Did pediatric drug development advance epilepsy treatment in young patients?It is time for new research goals

Modern drugs have changed epilepsy,which affects people of all ages.However,for young people with epilepsy,the framework of drug development has stalled.In the wake of the thalidomide catastrophe,the misconception emerged that for people<18 years of age drugs,including antiseizure medications(ASMs),need separate proof of efficacy and safety,overall called"pediatric drug development".For ASMs,this has changed to some degree.Authorities now accept that ASMs are effective in<18 years as well,but they still require"extrapolation of efficacy,"as if minors were another species.As a result,some of the pediatric clinical epilepsy research over the past decades was unnecessary.Even more importantly,this has hampered research on meaningful research goals.We do not need to confirm that ASMs work before as they do after the 18th birthday.Instead,we need to learn how to prevent brain damage in young patients by preventing seizures and optimize ASMs’uses.Herein we discuss how to proceed in this endeavor.

Fatal cases in pediatric patients after post-exposure prophylaxis for rabies:A report of two cases

Rationale:Rabies is a zoonotic disease with a high mortality,primarily transmitted through the bite of infected mammals,particularly dogs and cats.Despite being a well-known disease since ancient times,it continues to cause a significant number of human deaths worldwide,with approximately 65000 fatalities reported annually.Patient concerns:We present two fatal cases of rabies in a 12-year-old immigrant boy and a 7-year-old boy.The first case was subject to a 24-hour delay in receiving appropriate medical attention and rabies preventive measures due to the lack of awareness among emergency hospital staff,leading to the administration of wound dressing only.The second case received timely rabies immunoglobulin administration;however,there was a 4-day delay in administering the fourth dose of the rabies vaccine,despite presenting evident symptoms of rabies.Diagnosis:Postmortem examination of brain samples from both patients confirmed the presence of rabies virus.Interventions:Post-exposure prophylaxis for rabies.Outcomes:Both patients were admitted to the hospital after the manifestation of rabies-related symptoms,with the 12-year-old child seeking medical care 47 days after the animal bite and the 7-year-old child seeking medical care 58 days after the exposure.Finally,the first patient died after 27 days and the second patient died after 40 days of hospitalization.Lessons:There is an urgent need for heightened awareness and education among both healthcare professionals and the public regarding the urgency of seeking immediate medical attention after potential rabies exposure.Timely recognition and initiation of post-exposure prophylaxis are pivotal in preventing the progression of the disease.Strengthening surveillance and reporting systems,coupled with continuous training for healthcare professionals,can contribute to early detection and management of rabies cases.

Comparison of Propofol and Fentanyl for Preventing Emergence Agitation Following Sevoflurane Anesthesia in Pediatric Patients: A Single-Center Study in Bangladesh

Background: Emergence agitation (EA) is a common phenomenon observed in pediatric patients following general anesthesia. This study aimed to assess the efficacy of propofol and fentanyl in preventing EA and to compare their associated complications or side effects. Methods: This prospective randomized observational comparative study was conducted at Dhaka Medical College Hospital from July 2013 to June 2014. The study aimed to evaluate the effects of propofol and fentanyl on EA in children aged 18 to 72 months undergoing circumcision, herniotomy, and polypectomy operations. Ninety children were included in the study, with 45 in each group. Patients with psychological or neurological disorders were excluded. Various parameters including age, sex, weight, American Society of Anesthesiologists (ASA) class, duration of anesthesia, Saturation of Peripheral Oxygen (SPO2), heart rate (HR), respiratory rate (RR), Pediatric Anesthesia Emergence Delirium (PAED) score, duration of post-anesthesia care unit (PACU) stay, incidence of laryngospasm, nausea, vomiting, and rescue drug requirement were compared between the two groups. Results: Age, sex, weight, ASA class, and duration of anesthesia were comparable between the two groups. Perioperative SpO2 and HR were similar in both groups. However, the PAED score was significantly higher in the fentanyl group during all follow-ups except at 30 minutes postoperatively. The mean duration of PACU stay was significantly longer in the fentanyl group. Although the incidence of laryngospasm was higher in the fentanyl group, it was not statistically significant. Conversely, nausea or vomiting was significantly higher in the fentanyl group. The requirement for rescue drugs was significantly higher in the fentanyl group compared to the propofol group. Conclusion: Both propofol and fentanyl were effective in preventing emergence agitation in pediatric patients undergoing various surgical procedures under sevoflurane anesthesia. However, propofol demonstrated a better safety profile with fewer incidences of nausea, vomiting, and rescue drug requirements compared to fentanyl.

