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Objectives Subjective memory impairment ( SMI) may precede mild cognitive impairment ( MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose ( rCMRglc) among elderly women with SMI. Materials and methods Clinical evaluation, comprehensive neuropsychological test, and 18F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. Results All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: −0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus ( β = 0.43, P = 0.02). Conclusions Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time. [ABSTRACT FROM AUTHOR]

JiEun Kang,1,2,* Kiyon Rhew,3,* Jung Mi Oh,4 NaYoung Han,4 Iyn-Hyang Lee,5 Nam Kyung Je,6 Eunhee Ji,7 Euni Lee,4 Jeong-Hyun Yoon,6 Sandy Jeong Rhie1 1Division of Life and Pharmaceutical Sciences Graduate School, Ewha Womans University, Seoul, Republic of Korea; 2Department of Pharmacy, National Medical Center, Seoul, Republic of Korea; 3College of Pharmacy, Dongduk Women’s University, Seoul, Republic of Korea; 4College of Pharmacy, Seoul National University, Seoul, Republic of Korea; 5College of Pharmacy, Yeungnam University, Gyeongbuk, Republic of Korea; 6College of Pharmacy, Pusan National University, Busan, Republic of Korea; 7College of Pharmacy, Gachon University, Incheon, Republic of Korea *These authors contributed equally to this work Purpose: To assess the degree of satisfaction and expressed needs of pharmaceutical care services in patients with chronic diseases and explore the factors related to the needs from patients’ perspectives for the further development of pharmaceutical care service models. Patients and methods: A cross-sectional survey of 220 patients (mean age ± SD: 61.3±13.1, male:female: 104:116) was conducted. The questionnaire was structured to measure patients’ degree of satisfaction and expressed needs using a 5-point Likert scale. Additionally, preferred duration, methods of service delivery, and willingness to pay were surveyed. Responses were analyzed using an ordinal regression method to predict factors that were related to pharmaceutical care services. Results: Sixty-seven patients had experienced pharmaceutical care services. Their satisfaction levels were high in all categories; however, there were no significant differences between ­categories. The levels of expressed needs were similar among categories without significant differences. The preferred delivery method was a face-to-face conversation combined with being provided with written information (53.2%). The preferred duration was ≤10 min (70.5%). About 48% of the patients showed willingness to pay for the service. Education level and region influenced patients’ needs. Conclusion: The satisfaction and needs of pharmaceutical care services was very positive; however, noticing only a third of patients experienced pharmaceutical care services, this may indicate a lack of awareness and less appreciation of pharmacists by patients. Details concerning patients’ awareness and the value of pharmaceutical care services require further investigation. Keywords: pharmaceutical care service, satisfaction, needs, patient perspective

Hyekyung Jin,1 Yeonhee Kim,2 Sandy Jeong Rhie1,3 1College of Pharmacy, 2Center for Excellence in Teaching & Learning, 3Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea Background: Little is known about the functional health literacy (FHL) associated with medication adherence in elderly patients. The aim of this study was to examine the FHL among older adults and identify influencing factors that can predict medication adherence. Methods: This was a cross-sectional survey. Participants (n=160) aged 65 years and older were selected from outpatient clinics of 3 tertiary care hospitals, 6 community pharmacies, and 2 senior centers between November 1 and 30, 2014. The participants’ FHL was measured using the Korean Functional Health Literacy Test, which consists of 15 items including 8 numeracy and 7 reading comprehension items. Medication adherence was measured by the Adherence to Refills and Medication Scale. Descriptive statistics, chi-square or Fisher’s exact test, and multiple regression analyses were used to analyze the data. Results: The mean score of the total FHL was 7.72±3.51 (range 0–15). The percentage of the total number of correct answers for the reading comprehension subtest and numeracy subtest were 48.1% and 54.4%, respectively. Among 160 participants, 52.5% showed low adherence to medication. The factors affecting medication adherence included the patient’s degree of satisfaction with the service (β=-0.215, P=0.022), sufficient explanation of medication counseling (β=-0.335, P=0.000), education level (β=-0.153, P=0.045), health-related problems (β=-0.239, P=0.004), and dosing frequency (β=0.189, P=0.018). Conclusion: In this study, we found medication adherence of elderly patients was associated with education level, health-related problems, dosing frequency, satisfaction with patient counseling, and explanation of medication, but no association was found with FHL. Pharmacists should consider elderly patients’ individual characteristics such as educational background and specific patient-related health problems, provide sufficient information and explanation of medication, and ensure patient satisfaction with the counseling. Keywords: ARMS, elderly, health literacy, medication adherence

