Software. Additional sensitivity analyses were undertaken to evaluate the robustness of the overall results. RESULTS: Twenty-eight clinical studies with 1218 patients reported from year 2001 to 2018 were included. The mean IVIG dose used ranges from 387 to 560 mg/kg every 3 to 4 weekly, and mean IgG trough obtained ranges from 660 to 1280 mg/dL. Random-effects meta-regression slope shows that IgG trough level increases significantly by 73 mg/dL with every increase of 100 mg/kg dose of IVIG (p < 0.05). Overall infection rates reduced significantly by 13% with every increment of 100 mg/dL of IgG trough up to 960 mg/dL (p < 0.05). CONCLUSION: This meta-analysis concludes that titrating the IgG trough levels up to 960 mg/dL progressively reduces the rate of infections, and there is less additional benefit beyond that. Further studies to validate this result are required before it can be used in clinical practice.

Health-related quality of life among children with transfusion-dependent thalassemia: A cross-sectional study in Malaysia.

BACKGROUND: The treatment of children with transfusion-dependent thalassemia (TDT) in Malaysia has progressed since 2005. This study provides an updated health-related quality of life (HRQoL) assessment for children with the disorder and the factors affecting the HRQoL. METHODS: A cross-sectional HRQoL survey of Malaysian children with TDT was conducted using the PedsQL™ 4.0 Generic Core Scales. Patients with non-transfusion dependent thalassemia and other haemoglobinopathies were excluded. Parent-proxy and self-reported HRQoL scores were obtained using a multi-stage convenient sampling. The relationship between HRQoL scores and demographic factors were tested using association, correlation and regression analysis. RESULTS: A total of 368 patients were recruited. The mean (SD) Total Summary Score (TSS) was 80.12(13.87). Predictors for a lower TSS was an increasing age group and the use of dual chelating agents (R2 = 0.057, F (4, 359) = 5.40, p = < 0.001). The mean (SD) Physical Health Summary Score (PHSS) was 82.21 (16.82). Predictors of a higher PHSS score was being male, while predictors of a lower score was an increasing age group and parent-proxy reports(R2 = 0.075, F (5,358) = 5.80, p = < 0.001). The mean (SD) Psychosocial Health Summary Score (PCHS) was 79.39 (14.81). Predictors for a lower PCHS was the use of dual chelating agents(R2 = 0.041, F (1, 362) = 15.60, p = < 0.001). The school functioning score had the lowest mean (SD) score of 69.52(20.92) in the psychosocial dimension. CONCLUSION: The HRQoL of TDT children in Malaysia has improved over the last decade owing to the better access in treatment. However, further effort is needed to improve the school functioning dimension.

Behavioral outcome among survivors of childhood brain tumor: a case control study.

BACKGROUND: Advances in the treatment of childhood brain tumors have significantly improved survival rates. With improved survival rates, long-term treatment-related toxicities have become important, and the resulting complications can affect patients' emotion and behavior. This study aimed to 1) evaluate behavioral outcomes among survivors of childhood brain tumors, 2) compare behavioral outcomes among survivors of childhood brain tumors with survivors of childhood leukemia and healthy children, and 3) determine any demographic, disease, and/or treatment-related factors that could affect the behavioral outcomes of survivors of childhood brain tumors. METHODS: A comparative cross-sectional study was conducted over a period of 1 year (June 1st, 2018-May 31st, 2019) in two tertiary referral centers in Kuala Lumpur, Malaysia. Thirty-eight survivors of childhood brain tumors aged 6 to 18 years old who had been off-treatment for at least 1 year and were in remission, 38 age- and gender-matched survivors of childhood leukemia who had been off-treatment for at least 1 year and were in remission, and 38 age- and gender-matched unrelated healthy children were recruited. The Child Behaviour Checklist (CBCL) parent report and Youth Self-Report (YSR) questionnaires were used to assess behavioral outcomes. RESULTS: Survivors of childhood brain tumors showed statistically significantly worse behavioral outcomes than healthy children for social problems and attention problems (p < 0.05, respectively). A significantly worse outcome was found for "social problems" (p < 0.05) in survivors of childhood brain tumors compared to survivors of childhood leukemia. Significant associations were also found between physical disability, visual impairment, education level of survivors, and father's occupation and behavioral outcomes among survivors of childhood brain tumors. CONCLUSIONS: Survivors of childhood brain tumors in our center showed poor behavioral outcomes for social problems and attention problems. Thus, effective psychosocial support interventions tailored to individual patients as soon as treatment is completed are important to prevent potentially debilitating emotional problems.