Is it a normal phenomenon for pediatric patients to have brain leptomeningeal contrast enhancement on 3-tesla magnetic resonance imaging?

Determining whether sevoflurane sedation in children leads to“pseudo”prominent leptomeningeal contrast enhancement(pLMCE)on 3 Tesla magnetic resonance imaging will help reduce overdiagnosis by radiologists and clarify the pathophysiological changes of pLMCE.

Time to recovery from severe pneumonia and its predictors among pediatric patients admitted in Mizan-Tepi University Teaching Hospital,South West Ethiopia,2022

Objective:Despite trials and programs for the prevention of childhood mortality due to pneumonia,Ethiopia is among the top five countries with the highest number of deaths due to pneumonia.Although the prevalence of pneumonia has increased in the abovementioned trials,little is known about the recovery time from severe pneumonia and its predictors in the study area.Therefore,this study aimed to assess the time to recovery from severe pneumonia and its predictors among pediatric patients admitted to Mizan-Tepi University Teaching Hospital,Ethiopia,in 2022.Methods:A total of 591 children admitted for severe pneumonia were selected using simple random sampling.Data were entered into Epi-data version 4.4.2.1 and expor ted to STATA version 14 for analysis,and the assumptions of Cox propor tional hazard models and goodness of fit were assessed through Shoenfeld residual and Cox-Snell residual,respectively.Bivariate and multivariable Cox regression models were used to identify the predictors of mor tality.Results:This study revealed that 91.54%(95%confidence interval[CI]:89.00–93.53)of participants recovered with an incidence rate of 24.10(95%CI:22.15–26.21)per 100 person-day–observations.The hmedian recovery time of children was 4 days(95%CI:2–6).Children who were not exclusively breastfed(AHR=1.3;95%CI:1.03–1.66),who had a history of inability to suck/feed(AHR=0.81;95%CI:0.65–0.99)were independent predictors of the time to recovery.Conclusions:Children with severe pneumonia who had not exclusively breastfed and who had a history of inability to suck/feed were independent predictors of time to recovery.Therefore,all stakeholders and concerned health care providers should focus more on early diagnosis and management and hasten early recovery based on the identified factors.

Noninvasive methods for prediction of esophageal varices in pediatric patients with portal hypertension

AIM: To evaluate clinical and laboratory parameters for prediction of bleeding from esophageal varices (EV) in children with portal hypertension. METHODS: Retrospective study of 103 children (mean age: 10.1 ± 7.7 years), 95.1% with intrahepatic portal hypertension. All patients had no history of bleeding and underwent esophagogastroduodenoscopy for EV screening. We recorded variceal size (F1, F2 and F3), red-color signs and portal gastropathy, according to the Japanese Research Society for Portal Hypertension classification. Patients were classified into two groups: with and without EV. Seven noninvasive markers were evaluated as potential predictors of EV: (1) platelet count; (2) spleen size z score, expressed as a standard deviation score relative to normal values for age; (3)platelet count to spleen size z score ratio; (4) platelets count to spleen size (cm) ratio; (5) the clinical prediction rule (CPR); (6) the aspartate aminotransferase to platelet ratio index (APRI); and (7) the risk score. RESULTS: Seventy-one children had EV on first endoscopy. On univariate analysis, spleen size, platelets, CPR, risk score, APRI, and platelet count to spleen size z score ratio showed significant associations. The best noninvasive predictors of EV were platelet count [area under the receiver operating characteristic curve (AUROC) 0.82; 95%CI: 0.73-0.91], platelet: spleen size z score (AUROC 0.78; 95%CI: 0.67-0.88), CPR (AUROC 0.77; 95%CI: 0.64-0.89), and risk score (AUROC 0.77; 95%CI: 0.66-0.88). A logistic regression model was applied with EV as the dependent variable and corrected by albumin, bilirubin and spleen size z score. Children with a CPR < 114 were 20.7-fold more likely to have EV compared to children with CPR > 114. A risk score > -1.2 increased the likelihood of EV (odds ratio 7.47; 95%CI: 2.06-26.99). CONCLUSION: Children with portal hypertension with a CPR below 114 and a risk score greater than -1.2 are more likely to have present EV. Therefore, these two tests can be helpful in selecting children for endoscopy.