Background/objectives: Understanding the impact of early-life nutritional choices on neurodevelopment in children is a growing area of research. To investigate the association between dietary patterns at multiple timelines and neurodevelopmental outcomes in 6-year-old children., Subjects/methods: This administrative observational study utilized a merged data from the national health insurance database and the health screening program for children. Information on the diet patterns from infancy to 3 years of age was obtained from parent-administered questionnaires. Dietary pattern clusters of the participants were identified using Polytomous Latent Class Analysis. The outcome was neurodevelopment using the Korean Developmental Screening Test (K-DST) at the age of 6 years., Results: The study identified four distinct clusters among with the 133,243 eligible children (49.6% male, birth weight 3.22 kg, head circumference 42.7 cm at 4 months). The control cluster (53.4%) exhibited a diet including breast milk feeding and a variety of dietary patterns at the age of 1 year. In contrast, cluster 1 (36.0%) showed a skewed dietary pattern at the same age. Cluster 2 (6.6%) displayed diverse dietary patterns at one year but primarily consumed formula at four months, while cluster 3 (4.0%) had reduced dietary diversity and formula feeding. Compared with the control cluster, the adjusted odds ratio for unfavorable development was 1.209 (95% CI, 1.156-1.266) in cluster 1, 1.418 (95% CI, 1.312-1.532) in cluster 2, and 1.741 (95% CI, 1.593-1.903) in cluster 3. These findings remained consistent across individual domains of the K-DST., Conclusions: Dietary patterns during infancy and early childhood may be associated with neurodevelopment at the age of 6 years., (© 2024. The Author(s).)

Background: Sitosterolemia is a rare inherited lipid metabolic disorder characterized by increased levels of plant sterols and accelerated atherosclerosis. Although early detection is beneficial for the prevention of disease progression, it is largely underdiagnosed by routine screening based on conventional lipid profiles., Materials and Methods: A gas chromatography-mass spectrometry (GC-MS)-based profiling has been developed and validated to measure the levels of biologically active free sterols, including five endogenous sterols and three plant sterols (sitosterol, campesterol, and stigmasterol) in dried blood spot (DBS)., Results: Within- and between-run precisions were 1.4-11.1 % and 2.2-14.1 %, respectively, while the accuracies were all 86.3 ∼ 121.9 % with the correlation coefficients (r 2 ) > 0.988 for all the sterols. In the patients (four girls and two boys, 6.5 ± 2.8 years), sitosterol levels were significantly increased, with an optimal cut-off value of 2.5 µg/mL distinguishing them from ninety-three age-matched healthy children. A cut-off value of 31.9 µg/mL differentiated the patients from six ABCG5/ABCG8 heterozygous carriers. In addition, the molecular ratios of sitosterol to cholesterol, desmosterol, and 7-dehydrocholesterol provided excellent cut-off values of 26.3, 67.6, and 21.6, respectively, to distinguish patients from both healthy controls and heterozygous carriers., Conclusions: The novel DBS-based GC-MS profiling of free sterols accurately identified patients with sitosterolemia, with a performance comparable to that of a serum assay. The DBS profiling could be more feasible method in clinical practice as well as population screening programs, and it can provide diagnostic cut-off values for individual plant sterols., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Importance: The widespread use of antihistamines in children for treatment of common cold symptoms and their central nervous system effects, like drowsiness, underscore the importance of being aware of the associated risks., Objective: To assess associations between prescriptions of first-generation antihistamines and seizures in children using a comprehensive and nationwide dataset., Design, Setting, and Participants: This cohort study used a self-controlled case-crossover design. Data were obtained from the National Health Insurance Service database in Korea. Children born between January 1, 2002, and December 31, 2005, who visited the emergency department for seizure events (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes R56.8, G40, and G41) during the follow-up period were included. Follow-up was completed on December 31, 2019, and data were analyzed from June 3, 2023, to January 30, 2024., Exposure: First-generation antihistamine prescription., Main Outcomes and Measures: Primary outcome consisted of an index seizure event. Odds ratios (ORs) for seizure events were estimated using a conditional logistic regression model, comparing first-generation antihistamine prescription 1 to 15 days before seizure (hazard period) against control period 1 (31-45 days before the event) and control period 2 (61-75 days before the event) using the same period windows. Stratified analyses were conducted to examine the association with individual participant characteristics., Results: Of 11 729 children who had a seizure event, 3178 (1776 [55.9%] boys) were identified as having been prescribed antihistamines during the hazard or the control period, but not both. Seizure events were predominantly observed in children aged 6 to 24 months (985 [31.0%]) and 25 months to 6 years (1445 [45.5%]). During the hazard period, 1476 first-generation antihistamine prescriptions were recorded, in contrast to 1239 and 1278 prescriptions during control periods 1 and 2, respectively. After multiple confounder adjustments, first-generation antihistamine prescription was associated with an increased seizure event risk during the hazard period (adjusted OR [AOR], 1.22 [95% CI, 1.13-1.31]). Stratified subgroup analyses showed consistent results, particularly in children aged 6 to 24 months who were prescribed first-generation antihistamines having a higher risk (AOR, 1.49 [95% CI, 1.31-1.70]) than children aged 25 months to 6 years (AOR, 1.11 [95% CI, 1.00-1.24]; P = .04 for interaction). Furthermore, sensitivity analyses, including adjustment for exposure window periods, evaluation of new first-generation antihistamine prescriptions, comparison of control points from the same period 1 year prior, and exclusion of individuals using combination drugs, confirmed a similarly high risk., Conclusions and Relevance: In this cohort study, prescriptions for first-generation antihistamines were associated with a 22.0% higher seizure risk in children, especially in those aged 6 to 24 months. These findings emphasize the need for careful and judicious prescription of first-generation antihistamines in young children and underline the need for further research to elucidate associations between antihistamine prescriptions and seizure risk.