A Unique Interaction of IVS-I-1 (G>A) (HBA2: c.95+1G>A) with Hb Adana (HBA2: c.179G>A) Presenting as Transfusion-Dependent α-Thalassemia.

Nondeletional α-globin mutations are known to cause more serious clinical effects than deletional ones. A rare IVS-I-1 (G>A) (HBA2: c.95+1G>A) donor splice site mutation interferes with normal splicing of pre mRNA and results in activation of a cryptic splice site as well as a frameshift mutation. Hb Adana [HBA2: c.179G>A (or HBA1)] is a highly unstable variant hemoglobin (Hb) resulting from a mutation at codon 59 on the HBA2 or HBA1 gene, recognized to cause severe α-thalassemia (α-thal) syndromes. We report a unique case of compound heterozygosity for these two mutations in a 9-year-old boy who presented with a Hb level of 5.3 g/dL and hepatomegaly at the age of 15 months. He required regular blood transfusions in view of a Hb level of <7.0 g/dL and failure to thrive. He had thalassemic red cell indices and peripheral blood film. The Hb electrophoresis only showed a raised Hb F level (3.3%) and a pre run peak but the Hb H inclusion test was negative. His father had thalassemic red cell indices but a normal Hb level. His mother had almost normal Hb levels and red cell indices. Hb Adana involving the HBA2 gene was detected by mutiplex amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in the proband and his father. DNA sequencing of the HBA2 gene confirmed the IVS-I-1 mutation in the proband and his mother. This case highlighted the unique interaction of the IVS-I-1 mutation with Hb Adana in a young Malay boy presenting with transfusion-dependent α-thal.

Meta-analysis of gene expression in relapsed childhood B-acute lymphoblastic leukemia.

BACKGROUND: Relapsed pediatric B-acute lymphoblastic leukemia (B-ALL) remains as the leading cause of cancer death among children. Other than stem cell transplantation and intensified chemotherapy, no other improved treatment strategies have been approved clinically. Gene expression profiling represents a powerful approach to identify potential biomarkers and new therapeutic targets for various diseases including leukemias. However, inadequate sample size in many individual experiments has failed to provide adequate study power to yield translatable findings. With the hope of getting new insights into the biological mechanisms underpinning relapsed ALL and identifying more promising biomarkers or therapeutic targets, we conducted a meta-analysis of gene expression studies involving ALL from 3 separate studies. METHOD: By using the keywords "acute lymphoblastic leukemia", and "microarray", a total of 280 and 275 microarray datasets were found listed in Gene Expression Omnibus database GEO and ArrayExpress database respectively. Further manual inspection found that only three studies (GSE18497, GSE28460, GSE3910) were focused on gene expression profiling of paired diagnosis-relapsed pediatric B-ALL. These three datasets which comprised of a total of 108 matched diagnosis-relapsed pediatric B-ALL samples were then included for this meta-analysis using RankProd approach. RESULTS: Our analysis identified a total of 1795 upregulated probes which corresponded to 1527 genes (pfp < 0.01; FC > 1), and 1493 downregulated probes which corresponded to 1214 genes (pfp < 0.01; FC < 1) respectively. S100A8 appeared as the top most overexpressed gene (pfp < 0.01, FC = 1.8) and is a potential target for further validation. Based on gene ontology biological process annotation, the upregulated genes were most enriched in cell cycle processes (enrichment score = 15.3), whilst the downregulated genes were clustered in transcription regulation (enrichment score = 12.6). Elevated expression of cell cycle regulators (e.g kinesins, AURKA, CDKs) was the key genetic defect implicated in relapsed ALL, and serve as attractive targets for therapeutic intervention. CONCLUSION: We identified S100A8 as the most overexpressed gene, and the cell cycle pathway as the most promising biomarker and therapeutic target for relapsed childhood B-ALL. The validity of the results warrants further investigation.

