Off-label use of long-acting injectable antiretroviral therapy: A Single Center Retrospective Review of Youth Living with HIV with detectable HIV RNA starting Injectable Therapy.

Nineteen youth living with HIV (YLWH) opted for injectable cabotegravir and rilpivirine without oral lead in and without achieving an undetectable HIV viral load (VL) for the 3 months prior to initiation. All achieved undetectable status within 3 months (3 injections) and maintained an undetectable status through 6-12 months of therapy.

Pharmacokinetics and safety of coformulated bictegravir, emtricitabine, and tenofovir alafenamide in children aged 2 years and older with virologically suppressed HIV: a phase 2/3, open-label, single-arm study.

BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.

Treasure (Hunt for) Your Health! Addressing Pediatric Social Determinants of Health Through Child-Friendly Community Engagement Events.

Social determinants of health (SDoH), including factors such as education level, housing, poverty, racism, and food insecurity and their impact on health outcomes have been well documented. The "Wayne Pediatrics Health and Nutrition Expo" held at Detroit's Eastern Market was an activity-based health and nutrition event addressing pediatric SDoH. Partnering with community organizations, the event had 10 stations addressing SDoH: access to a primary-care pediatrician; HIV-care and prevention; childhood literacy; clothing & winter coats; mental health and childhood development; nutrition; staying active; vaccination; and food insecurity. The free, public event featured a child-themed treasure hunt and map, music, giveaways, and live demonstrations, all in a family-friendly park atmosphere. While SDoH are considered "non-medical" factors that contribute to health and may be difficult to completely address for any individual child, our practice addressed several key SDoH at a single-day, hands-on, child-friendly community event based on the local needs of children.

A tale of two intensive care units (ICUs): Baseline Staphylococcus aureus colonization and mupirocin susceptibility in neonatal and pediatric patients requiring intensive care.

OBJECTIVE: To assess the incidence rate of S. aureus colonization at baseline along with the mupirocin susceptibility (or resistance) rate in patients in a neonatal intensive care unit (NICU) and a pediatric intensive care unit (PICU) in conjunction with the implementation of universal decolonization as the standard of care. DESIGN: Prospective cohort study. SETTING: Children's Hospital of Michigan (CHM) inpatient intensive care units (ICUs). PARTICIPANTS: Newly admitted pediatric patients to the CHM NICU or PICU aged between 1 day and ≤21 years. INTERVENTIONS: Baseline and follow-up S. aureus screening cultures were obtained before patients underwent universal decolonization with mupirocin 2% antibiotic ointment (intranasal and umbilical) and chlorhexidine baths as standard of care to reduce CLABSI rates. RESULTS: Baseline S. aureus colonization rates of new admissions to the CHM NICU and PICU were high at 32% and 29%, respectively. Baseline mupirocin susceptibility to any S. aureus growth was 98.4%. All baseline culture isolates whether positive for MRSA or MSSA, with one exception, had minimum inhibitory concentrations (MICs) of ≤0.19 µg/mL. All follow-up study cultures after universal decolonization at 7 days or beyond with any S. aureus growth had mupirocin MICs of ≤0.125 µg/mL. CONCLUSIONS: Baseline S. aureus colonization rates of new admissions to the CHM ICUs were high as was baseline mupirocin susceptibility. Follow-up cultures, albeit limited in number, did not detect increasing mupirocin MICs over 1 year, despite broad mupirocin exposure due to the implementation of universal decolonization.

Emergence of Vaccine-Preventable Diseases: The Perfect Storm of Hesitancy, Refusal, a Pandemic, and War.

The landscape of pediatric vaccination has changed dramatically due to changing attitudes toward immunizations and recent world events. The rise of vaccine hesitancy and refusal related to the concurrent rise of social media and anti-vaccination messages with misinformation campaigns have led to populations of children being unimmunized or under-immunized. These populations have been left vulnerable to the rapid spread of vaccine-preventable infection. Additionally, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the clinical syndrome known as coronavirus disease 2019 (COVID-19) resulted in the emergence of a worldwide pandemic. Control measures to mitigate the spread of COVID-19 resulted in numerous reports of children missing routine vaccines along with the stopping of many public health immunization programs. Finally, armed conflicts and war have led to large family migrations from their homelands to various countries and regions leading to increased risk for missed maternal and child immunization as well as difficulty in keeping vaccination records. [Pediatr Ann. 2022;51(11):e426-e430.].

