Episodes In Pediatric Patients Research Articles

Prophylaxis Options in Children With a History of Recurrent Urinary Tract Infections: A Systematic Review.

The prevention of urinary tract infection recurrence (UTI) in children has been a challenge yet to be solved. Current practice in children with recurrent UTI (RUTI) suggests that antibiotic prophylaxis may prevent further episodes of UTI and future complications. To conduct a systematic review and meta-analysis of randomized controlled trials comparing prophylaxis options for the prevention of UTI and kidney scarring in children with a history of RUTI. We conducted a systematic literature search through major electronic databases (PubMed/Medline, Scopus and Cochrane Library) up to November 26th, 2023. Mean difference and SD were used for continuous outcomes and odds ratio for dichotomous outcomes. Our meta-analysis included 3335 participants from 23 studies. The primary outcome was the effect of the different prophylaxis options on the incidence of symptomatic UTI in children with RUTI during prophylactic treatment. Cranberry products and nitrofurantoin lead to lower odds of symptomatic UTI episodes during prophylaxis compared with the control group and control, trimethoprim-sulfamethoxazole, or trimethoprim groups accordingly. Nitrofurantoin may be the best option for UTI incidence reduction compared with all available documented interventions. No prophylaxis option has been shown to reduce kidney scarring. Nitrofurantoin and cranberry products may decrease the incidence of symptomatic UTI episodes in pediatric patients with a history of RUTI. Future randomized control trials studying nonantibiotic prophylaxis options focusing on children with UTI recurrence and the risk for kidney scarring are needed to draw further conclusions.

Role of new generation implantable loop recorders in managing undiagnosed pediatric cardiac symptoms

Pediatric cardiac symptoms such as palpitations, syncope, or seizure-like episodes pose diagnostic challenges for general pediatricians. These symptoms, though often benign, may reveal underlying arrhythmias or inherited cardiac conditions (ICCs), affecting the quality of life and limiting activity participation. The purpose of this study is to determine the effectiveness and safety of implantable loop recorders (ILRs) in diagnosing and managing arrhythmias in pediatric patients. A retrospective cohort study conducted over an 8-year period from January 2016 to December 2023 in a single pediatric cardiology center. A cohort of 155 pediatric patients (median age 11.4 years) who underwent ILR implantation were selected based on symptoms such as palpitations, chest pain, or syncope, and those with previously recorded arrhythmias or high-risk ICCs. The primary outcomes were the diagnostic yield of ILRs for arrhythmias and subsequent changes in patient management. Diagnostic yield was defined as the detection of relevant arrhythmias, such as pauses of 3 s or longer, high-degree AV block, sinus node dysfunction, supraventricular tachycardia, ventricular tachycardia, or inappropriate sinus tachycardia. The median follow-up period was 2.3 years (845 days). Diagnostic arrhythmias were recorded in 60% of patients with symptom-activated transmissions and 80% of device-activated transmissions. Sinus pauses (37.5%) and VT (30%) were the most common arrhythmias detected. In patients with syncope (n = 76), 30% had relevant arrhythmias. In the palpitations group (n = 20), 35% had relevant arrhythmias. Approximately 80% of patients with ILR-diagnosed arrhythmias underwent targeted management, including medication changes and additional procedures. No significant complications were observed; minor complications occurred in 2.5% of patients.Conclusions: New generation ILRs are effective and safe for diagnosing and managing pediatric arrhythmias, providing significant reassurance to patients and families. Further studies are needed to evaluate the impact of ILRs on quality of life and sports participation in high-risk young patients.What is Known:• Pediatric Cardiac Symptoms: Symptoms like palpitations, syncope, and seizure-like episodes in pediatric patients pose significant diagnostic challenges.• Diagnostic Tools: Traditional diagnostic tools such as ECG, Holter monitors, and external loop recorders often have low diagnostic yields due to the sporadic nature of symptoms.• Implantable Loop Recorders (ILRs): ILRs have been shown to improve the diagnostic yield for arrhythmias in adults and provide long-term rhythm monitoring.What is New:• Effectiveness in Pediatrics: This study demonstrates that new generation ILRs significantly enhance the diagnostic yield for arrhythmias in pediatric patients with undiagnosed cardiac symptoms.• Safety and Efficacy: The study confirms that ILRs are both safe and effective in the pediatric population, with minimal complications and high diagnostic accuracy.• Targeted Management: Findings show that ILR-diagnosed arrhythmias lead to targeted management changes in approximately 80% of cases, including medication adjustments and additional procedures.• Long-term Monitoring: ILRs provide continuous long-term monitoring, offering reassurance to patients and families, and potentially improving quality of life and participation in activities for high-risk young patients.

