Pediatric Studies Research Articles

Non-pharmaceutical interventions for COVID-19 transiently reduced pneumococcal and Haemophilus influenzae carriage in a cross-sectional pediatric cohort in Southampton, UK.

The Southampton pneumococcal carriage study of children under 5 years old continued during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present data from October 2018 to March 2023 describing prevalence of pneumococci and other pathobionts during the winter seasons before, during, and after the introduction of non-pharmaceutical interventions (NPIs) to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Nasopharyngeal swabs were collected from children attending outpatient clinics at a secondary care hospital and community healthcare sites. Pre-NPIs, in 2019/2020, the carriage prevalence of pneumococci at the hospital site was 32% (n = 161 positive/499 participants). During NPIs, this fell to 19% (n = 12/64), although based on fewer participants compared to previous years due to COVID-19 restrictions on health-care attendance. In 2021/2022, after NPIs had eased, prevalence rebounded to 33% (n = 15/46) [compared to NPIs period, χ2 (1, N = 110) =2.78, P = 0.09]. Carriage prevalence at community healthcare sites fell significantly from 27% (n = 127/470) in 2019/2020 to 19% during the NPI period (n = 44/228) in 2020/2021 [χ2 (1, N = 698) =4.95, P = 0.026]. No rebound was observed in 2021/2022 [19% (n = 56/288)]. However, in a multivariate logistic regression model, neither site had a significantly lower carriage prevalence during the NPI period compared to the post NPI period. A reduction in serotype diversity was observed in 2020/2021. Carriage of Haemophilus influenzae was particularly affected by NPIs with a significant reduction observed. In conclusion, among children under 5 years of age, transient, modest, and statistically non-significant alterations in carriage of both Streptococcus pneumoniae and H. influenzae were associated with SARS-CoV-2 NPIs.IMPORTANCEStreptococcus pneumoniae (the pneumococcus) continues to be a major contributor to global morbidity and mortality. Using our long-running pediatric study, we examined changes in pneumococcal carriage prevalence in nearly 3,000 children under the age of 5 years between the winters of 2018/2019 and 2022/2023. This period coincided with the severe acute respiratory syndrome coronavirus 2 pandemic and, in particular, the implementation of national strategies to limit disease transmission in the UK. We observed a transient reduction of both Streptococcus pneumoniae and Haemophilus influenzae in these populations during this period of non-pharmaceutical interventions. This aligned with the reduction in invasive pneumococcal disease seen in the UK and is therefore a likely contributor to this phenomenon.

Pulse Oximetry Accuracy in Children with Dark Skin Tones: Relevance to Acute Lower Respiratory Infection Care in Low- and Middle-Income Countries.

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) <90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.

Congenital Heart Defects and Concurrent Diagnoses in Influenza Hospitalization in the Pediatric Health Information System Study, 2004-2019.

Influenza is associated with adverse outcomes in children, although modification by additional medical conditions is not well-documented. We aimed to compare outcomes in children with versus without congenital heart defects (CHDs) who were hospitalized for influenza. We retrospectively evaluated patients 1-18y hospitalized for influenza in the Pediatric Health Information (PHIS) databasefrom 2004to2019. Outcomes were compared by CHD presence and then by CHD severity (minor biventricular, major biventricular, and single ventricle disease) using log-binomial regression adjusted for propensity scores accounting for ageat admission, sex, and history of asthma. Outcomes included inpatient mortality, intensive care unit (ICU) admission, mechanical ventilation, and length of stay (LOS) > 12days. To evaluate foreffect modification by genetic diagnoses, analyses were repeated stratified by CHD and genetic diagnosis. Among 55,161 children hospitalized for influenza, 2369 (4.3%) had CHDs, including 963 with minor biventricular, 938 with major biventricular, and 468 with single ventricle CHDs. Adjusting for propensity scores, children with CHDs had higher mortality (4.1% versus 0.9%) compared to those without CHDs (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.9-3.4). Children with CHDs were at higher risk of mechanical ventilation (RR 1.6, 95% CI 1.6-1.7), ICU admission (RR 1.9, 95% CI 1.8-2.1), and LOS > 12days (RR 2.2, 95% CI 2.0-2.3). Compared to those with neither CHD nor genetic condition, children with both had significantly higher risk of all outcomes, with the largest difference for LOS > 12days (RR 2.3, 95% CI 2.0-2.7). Children with CHDs hospitalized for influenza are particularly susceptible to adverse outcomes compared to those without CHDs. Future studies are needed to corroborate findings in light of influenza vaccination.