Giant Cell Tumor of the Ribs and Aneurysmal Bone Cyst Presenting With Hemothorax in a Child.

Giant cell tumor (GCT) is one of the most common tumors of bone and is the most common precursor of aneurysmal bone cysts (ABC). The clinical behavior of concurrent GCT and ABC can be very aggressive in children. GCT of the ribs, with or without ABC, is rarely seen in children. We report a case of an 8-year-old girl with GCT and associated ABC of the ribs who presented with sudden onset of chest pain and breathlessness due to a hemothorax. The patient was successfully treated by surgical resections and arterial embolization. She has remained well for 4 years after the initial surgery.

Hb lepore/ß0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall.

Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δß-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/ß-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

A case series of α-thalassemia intermedia due to compound heterozygosity for Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] with other α-thalassemias in Malay families.

Hb Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a rare hemoglobin (Hb) variant due to a mutation at codon 59 of the α2- or α1-globin gene resulting in a glycine to aspartic acid substitution. Two siblings with a unique coinheritance of Hb Adana and Hb Constant Spring (Hb CS, α142, Term→Gln, TAA>CAA; HBA2: c.427 T>C) (α(codon 59)α/α(CS)α), were compared phenotypically with another two siblings carrying the Hb Adana mutation and a 3.7 kb deletion (α(codon 59)α/-α(3.7)). Although they all had α-thalassemia intermedia (α-TI), the former were clinically more severe than the latter. The first pair of siblings presented at a much younger age than the second pair and showed lower Hb levels and significant extramedullay hemopoiesis. Another case of a hydropic fetus as a result of Hb H/Hb Adana is also described. Their clinical phenotypes and hematological parameters are all presented for comparison.

Fertility preservation in Malaysian pediatric cohort: a survey of healthcare providers' knowledge, practice, attitude, perceptions and barriers.

Introduction: Impaired future fertility potential secondary to gonadotoxic therapies for childhood cancer is a shattering aftermath faced by childhood cancer survivors. Fertility preservation (FP) has emerged as a key to mitigate this unwelcomed sequelae. FP services catering to the needs of children and adolescents (C&A) population in developing countries are limited. Malaysia recently launched its pioneering pediatrics FP services. Aims of study: To evaluate healthcare providers' (HCPs) FP knowledge, practice behaviors, attitudes, perceptions, and barriers towards FP counseling/services (C/S) for the C&A cohort. Methods: A questionnaire-based study was conducted utilizing a questionnaire consisting of 51 items which was adapted from G.Quinn et al. The questionnaire was distributed both online and physically amongst HCPs in a tertiary center. Ethical committee approval was granted by the Research Ethical Committee, Universiti Kebangsaan Malaysia. Results: A total of 102 HCPs completed the questionnaires. The majority of respondents were Malays (74.5%), females (80.4%), gynecology/pediatrics specialty (76.5%), and had children (88.2%). Nearly 72% of HCPs demonstrated good knowledge of FP. Almost 73% of HCPs consulted reproductive specialists (RES) on potential fertility issues and over 80% of HCPs referred patients who enquired on fertility issues to RES. Only 17% of HCPs practiced FP discussion, 12% reported no available person to discuss FP, and 10% of HCPs were unaware of who to discuss FP with. Patients' inability to afford FP (30.4%) tops the list of barriers to FP C/S, followed by limited available information on FP for patients (17.6%) and patients too ill to delay treatment (12.7%). Most HCPs (88.2%) demonstrated unfavorable attitudes towards FP C/S. Discussions: In general, the majority of our HCP respondents demonstrated good current FP knowledge and practice behaviors. Mitigating several controversial issues in FP would improve HCPs' attitude towards FP. Main barriers to the uptake of FP C/S for C&A were patient and resource barriers. Addressing these issues by funding aid for FP procedures, increasing FP knowledge dispersion, as well as developing age-appropriate FP-related educational materials would improve FP service provision for C&A in the future. Conclusions: In conclusion, successful corrective action combined with strategic planning points to a promising future for Malaysia's FP services provision for C&A.

Advances in next-generation sequencing for relapsed pediatric acute lymphoblastic leukemia: current insights and future directions.