A Post-Authorization Safety Surveillance Study to Report Clinical Experience with Purified Factor IX Concentrate in Pediatric Patients with Hemophilia B.

Purified factor IX (FIX) concentrate (IMMUNINE®, Takeda Manufacturing Austria AG, Vienna, Austria) is indicated for the treatment and prophylaxis of bleeding episodes in patients with congenital hemophilia B. Data on the use of purified FIX concentrate in patients ≤6 years old with congenital hemophilia B are limited. Document real-world clinical experience with purified FIX concentrate in routine practice for pediatric patients with hemophilia B. This prospective post-authorization safety surveillance study enrolled patients ≤6 years old with moderate or severe hemophilia B (baseline FIX ≤5%) who were prescribed purified FIX concentrate, as determined by the treating physician. The planned observation period for each patient was either 12 months or ≥50 exposure days, whichever occurred first. The primary endpoints were the occurrence of treatment-related adverse events (AEs) and serious AEs (SAEs), and inhibitor development. Thirteen male patients (mean ± standard deviation age, 3.80 ± 1.76 years) enrolled and received ≥1 treatment with purified FIX concentrate. Thirty-two AEs were reported in 6 patients; 4 were SAEs. No AEs were considered related to purified FIX concentrate. No patients developed inhibitory antibodies. Inhibitor testing was not conducted in 2 patients. Eighteen bleeding episodes were treated with purified FIX concentrate in 6 patients. Hemostatic efficacy was rated as either "excellent" or "good" in all patients with an available rating. No treatment-related AEs were reported, and purified FIX concentrate was shown to be effective in treating and preventing bleeding episodes in pediatric patients ≤6 years old with hemophilia B.

#75: Microbial Cell-free DNA Sequencing for Prediction of Culture-Negative Infection Events in Children with Cancer