Risk Identification of Bronchopulmonary Dysplasia in Premature Infants Based on Machine Learning.

Bronchopulmonary dysplasia (BPD) is one of the most common complications in premature infants. This disease is caused by long-time use of supplemental oxygen, which seriously affects the lung function of the child and imposes a heavy burden on the family and society. This research aims to adopt the method of ensemble learning in machine learning, combining the Boruta algorithm and the random forest algorithm to determine the predictors of premature infants with BPD and establish a predictive model to help clinicians to conduct an optimal treatment plan. Data were collected from clinical records of 996 premature infants treated in the neonatology department of Liuzhou Maternal and Child Health Hospital in Western China. In this study, premature infants with congenital anomaly, premature infants who died, and premature infants with incomplete data before the diagnosis of BPD were excluded from the data set. After exclusion, we included 648 premature infants in the study. The Boruta algorithm and 10-fold cross-validation were used for feature selection in this study. Six variables were finally selected from the 26 variables, and the random forest model was established. The area under the curve (AUC) of the model was as high as 0.929 with excellent predictive performance. The use of machine learning methods can help clinicians predict the disease so as to formulate the best treatment plan.

Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide in adolescents and children with HIV: week 48 results of a single-arm, open-label, multicentre, phase 2/3 trial.

BACKGROUND: Bictegravir is a potent integrase strand-transfer inhibitor (INSTI) with a high genetic barrier to resistance. Bictegravir, coformulated with emtricitabine and tenofovir alafenamide, is recommended by key European and US HIV treatment guidelines as the preferred single-tablet regimen for adults and adolescents. The aim of this study was to assess the pharmacokinetics, safety, and efficacy of switching to this regimen in virologically suppressed children and adolescents with HIV. METHODS: In this single-arm, open-label trial, we enrolled virologically suppressed children and adolescents (aged 6 to <18 years) with HIV at 22 hospital clinics in South Africa, Thailand, Uganda, and the USA. Eligible participants had a bodyweight of at least 25 kg, were virologically suppressed (HIV-1 RNA <50 copies per mL) on a stable ART regimen for at least 6 months before screening, had a CD4 count of at least 200 cells per µL, and an estimated glomerular filtration rate of at least 90 mL/min per 1·73 m2 by the Schwartz formula at screening. All participants received the fixed-dose regimen of coformulated bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily. Pharmacokinetic analysis was used for dosing confirmation, and results compared with adult values. The primary outcomes were area under the curve at the end of the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) of bictegravir, and incidence of treatment-emergent adverse events and laboratory abnormalities at week 24. Efficacy and safety analyses included all participants who received at least one dose of study drug. We report the 48-week results. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Between Sept 29, 2016 and Feb 16, 2018, we enrolled 102 participants. 100 participants received bictegravir, emtricitabine, and tenofovir alafenamide (cohort 1 [adolescents aged 12 to <18 years], n=50; cohort 2 [children aged 6 to <12 years], n=50). The mean bictegravir AUCtau was 89 100 ng × h/mL (coefficient of variation 31·0%) in adolescents (cohort 1) and 128 000 ng × h/mL (27·8%) in children (cohort 2). Compared with adults, bictegravir Ctau was 35% lower in adolescents and 11% lower in children. The 90% CIs of both parameters were within the predefined pharmacokinetic equivalence boundary and within overall range of exposures observed in adults and deemed to be safe and efficacious (geometric least-squares mean ratio [GLSM] 86·3% [90% CI 80·0-93·0] for AUCtau and 65·4% [58·3-73·3] for Ctau in adolescents; GLSM 125% [90% CI 117-134] for AUCtau and 88·9% [80·6-98·0] for Ctau for children). Bictegravir, emtricitabine, and tenofovir alafenamide was well tolerated; most adverse events were grade 2 or less in severity and no study drug-related serious adverse events were reported. One participant discontinued study drug due to adverse events (grade 2 insomnia and anxiety). Virological suppression (HIV-1 RNA <50 copies per mL) was maintained by all 100 participants at week 24 and by 98 (98%) of 100 at week 48; no participants had treatment-emergent resistance. INTERPRETATION: In adolescents and children with HIV, the bictegravir, emtricitabine, and tenofovir alafenamide single-tablet regimen was well tolerated and maintained virological suppression. Our data support the treatment of HIV in adolescents and children with this single-tablet regimen. At present, the single-tablet regimen is recommended as first-line treatment in the USA for adolescents and as an alternative regimen in children and has the potential to represent an important regimen in the paediatric population. FUNDING: Gilead Sciences.