Cystatin C as a Marker of Kidney Function in Children.

This review examines the reliability of cystatin C as a biomarker for kidney function in paediatric populations. Chronic kidney disease (CKD) affects a significant number of children globally, leading to severe health complications such as anaemia, hypertension, and growth disorders. Traditionally, kidney function has been assessed using the estimated glomerular filtration rate derived from serum creatinine, though this method is flawed due to variability in muscle mass, age, gender, and diet. Cystatin C offers an alternative as it is less influenced by these factors. Evidence from various studies indicates that cystatin C provides a more accurate assessment of kidney function, especially in neonates and children with urinary tract malformations. Additionally, it is more reliable in early detection of acute kidney injury in paediatric intensive care units. Despite its potential, cystatin C is not yet widely adopted in clinical guidelines, primarily due to a lack of large-scale paediatric studies. Nonetheless, existing research supports its utility in providing a consistent and precise measure of kidney function across different paediatric age groups, suggesting that it could enhance early diagnosis and management of CKD in children if more extensive validation studies are conducted.

Feasibility and success of a non-sedated brain MRI training protocol in 7-year-old children from rural and semi-rural Colombia.

Brain magnetic resonance imaging (MRI) is a crucial tool for clinical evaluation of the brain and neuroscience research. Obtaining successful non-sedated MRI in children who live in resource-limited settings may be an additional challenge. To present a feasibility study of a novel, low-cost MRI training protocol used in a clinical research study in a rural/semi-rural region of Colombia and to examine neurodevelopmental factors associated with successful scans. Fifty-seven typically developing Colombian children underwent a training protocol and non-sedated brain MRI at age 7. Group training utilized a customized booklet, an MRI toy set, and a simple mock scanner. Children attended MRI visits in small groups of two to three. Resting-state functional and structural images were acquired on a 1.5-Tesla scanner with a protocol duration of 30-40minutes. MRI success was defined as the completion of all sequences and no more than mild motion artifact. Associations between the Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Movement Assessment Battery for Children (MABC), Behavioral Rating Inventory of Executive Function (BRIEF), Child Behavior Checklist (CBCL), and Adaptive Behavior Assessment System (ABAS) scores and MRI success were analyzed. Mean (SD) age at first MRI attempt was 7.2 (0.2) years (median 7.2 years, interquartile range 7.1-7.3 years). Twenty-six (45.6%) participants were male. Fifty-one (89.5%) children were successful across two attempts; 44 (77.2%) were successful on their first attempt. Six (10.5%) were unsuccessful due to refusal or excessive motion. Age, sex, and scores across all neurodevelopmental assessments (MABC, TVIP, ABAS, BRIEF, CBCL, NIH Toolbox Flanker, NIH Toolbox Pattern Comparison, WPPSI) were not associated with likelihood of MRI success (P=0.18, 0.19, 0.38, 0.92, 0.84, 0.80, 1.00, 0.16, 0.75, 0.86, respectively). This cohort of children from a rural/semi-rural region of Colombia demonstrated comparable MRI success rates to other published cohorts after completing a low-cost MRI familiarization training protocol suitable for low-resource settings. Achieving non-sedated MRI success in children in low-resource and international settings is important for the continuing diversification of pediatric research studies.

Crohn's Disease-Associated Pathogenic Mutation in the Manganese Transporter ZIP8 Shifts the Ileal and Rectal Mucosal Microbiota Implicating Aberrant Bile Acid Metabolism.