Phakic posterior chamber intraocular lens for unilateral high myopic amblyopia in Chinese pediatric patients

AIM： To assess the outcomes of posterior chamber implantable collamer lens （ICL） implantation in Chinese pediatric patients with unilateral high myopic amblyopia.METHODS： Eleven eyes of 11 amblyopic patients aged 11.02±3.34y underwent ICL （model V4, Staar Surgical Inc.） implantation to treat unilateral anisometropia were studied. Visual acuity, cycloplegic refraction, contrast sensitivity, stereopsis, intraocular pressure （IOP）, vaulting, corneal endothelial cell count and complications were evaluated. Patients completed follow-up at 3d, 1, 3mo and the last follow-up time （mean 8.18±2.82mo） after surgery.RESULTS： The mean myopic anisometropia was -13.70±3.25 D preoperatively and ＋0.69±2.63 D at 8mo postoperatively. The logMAR corrected distance visual acuity （CDVA） of the amblyopic eye was 1.51±0.72 preoperatively and 0.75±0.40 at 8mo postoperatively. The logMAR CDVA at 3d, 1, 3 and 8mo postoperatively improved by a mean of 0.64, 1.55, 1.82 and 2.64 lines and gained more than 2 lines accounted for 18%, 45%, 45%, 64%, respectively. The contrast sensitivity of 0.5, 1 and 2 cpd in amblyopic eyes was significantly increased after surgery. No patient had near stereopsis recovery. The vaulting at 3 and 8mo was significantly lower than that at 1mo postoperatively. No other intraoperative or postoperative complications were observed, except an acute pupillary block glaucoma happened in a patient at two weeks postoperatively.CONCLUSION： This short-term results indicate that ICL implantation can be a promising alternative therapy for high myopic anisometropic amblyopia in pediatric patients who have failed with conventional treatments and not suitable to corneal refraction surgery.

Clinical Characteristics, Imaging Findings and Surgical Outcomes of Chiari Malformation Type I in Pediatric and Adult Patients

A growing number of children and adolescents are being diagnosed as Chiari malformation type I （CM- I ） for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM- I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM- I underwent surgical treatment in our department. We divided the patients into two groups： pediatric group （n=l 1, age 〈18 years） and adult group （n=73, age 〉18 years）. Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis （36.4%） and developmental delay （36.4%） were more common in pediatric patients, whereas, sensory disturbance （58.9%） and motor weakness （41. 1%） were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group （P〈0.05）. Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments （P〈0.05）. The total Chicago Chiari Outcome Scale （CCOS） score in pediatric patients at the last follow- up was significantly higher than that in adult patients （P=0.002）. In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM- I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.

