Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study.

STUDY OBJECTIVES: The effect of recombinant human growth hormone (rhGH) on sleep-disordered breathing (SDB) in Malaysian children with Prader-Willi syndrome (PWS) is under-investigated. We determined (a) the short- and long-term effects of rhGH and (b) factors associated with worsening SDB, in children with PWS on rhGH. METHODS: This retrospective study included children with PWS (with and without rhGH) who had at least one polysomnography (PSG). Outcomes measured were the presence of SDB: before and after starting rhGH and the progress of SDB with and without rhGH. Serial insulin-like growth factor-1 (IGF-1) measurements were recorded. RESULTS: One-hundred and thirteen PSGs were analyzed. The majority (92.3%) of initial PSGs had SDB with AHI median (IQR) 5.0 (2.6,16.3) events/h. The age for receiving rhGH was median (IQR) 1.9 (0.7, 3.4) years old. A third (36.8%) had worsening SDB after initiating rhGH, which was associated with higher IGF-1 levels post-rhGH (p=0.007). After a median of 5 years of rhGH, 73.6% maintained or reduced their positive airway pressure (PAP) settings. Without rhGH, 80% had increased their PAP settings. Worsening SDB while on rhGH was associated with higher BMI, lower rhGH dose, higher IGF-1 levels and non-15q deletion. CONCLUSIONS: Majority of Malaysian children with PWS had SDB. At initiation rhGH, one-third of patients had worsening SDB, associated with increased IGF-1 levels. Stabilization of SDB was more frequently seen in those on long-term rhGH. Worsening SDB while on rhGH was associated with a higher BMI, on a lower dose of rhGH, higher IGF-1 levels and non-15q deletion.

Effectiveness of education intervention, with regards to physical activity level and a healthy diet, among Middle Eastern adolescents in Malaysia: A study protocol for a randomized control trial, based on a health belief model.

BACKGROUND: Among the most urgent public health challenges, of the twenty-first century, is obesity. This can be attributed to its relationship with several non-communicable diseases (NCDs), as well as premature mortality. Being overweight or obese is a major concern not only in high-income countries, but also in low-income and middle-income countries, particularly in urban areas. Several studies have highlighted the prevalence of obesity, among Middle Eastern-descent adolescents, studying in Arabic secondary schools, located in Malaysia. Intervention studies, directed at Middle Eastern adolescents in Malaysia, are limited. This paper, describes the protocol, for an integrated health education intervention process. Titled 'Healthy lifestyle', it is a primary prevention process, aimed at curbing obesity and disordered eating, among Middle Eastern secondary school adolescents, aged 13-14 years old, residing in Malaysia. METHODS AND ANTICIPATED RESULTS: A cluster randomized controlled study will be conducted, involving 250 Middle Eastern adolescents, in Arabic schools in Malaysia. The participants will be randomly assigned to the intervention and control groups. While the intervention group participates in six weeks of fortnightly six sessions (45 minutes per session), the control group will carry on with their regular curriculums, and normal physical activity routines. The variables which will be evaluated include anthropometric measurements, knowledge, attitude, daily routines, physical activity, sedentary behaviour, food assessment, eating attitudes test-26, and a structured questionnaire based on the HBM. Data will be collected from the intervention and control groups at baseline, post-intervention, and two months following the intervention. Data analysis will be performed by way of the SPSS Statistics software version 26. The generalized estimating equation (GEE) will be used, to test the effect of the intervention program, with regards to the selected variables (outcomes), between and within-group at baseline, as well as six weeks and two months following intervention, after adjusting for clustering. Outcomes will be assessed at each time point, along with a derived average over all three-time points; thus, ensuring that both the cumulative and overall effects are determined. CONCLUSIONS: This trial will provide useful information for improving the knowledge, attitude, and practices of Middle Eastern adolescents, with regards to body weight status, physical activity level, nutrition status (BMI and dietary intake), and disordered eating. This will go a long way, towards ensuring their adherence to appropriate physical activities, and a healthy diet, to keep non-communicable diseases at bay. TRIAL REGISTRATION: This study is registered at NCT: NCT05694143.

Abusive head trauma in infants: An observational single centre study comparing developmental and functional outcome between 18 months and 5 years.