Abstract Background New culture-independent diagnostics are being investigated for diagnosis and prediction of infection. One method is microbial cell-free DNA sequencing (mcfDNA-seq), which can detect a wide range of pathogens directly from plasma. Immunocompromised children who develop febrile neutropenia (FN) without documented bloodstream infection (BSI) may have an undiagnosed bacterial infection, but identification of this subset is difficult. The percentage of episodes of FN caused by bacterial pathogens that did not grow in culture is unknown, as is the relative contribution of other specific etiologies such as viruses, fungi, immunotherapies, and immune reconstitution or graft vs. host disease. The value of mcfDNA-seq in FN patients is also unknown. As part of a larger study evaluating the ability of mcfDNA-seq to predict BSI in a cohort of pediatric patients with relapsed or refractory leukemia, we analyzed mcfDNA-seq results in a sample of cases of FN for which the definitive etiology was unknown. Methods Eligible participants were <25 years of age and undergoing treatment for cancer. Remnant plasma from clinical testing was prospectively obtained and stored. Samples collected on the day of onset of FN (Day 0) and the day prior (Day –1) underwent mcfDNA-seq by Karius Inc. in a CLIA and CAP-accredited laboratory. Pathogen detection results were reported in molecules per microliter (MPM) of plasma. Negative control samples from study participants without impending or recent fever or infection were also obtained. Testing was batched and blinded, so results were not clinically available. Results mcfDNA-seq results were obtained from eight episodes of FN in seven patients. Five episodes occurred in participants awaiting engraftment after HCT and three were receiving chemotherapy only. All participants receiving chemotherapy were receiving antibacterial prophylaxis with vancomycin and ciprofloxacin, antifungal prophylaxis with micafungin or voriconazole, and PJP prophylaxis with TMP-SMX or pentamidine. No HCT recipients were receiving antibacterial prophylaxis, but all received PJP prophylaxis, antifungal prophylaxis or treatment, and antiviral prophylaxis or treatment. Of 8 FN episodes, 4 (50%) had a common bacterial pathogen identified by mcfDNA-seq on Day 0 (Table 1). In 2 (50%) of these cases, the same organism was also identified on Day –1, at a lower concentration. One fungal pathogen was identified prior to and at the onset of FN. A common bacterial pathogen was identified in 3/64 (5%) control samples from the study population. Culture-negative sepsis was the final diagnosis in one episode; in this case, Streptococcus mitis, an important cause of sepsis in neutropenic patients, was identified in both Day 0 and Day –1 samples. In another episode where E. coli was identified, antibiotics were discontinued after 48 hours, but the patient was re-admitted within 24 hours for recurrent FN. Conclusions In this sample of culture-negative FN episodes in pediatric patients with relapsed or refractory leukemia, mcfDNA-seq identified a common bacterial pathogen in 50% of cases. The same organism was identifiable on the day prior to FN in 50% of cases, suggesting that predictive testing might be feasible. More data regarding sensitivity and specificity of mcfDNA-seq to diagnose and predict FN are needed.

Patient Safety and Unplanned Extubation in a Pediatric Intensive Care Unit: A Analytical Observational Study

Introduction: Unplanned extubation (UE) is characterized by the removal or displacement of the endotracheal tube (ETT). Objectives: To analyze the incidence of unplanned extubation, characterize the most prevalent cases of unplanned extubation and analyze an extubation protocol. Methodology: This study is characterized as an analytical observational study design, performed in two stages: field research to collect and analyze data from medical records and analysis of the NPE protocol used by a large hospital. Results: In the collected medical records, rates of 7.75 UE/100 days of MV for general and surgical ICU and 4.68 UE/100 days of MV for cardiopediatric ICU were found. The female gender was predominant in the group of patients evaluated and the cause of unknown origin was the most prevalent. We identified 19 unplanned extubations in the general and surgical ICU, and 9 episodes of unplanned extubation in the cardiopediatric ICU, 28 occurrences. For the protocol evaluation the AGREE II instrument was used and the following scores were obtained: domain 1 with 85.19%; domain 2 with 72.22%; domain 3 with 35.42%; domain 4 with 96.30%; domain 5 with 76.39% and domain 6 with 100%. The general score of the protocol evaluation was grade four. Conclusion: The data presented can be of great benefit for prevention, identification and early intervention of UE episodes in pediatric patients with higher risk factors.

Differential cytokine profiles in pediatric patients with PFAPA syndrome and recurrent tonsillitis.

Objective : An attempt was made to identify characteristic cytokine profiles to distinguish periodic fever with aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPAS) from recurrent tonsillitis, of which clinical manifestations are similar to those of PFAPAS in children. Methods : Serum concentrations of IL-6, IL-4 and IFN-γ were measured during febrile episodes in pediatric patients. Results : The levels of IL-6 during febrile episodes were markedly increased above the upper limit of normal ranges in patients with both PFAPAS and recurrent tonsillitis, but there were no significant differences between groups. The levels of IL-4 during febrile episodes in PFAPAS patients were significantly lower than those in recurrent tonsillitis patients. The levels of IFN-γ during febrile episodes in PFAPAS patients were significantly higher than those in recurrent tonsillitis patients. Conclusion : In pediatric patients with PFAPAS, despite an increase of IL-6, IL-4 was suppressed with a marked increase of IFN-γ during febrile episodes. On the contrary, in febrile pediatric patients with recurrent tonsillitis, both IL-6 and IL-4, but not IFN-γ were increased. The characteristic cytokine profiles of IL-6, IL-4 and IFN-γ can be used for differential diagnosis of PFAPAS from recurrent tonsillitis in children in clinical ear, nose and throat (ENT) settings. J. Med. Invest. 68 : 38-41, February, 2021.