COVID-19 among Minority Children in Detroit, Michigan during the Early National Surge of the Pandemic.

Background. The COVID-19 pandemic has shed light on communities of racial/ethnic minority groups in the US where long-standing health issues and structural inequities are now known to have resulted in increased risk for infection, severe illness, and death from the virus. The objective of our study was to describe demographic characteristics, clinical presentations, medical interventions and outcomes of pediatric patients with COVID-19 treated at Children's Hospital of Michigan (CHM), a tertiary care center in urban Detroit, an early hotspot during the initial surge of the SARS-CoV-2 pandemic. Methods. A retrospective chart review was performed of children ≤18 years of age who had polymerase chain reaction (RT-PCR) testing via NP swab or serum IgG antibody testing for SARS-CoV-2 during March 1, 2020-June 30, 2020. Results. Seventy-eight COVID-19 infected children were identified of whom 85.8% (67/78) were from minority populations (African American, Hispanic). Hospitalization rate was 82% (64/78). About 44% (34/78) had an associated comorbidity with asthma and obesity being most common. Although all ages were affected, infants <1 year of age had the highest hospitalization rate (19/64, 30%). In all disease severity categories, dichotomized non-whites had more severe disease by percentage within race/ethnicity than Whites, and also within percent disease severity (P-value = .197). Overall, 37% of hospitalized patients required intensive care. Conclusions. Extremely high rates of COVID-19 hospitalization and requirement of ICU care were identified in our patient population. Further studies are needed to better understand the contributing factors to this health disparity in disadvantaged communities.

SARS-CoV-2-associated multisystem inflammatory syndrome in children: clinical manifestations and the role of infliximab treatment.

This study was conducted to assess the clinical spectrum, management, and outcome of SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C). We reviewed medical records of children with MIS-C diagnosis seen at the Children's Hospital of Michigan in Detroit between April and June 2020. Thirty-three children were identified including 22 who required critical care (group 1) and 11 with less intense inflammation (group 2). Children in group 1 were older (median 7.0 years) than those in group 2 (median 2.0 years). Abdominal pain was present in 68% of patients in group 1. Hypotension or shock was present in 17/22 patients in group 1. Thirteen (39.4%) had Kawasaki disease (KD)-like manifestations. Five developed coronary artery dilatation; All resolved on follow-up. Intravenous immunoglobulin (IVIG) was given to all patients in group 1 and 7/11 in group 2. Second-line therapy was needed in 13/22 (group 1) for persisting inflammation or myocardial dysfunction; 12 received infliximab. All patients recovered.Conclusion: MIS-C clinical manifestations may overlap with KD; however, MIS-C is likely a distinct inflammatory process characterized by reversible myocardial dysfunction and rarely coronary artery dilatation. Supportive care, IVIG, and second-line therapy with infliximab were associated with a favorable outcome. What is Known: • Multisystem inflammatory syndrome in children (MIS-C) manifestations include fever, gastrointestinal symptoms, shock, and occasional features of Kawasaki disease (KD). • Treatment includes immunomodulatory agents, most commonly IVIG and corticosteroids. What is New: • Spectrum of MIS-C varies from mild to severe inflammation and coronary artery dilatation occurred in 5/22 (23%) critically ill patients. • IVIG and infliximab therapy were associated with a favorable outcome including resolution of coronary dilatation; only 2/33 received corticosteroids.