Rotavirus is linked to severe childhood gastroenteritis and neurological complications, but its impact on neurodevelopment remains uncertain. We examined data from 1,420,941 Korean children born between 2009 and 2011, using the Korean National Health Insurance System. At age 6, we assessed neurodevelopmental outcomes using the validated Korean Developmental Test, covering six major domains. Utilizing propensity score-based Inverse Probability Weighting to ensure covariates including considering covariates including sex, birth weight, changes in body weight from birth to 4-6 months of age, head circumference at 4-6 months of age, residence at birth, economic status, infant feeding types, and birth year. The main analysis that encompassed 5,451 children with rotavirus hospitalization and 310,874 unexposed individuals reveled heightened odds of suspected delays in fine motor skills and cognition among exposed children. Our results suggest an association between rotavirus-related hospitalization in infancy and suspected delays in fine motor function and cognition in 6-year-olds., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Sickle cell disease (SCD), a group of inherited blood cell disorders that primarily affects Black or African American persons, is associated with severe complications and a >20-year reduction in life expectancy. In 2014, an expert panel convened by the National Heart, Lung, and Blood Institute issued recommendations to prevent or reduce complications in children and adolescents with the most severe SCD subtypes, known as sickle cell anemia (SCA); recommendations included 1) annual screening of children and adolescents aged 2-16 years with transcranial Doppler (TCD) ultrasound to identify those at risk for stroke and 2) offering hydroxyurea therapy to children and adolescents aged ≥9 months to reduce the risk for several life-threatening complications., Methods: Data from the IBM MarketScan Multi-State Medicaid Database were analyzed. TCD screening and hydroxyurea use were examined for 3,352 children and adolescents with SCA aged 2-16 years and continuously enrolled in Medicaid during 2019. Percentage change during 2014-2019 and variation by health subgroups were assessed. Analyses were stratified by age., Results: During 2014-2019, TCD screening increased 27% among children and adolescents aged 10-16 years; hydroxyurea use increased 27% among children aged 2-9 years and 23% among children and adolescents aged 10-16 years. However, in 2019, only 47% and 38% of children and adolescents aged 2-9 and 10-16 years, respectively, had received TCD screening and 38% and 53% of children and adolescents aged 2-9 years and 10-16 years, respectively, used hydroxyurea. For both prevention strategies, usage was highest among children and adolescents with high levels of health care utilization and evidence of previous complications indicative of severe disease., Conclusion and Implications for Public Health Practice: Despite increases since 2014, TCD screening and hydroxyurea use remain low among children and adolescents with SCA. Health care providers should implement quality care strategies within their clinics and partner with patients, families, and community-based organizations to address barriers to delivering and receiving recommended care., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Lewis L. Hsu reports institutional support from the Health Resources and Services Administration, the National Institutes of Health (NIH), the European Commission, the Illinois Department of Public Health, the Joy in Childhood Foundation, Global Blood Therapeutics, Forma Therapeutics, Imara, Baxalta, Cyclerion, and Eli Lilly; consulting fees from DuPont Nemours Children’s Hospital, Hoffman-LaRoche, DisperSol, Guidepoint, Magellan, Deerfield, and Kuwait University; speaker honoraria from the Foundation for Sickle Cell Disease Research, Bridgeport Hospital, and Tova Health Center; participation on an Aruvant Data Safety Monitoring Board and service as a scientific advisor or member of an expert advisory board for the NIH Sickle Cell Disease Advisory Committee, Hilton Publishing, and the Illinois Universal Newborn Screening Advisory Committee; and unpaid memberships in the Sickle Cell Disease Association of America, the Sickle Cell Disease Association of Illinois, and the National Alliance of Sickle Cell Centers. No other potential conflicts of interest were disclosed.