Clinical and Laboratory Characteristics of Herpes Zoster in Patients With HIV/AIDS and Those With Juvenile Systemic Lupus Erythematosus

HIV infection and juvenile systemic lupus erythematosus (jSLE) are risk factors for the development of herpes zoster (HZ) and its complications. Both diseases share similar immunologic aspects, such as immunodeficiency and immune activation. Therefore, our objective was to evaluate and compare the frequency and characteristics of HZ episodes in pediatric patients with HIV infection and jSLE. A retrospective cohort study was carried out with the evaluation of 2 pediatric cohorts: HIV patients who were followed from January 1987 to December 2014 and patients with jSLE followed up from January 1990 to December 2014 in outpatient clinics. Of the 190 HIV patients, 48 had HZ (25.3%), with 67 episodes; of the 92 patients with jSLE, 27 had HZ (29.3%), totaling 28 episodes. The median age at the first episode of HZ was higher in the jSLE than in the HIV group (8.9 vs. 12.5 years, respectively) (P = 0.020). HIV patients were more likely to have recurrent HZ (P = 0.025). In addition, there was a tendency for HIV patients to present with disseminated HZ more frequently (P = 0.060). Although the hospitalization rate was similar between groups, patients with jSLE received intravenous acyclovir more frequently (P = 0.014). When HIV non-immune reconstitution syndrome patients were compared with jSLE group, recurrence of HZ in HIV was the only significant difference between groups (P = 0.017). Patients with HIV had more recurrent HZ than patients with jSLE.

Safety and Efficacy of Low‐dose Domperidone for Treating Nausea and Vomiting Due to Acute Gastroenteritis in Children

This study was conducted based on a request from the European Medicines Agency to generate robust data on domperidone efficacy in children in the relief of symptoms of nausea and vomiting by assessing the effect of a low-dose and short treatment duration. In this randomized, double-blind, phase 3 study, children ages 6 months to 12 years with acute gastroenteritis randomly (1:1) received oral domperidone 0.25 mg/kg with oral rehydration therapy (ORT) or matching placebo thrice daily for 2 to 7 days. The proportion of patients with no vomiting episodes (primary endpoint) and patients ages ≥4 years with no nausea episodes (key secondary endpoint) within 48 hours of first treatment administration were evaluated. The study was terminated early following futility analysis. At early termination, 292 patients randomly received domperidone (n = 147) or placebo (n = 145). The proportion of patients with no vomiting episodes within 48-hours of first treatment administration was similar between domperidone (32.0%) and placebo groups (33.8%). Similarly, there was no significant difference in proportion of patients ages ≥4 years with no nausea episodes within 48 hours of first treatment administration between domperidone (35.7%) and placebo (38.6%). Total 13 patients (domperidone, 3.4% [5/147] vs placebo, 5.5% [8/145]) reported ≥1 treatment-emergent adverse events. No deaths or adverse events of special interest (extrapyramidal symptoms and QT prolongation) were reported. Low-dose of domperidone with ORT did not significantly differ from placebo in reducing vomiting and nausea episodes in pediatric patients with acute gastroenteritis (AG), and the safety profile was similar between both groups.

Pilot study to explore the prophylactic efficacy of oral probiotic Streptococcus salivarius K12 in preventing recurrent pharyngo-tonsillar episodes in pediatric patients.

