OBJECTIVE: To summarize the current information on popPK of polyclonal IgG therapy.
METHOD: A systematic search was conducted in the PubMed and Web of Science databases from inception to December 2020. Additional relevant studies were also included by reviewing the reference list of the reviewed articles. All popPK studies that employed the NLME modeling approach were included and data were synthesized descriptively.
RESULTS: This review included seven studies. Most of the popPK models were developed in patients with primary immunodeficiency (PID). IgG pharmacokinetics was described as a two-compartment model in five studies, while it was described as a one-compartment model in two other studies. Among all tested covariates, weight was consistently identified as a significant predictor for clearance (CL) of IgG. Whereas, weight and disease type were found to be significant predictors for the volume of distribution in central compartment (Vc). In a typical 70 kg adult, the median estimated values of Vc and CL were 4.04 L and 0.144 L/day, respectively. The between subject variability of Vc was considered large. Only two studies evaluated their models using external data.
CONCLUSIONS: Seven popPK studies of IgG were found and discussed, with only weight being a significant covariate across all studies. Future studies linking pharmacokinetics with pharmacodynamics in PID and other patient populations are required.
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
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.
Materials and Methods: This is a retrospective descriptive study. A total of 29 patients diagnosed with MB from January 2005 to December 2015 were included in this study. The MRI brain and spine studies of these patients were retrieved and reviewed by a pediatric radiologist and a neuroradiologist independently, both blinded from the histological type of the MB. The HPE slides were also retrieved and reviewed by a pathologist.
Results: 80% of desmoplastic MB showed the presence of intracranial leptomeningeal seeding and 57.1% of anaplastic MB showed the presence of necrosis. The presence of intracranial leptomeningeal seeding (P = 0.002) and necrosis (P = 0.019) was predictive of the histological subtypes. There is a significant correlation between the enhancement pattern and the 2-year outcome (P = 0.03) with 6 out of 8 patients whose tumors showed minimal enhancement having disease progression within 2 years. A significant correlation was also seen between the presence of necrosis with a poorer outcome (P = 0.03) and between the HPE subtype and 2-year outcome (P = 0.03) with anaplastic MB having the poorest prognosis.
Conclusion: MR imaging features of intracranial leptomeningeal seeding and the presence of necrosis were correlated with a specific histologic subtype of MB. The enhancement pattern as well as necrosis correlated with 2-year poorer outcome of the disease.
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 1), and 1493 downregulated probes which corresponded to 1214 genes (pfp
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.
METHODS: A web-based cross-sectional survey was conducted between 12th and May 13, 2020. Quota sampling was used to attain equal gender and age distributions representative of the Japanese population.
RESULTS: A total of 4127 complete responses were analysed. Higher educational level (B = 0.045, p = 0.002) and household income (B = 0.04, p = 0.009) were associated with a higher increase in preventive measures when comparing before and after the state of emergency was declared. The highest reported social anxiety was a feeling of fear (65.6%), followed by embarrassment (43.8%), keeping infection a secret (41.3%), avoidance (41.3%), and stigma (25.5%). A total of 86.1% of the respondents reported moderate to severe anxiety. The partial least square-based structural equation modelling (PLS-SEM) revealed that being female has the greatest effect (B = 0.246, p