Objectives: To identify computed tomography (CT)-based radiomic signatures of cluster of differentiation 8 (CD8)-T cell infiltration and programmed cell death ligand 1 (PD-L1) expression levels in patients with clear-cell renal cell carcinoma (ccRCC)., Methods: Seventy-eight patients with pathologically confirmed localized ccRCC, preoperative multiphase CT and tumor resection specimens were enrolled in this retrospective study. Regions of interest (ROI) of the ccRCC volume were manually segmented from the CT images and processed using a radiomics panel comprising of 1708 metrics. The extracted metrics were used as inputs to three machine learning classifiers: Random Forest, AdaBoost, and ElasticNet to create radiomic signatures for CD8-T cell infiltration and PD-L1 expression, respectively., Results: Using a cut-off of 80 lymphocytes per high power field, 59 % were classified to CD8 highly infiltrated tumors and 41 % were CD8 non highly infiltrated tumors, respectively. An ElasticNet classifier discriminated between these two groups of CD8-T cells with an AUC of 0.68 (95 % CI, 0.55-0.80). In addition, based on tumor proportion score with a cut-off of > 1 % tumor cells expressing PD-L1, 76 % were PD-L1 positive and 24 % were PD-L1 negative. An Adaboost classifier discriminated between PD-L1 positive and PD-L1 negative tumors with an AUC of 0.8 95 % CI: (0.66, 0.95). 3D radiomics metrics of graylevel co-occurrence matrix (GLCM) and graylevel run-length matrix (GLRLM) metrics drove the performance for CD8-Tcell and PD-L1 classification, respectively., Conclusions: CT-radiomic signatures can differentiate tumors with high CD8-T cell infiltration with moderate accuracy and positive PD-L1 expression with good accuracy in ccRCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors.)

Background: Congenital muscular torticollis (CMT) is a common musculoskeletal disorder occurring at birth or in infancy., Purpose: This study aimed to investigate the risk of comorbidities in CMT and explore the differences in neurodevelopmental outcomes between children who received physical therapy and those who did not., Methods: Children with CMT born in 2008 and 2009 in Korea were included. CMT was defined as a primary diagnosis of congenital deformity of sternocleidomastoid muscle according to the International Classification of Diseases 10th revision. Here we investigated the associated neurological/musculoskeletal comorbidities of children with CMT versus those of the general population. We divided those with torticollis into treatment and nontreatment groups and assessed their developmental outcomes within both groups of children using the Korean-Ages and Stages Questionnaire (K-ASQ)., Results: Of the 917,707 children, 0.2% (n=1,719) were diagnosed with CMT. In children with torticollis, the prevalence of congenital hip deformities significantly increased to 4.5% (n=78). The prevalence of congenital head/spine deformities and other congenital malformations of the skull and facial bones increased to 2.6% (n=44), while the prevalence of congenital foot deformities was 2.4% (n=42). The risk ratio (RR) for delayed development based on the K-ASQ was higher for the total assessment (adjusted RR=0.97; 95% confidence interval, 0.93-0.99) in the CMT patients without physical therapy than in those with therapy. There was no significant intergroup difference in the assessment of each developmental area., Conclusion: The prevalence of comorbid musculoskeletal deformities was higher in children with CMT than in the control group. The risk of developmental delay was higher in children who did not receive physical therapy than in those who did.