Analysis of Pathogen Distribution and Drug Resistance of Nosocomial Infections Accompanied in Patients with Malignant Tumor

Objective： To investigate the pathogen distribution and drug resistance of nosocomial infections accompanied in patients with malignant tumor. Methods： The pathogen culture and drug-sensitivity data of 107 specimens isolated from malignant tumor patients accompanied with nosocomial infection were retrospectively analyzed. Results： Among 118 strains of pathogens isolated from 107 specimens, 77 were gram-negative bacillus（65.3%）, 26 were gram-positive coccus（65.3%）, and 15 were fungus（12.7%）. Eleven specimens were revealed to have combined infection of bacterium and fungus. Gram-negative bacillus showed high sensitivity to amikacin, ciprofloxacin, and tienam. Gram-positive cocci were highly sensitive to tienam and vancomycin. The bacteria were resistant to other antibiotics in different degrees, Vancomycin-resistant staphylococcus was not detected, Candida was sensitive to antifungals. Conclusion： Conditional pathogenic bacteria were mainly responsible for nosocomial infections in malignant tumor patients with considerable drug resistance. This shows that bacterial tests and the rational use of antibiotics should be emphasized in clinical practice to prevent the formation of drug resistant strains and further endogenous infections.

HIV Drug Resistance Profiles and Clinical Outcomes in Patients with Viremia Maintained at Very Low Levels

We describe an observational study of clinical, virologic and drug resistance profiles in HIV-positive antiretroviral adherent subjects with stable low level viremia (LLV) 50 - 1000 copies/mL for more than 12 months. Subjects were followed from time of first detectable viral load (VL). In total, 102 episodes of LLV were detected among 80 individuals. The median (mean, range) HIV copy number at genotyping was 250 (486, - 3900) copies/mL after 14 (17.9, 0 - 58) months of LLV. Few patients maintained LLV for the entire 9 years period of observation, with half (52%) experiencing viremic progression following a stable period of LLV either spontaneously or after treatment interruption or failed regimen intensification. In the setting of prolonged periods of sustained LLV, mean duration 22 (range 8 - 106) months, drug resistance (DR) was almost universal. Resistance to ≥1 on-treatment drugs was defined in 97% of specimens and DR to all drugs in the treatment regimen in over half of all patients. Evolution of DR mutations during the period of LLV was observed in 20/28 (71%) subjects with specimens available for follow-up testing. This evolution was associated with viremic progression to levels >1000 copies/mL (p = 0.03). Our data suggest that DR present in patients with LLV is likely to impact long term clinical outcomes, highlighting the importance of optimizing techniques to detect the presence of drug resistant HIV in the setting of LLV and the need for larger prospective studies to assess the emergence of DR in the setting of sustained LLV and the impact of this DR on treatment outcomes.

Comparison of Clinical Characteristics and Outcomes of Pediatric and Adult Patients with Coronavirus Disease 2019 in Shenzhen,China

Objective Here we aimed to investigate the difference in clinical characteristics and outcomes between pediatric and adult patients with COVID-19.Methods A total of 333 consecutive patients with laboratory-confirmed SARS-CoV-2 infection treated in the departments of Internal medicine of Shenzhen Third People’s Hospital from January 11 th to February 10 th,2020 were included.The data were obtained from electronic medical records.The epidemiological data,clinical characteristics,length of hospital stays,and outcomes of pediatric and adult patients were compared.Results Compared with adult patients,pediatric patients had a shorter time of symptom onset to hospitalization than adults[median time,1(IQR,1.0-1.0)d vs.3(IQR,2.0-6.0)d,P<0.001],milder or fewer symptoms,less severe chest CT findings.The clinical severity classification of children was less severe than adults.Up to 15 th March,the end of the follow-up,33(100%)children and 292(97.3%)adult patients had been discharged from hospital.Only 2(0.7%)adult patients died,with an overall case mortality of 0.6%.The median length of hospital stay of pediatric patients was shorter than that of adult patients[19(95%CI:16.6-21.4)d vs.21(95%CI:19.9-22.1)d,P=0.024].Conclusion Pediatric patients with COVID-19 had milder or less clinical symptoms,less evident pulmonary imaging changes,better prognosis,and shorter length of hospital stay.