A pathogenic mutation in the manganese transporter ZIP8 (A391T; rs13107325) increases the risk of Crohn's disease. ZIP8 regulates manganese homeostasis and given the shared need for metals between the host and resident microbes, there has been significant interest in alterations of the microbiome in carriers of ZIP8 A391T. Prior studies have not examined the ileal microbiome despite associations between ileal disease and ZIP8 A391T. Here, we used the Pediatric Risk Stratification Study (RISK) cohort to perform a secondary analysis of 16S ribosomal RNA gene sequencing data obtained from ileal and rectal mucosa to study associations between ZIP8 A391T carrier status and microbiota composition. We found sequence variants mapping to Veillonella were decreased in the ileal mucosa of ZIP8 A391T carriers. Prior human studies have demonstrated the sensitivity of Veillonella to bile acid abundance. We therefore hypothesized that bile acid homeostasis is differentially regulated in carriers of ZIP8 A391T. Using a mouse model of ZIP8 A391T, we demonstrate an increase in total bile acids in the liver and stool and decreased fibroblast growth factor 15 (Fgf15) signaling, consistent with our hypothesis. We confirmed dysregulation of FGF19 in the 1000IBD cohort, finding that plasma FGF19 levels are lower in ZIP8 A391T carriers with ileocolonic Crohn's disease. In the search for genotype-specific therapeutic paradigms for patients with Crohn's disease, these data suggest targeting the FGF19 pathway in ZIP8 A391T carriers. Aberrant bile acid metabolism may precede development of Crohn's disease and prioritize study of the interactions between manganese homeostasis, bile acid metabolism and signaling, and complicated ileal Crohn's disease.

Age-Dependent Signature of Serum Inflammatory Cytokines in Healthy Children and Young Adults.

The study of sensitive and specific biomarkers, such as blood inflammatory cytokines, could provide an answer to the challenges faced in the differential diagnosis of patients with systemic inflammation. Limited data exist on the impact of age on serum levels of inflammatory cytokines. We collected serum samples of 42 healthy children and young adults (1 month to 21 years). Serum levels of interleukin 1 receptor antagonist (IL-1Ra), IL-1β, IL-6, IL-18, tumor necrosis factor-alpha (TNF-α), CXCL9, and CXCL10 were measured. Data were analyzed for three different age groups (<6, 6-17, and 18-21 years). IL-18, TNF-α, and CXCL9 values varied significantly according to age group. Median values of IL-18 and TNF-α decline with age, whereas CXCL9 and CXCL10 are lowest at 6-17 years. IL-1Ra is stable among age groups. In the majority of cases, IL-1β and IL-6 are not measurable above the lower limit of quantification. A scoping literature review revealed highly variable data on IL-1Ra, IL-18, TNF-α, and CXCL10. For CXCL9, pediatric reference data are scarce. In conclusion, we report an age-dependent signature of multiple inflammatory cytokines measured in the serum of healthy children and young adults, suggesting the need to use age-specific reference values in future pediatric studies.

Effective diameter of the abdominal aorta in children.

Measure out of the standard interval in the aorta diameter is a clue for aortic aneurysm or hypoplasia. Pediatric studies focusing specifically on the normal diameter of the abdominal aorta (AA) were limited in the literature. Therefore, the main goal of this work was to determine changes in the effective diameter of AA in healthy children aged 1-18years for diagnosis of vascular diseases. This retrospective work focused on abdominopelvic computed tomography views of 180 children (sex: 90 males / 90 females, average age: 9.50 ± 5.20years) without any abdominopelvic disease to measure diameters of AA, common iliac artery (CIA), external iliac artery (EIA), and first lumbar vertebra (L1). Vessel and vertebra diameters increased in pediatric subjects between 1 and 18years (p < 0.001). Considering pediatric age periods, vessel diameters increased steadily, but L1 diameter showed an irregular growth pattern between age periods. All parameters were greater in males than females (p < 0.05), except from effective diameters of AA over the coeliac trunk (p = 0.084) and over the renal artery (p = 0.051). The ratios of diameters of vessels to L1 increased depending on ages between 1 and 18years. Considering pediatric age periods, the ratios increased from infancy period to postpubescent period in irregular pattern; however, the ratios for right and left CIA, and AA over the aortic bifurcation did not alter after late childhood period. All ratios for males were similar to females (p > 0.05). Our age-specific ratios may be beneficial for surgeons and radiologists for the diagnosis of vascular disorders such as aortic aneurysm.

Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua.

Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease. This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and sudy participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients. We enrolled a total of 15,266 participants, of whom 3,227 (21%) were positive for DENV infection. Of 2,630 cases with serotype result by RT-PCR, 557 corresponded to DENV1, 992 to DENV2, 759 to DENV3 and 322 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 caused a higher proportion of severe disease compared to other serotypes, whereas DENV3 caused the greatest percentage of severity according to the WHO-2009 classification. DENV2 was associated with increased odds of pleural effusion and low platelet count, while DENV3 was associated with both hypotensive and compensated shock. These findings demonstrate differences in dengue severity by serotype and immune status and emphasize the critical need for a dengue vaccine with balanced effectiveness against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and serostatus.

Percutaneous Transluminal Angioplasty Alleviate Pediatric Postthrombotic Syndrome: A Case Report and Literature Review.

Postthrombotic syndrome (PTS) is one of the long-term sequelae of deep vein thrombosis (DVT), and effective symptom management in pediatric PTS remains a challenge, with interventional therapy rarely explored in this population. We present a successful case of interventional treatment pediatric PTS, resulting in a remarkable amelioration of her symptoms. This case features a 6-year-old girl diagnosed with hyperinsulinemia, leading to a hypoglycemic coma. Following a mini-pancreatic partial pancreatectomy, she required further intensive care in the pediatric intensive care unit. It was during this period that left lower extremity DVT was identified, prompting warfarin anticoagulation therapy. During the anticoagulation period, she had several bleeding events and was switched to anticoagulation with low molecular heparin. One month later, the left common iliac vein and external iliac vein was found to be completely occluded. Over time, she experienced a gradual onset of lower limb swelling and pain, which, after 6 months, was accompanied by perineal edema and venous claudication. As a result, she underwent successful percutaneous transluminal angioplasty. In addition, the anticoagulation regimen was adjusted to rivaroxaban. At the 8-month follow-up, we observed significantly improvement in her postoperative lower extremity swelling and symptoms related to venous occlusion had completely disappeared. Moreover, vascular imaging confirmed improvement in stenosis and uninterrupted blood flow. In our review of pediatric PTS studies, we observed limited options to alleviate symptoms, and interventional treatments have not been reported. Our case study, demonstrating the safe and effective use of percutaneous transluminal angioplasty, helps to illuminate this area and alleviate pediatric PTS symptoms. This case validates the efficacy and safety of using percutaneous transluminal angioplasty (PTA) for the treatment of postthrombotic syndrome (PTS) in pediatric patients. This interventional approach offers significant symptomatic relief and improves quality of life, especially in cases where traditional anticoagulation therapies fail or lead to complications. The successful case presented emphasizes the necessity of considering endovascular interventions for children with moderate to severe PTS, particularly when conservative management is ineffective. This research underscores the potential for PTA to be adopted in clinical practice, offering a promising new approach for managing pediatric PTS.

Localized incompletely resected standard risk rhabdomyosarcoma in children and adolescents: Results from the European Paediatric Soft Tissue Sarcoma Study Group RMS 2005 trial.

The authors report the prospective evaluation of reduced dose alkylator chemotherapy combined with radiotherapy for European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) standard risk nonalveolar rhabdomyosarcoma (NA-RMS). Localized node negative Intergroup Rhabdomyosarcoma Study (IRS) II/III NA-RMS at favorable sites (subgroup C), <25 years old, received five cycles of ifosfamide, vincristine, and dactinomycin (IVA) chemotherapy (30 g/m2 ifosfamide) and four cycles of vincristine and dactinomycin (if receiving radiotherapy), or nine cycles of IVA (54 g/m2 ifosfamide) ± radiotherapy. Delayed primary tumor excision was considered for IRS III tumors. The primary end points were event-free survival (EFS) and overall survival (OS). From October 2005 to December 2016, 359 evaluable patients were recruited: orbit, 164 (45.7%); head and neck nonparameningeal, 77 (21.4%); and genitourinary non-bladder/prostate, 118 (32.9%). EFS and OS were 77.4% (95% confidence interval [CI], 72.5-81.6) and 93.5% (95% CI, 90.1-95.8), respectively. Lower dose alkylator chemotherapy and radiotherapy achieved 5-year OS of 93.7% but the difference with higher dose alkylator chemotherapy +/- radiotherapy was not significant (p=0.8003). Adjuvant radiotherapy improved EFS with 5-year estimates of 84.7% versus 65.2% for nonirradiated (p<.0001), but not OS (p=.9298). Omitting radiotherapy for orbital tumors reduced OS (5-year was 87.1% vs. 97.3% for irradiated, p=.0257). Following R0 resection (n=60), radiotherapy did not significantly improve EFS or OS. Radiotherapy for local tumor control allows for reduction of cumulative dose of alkylators in EpSSG standard risk subgroup C RMS patients. The omission of radiotherapy did not affect OS in all patients except those with orbital RMS and was associated with inferior EFS.