Background: The diagnostic yield of whole-exome sequencing (WES) varies from 30%-50% among patients with mild to severe neurodevelopmental delay (NDD)/intellectual disability (ID). Routine retrospective reanalysis of undiagnosed patients has increased the total diagnostic yield by 10-15%. Here, we performed proband-only WES of 1065 patients with NDD/ID and applied a prospective, daily reanalysis automated pipeline to patients without clinically significant variants to facilitate diagnoses., Methods: The study included 1065 consecutive patients from 1056 nonconsanguineous unrelated families from 10 multimedical centers in South Korea between April 2018 and August 2021. WES data were analyzed daily using automatically updated databases with variant classification and symptom similarity scoring systems., Results: At the initial analysis, 402 patients from 1056 unrelated families (38.0%, 402/1,056 families) had a positive genetic diagnosis. Daily prospective, automated reanalysis resulted in the identification of 34 additional diagnostic variants in 31 patients (3%), which increased our molecular diagnostic yield to 41% (433/1056 families). Among these 31 patients, 26 were diagnosed with 23 different diseases that were newly discovered after 2019. The time interval between the first analysis and the molecular diagnosis by reanalysis was 1.2 ± 0.9 years, which was shorter in the patients enrolled during the latter part of the study period., Conclusion: Daily updated databases and reanalysis systems enhance the diagnostic performance in patients with NDD/ID, contributing to the rapid diagnosis of undiagnosed patients by applying the latest molecular genetic information., (© 2022. The Author(s).)

Objectives: This study aimed to investigate the association between adenotonsillectomy (T&A) and serial changes in growth in children through a population-based nationwide study as well as the national health insurance service (NHIS) database., Methods: Propensity score (PS) matched children with and without T&A were selected in NHIS database, which includes all individuals born in Korea in 2008-2009. Serial changes of BMI and height were compared in children with and without T&A, and growth changes depending on the time of operation were also considered. The outcomes were differences in age-/sex-standardized BMI (BMI-z) and height (height-z) between the groups. Changes in BMI-z and height-z were further analyzed according to the timing of operation., Results: Of 919,707 individuals born in Korea in 2008-2009, 3172 children were included in the operation group and 31,663 PS-matched children were included in the control group. T&A was related to increased weight and height in the operation group than in the control group. At 66-71 months of age, BMI-z and height-z were 0.41 (0.02) and 0.42 (0.02), respectively, in the operation group and 0.18 (0.01) and 0.35 (0.01), respectively, in the control group. On adjustment with preoperative BMI-z, more weight gain was noted in the operation group (p < 0.001). Shortly after T&A, BMI-z increased significantly in the operation group; a significant increase in height-z was observed more than 1 year after T&A., Conclusions: Children who underwent T&A tended to experience a growth spurt; when surgical intervention such as T&A is required, care should be taken to minimize or reverse the anticipated weight gain., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Previous research reported associations of excessive daytime sleepiness (EDS) with a low vitamin D level, obesity, and sexual maturity. The aim of this study was to identify the association and rank the importance of these with EDS. This study examined 618 children who were 10-12 year-old. The pediatric daytime sleepiness scale (PDSS) was used to evaluate EDS and sleep patterns. EDS was defined as a total PDSS score above 17. We ranked the importance of the relationship of these factors with EDS using random forest analysis. EDS (n = 111, 18%) was positively associated with more advanced pubertal stage in girls, chronic cough, urticaria, and allergic rhinitis. Multivariable analysis with adjustment for confounding indicated that children with low level of 25-hydroxyvitaminD 3 (25(OH)D 3 (<20 ng/mL) and high-density lipoprotein-cholesterol (HDL-C) (<40 mg/dL) levels had an increased risk of EDS (25(OH)D 3 :adjusted odds ratio [aOR] = 1.73; 95% confidence interval [CI]: 1.06 to 2.81; P = 0.028; HDL-C: aOR = 2.84; 95% CI: 1.05 to 7.68; P = 0.039). Random forest analysis indicated that 25(OH)D 3 level, exercise, and body mass index (BMI) were over three. This study indicated high levels of 25-(OH)D 3 and HDL-C and performing regular exercise decreased the risk of EDS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 × 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP., Methods: Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for ≥ 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of ≥ 3 × 10 7 /kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored., Results: Eighty-eight of 92 children enrolled (3.05 ± 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month (△2.30 vs. △0.71, P = 0.025) and 12 months (△6.85 vs. △2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age ≥ 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration., Conclusions: These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects., Trial Registration: ClinicalTrials.gov, NCT01991145 , registered 25 November 2013.