Leukemia is one of the most common cancers in children; and its genetic diversity in the landscape of acute lymphoblastic leukemia (ALL) is important for diagnosis, risk assessment, and therapeutic approaches. Relapsed ALL remains the leading cause of cancer deaths among children. Almost 20% of children who are treated for ALL and achieve complete remission experience disease recurrence. Relapsed ALL has a poor prognosis, and relapses are more likely to have mutations that affect signaling pathways, chromatin patterning, tumor suppression, and nucleoside metabolism. The identification of ALL subtypes has been based on genomic alterations for several decades, using the molecular landscape at relapse and its clinical significance. Next-generation sequencing (NGS), also known as massive parallel sequencing, is a high-throughput, quick, accurate, and sensitive method to examine the molecular landscape of cancer. This has undoubtedly transformed the study of relapsed ALL. The implementation of NGS has improved ALL genomic analysis, resulting in the recent identification of various novel molecular entities and a deeper understanding of existing ones. Thus, this review aimed to consolidate and critically evaluate the most current information on relapsed pediatric ALL provided by NGS technology. In this phase of targeted therapy and personalized medicine, identifying the capabilities, benefits, and drawbacks of NGS will be essential for healthcare professionals and researchers offering genome-driven care. This would contribute to precision medicine to treat these patients and help improve their overall survival and quality of life.

Population Pharmacokinetic Model of Intravenous Immunoglobulin in Patients Treated for Various Immune System Disorders.

PURPOSE: Intravenous immunoglobulin (IVIG) is used to treat various immune system disorders, but the factors influencing its disposition are not well understood. This study aimed to estimate the population pharmacokinetic parameters of IVIG and to investigate the effect of genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor (FcRn) and clinical variability on the pharmacokinetic properties of IVIG in patients with immune system disorders. METHODS: Patients were recruited from 4 hospitals in Malaysia. Clinical data were recorded, and blood samples were taken for pharmacokinetic and genetic studies. Population pharmacokinetic parameters were estimated by nonlinear mixed-effects modeling in Monolix. Age, weight, baseline immunoglobulin G concentration, ethnicity, sex, genotype, disease type, and comorbidity were investigated as potential covariates. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive checks, and bootstrap analysis. FINDINGS: A total of 292 blood samples were analyzed from 79 patients. The IVIG concentrations were best described by a 2-compartment model with linear elimination. Weight was found to be an important covariate for volume of distribution in the central compartment (Vc), volume of distribution in the peripheral compartment (Vp), and clearance in the central compartment, whereas disease type was found to be an important covariate for Vp. Goodness-of-fit plots indicated that the model fit the data adequately. Genetic polymorphism of the FCGRT gene encoding the neonatal Fc receptor did not affect the pharmacokinetic properties of IVIG. IMPLICATIONS: This study supports the use of dosage based on weight as per current practice. The study findings highlight that Vp is significantly influenced by the type of disease being treated with IVIG. This relationship suggests that different disease types, particularly inflammatory and autoimmune conditions, may alter tissue permeability and fluid distribution due to varying degrees of inflammation. Increased inflammation can lead to enhanced permeability and retention of IVIG in peripheral tissues, reflecting higher Vp values.

Neuropsychological task outcomes among survivors of childhood acute lymphoblastic leukemia in Malaysia.

This study intended to explore the neuropsychological ramifications in childhood acute lymphoblastic leukemia (ALL) survivors in Malaysia and to examine treatment-related sequelae. A case-control study was conducted over a 2-year period. Seventy-one survivors of childhood ALL who had completed treatment for a minimum of 1 year and were in remission, and 71 healthy volunteers were enlisted. To assess alertness (processing speed) and essential executive functioning skills such as working memory capacity, inhibition, cognitive flexibility, and sustained attention, seven measures from the Amsterdam Neuropsychological Tasks (ANT) program were chosen. Main outcome measures were speed, stability and accuracy of responses. Mean age at diagnosis was 4.50 years (SD ± 2.40) while mean age at study entry was 12.18 years (SD ± 3.14). Survivors of childhood ALL underperformed on 6 out of 7 ANT tasks, indicating poorer sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Duration of treatment, age at diagnosis, gender, and cumulative doses of chemotherapy were not found to correlate with any of the neuropsychological outcome measures. Childhood ALL survivors in our center demonstrated significantly poorer neuropsychological status compared to healthy controls.