Background: In the pediatric population, acute pharyngo-tonsillitis represents one of the most frequent causes of access to outpatient treatment and use of antibiotics. In frequent tonsillitis, the pharmacological approach is no longer effective, and, therefore, surgery becomes the treatment of choice.Methods: This study compares the prophylactic efficacy of Streptococcus salivarius K12 (Bactoblis®) in children with recurrent pharyngo-tonsillitis treated vs untreated, with a 12 -month follow-up. The primary objectives are: The incidence of recurrence of pharyngo-tonsillar episodes and the concomitant use of other drugs. Secondary objectives are: tolerability of the treatment, the effectiveness in terms of clinical improvement, days of absence from school, reduction of the use of standard therapies, and cancellation from the surgical planning list.Results: Patients belonging to group A (treated with K12 for 90 days) were 24 males and 26 females, mean age 6.6 years (SD=1.57), those belonging to group B (untreated) were 23 males and 27 females, average age 6.8 years (SD=1.72). In the follow-up, group A reported 26 inflammatory pharyngo-tonsillary episodes in the first trimester, unlike group B, who reported 72 in the second trimester. This has shown a lower incidence (3.38%) of the disease compared to group B (6.66%), for a total of 169 inflammatory pharyngo-tonsillary episodes in group A against 333 in group B. A reduction in days of school absence of 429 days in group A and 927 days in the control group (P<0.01) was also noted. Finally, 14 children of group A (28%) underwent adenotonsillectomy, against the whole group B. No adverse events were reported.Conclusion: The efficacy of K12 on the prevention of pharyngo-tonsillar infections, the decrease in the use of antibiotics and the improvement of the overall quality-of-life was confirmed, with a decreased number of absences from school and fewer patients undergoing surgery.

Blood Stream Infections and Antibiotic Utilization in Pediatric Leukemia Patients With Febrile Neutropenia.

Frequent surveillance of bacterial pathogens responsible for microbiologically defined-blood stream infections (MD-BSI), and their respective antibiotic susceptibilities is central to tailoring empiric antibiotic therapy in febrile neutropenia (FN) episodes in pediatric patients with leukemia. The safety of deescalating antibiotic therapy in pediatric patients with leukemia and neutropenia is incompletely understood. A retrospective chart review of 194 FN episodes occurred between the years of 2013 and 2016 in 67 patients with leukemia. Clinical and microbiologic data were recorded. MD-BSI occurred in 36 of 194 (18%) of FN episodes. Deescalation of empiric antibiotic therapy based on antibiotic susceptibilities was possible in 25 of 36 (69.4%) episodes. In those 25 episodes, where there was an opportunity to deescalate the antibiotic spectrum, it was clinically appropriate to do so in 19. Deescalation occurred in 9 (47.4%) of these episodes without complication. The remaining 10 patients received a median of 20 additional days of broad-spectrum antibiotic therapy (range, 12 to 30 d). In our small cohort of patients, deescalation of antibiotic therapy based on antimicrobial susceptibilities did not result in complication. Larger prospective studies are needed to address the safety of deescalating antibiotic therapy in this population.

Oral Magnesium for Reduce Febrile Neutropenia in Children with Solid Tumors Treated with Cisplatin-Based Chemotherapy: Randomized Clinical Trial