BACKGROUND: Abusive head trauma (AHT) is a major cause of traumatic brain injury in infancy. This exploratory study compared standardized developmental assessment versus functional outcome assessment between 18 months and 5 years of age following AHT in infancy. METHODS: Observational cross-sectional study after surviving AHT in infancy. Seventeen children between 18 months and 5 years of age underwent clinical examination, developmental assessment using the Schedule of Growing Skills II (SGS II) and functional assessment using the Glasgow Outcome Scale-Extended Pediatric Revision (GOS-E Peds). Additional clinical information was extracted from medical records. RESULTS: Age at assessment ranged from 19 to 53 months (median 26 months). Most (n = 14) were delayed in at least 1 domain, even without neurological or visual impairment or visible cortical injury on neuroimaging, including 8 children with favourable GOS-E Peds scores. The most affected domain was hearing and language. Delay in the manipulative domain (n = 6) was associated with visual and/or neurological impairment and greater severity of delay across multiple domains. Eleven (64.7 %) had GOS-E Peds scores indicating good recovery, with positive correlation between GOS-Peds scores and number of domains delayed (r = 0.805, p < 0.05). CONCLUSION: The SGS-II detects behavioural and cognitive deficits not picked up by the GOS-E Peds. Combining both tools for assessment of AHT survivors under 5 years of age provides a comprehensive profile which addresses multiple domains of development and function, facilitating targeted intervention. Detection of developmental problems in the majority of survivors makes AHT prevention a public health priority.

Poor sleep quality in children with atopic dermatitis and its effects on behavior: A multicenter cross-sectional study from a low-middle-income country.

BACKGROUND: Sleep disturbance in children with atopic dermatitis (AD) frequently goes unnoticed and can be associated with behavioral challenges. The aims of this study were to determine (a) the prevalence and factors associated with sleep disturbance and behavioral problems and (b) the correlation between sleep disturbance and behavioral problems in children with AD. METHODS: This cross-sectional study involved children aged 4-12 years old with moderate to severe AD. Age and sex-matched healthy children were recruited as the comparison group. The Children's Sleep Habits Questionnaire (CSHQ) and the Strengths and Difficulties Questionnaire (SDQ) were used to assess sleep disturbance and behavioral problems, respectively. Higher scores in both questionnaires signify more disturbance. RESULTS: Seventy patients and 141 controls were recruited. Median (interquartile range) age of patients was 5 (4,8) years. Patients had later sleep time (p < 0.001), longer night awakening (p < 0.001), and shorter sleep duration (p < 0.001) compared to controls. CSHQ total scores and all its domains, except for sleep-disordered breathing were significantly higher in patients compared to controls. Patients also had significantly higher SDQ total difficulties scores in all domains, except for peer problems. Severity of AD was significantly associated with high CSHQ and SDQ scores. There was a moderate positive correlation between the total CSHQ score and total SDQ score in patients (r = 0.532). CONCLUSIONS: Children with moderate-to-severe AD had significantly more sleep disturbance and more behavioral problems than their healthy peers. Sleep disturbance had a positive correlation with behavioral problems. Severity of AD was associated with sleep disturbance and behavioral problems.

Manipulating the Gut Microbiome as a Therapeutic Strategy to Mitigate Late Effects in Childhood Cancer Survivors.

Recent studies have identified causal links between altered gut microbiome, chronic inflammation, and inflammation-driven conditions such as diabetes and cardiovascular disease. Childhood cancer survivors (CCS) show late effects of therapy in the form of inflammaging-related disorders as well as microbial dysbiosis, supporting a hypothesis that the conditions are interconnected. Given the susceptibility of the gut microbiome to alteration, a number of therapeutic interventions have been investigated for the treatment of inflammatory conditions, though not within the context of cancer survivorship in children and adolescents. Here, we evaluate the potential for these interventions, which include probiotic supplementation, prebiotics/fiber-rich diet, exercise, and fecal microbiota transplantation for prevention and treatment of cancer treatment-related microbial dysbiosis in survivors. We also make recommendations to improve adherence and encourage long-term lifestyle changes for maintenance of healthy gut microbiome in CCS as a potential strategy to mitigate treatment-related late effects.

Premature Ocular Aging Features in Childhood Acute Lymphoblastic Leukemia Survivors.