Tailored approach to participant recruitment and retention to maximize health equity in pediatric cancer research

BackgroundLack of diversity in participants throughout the research process limits the generalizability of findings and may contribute to health disparities. There are unique challenges to recruitment of families to pediatric cancer research studies, especially for those from disadvantaged backgrounds. Thus, there is a need to evaluate the most effective recruitment and retention strategies to optimize equitable recruitment of diverse participants.MethodsThe present study adapted and implemented methods outlined previously in the literature. These previous efforts were developed to address barriers to pediatric research, behavioral health intervention research and research with Black adolescents. Recruitment and retention strategies are described across four different time points: pre-approach, initial connection, building connection and follow-up. Eligible families of children with a pediatric cancer diagnosis were approached during a routine oncology visit. Once consented, enrollment and retention rates over three timepoints of data collection were recorded and evaluated.ResultsResults indicated high rates of enrollment (86%) and retention (95%) for eligible participants. There were no trends in heightened attrition for any specific subgroup.ConclusionsThe findings of this study are promising and suggest these recruitment and retention strategies may be useful in recruiting individuals from disadvantaged backgrounds.

Opioid analgesic dose and route conversion ratio studies: a scoping review to inform an eDelphi guideline.

Clinicians regularly prescribe opioids to manage acute and chronic cancer pain, frequently to address acute postoperative pain, and occasionally to manage chronic non-cancer pain. Clinical efficacy may be suboptimal in some patients due to side effects and/or poor response, and opioid rotation/switching (conversions) is frequently necessary. Despite the widespread practice, opioid conversion ratios are inconsistent between clinicians, practices, and countries. Therefore, we performed a scoping systematic review of opioid conversion studies to inform an international eDelphi guideline. To ensure a comprehensive review, we conducted a systematic search across multiple databases (OVID Medline, PsycINFO, Embase, EBM-Cochrane Database of Systematic Reviews and Registered Trials, LILACS, IMEMR, AIM, WPRIM) using studies published up to June 2022. Additionally, we performed hand and Google Scholar searches to verify the completeness of our findings. Our inclusion criteria encompassed randomized and non-randomized studies with no age limit, with only a few pediatric studies identified. We included studies on cancer, non-cancer, acute, and chronic pain. The level and grade of evidence were determined based on the Multinational Supportive Care in Cancer (MASCC) criteria. Our search yielded 21,118 abstracts, including 140 randomized (RCT) and 68 non-randomized (NRCT) clinical trials. We compared these results with recently published conversion ratios. Modest correlations were noted between published reviews and the present scoping systematic review. The present scoping systematic review found low-quality evidence to support an opioid conversion guideline. We will use these data, including conversion ratios and type and route of administration, to inform an eDelphi guideline.

Co-producing research study recruitment strategies with and for children and young people for paediatric chronic pain studies.

Children and young people experiencing chronic pain are at greater risk of inequitable and poor-quality pain management, which has implications for future management of pain in adulthood. Most chronic pain research is conducted with adults who are more likely to be middle-class, white and monocultured. Inclusive and diverse recruitment practices in paediatric pain research can be an area in which we can address this imbalance of representation. The aim of this current work was to explore these practices and to co-produce recommendations regarding recruitment strategies for paediatric pain research. The research team worked with Your Rheum, a United Kingdom young person's advisory group (ages 11-24 years) and diagnosed with rheumatic condition(s), the opportunity to input into rheumatology research. At a virtual Your Rheum meeting, eight young people (female = 7, male = 1, age range 12-24) took part in group discussions, sharing their experiences of taking part in research and their decision process. Online tools, including Mentimeter and Miro, were used to aid conversations and share ideas. Most young people had experience of taking part in research as a study participant (n = 5). Recommendations synthesised included increased awareness of research in general. The young people discussed being open to hearing about research opportunities; they reflected that they are rarely exposed to these invitations or hear about current research. The clinic environment was highlighted as a "good and trustworthy" recruitment area - being approached by a member of the research team was considered ideal, even if it was someone they had not met previously. Many young people recalled little discussions of research at their clinical appointments. Deciding to participate in research included the following considerations: benefit/impact; connecting with others; research topic; which is then balanced against convenience, and reimbursement. The young people felt that taking part in research was empowering and helped them take ownership of their pain management. It is essential to understand the perspectives of potential study participants, to plan successful recruitment strategies. Ensuring we consider these factors when designing our studies and recruitment strategies is beneficial to all involved. Co-produced recruitment strategies would aid inclusive (and increased) research participation.

