Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Incidence of Type 2 Diabetes in Children With Nonalcoholic Fatty Liver Disease

Background & aimsType 2 diabetes (T2D) is a growing problem in children. Children with NAFLD are at potentially high risk for developing T2D; however, the incidence of T2D in this population is unknown. This study aimed to determine the incidence of T2D in children with NAFLD and identify associated risk factors.MethodsChildren with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network were followed longitudinally. Incidence of T2D was determined by using clinical history and fasting laboratory values. Cumulative incidence curves were developed for time to T2D. A Cox regression multivariable model was constructed using best subsets Akaike's Information Criteria selection.ResultsThis study included 892 children with NAFLD and with a mean age of 12.8 years (2.7) followed for 3.8 years (2.3) with a total 3234 person-years at risk. The incidence rate of T2D was 3000 new cases per 100,000 person-years at risk. At baseline, 63 children had T2D, and during follow-up, an additional 97 children developed incident T2D, resulting in a period prevalence of 16.8%. Incident T2D was significantly higher in females versus males (hazard ratio [HR], 1.8 [1.0-2.8]), associated with BMI z-score (HR, 1.8 [1.0-3.0]), and more severe liver histology including steatosis grade (HR, 1.3 [1.0-1.7]), and fibrosis stage (HR, 1.3 [1.0-1.5]).ConclusionsChildren with NAFLD are at high risk for existing and incident T2D. In addition to known risk factors for T2D (female and BMI z-score), severity of liver histology at the time of NAFLD diagnosis was independently associated with T2D development. Targeted strategies to prevent T2D in children with NAFLD are needed

Durability and extent of protection of SARS-CoV-2 antibodies among patients with COVID-19 in Metro Manila, Philippines

IntroductionInformation on the magnitude and durability of humoral immunity against COVID-19 among specific populations can guide policies on vaccination, return from isolation and physical distancing measures. The study determined the durability of SARS-CoV-2 antibodies after an initial infection among Filipinos in Metro Manila, Philippines, and the extent of protection SARS-CoV-2 antibodies confer against reinfection.MethodsWe conducted a cohort study to monitor the antibody levels of patients diagnosed with COVID-19. Receptor-binding domain (RBD)-specific antibodies were measured at Days 21, 90, 180, 270 and 360. Antibody levels were reported as geometric mean titers (GMT) with geometric standard deviation (GSD). Differences in GMT were tested using Friedman test and Kruskal Wallis test, with Bonferroni multiple comparisons procedure. Adjusted hazard ratios on the development of probable reinfection were estimated using Cox proportional models.ResultsThere were 307 study participants included in the study, with 13 dropouts. Study participants received SARS-CoV-2 vaccines at varying times, with 278 participants (90.5%) fully vaccinated by the end of study. The GMT of the study cohort increased over time, from 19.7 U/mL (GSD 11) at Day 21; to 284.5 U/mL (GSD 9.6) at Day 90; 1,061 U/mL (GSD 5.3) at Day 180; 2,003 U/mL (GSD 6.7) at Day 270; and 8,403 U/mL (GSD 3.1) at Day 360. The increase was statistically significant from Day 21 to Day 90 (p<0.0001), Day 90 to Day 180 (p=0.0005), and Day 270 to Day 360 (p<0.0001). Participants with more severe initial infection demonstrated significantly higher antibody levels compared to those with milder infection at Day 21. Sixty-four patients had probable COVID-19 reinfection (incidence of 20.8%, 95% CI 16.4, 25.8%). The GMT of these 64 patients was 411.8 U/mL (GSD 6.9) prior to the occurrence of the probable reinfection. Majority (87.5%) were fully vaccinated. Antibody titers significantly affected the risk of developing reinfection, with adjusted hazard ratio of 0.994, 95% CI 0.992-0.996, p<0.001.ConclusionAntibody levels against SARS-CoV-2 increased over a one-year follow-up. Higher antibody levels were observed among those with more severe initial infection and those vaccinated. Higher antibody levels are associated with a lower risk of probable reinfection

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis

Sociodemographic Differences in COVID-19 Pandemic Experiences Among Families in the United States