Purpose: Childhood cancer survivors (CCS) demonstrate features of premature aging in a multitude of organ systems. The aim of this pilot study is to determine the presence of premature ocular aging features in CCS, specifically childhood acute lymphoblastic leukemia (ALL) survivors. Methods: This prospective case-control study was conducted over a period of 21 months, starting July 2015 till March 2017. A total of 59 childhood ALL survivors who attended the Paediatric Oncology Clinic of University Malaya Medical Centre (UMMC) and 48 age, race, and gender-matched controls went through a series of ocular examinations and tests. Inclusion criteria used to recruit survivors were age above 16 years, history of ALL in childhood, completion of treatment for ALL, and a remission period of at least 5 years. Patients with ocular disease and those who received hematopoietic stem cell transplantation were excluded. The parameters measured were visual acuity, amplitude of accommodation, pupil cycle time (PCT), and tear break-up time (TBUT). Results: Survivors of childhood ALL demonstrated significant differences in amplitude of accommodation, PCT, and TBUT compared to age-matched controls. Survivors had a lower median (interquartile range [IQR]) amplitude of accommodation compared to controls (11.0 D [9.0-13.0] vs. 12.0 D [10.5-15]; p = 0.045). Survivors also showed a longer median (IQR) PCT in comparison to controls (931.00 mseconds (857.00-1063.00) vs. 875.50 mseconds (825.75-966.00); p = 0.024). In addition, median (IQR) TBUT was worse in survivors in comparison to the control group (9 seconds [6-13] vs. 11 seconds [10-15]; p = 0.001). Conclusion: Survivors of childhood ALL demonstrate premature ocular aging features compared to age-matched controls. Thus, survivors may benefit from having ocular examinations as part of their routine late-effects screening to detect age-related ocular morbidities early in its course.

Assessing dehydration status in dengue patients using urine colourimetry and mobile phone technology.

BACKGROUND: Dengue is a systemic and dynamic disease with symptoms ranging from undifferentiated fever to dengue shock syndrome. Assessment of patients' severity of dehydration is integral to appropriate care and management. Urine colour has been shown to have a high correlation with overall assessment of hydration status. This study tests the feasibility of measuring dehydration severity in dengue fever patients by comparing urine colour captured by mobile phone cameras to established laboratory parameters. METHODOLOGY/PRINCIPAL FINDINGS: Photos of urine samples were taken in a customized photo booth, then processed using Adobe Photoshop to index urine colour into the red, green, and blue (RGB) colour space and assigned a unique RGB value. The RGB values were then correlated with patients' clinical and laboratory hydration indices using Pearson's correlation and multiple linear regression. There were strong correlations between urine osmolality and the RGB of urine colour, with r = -0.701 (red), r = -0.741 (green), and r = -0.761 (blue) (all p-value <0.05). There were strong correlations between urine specific gravity and the RGB of urine colour, with r = -0.759 (red), r = -0.785 (green), and r = -0.820 (blue) (all p-value <0.05). The blue component had the highest correlations with urine specific gravity and urine osmolality. There were moderate correlations between RGB components and serum urea, at r = -0.338 (red), -0.329 (green), -0.360 (blue). In terms of urine biochemical parameters linked to dehydration, multiple linear regression studies showed that the green colourimetry code was predictive of urine osmolality (ß coefficient -0.082, p-value <0.001) while the blue colourimetry code was predictive of urine specific gravity (ß coefficient -2,946.255, p-value 0.007). CONCLUSIONS/SIGNIFICANCE: Urine colourimetry using mobile phones was highly correlated with the hydration status of dengue patients, making it a potentially useful hydration status tool.

Nonclonal Chromosomal Aberrations in Childhood Leukemia Survivors.

BACKGROUND: Survivors of childhood cancer are at risk of developing a second malignancy. One possible mechanism for neoplastic transformation of cells is through induction of persistent genomic instability. This study aims to seek evidence of chromosomal instability in long-term childhood leukemia survivors (CLS) in one of the largest pediatric academic oncology centers in South East Asia. METHODS: 50 asymptomatic (subjects have remained leukemia-free since treatment cessation) CLS and 50 healthy controls were recruited in this cross-sectional study. Of 50 CLS, 44 had acute lymphoblastic leukemia and 6 had acute myeloid leukemia. G-banded karyotyping was performed on unstimulated peripheral blood leukocytes of all subjects. RESULTS: CLS had significantly higher occurrence of karyotypic abnormalities compared to controls. Five CLS harbored six nonclonal abnormalities (mostly aneuploidy) while none were found in controls. CONCLUSION: Subpopulations with nonclonal chromosomal aberrations were present in peripheral blood leukocytes of our cohort of childhood leukemia long-term survivors.