Values of peripapillary retinal nerve fibre layer thickness are different in children and adults

ABSTRACT Clinical relevance The detection of abnormal values of peripapillary nerve fibre layer (pRNFL) thickness measured with optical coherence tomography (OCT) is important for detecting optic nerve disease in children. Background To evaluate the level of agreement between the adult reference database supplied with an OCT device and the present paediatric study database for the measurement of pRNFL thickness in children. This study also aimed to provide reference values for pRNFL thickness according to the spherical equivalent in the paediatric population. Methods This was a cross-sectional study. One hundred and twenty-six healthy children were included, who had undergone a full ophthalmological examination including cycloplegic refraction and examination of pRNFL thickness using the Topcon 3D OCT 2000 device (Topcon Corporation, Tokyo, Japan). Values equal to or below the fifth percentile (≤p5) and above the 95th percentile (>p95) were considered abnormal. Observed agreement and specific agreement were investigated between OCT measurements classified with paediatric and adult reference values for normality. Results Values ≤ p5 in the adult database were recorded for 2 of the 30 values (6.6%) of the pRNFL values by quadrants ≤p5 in the paediatric database and 17 of the 88 (19.3%) values by sectors ≤p5. For values >p95 in the adult database, 88% by quadrants and 72% by sectors would have been classified as being within the normal range using the paediatric database. Conclusion The use of adult reference values currently available in OCT devices can lead to classification errors concerning the normal range of pRNFL thickness in a large proportion of paediatric patients. The use of normative paediatric databases, such as the one discussed in this study, should be taken into consideration.

Ambulatory isolated diastolic hypertension and risk of left ventricular hypertrophy in children with primary and secondary hypertension

BackgroundPediatric blood pressure (BP) assessment and management is increasingly important. Uncontrolled systolic and combined hypertension leads to hypertension-mediated organ damage. The impact of isolated diastolic hypertension is less clearly understood.MethodsWe analyzed the prevalence of ambulatory isolated diastolic hypertension (IDH) in primary (PH) and secondary (SH) hypertension, and associations with BMI Z-score (BMIz) and left ventricular mass index adjusted to the 95th percentile (aLVMI) in a large, multicenter cohort of hypertensive children. Hypertensive children were divided and analyzed in three ambulatory hypertension subgroups: 24-h, daytime, and nighttime. Specifically, we sought to determine the prevalence of ambulatory 24-h, daytime, or nighttime IDH.ResultsPrevalence of IDH varied based on ambulatory phenotypes, ranging from 6 to 12%, and was highest in children with SH. Children with IDH tended to be more likely female and, in some cases, were leaner than those with isolated systolic hypertension (ISH). Despite previous pediatric studies suggesting no strong association between diastolic blood pressure and left ventricular hypertrophy (LVH), we observed that children with IDH were equally likely to have LVH and had comparable aLVMI to those with ISH and combined systolic-diastolic hypertension.ConclusionsIn summary, ambulatory IDH appears to be a unique phenotype with a female sex, and younger age predilection, but equal risk for LVH in children with either PH or SH.Graphical abstractA higher-resolution version of the Graphical abstract is available as Supplementary information

Two-dimensional facial photography for assessment of craniofacial morphology in sleep breathing disorders: a systematic review.