Acute pyelonephritis (APN) should be detected and treated as soon as possible to reduce the risk of the development of acquired renal scarring. However, in the medical field, urine culture results are not available or considered when the prompt discrimination of APN is necessary and empirical treatment is started. Furthermore, urine culture cannot discriminate APN among children with febrile urinary tract infection (UTI) (pyelitis, lower UTI with other fever focus). Therefore, the usefulness of urine culture for diagnostic purposes is small and the sampling procedure is invasive. Congenital hypoplastic kidney is the most common cause of chronic kidney injury in children. Thus, it is desirable that a main target be detected as early as possible when imaging studies are performed in children with APN. However, if APN does not recur, no medical or surgical treatment or imaging studies would be needed because the acquired renal scar would not progress further. Therefore, the long-term prognosis of APN in young children, particularly infants, depends on the number of recurrent APN, not other febrile UTI. New methods that enable prompt, practical, and comfortable APN diagnosis in children are needed as alternatives to urinary catheterization for urine culture sampling.

Delaying the time of start of school allows for longer sleep duration, better mood, and better school performance. In South Korea, a campaign was launched in 2014 to delay the school start time to 9 a.m. We analyzed the campaign's effects on adolescents' total sleep duration, sleepiness (presented as weekend catch-up sleep), emotions, and school performance. Based on data from 2013, changes of sleep patterns, emotions, and academic achievement in adolescents were evaluated using the 2012-2016 Korea Youth Risk Behavior Web-based survey from two educational districts: Gyeonggi (fully participated in the delayed school start time campaign; intervention group) and Daegu/Gyeongbuk/Ulsan (DGU, never participated; control group). The primary outcomes were sleep duration, time of sleep onset, and difference in sleep duration between weekdays and the weekend. Secondary outcomes were the proportional changes of mood, stress, and school performance. The sleep duration of students in the intervention group temporarily increased in 2015. However, because there was a simultaneous delay in time of sleep onset, sleep duration returned to pre-campaign levels in 2016. Although sleep duration did not increase, weekend catch-up sleep decreased by approximately 19 minutes for students in the intervention group. Meanwhile, in the control group sleep duration tended to decrease over the same period. The impact of the campaign on students' emotions and school performance could not be confirmed. This study demonstrated that delaying the school start time to 9 a.m. reduced duration of weekend catch-up sleep with a transient increase in sleep duration in adolescents., Competing Interests: The authors have declared that no competing interests exist.

We investigated whether antinatriuretic phenomena [decreases in urinary sodium (uNa) and fractional excretion of sodium (FENa)] seen in children with acute pyelonephritis (APN) are associated with the renin-angiotensin-aldosterone system (RAAS).We examined 114 children experiencing their first episode of febrile urinary tract infection (fUTI) consecutively admitted to our hospital from July 2012 to June 2014. Blood tests [C-reactive protein, white blood cell count, erythrocyte sedimentation rate, and aldosterone (Aldo)] and urine tests [uNa, urine potassium (uK) and FENa] were performed upon admission. All enrolled children underwent a 99m-dimercaptosuccinic acid renal scanning (DMSA) at admission. Areas with cortical defects (AreaCD) and uptake counts (UptakeCD) on their DMSA scans were calculated. Data were compared between children with positive DMSA results (APN), lower urinary tract infection (L-UTI), and controls; and between children with high and low Aldo levels.uNa, uNa/K, and FENa negatively correlated with AreaCD%, UptakeCD, and Aldo; were significantly lower in APN patients than in LUTIs and controls regardless of Aldo level; were lower in the high Aldo group than in the low Aldo group. However, there is no difference in AreaCD% and UptakeCD between APN children with the high and low Aldo level.Decreases in uNa, uNa/K, and FENa in children with APN may result from an antinatriuretic effect of RAAS and be related to the activation of the intrarenal RAAS.