Caring for a child with cancer during COVID-19 pandemic: an assessment of the parents' perception and stress level.

Background: The emergence of COVID-19 pandemic has led to heightened fear and uncertainty among parents of children with cancer. This study was conducted to evaluate the parental perceptions toward effects of COVID-19 infection to children with cancer, determine their stress level and factors contributing to high stress level during the pandemic. Methods: This cross-sectional study was conducted in three paediatric oncology centres in Malaysia from September 2020 until December 2022. A total of 167 parents were recruited. Parents completed a set of questionnaires to assess their perception on effect of COVID-19 infection to children with cancer and COVID Stress Scale (CSS) to assess the parents' stress level. Results: Patients' mean age at study entry was 8.75 years (SD 4.38). Ninety-one (54.5%) patients were still on active treatment. More than 80% of the parents obtained information regarding COVID-19 infection from mass media and social networking. Fear of their children contracting COVID-19 infection was high especially among patients who were still on treatment. Forty-nine (29.3%) parents were significantly affected by the pandemic leading to loss of job or monthly income. Twenty-nine (17.4%) patients required treatment modification during the pandemic. The median total score for CSS was 78.0 (IQR 25th 64.0; 75th 95.0). Ninety-one (54.5%) respondents were very/extremely stressed based on the CSS scores. Components with high scores were xenophobia (median score 18.0; IQR 25th 13.0, 75th 22.0), fear of danger (median score 17.0; IQR 25th 14.0, 75th 20.0) and contamination fears (median score 16.0; IQR 25th 12.0, 75th 19.0). Lower household income was associated with higher stress level (p = 0.006). Conclusion: Our study demonstrated high awareness regarding risk of COVID-19 infection among parents of oncology children. Half of the parents had high stress level, with low household income identified as a factor associated with high stress level.

Spiritual Coping Among Families of Children With Cancer: A Qualitative Study.

The impact of a childhood cancer diagnosis precipitates caregiver's engagement in spiritual coping. This study aimed to explore spirituality among Malaysian Muslim caregivers of children with acute lymphoblastic leukemia. A total of 13 eligible caregivers participated in this qualitative semi-structured interview via purposive sampling. Each interview was audio recorded, transcribed verbatim, and analyzed using NVivo 12 via thematic analysis. Three main themes revolved around hope through the act of praying and recitation (du'a' and dhikr), acceptance of God's will (redha), and faith toward God as the Provider of sustenance (rezeki). The findings of this study contribute to a holistic supportive care system in pediatric oncology as it informs health care providers the role of spirituality in mitigating the emotional impact of a cancer diagnosis and promoting psychological adaptation. As a multicultural country, future studies may explore spirituality in other cultures and religion in the country.

Predictors of Post-traumatic Stress Symptoms (PTSS), Depression, and Anxiety among Caregivers of Children with Acute Lymphoblastic Leukaemia (ALL).

OBJECTIVE: The caregivers of children diagnosed with acute lymphoblastic leukaemia (ALL) are believed to experience post-traumatic stress symptoms (PTSS), depression and anxiety. This present study endeavoured to explore the prevalence and predictors of PTSS, depression, and anxiety among the caregivers of children with ALL. METHODS: Purposive sampling was used to select the 73 caregivers of children with ALL who participated in this cross-sectional study. The Post-traumatic Stress Disorder Checklist for DSM-5 (PCL-5), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to measure psychological distress. RESULT: There was a low prevalence (11%) of post-traumatic stress disorder (PTSD) among the participants. Although all the criteria for PTSD were not met, a few post-traumatic symptoms remained, suggesting that PTSS was likely present. Most of the participants reported minimal symptoms of depression (79.5%) and anxiety (65.8%). Anxiety, depression, and ethnicity predicted the PTSS scores (R2 = .77, p =.000). Subsequently, depression predicted the PTSS scores (R2 = 0.42, p =0.000). Participants of 'Other' or 'Indigenous' ethnicity had lower PTSS scores and higher anxiety scores (R2 = 0.75, p =0.000) than participants of Malay ethnicity. CONCLUSION: The caregivers of children with ALL experience post-traumatic stress symptoms (PTSS), depression, and anxiety. These variables co-exist and may have different trajectories in different ethnic groups. Therefore, healthcare providers should take ethnicity and psychological distress into consideration when providing paediatric oncology treatment and care.