Potentially inappropriate prescribing of cardiovascular system and antiplatelet/anticoagulant drugs among elderly patients:a Korean population-based national study

OBJECTIVES To investigate the prevalence of potentially inappropriate prescribing(PIP)for cardiovascular system(CVS)and antiplatelet/anticoagulant(AP/AC)drugs among Korean elderly patients,using the Screening Tool of Older Persons’Prescriptions(STOPP)criteria version 2 and to identify the risk factors related to PIP.METHODS The 2016 National Aged Patient Sample data,comprising National Health Insurance claim records for a random sample of 20%of patients aged≥65 years,were used to calculate PIP prevalence of outpatient prescriptions.For criteria including drugdisease interactions,PIP prevalence per indication was estimated.RESULTS Among 1,274,148 elderly patients and 27,062,307 outpatient prescription claims,100,085 patients(7.85%)and 341,664 claims(1.27%)had one or more PIP.The most frequent PIP was“nonsteroidal antiinflammatory drug with concurrent antiplatelet agent(s)without protonpump inhibitor prophylaxis”in the claimlevel(0.97%)and patientlevel(6.33%)analyses.“Betablocker with bradycardia”(16.47%of claims)and“angiotensin receptor blockers in patients with hyperkalaemia”(23.89%of claims)showed the highest PIP prevalence per indication.Logistic regression analysis revealed that,among the patient and health care provider characteristics,female,older age,more severe comorbidities,polypharmacy,higher level of healthcare organization,and specialty of prescriber were significantly associated with a higher risk of PIP.CONCLUSIONS Our findings of a high prevalence of PIP for CVS and AP/AC drugs among the elderly suggest that an effective strategy is urgently needed to improve the prescription practices of these drugs.

Comment on review article:Chronic hepatitis C virus infection cascade of care in pediatric patients

An enhanced cascade of care should include a younger population,helping to achieve the goal of the World Health Organization with a focus on elimination in the pediatric population.Furthermore,enhanced screening and awareness efforts and continued education of health care providers will improve the outcomes of chronic hepatitis C virus(HCV)infection in the pediatric population.The present work discusses and comments on the topic"cascade of care in HCV chronic pediatric patients".

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive （ss＋ and/or c＋） two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination.

Lipoprotein based drug delivery: Potential for pediatric cancer applications

While survival rates for patients with childhood cancershave substantially improved, the quality of life of thesurvivors is often adversely impacted by the residualeffects of chemo and radiation therapy. Because of the existing metabolic and physiological disparities between pediatric and adult patients, the treatment of pediatric cancer patients poses special challenges to oncologists. While numerous clinical trials being conducted, to improve treatment outcomes for pediatric cancer patients, new approaches are required to increase the effcacy and to minimize the drug related toxic side effects. Nanotechnology is a potentially effective tool to overcome barriers to effective cancer therapeutics including poor bioavailability and non-specifc targeting. Among the nano-delivery approaches, lipoprotein based formulations have shown particularly strong promise to improve cancer therapeutics. The present article describes the challenges faced in the treatment of pediatric cancers and reviews the potential of lipoprotein-based therapeutics for these malignancies.

Potential drug–drug interactions in pediatric wards of Gondar University Hospital,Ethiopia:A cross sectional study

Objective: To determine the prevalence, level of severity of potential drug–drug interactions(PDDIs) and the associated factors for PDDIs in hospitalized pediatric patients of Gondar University Hospital.Methods: A retrospective cross-sectional study was conducted for a period of 3 months from March to May 2014 in pediatric wards of Gondar University Hospital. Systematic random sampling technique was used to select charts from all pediatric patients' charts with every 7th interval to get sample size of 384. Univariate and multivariate analysis were performed to compute crude odds ratio and adjusted odds ratio respectively. Statistical significance was set at P value < 0.05.Results: A total of 176(45.8%) patients had at least one PDDI. A total of 393 PDDIs,which were comprised of 283 types of interacting combinations, were identified. Of the total of 393 PDDIs, most were of moderate severity [201(51%)] followed by minor [152(39%)] and major severity [40(10%)]. The most common interacting pairs of major severity were gentamicin + furosemide(6), cotrimoxazole + methotrexate(4) and phenytoin + artemether(4). The occurrence of PDDIs was significantly associated with age and polypharmacy.Conclusions: The study showed that most of the interactions had moderate severity followed by minor severity. Age and polypharmacy were found to show statistically significant association with the occurrence of PDDIs. Due to sensitive nature of pediatrics population, close monitoring is recommended for the detection and management of PDDIs to prevent its negative consequences.