Craniofacial morphology is integral to Sleep Breathing Disorders (SBD), particularly Obstructive Sleep Apnea (OSA), informing treatment strategies. This review assesses the utility of two-dimensional (2D) photogrammetry in evaluating these metrics among OSA patients. Following PRISMA guidelines, a systematic review was conducted. PubMed, Embase, and Lilacs databases were systematically searched for studies utilizing 2D photography in SBD. Findings were narratively synthesized. Thirteen studies involving 2,328 patients were included. Significant correlations were found between craniofacial measurements-specifically neck parameters and facial width-and OSA severity, even after BMI adjustment. Ethnic disparities in craniofacial morphology were observed, with photogrammetry effective in predicting OSA in Caucasians and Asians, though data for other ethnicities were limited. Pediatric studies suggest the potential of craniofacial measurements as predictors of childhood OSA, with certain caveats. 2D photogrammetry emerges as a practical and non-invasive tool correlating with OSA severity across diverse populations. However, further validation in various ethnic cohorts is essential to enhance the generalizability of these findings.

Obesity is associated with increased pediatric dengue virus infection and disease: A 9-year cohort study in Managua, Nicaragua.

Obesity is on the rise globally in adults and children, including in tropical areas where diseases such as dengue have a substantial burden, particularly in children. Obesity impacts the risk of severe dengue disease; however, the impact on dengue virus (DENV) infection and dengue cases remains an open question. We used 9 years of data from 5,940 children in the Pediatric Dengue Cohort Study in Nicaragua to examine whether pediatric obesity is associated with increased susceptibility to DENV infection and symptomatic presentation. Analysis was performed using Generalized Estimating Equations adjusted for age, sex, and pre-infection DENV antibody titers. From 2011 to 2019, children contributed 26,273 person-years of observation, and we observed an increase in the prevalence of overweight (from 12% to 17%) and obesity (from 7% to 13%). There were 1,682 DENV infections and 476 dengue cases in the study population. Compared to participants with normal weight, participants with obesity had higher odds of DENV infection (Adjusted Odds Ratio [aOR] 1.21, 95% confidence interval [CI] 1.03-1.42) and higher odds of dengue disease given infection (aOR 1.59, 95% CI 1.15-2.19). Children with obesity infected with DENV showed increased odds of presenting fever (aOR 1.46, 95% CI 1.05-2.02), headache (aOR 1.51, 95% CI 1.07-2.14), and rash (aOR 2.26, 95% CI 1.49-3.44) when compared with children with normal weight. Our results indicate that obesity is associated with increased susceptibility to DENV infection and dengue cases in children, independently of age, sex, and pre-infection DENV antibody titers.

Utility of the WHO dengue guidelines in pediatric immunological studies.

Dengue is a significant health problem due to the high burden of critical infections during outbreaks. In 1997, the World Health Organization (WHO) classified dengue as dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). It was revised in 2009 (updated in 2015), and the new guidelines recommended classifying patients as dengue without warning signs (DNS), dengue with warning signs (DWS), and severe dengue (SD). Although the utility of the revised 2009 classification for clinical studies is accepted, for immunological studies it needs to be clarified. We determined the usefulness of the 2009 classification for pediatric studies that analyze the circulating interleukin (IL)-6 and IL-8, two inflammatory cytokines. Plasma levels of IL-6 and IL-8 were evaluated in the acute and convalescent phases by flow cytometry in children with dengue classified using the 1997 and 2009 WHO guidelines. The plasma levels of IL-6 and IL-8 were elevated during the acute and decreased during convalescence, and both cytokines served as a good marker of acute dengue illness compared to convalescence. There were no differences in the plasma level of the evaluated cytokines among children with different clinical severity with any classification, except for the IL-8, which was higher in DWS than DNS. Based on the levels of IL-8, the 2009 classification identified DWS plus SD (hospital-treated children) compared to the DNS group [area under the curve (AUC): 0.7, p = 0.028]. These results support the utility of the revised 2009 (updated in 2015) classification in studies of immune markers in pediatric dengue.

Study APV20002: Safety and Efficacy Results Through Week 684 for Pediatric Participants Living with HIV-1 Treated with Ritonavir-Boosted Fosamprenavir Oral Solution-Based Antiretroviral Therapy.

APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4+ cell count was 1,235 cells/mm3 [n = 51] at baseline, 1,690 cells/mm3 (n = 41) at Week 48, and 1,280 cells/mm3 (n = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.