Background: Hypomagnesemia has been associated with febrile neutropenia (FN) in pediatric patients receiving cisplatin-based chemotherapy (CDDPBC). The primary aim was to determine whether oral magnesium supplementation reduces FN episodes in pediatric patients with solid tumors treated with CDDPBC. Methods: This randomized clinical trial, open label, single center, parallel groups and superiority design was conducted in Hospital Infantil de Mexico Federico Gomez at Mexico City. Children ≥ 9 years with solid tumors that were to receive a CDDPBC cycle were invited to participate. Each cycle of chemotherapy with CDDPBC were randomly assigned to receive oral magnesium supplementation (250 mg per day) or not receive magnesium supplementation (control group). Efficacy was determined by relative risks (RR) with 95% confidence intervals (95%CI) as well as with numbers needed to treat (NNT). Active surveillance was conducted to assess safety in both groups. Analyzes were made by intention to treat. This study is registered with ClinicalTrials.gov, number NCT03449693. Findings: between October 2017 and February 2019, eighty-two cycles of chemotherapy with CDDP were analyzed (42 in the magnesium supplement arm and 40 in control group). Baseline clinical characteristics were similar comparing both groups. Oral magnesium supplementation reduces FN episodes compared to control group (RR= 0.48, [95%CI, 0.26 to 0.89], NNT= 4). In the group supplemented with magnesium presented lower risk of septic shock secondary to FN (RR= 0.29, [95%CI, 0.09 to 0.96], NNT= 6). Adverse evets were similar across both groups. Interpretation: Oral supplementation with magnesium reduces episodes of febrile neutropenia in pediatric patients with solid tumors treated with CDDPBC. Trial Registration Number: This study is registered with ClinicalTrials.gov, number NCT03449693. Funding: This work was supported by Direccion General de Asuntos del Personal Academico, Universidad Nacional Autonoma de Mexico (DGAPA, UNAM), PAPIIT Grant IA207417. Declaration of Interest: Nothing to declare. Ethical Approval: The study was approved by HIMFG Institutional Review Board (HIM 2017-85) and registered prospectively in Clinical Trial Registry (NCT03449693).

86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency

BackgroundHereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH.Methods50 pediatric patients (23 boys, 27 girls; 45 HAE type I, 5 HAE type II patients) were enrolled. The follow-up period began at the time of diagnosis and ended when the patient turned 18 years old. The indications for the use of C1-INH concentrate were upper airway oedema of any severity; moderate-to-severe abdominal edema; edema of face, neck, or lips and severe edema of the extremities and trunk. Clinical and laboratory data were entered into the Hungarian HAE Registry.Results152 attacks out of 1392 experienced by 42 patients were treated with C1-INH concentrate (28% of attacks at home and 72% at the clinic). The distribution of C1-INH-treated attacks by location was as follows: 38% subcutaneous, 32% abdominal, 30% upper airway. In all locations, the clinical symptoms were consistently relieved by 500 IU C1-INH concentrate. An additional 500 IU dose of C1-INH concentrate was required in 4 cases only. The symptoms improved within 15 to 60 minutes of drug administration. Time to complete resolution was 24 to 48 hours in subcutaneous edema, 12 to 24 hours in abdominal attacks, and less than 12 hours when the edema involved the upper airways. No progression or recurrence of the attack was observed. Repeated administration did not reduce therapeutic efficacy of the drug. Adverse events did not occur. Transmission of viral infections (HIV, HBV, HBC, Parvo virus B19) was not detected. Comparing the first and last year of follow-up, anti-C1-INH antibodies (IgA, IgG, IgM types) did not show any relationship with the administration of C1-INH concentrate.ConclusionsOur prospective study demonstrated that the administration of C1-INH concentrate is highly effective and safe for the treatment of edematous attacks – regardless their location – in pediatric patients with HAE-C1-INH.

Current approach to pediatric syncope.

Syncope is the abrupt loss of consciousness and postural tone that reverses without intervention. Typically, syncopal episodes in pediatric patients are brief, lasting seconds (rarely minutes), and are followed by complete recovery without residual neurological sequelae. Syncopal presentations may be dramatic and lead family members and primary care providers to suspect a malignant cardiac condition, prompting referral to a pediatric cardiologist. Significant advances in the understanding of syncope in infants, children, and adolescents have occurred in the past decade. This review emphasizes neurally mediated syncope, but other etiologies are reviewed to complete the spectrum encountered by pediatric cardiologists. Some clues are provided to distinguish the more common and benign forms of syncope from those due to significant underlying heart disease.