Molecular epidemiology of Streptococcus pneumoniae isolated from pediatric community-acquired pneumonia in pre-conjugate vaccine era in Western China.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is one of the most common pathogens which can cause morbidity and mortality in pediatric infections worldwide. This study aimed to describe the phenotypic and molecular characteristics of community-acquired pneumonia (CAP)-causing S. pneumoniae recovered from children in Western China. METHODS: We retrospectively enrolled pediatric patients younger than 5 years diagnosed with CAP. All 419 S. pneumoniae isolates were tested for antibiotic susceptibility, serotypes, virulence genes, resistance genes, and sequence types. The potential relationships between molecular characteristics were tested by correspondence analysis. RESULTS: Most of S. pneumoniae isolates were resistant to erythromycin, tetracycline, clindamycin and trimethoprim-sulfamethoxazole, with 93.8% isolates classified as multidrug resistant. The dominant STs were ST271 (30.8%) and ST320 (12.2%), while the prevailing serotypes were 19F (46.8%), 6B (11.5%), 23F (9.5%) and 19A (9.3%). The coverage rates of PCV-7 and PCV-13 were 73.03% and 86.16%, while the coverage rates of PCV13 among children aged < 1 year and 1-2 years were high in 93.18% and 93.62%. We also observed that CC271 expressed more of mef (A/E), lytA, rlrA and sipA than non-CC271 isolates. Moreover, there were strong corresponding relationships between molecular characteristics. CONCLUSIONS: The high coverage rate of PCV13 suggests the necessity of introducing the PCV13 vaccine in Western China. Our findings underscore the value of monitoring multiple molecular characteristics to provide new guidance for developing future pneumococcal vaccines.

Elevated Glycated Hemoglobin Is Associated with Reduced Antibody Responses to Vaccinations in Children.

Background: Childhood obesity is a major health concern, and it is associated with an increased risk of infectious morbidity. Previous studies found a decrease in protective antibody titers in obese adults after hepatitis B, influenza, and tetanus vaccination. Objective: We aimed at determining whether obesity or abnormal hemoglobin A1C (HBA1C) levels are associated with altered antibody responses in children. Methods: Children (8-18 years) who have completed routine childhood immunization were recruited. Serum samples were tested by the enzyme-linked immunosorbent assay method for antibody levels to Diphtheria, Tetanus, Haemophilus influenzae type B (HIB), and Streptococcus pneumoniae, along with serum HBA1C levels. An electronic medical record review on the frequency of emergency visits for infection was conducted. Spearman rank correlation, Fisher-exact, and Pearson's Chi-squared tests were used for statistical analysis. Results: There was an overall negative correlation between body mass index (BMI) percentile and the majority of pneumococcal subtypes, Diphtheria and Tetanus titers, although not statistically significant. There was a statistically significant negative correlation between HBA1C level and the S. pneumoniae serotype P9N (P = 0.037), P4 (P = 0.017), P12 (P = 0.023), P19F (P = 0.050), and HIB (P = 0.001). On average, individuals with elevated HBA1C levels had more frequent emergency room visits for infection (P = 0.029) and more viral infections (P = 0.023) as compared with children with normal HBA1C. Conclusion: Children with higher HBA1C levels were more likely to have lower pneumococcal and HIB titers and increased rates of emergency room visits for infection in a prospective, population-based cohort study. Although not statistically significant, there was an overall negative correlation between BMI percentile and titers for routine childhood vaccines.

Growth of HIV-Exposed Infants in Southwest China: A Comparative Study.

Objectives. Prevention of mother-to-child HIV transmission has been globally successful leading to a decline in HIV-infected infants. Thus, the number of HIV-exposed, but uninfected, infants is increasing. As growth is an important indicator of child health, this study aimed to evaluate growth parameters of HIV-exposed Chinese infants. Methods. A prospective study was conducted among HIV-exposed (HIV-infected and uninfected) infants born during 2007 to 2015 in Liuzhou, China. Their weight and length were assessed longitudinally from birth to 18 months of age and compared with HIV-unexposed, uninfected (HUU) infants from the same region. Results. There were 467 HIV-exposed infants. Four percent of infants were HIV-infected. The mean weight-for-age (WAZ) and length-for-age (LAZ) z scores of HIV-infected infants were significantly lower than those of HIV-exposed but uninfected (HEU) infants during 9 to 18 months and 12 to 18 months of age, respectively. Additionally, the mean WAZ and LAZ scores of HIV-infected infants were significantly lower than HUU infants during the first 12 months and 18 months of life, respectively. The mean WAZ and LAZ scores of HEU infants were significantly lower than HUU infants during the first 12 months and 6 months of life, respectively. HEU infants also had a lower mean weight-for-length z score than HUU infants during the first 6 months. Conclusion. We demonstrated poor growth among HIV-exposed Chinese infants, including HIV-uninfected, compared with HUU infants. The results emphasize the need for nutritional monitoring and interventions for HIV-exposed infants regardless of HIV infection status. Research is needed on long-term growth trajectories and factors affecting growth of HIV-exposed infants in China.