Few population-based studies in the US collected individual-level data from families during the COVID-19 pandemic.To examine differences in COVID-19 pandemic–related experiences in a large sociodemographically diverse sample of children and caregivers.The Environmental influences on Child Health Outcomes (ECHO) multi-cohort consortium is an ongoing study that brings together 64 individual cohorts with participants (24 757 children and 31 700 caregivers in this study) in all 50 US states and Puerto Rico. Participants who completed the ECHO COVID-19 survey between April 2020 and March 2022 were included in this cross-sectional analysis. Data were analyzed from July 2021 to September 2022.Exposures of interest were caregiver education level, child life stage (infant, preschool, middle childhood, and adolescent), and urban or rural (population &lt;50 000) residence. Dependent variables included COVID-19 infection status and testing; disruptions to school, child care, and health care; financial hardships; and remote work. Outcomes were examined separately in logistic regression models mutually adjusted for exposures of interest and race, ethnicity, US Census division, sex, and survey administration date.Analyses included 14 646 children (mean [SD] age, 7.1 [4.4] years; 7120 [49%] female) and 13 644 caregivers (mean [SD] age, 37.6 [7.2] years; 13 381 [98%] female). Caregivers were racially (3% Asian; 16% Black; 12% multiple race; 63% White) and ethnically (19% Hispanic) diverse and comparable with the US population. Less than high school education (vs master’s degree or more) was associated with more challenges accessing COVID-19 tests (adjusted odds ratio [aOR], 1.88; 95% CI, 1.06-1.58), lower odds of working remotely (aOR, 0.04; 95% CI, 0.03-0.07), and more food access concerns (aOR, 4.14; 95% CI, 3.20-5.36). Compared with other age groups, young children (age 1 to 5 years) were least likely to receive support from schools during school closures, and their caregivers were most likely to have challenges arranging childcare and concerns about work impacts. Rural caregivers were less likely to rank health concerns (aOR, 0.77; 95% CI, 0.69-0.86) and social distancing (aOR, 0.82; 95% CI, 0.73-0.91) as top stressors compared with urban caregivers.Findings in this cohort study of US families highlighted pandemic-related burdens faced by families with lower socioeconomic status and young children. Populations more vulnerable to public health crises should be prioritized in recovery efforts and future planning

Goal Attainment Scaling and Quality of Life of Autistic Children Receiving Speech and Language Therapy in a Higher Educational Institution in the Philippines

Objectives. This study aimed to describe the demographic profile, intervention sessions, goal attainment scaling (GAS), and health-related quality of life (HRQOL) of autistic children receiving speech and language therapy (SLT) in a higher educational institution in the Philippines. Methods. Deidentified data from 18 autistic children aged 4–16 years (mean=8.2; SD=2.9) who received SLT for two months were analyzed. Their demographic profile, intervention sessions, GAS scores, and generic HRQOL scores were documented. Results. Most participants were school-age children (n=12; 66%) and were boys (n=14; 78%). After two months, the GAS scores of 11 participants (61%) increased by 1–2 points, whereas the scores of the remaining participants decreased (n=6; 33%) or did not change (n=1; 6%). Their mean generic HRQOL scores before and after SLT were 65.6 (SD=15.2) and 61.2 (SD=17.4), respectively. Conclusions. While the GAS scores increased for most participants, their generic HRQOL scores did not show clinically significant changes after two months of SLT. This can be attributed to the few therapy sessions and short follow-up period. The findings highlight the need to provide long-term support to SLT services of autistic children in the Philippines to document more desirable quality of life outcomes

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Background: Mucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female relatives. Results: The mean age of the patients was 11.28 (SD 4.10) years with an average symptom onset at 1.2 (SD 1.4) years. The mean age at biochemical diagnosis was 8 (SD 3.2) years. The early clinical characteristics were developmental delay, joint stiffness, coarse facies, recurrent respiratory tract infections, abdominal distention and hernia. Majority of the patients had joint contractures, severe intellectual disability, error of refraction, hearing loss and valvular regurgitation on subspecialists' evaluation. The mean GAG concentration was 506.5 mg (SD 191.3)/grams creatinine while the mean plasma iduronate-2-sulfatase activity was 0.86 (SD 0.79) nmol/mg plasma/4 h. Fourteen (14) mutations were found: 6 missense (42.9%), 4 nonsense (28.6%), 2 frameshift (14.3%), 1 exon skipping at the cDNA level (7.1%), and 1 gross insertion (7.1%). Six (6) novel mutations were observed (43%): p.C422F, p.P86Rfs∗44, p.Q121∗, p.L209Wfs∗4, p.T409R, and c.1461-1462insN[710]. Conclusion: The age at diagnosis in this series was much delayed and majority of the patients presented with severe neurologic impairment. The results of the biochemical tests did not contribute to the phenotypic classification of patients. The effects of the mutations were consistent with the severe phenotype seen in the majority of the patients

Early experience with COVID-19 patients in a private tertiary hospital in the Philippines: Implications on surge capacity, healthcare systems response, and clinical care