Jaundice in pediatric visceral leishmaniasis (kala-azar) patients

Objective:Visceral leishmaniasis(Kala-azar) is endemic in many countries including Bangladesh.Clinical presentation of visceral leishmaniasis in children and adult may vary and at time may simulate many tropical and hepatobiliary diseases.Jaundice and ascites are not common in kala-azar patients.Methods:During the period of January 2005 to December 2006,all the records of the confirmed kala-azar patients presented with jaundice were included in this study.Kala-azar was confirmed by serology test ICT(Immuno Chromatography) and Bone Marrow study.Results:Total 12 kala-azar patients were encountered during this period.Among these twelve cases,presenting features were jaundice(7),splenomegaly(12),hepatomegaly(11) and ascites (4).Initial clinical diagnosis of chronic liver disease(CLD) was made in(5),Congenital hemolytic anaemia in(1) and kala-azar in rest of the patients(6 ).Common leucopenia and relative lymphocytosis was not observed in any patients.Conclusion:Kala-azar may present with various clinical manifestation in children and adult.Jaundice can be considered to be a common manifestation particularly in pediatric kala-azar patients.Otherwise,it may mislead to another diagnosis if it is taken as a rare feature in kala-azar.

Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients

Microsatellite instability (MSI) is used as a molecular marker for defective DNA mismatch repair (MMR) genes.We report here alterations of MSI in 15 malignant astrocytomas (WHO grade Ⅲ) and glioblastomas (GBM; WHO grade Ⅳ) of pediatric patients (2-21 years) and 12 GBM from adults (44-68 years) by comparative analysis of BAT25/BAT26 loci and 10 other microsatellite markers. High-level microsatellite instability (MSI-H) occurred in 4 of the 15 pediatric cases (26.7%) and in 1 of the 12 adult GBM cases (8.3%). Low-level mi-

Early vasopressin initiation for pediatric patients with vasodilatory shock after cardiac surgery

Objective Vasopressin has showed a beneficial use in pediatric patients with vasodilatory shock after cardiac surgery. However, the optimal timing of vasopressin initiation has not been investigated.Our aim was to evaluate the effect of early vasopressin initiation for these patients.

Trends of Pediatric Outpatients Prescribing in Umm Al Quwain, United Arab Emirates

Background: Data with regard to local drug prescribing in pediatric population is scarce. This study was carried out to investigate the patterns of drug prescribing for pediatric outpatient in a general hospital in the United Arab Emirates. Methods: A total of 707 prescriptions were collected from a governmental hospital in Umm Al Quwain, United Arab Emirates covering the months of June and July, 2014. Encounters issued for patients older than 12 years were rejected. A total of 520 prescriptions for age groups ranging from 1 week to 12 years were studied. Prescriptions were analyzed using WHO drug use indicators. Results: All prescriptions were electronic and head lettered by the name of the hospital. Average number of drugs per prescriptions was 2.6 and all drugs were generics. Name of patient, age and gender and prescriber’s name and E-signature were present in 100%. Patient’s address, allergy and diagnosis were present in 21.15%, 83.26% and 64.42% of prescriptions respectively. Complete dosage regimen was present in all encounters. Patients were prescribed one, two, three, four or more than four drugs per prescription in 23.84%, 27.88%, 26.53%, 12.69%, and 8.65% respectively. The most commonly prescribed therapeutic classes of drugs were antibiotics (44.60%), antihistamines (43.65%), and analgesics/antipyretics (32.30%). The most commonly prescribed drugs among each class were amoxicillin (40%), xylometazoline (61.23%), and paracetamol (87.5%). Conclusion: Present results indicate that prescribing trends for pediatric population seems to be rational. However, there is over use of antibiotics and there are some areas that warrant further attention by the prescribers for a more significantly rational prescribing.