Gefitinib is a drug used for the treatment of non-small cell lung cancer (NSCLC) patients. Severe hepatotoxicity was observed, but only a few cases have been reported on the hepatotoxicity of gefitinib. This study aimed to investigate the association between gefitinib-induced hepatotoxicity and various factors including concomitant medications in lung cancer patients. From January 2013 to December 2014, a retrospective study was performed with NSCLC patients who were treated with gefitinib. Associations between hepatotoxicity and various factors including concomitant drugs were analyzed. Based on multivariate models, it was found that H2 antagonists, proton pump inhibitors (PPIs), and H2 antagonists or PPIs increased hepatotoxicity by about 1.5- to 1.7-fold. Patients younger than 65 years showed 1.6 times higher hepatotoxicity than those older than 65 years. Patients with EGFR mutations had around 2-fold higher hepatotoxicity, and the percentage of incidence of hepatotoxicity because of exon 19 deletion was 32.7%. Our study showed that anti-acid-secreting agents in addition to age younger than 65 years and EGFR mutation were associated with gefitinib-induced hepatotoxicity. Thus, close monitoring of liver function is recommended, especially for patients using anti-acid-secreting agents., (© 2017, The American College of Clinical Pharmacology.)

Background: Sudden breath-holding episodes during sleep in young children are potentially related to sudden infant death syndrome and other life-threatening events. Additionally, these episodes can negatively affect child's growth and development., Case Presentation: Here, we present 3 cases of preschool children with similar paroxysmal nocturnal waking events associated with choking that had different etiologies (nocturnal frontal lobe epilepsy, nocturnal gastroesophageal reflux disease, and parasomnia, respectively)., Conclusions: It is important to take into consideration the fact that breath spells during sleep can occur as a rare manifestation of parasomnia due to gastroesophageal reflux or as a symptom of nocturnal frontal lobe epilepsy. Full video electroencephalography, polysomnography, and simultaneous gastric pH monitoring should be used for the differential diagnosis of sleep-related disorders, such as breath spells, in children.

Background: The aim of this study was to evaluate the results of sleep-wake cycle monitoring using amplitude-integrated EEG (aEEG) and neuroimaging in newborn infants with a possible perinatal hypoxic insult, investigate the correlation between the findings, and determine the relevance of the findings to reasonably predict neurological outcome., Methods: aEEG was recorded among newborn infants suspected of perinatal asphyxia between November, 2014 and June, 2015 in one neonatal intensive care unit facility. Brain imaging with serial ultrasonography and MRI when available were performed, and the infants were divided into two groups according to findings and potential neurological outcome: Group I (favorable findings) and Group II (severe findings such as high grade intraventricular hemorrhage, cerebral infarction or white matter injury). Established sleep-wake cycle times after birth was compared between the two groups., Results: Among 107 newborn infants, 85 subjects were classified as Group I and the remaining 22 subjects as Group II. The total number of aEEG sessions was 207 and recording time was 2,796 h with a mean of 14.43 ± 13.40 h per study. Estimated times of cyclicity were earlier in Group I (113.34 h, 95 % CI 82.31-144.37) as compared to Group II (504.39 h, 95 % CI 319.91-688.88; p < 0.001)., Conclusions: Delayed cyclicity on aEEG has a strong correlation with unfavorable brain neuroimages in newborns with possible perinatal asphyxia. If sleep-wake cycles do not appear during initial period after birth, follow-up aEEG studies are recommended., Trial Registration: Retrospectively registered Registration number: BD 2015-148 Name of registry: amplitude integrated EEG in neonate Date of registration: September 9, 2015.

Background: Many studies have investigated the association between Guillain-Barré syndrome (GBS) and vaccinations during the influenza A H1N1 pandemic of 2009 (pH1N1). Based on a nationally representative sample, we estimated the incidence of GBS during the pandemic period in Korea., Materials and Methods: All medical records of GBS cases were reviewed in 28 randomly selected hospitals during 2008-2010, and the number of GBS cases at the national level was extrapolated using emergency care utilization data. The GBS rate per 100,000 person-years was estimated in the reference and pandemic periods., Results: The incidence of GBS was 0.63 (95% CI: 0.37-0.89) per 100,000 person-years in the reference period and 0.87 (0.49-1.26) in the pandemic period. During the vaccination season, the pandemic period GBS incidence rate was not significantly higher than the reference period incidence rate (rate ratio: 1.52; 0.99-2.32), but difference was observed among persons aged 20-34 years. Rate of GBS increased after pH1N1 vaccination compared to the reference period (1.46, 1.26-1.68)., Discussion: The incidence of GBS increased slightly but not significantly during the pandemic period, although pH1N1 vaccination increased the GBS rate. Therefore, mass influenza vaccination programs should not be precluded on the basis of GBS., (Copyright © 2015 Elsevier Ltd. All rights reserved.)