Background: Our healthcare institution was one of the first to see SARS CoV-2 cases in the country. We describe the early COVID-19 experience of a private hospital in the Philippines and discuss the healthcare system response in the setting of surge capacity. Methods: We reviewed the medical records of adult COVID-19 hospitalized patients admitted in March 2020. We reported their demographic and clinical characteristics using descriptive statistics. Results: Of 40 patients admitted, 23 (57.5%) were male and 19 (47.5%) were aged <60 years. Most (n = 27, 67.5%) had moderate-risk, 9 (22.5%) had high-risk, and 4 (10%) had low-risk COVID-19. SARS-CoV-2 testing took 5.5 (range 1–10) days. Overall mortality rate was 6/40 (15.0%). Clinical cure was documented in all low-risk patients, 25 (92.6%) moderate-risk patients, and only 1 (11.1%) high-risk patient. In response to the surge, the hospital rapidly introduced one-way traffic systems, dedicated screening, triage and Emergency Department areas for COVID-19, a clinical pathway, engineering controls, patient cohorting, and strict infection prevention and control measures. Conclusion: Majority of patients recovered from COVID-19. Older age and high-risk pneumonia were associated with poor outcomes. Adaptations to hospital structure and staff were quickly made in response to surge capacity, although our response was hampered by prolonged time to COVID-19 confirmation. Our study underscores the urgent need for rapid adaptive response by the healthcare system to address the surge of cases

Selected Hiligayon Novels: Translation and Evaluation

This descriptive-evaluative study aimed to translate and evaluate selected Hiligaynon novels. In the translation, the following steps were followed: reading and understanding the work to fully capture the general thought, essence, and message; translation and development of the first manuscript; validation and improvement of the first manuscript based on the suggestions of experts/consultants; revising, refining, and developing the final form and evaluating the appropriateness of the translated Hiligaynon novels. Three teachers of Hiligaynon literature and language evaluated the appropriateness of the translation. The result of the evaluation showed that the translated novels were appropriate as a whole, and also appropriate according to various criteria. It was concluded that the translators possess the characteristics and knowledge of the translated works, and also have proficiency in the two languages ​​involved in the translation. It is suggested to further polish the translation of selected Hiligaynon novels. Moreover, it is proposed to include the translated novels as teaching and reference materials for teachers, students, and researchers in schools and libraries and to carry out further translation of other Hiligaynon novels towards the development of local Ilonggo literature

Reinfection rates, change in antibody titers and adverse events after COVID-19 vaccination among patients previously infected with COVID-19 in Metro Manila, Philippines: a secondary analysis of a completed cohort study

Abstract Background Variation in immune response to COVID-19 vaccines is observed among different ethnicities. We aimed to describe the reinfection rates, change in antibody titers, and adverse events among Filipinos. Methods This is a secondary analysis of a cohort study of 307 participants within one year of having COVID-19 infection. We measured COVID-19 antibody levels at pre-determined timepoints (Days 21, 90, 180, 270, and 360 from initial infection). We monitored for COVID-19 symptoms and obtained details on COVID-19 vaccination. An adjudication committee classified the participants as probable, possible, or unlikely COVID-19 reinfection. We determined the probable reinfection rate, adverse events, and the geometric mean titer (GMT) ratio of pre- and post-vaccination antibody levels according to type and brand of COVID-19 vaccine. Results At the end of the follow-up period, 287 (93.5%) out of 307 study participants were fully vaccinated, 1 was partially vaccinated (0.3%), and 19 were unvaccinated (6.2%). Among the fully vaccinated participants, those given mRNA vaccines had the lowest reinfection rate (19.2 cases/100 person-years, 95% CI 9.6, 38.4), followed by viral vector vaccines (29.8 cases/100 person-years, 95% CI 16.9, 52.4). We observed the highest reinfection rate among those given inactivated virus vaccines (32.7 cases/100 person-years, 95% CI 23.6, 45.3). The reinfection rate was 8.6 cases/100 person-years (95% CI 4.1, 17.9) for unvaccinated participants and 3.6 cases/100 person-years (95% CI 0.5, 25.3) for partially vaccinated participants. We observed the largest rise in antibody titers among those given mRNA vaccines (GMT ratio 288.5), and the smallest rise among those given inactivated virus vaccines (GMT ratio 16.7). We observed the highest percentage of adverse events following immunization with viral vector vaccines (63.8%), followed by mRNA vaccines (62.7%), and the lowest for inactivated virus vaccines (34.7%). No serious adverse events were reported. Conclusion Vaccinees given the mRNA vaccines had the lowest reinfection rate and the highest rise in antibody titers. Vaccinees given inactivated virus vaccines had the highest reinfection rate, smallest rise in antibody titers, and lowest percentage of adverse events. The small sample size and imbalanced distribution of the type of vaccines received limits the external generalizability of our results. Study Registration The cohort study was registered at the Philippine Health Research Registry on December 14, 2020 (PHRR201214-003199)