Young adult survivors of childhood acute lymphoblastic leukemia show evidence of chronic inflammation and cellular aging.

BACKGROUND: Large epidemiologic studies have reported the premature onset of age-related conditions, such as ischemic heart disease and diabetes mellitus, in childhood cancer survivors, decades earlier than in their peers. The authors investigated whether young adult survivors of childhood acute lymphoblastic leukemia (ALL) have a biologic phenotype of cellular ageing and chronic inflammation. METHODS: Plasma inflammatory cytokines were measured using a cytometric bead array in 87 asymptomatic young adult survivors of childhood ALL (median age, 25 years; age range, 18-35 years) who attended annual follow-up clinic and compared with healthy, age-matched and sex-matched controls. Leukocyte telomere length (LTL) was measured using Southern blot analysis. RESULTS: Survivors had significant elevation of plasma interleukin-2 (IL-2), IL-10, IL-17a, and high-sensitivity C-reactive protein levels (all P < .05). A raised high-sensitivity C-reactive protein level (>0.8 mg/dL) was related to increased odds of having metabolic syndrome (odds ratio, 7.256; 95% confidence interval, 1.501-35.074). Survivors also had significantly shorter LTL compared with controls (median, 9866 vs 10,392 base pairs; P = .021). Compared with published data, LTL in survivors was similar to that in healthy individuals aged 20 years older. Survivors who received cranial irradiation had shorter LTL compared with those who had not (P = .013). CONCLUSIONS: Asymptomatic young adult survivors of childhood ALL demonstrate a biologic profile of chronic inflammation and telomere attrition, consistent with an early onset of cellular processes that drive accelerated aging. These processes may explain the premature development of age-related chronic conditions in childhood cancer survivors. Understanding their molecular basis may facilitate targeted interventions to disrupt the accelerated aging process and its long-term impact on overall health. Cancer 2017;123:4207-4214. © 2017 American Cancer Society.

Reduced microbial diversity in adult survivors of childhood acute lymphoblastic leukemia and microbial associations with increased immune activation.

BACKGROUND: Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) have health problems that persist or develop years after cessation of therapy. These late effects include chronic inflammation-related comorbidities such as obesity and type 2 diabetes, but the underlying cause is poorly understood. RESULTS: We compared the anal microbiota composition of adult survivors of childhood ALL (N = 73) with healthy control subjects (N = 61). We identified an altered community with reduced microbial diversity in cancer survivors, who also exhibit signs of immune dysregulation including increased T cell activation and chronic inflammation. The bacterial community among cancer survivors was enriched for Actinobacteria (e.g. genus Corynebacterium) and depleted of Faecalibacterium, correlating with plasma concentrations of IL-6 and CRP and HLA-DR+CD4+ and HLA-DR+CD8+ T cells, which are established markers of inflammation and immune activation. CONCLUSIONS: We demonstrated a relationship between microbial dysbiosis and immune dysregulation in adult ALL survivors. These observations suggest that interventions that could restore microbial diversity may ameliorate chronic inflammation and, consequently, development of late effects of childhood cancer survivors.

Immunity in young adult survivors of childhood leukemia is similar to the elderly rather than age-matched controls: Role of cytomegalovirus.

Many treatment complications that occur late in childhood cancer survivors resemble age-related comorbidities observed in the elderly. An immune phenotype characterized by increased immune activation, systemic inflammation, and accumulation of late-differentiated memory CD57(+) CD28(-) T cells has been associated with comorbidities in the elderly. Here, we explored if this phenotype was present in young adult leukemia survivors following an average of 19 years from chemotherapy and/or radiotherapy completion, and compared this with that in age-matched controls. We found that markers of systemic inflammation-IL-6 and human C-reactive protein and immune activation-CD38 and HLA-DR on T cells, soluble CD (sCD)163 from monocytes and macrophages-were increased in survivors compared to controls. T-cell responses specific to cytomegalovirus (CMV) were also increased in survivors compared to controls while CMV IgG levels in survivors were comparable to levels measured in the elderly (>50years) and correlated with IL-6, human C-reactive protein, sCD163, and CD57(+) CD28(-) memory T cells. Immune activation and inflammation markers correlated poorly with prior chemotherapy and radiotherapy exposure. These data suggest that CMV infection/reactivation is strongly correlated with the immunological phenotype seen in young childhood leukemia survivors and these changes may be associated with the early onset of age-related comorbidities in this group.