Case report: Kaposi hemangioendothelioma of the right upper limb with the Kasabach-Merritt phenomenon: A potentially lethal diagnostic challenge.

Kaposi hemangioendothelioma (KHE) is a rare vascular neoplasm that presents usually within the first year of life. Because of its rarity and complexity, there is often a delay in diagnosis. KHE could be associated with a life-threatening consumptive coagulopathy named the Kasabach-Merritt phenomenon (KMP). Here, we present the case of a 2-month-old girl who presented with progressive redness and swelling of her right upper limb over 6 weeks. Multiple health practitioners misdiagnosed her condition as an insect bite, cellulitis, and necrotizing fasciitis and gave treatment accordingly, which proved futile. A full blood count revealed bicytopenia of anemia and thrombocytopenia, a normal coagulation cascade, low fibrinogen, and raised D-Dimer levels. The imaging was suggestive of a high-flow vascular tumor likely to be a KHE. Subsequently, she was started on single-agent oral sirolimus with a dose increment to achieve satisfactory therapeutic levels and was treated for 1 year. She successfully completed the treatment regimen and had only transient hypertriglyceridemia, which resolved upon the completion of treatment. Currently, she is in remission 3 years after treatment. Keeping her case as an example, we would like to highlight the potentially lethal misdiagnosis of KHE with KMP, the importance of an early diagnosis of this condition, and the successful treatment outcome with single-agent sirolimus.

Prescribing Practices of Intravenous Immunoglobulin in Tertiary Care Hospitals in Malaysia: A Need for a National Guideline for Immunoglobulin Use.

Rational use of drug involves the use of medicine as per clinical guidelines. Given the steady increase in the clinical utility of intravenous immunoglobulin (IVIG) either as licensed or off-label use, concerns are being raised about the possibility of supply shortages that could significantly impact patient care. Therefore, there is a need to regulate and to promote the rational use of this valuable medication. This cross-sectional chart review study attempts to evaluate the prescribing patterns of IVIG at two tertiary hospitals in Malaysia. Patients' medical files and dispensing records were examined and compared with current guidelines. A total of 348 prescriptions for IVIG were written during the 1-year study period. The highest usage of IVIG was for neurological (47.9%), immunological (27.5%), and hematological conditions (20%). The number of prescriptions with the US Food and Drug Administration (FDA) licensed indications and off-label indications was 148 (42.5%) and 200 (57.5%), respectively. Age (OR: 1.02, 95% CI: 1.01-1.03, p = 0.003) and those admitted to the critical care units (OR: 11.11, 95% CI: 5.60-22.05, p < 0.001) were significant factors for receiving IVIG for an off-label indication. Most prescriptions (79%) had appropriate dosing. Significant factors associated with receiving inappropriate dose of IVIG include age (OR: 0.93, 95% CI: 0.89-0.97, p = 0.001) and those admitted to the critical care units (OR: 10.15, 95% CI: 3.81-27.06, p < 0.001). This study advocates the development and implementation of evidence-based clinical guidelines with prioritization protocol to ensure rational use of IVIG.

Isolated Infiltrative Optic Neuropathy in an Acute Lymphoblastic Leukemia Relapse.

Optic nerve infiltration as the first sign of isolated central nervous system relapse of acute lymphoblastic leukemia (ALL) is rare. A seven-year-old girl with standard-risk B-cell ALL who was in remission presented with sudden onset of left eye pain and loss of vision. Examination revealed no perception to light in the left eye with positive relative afferent pupillary defect. The optic disc was hyperemic and swollen with total obscuration of the disc margin associated with central retinal artery and vein occlusion. Magnetic resonance imaging of the brain and optic nerve showed left intraorbital optic nerve thickening associated with perineural enhancement and intraconal fat involvement. Lumbar puncture revealed leukemic infiltration with blast cells after a week of eye symptoms, while bone marrow aspiration was negative for malignant cells. A diagnosis of left leukemic optic nerve infiltration with central retinal artery and vein occlusion was made. A high index of suspicion with repeat cerebrospinal fluid sampling is crucial to confirm the diagnosis as vitreous biopsy may fail to reveal infiltrative cells.