Drug Treatment In Children Research Articles

Off-Label, but on-Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy.

Many drugs are still prescribed off-label to the pediatric population. Although off-label drug use not supported by high level of evidence is potentially harmful, a comprehensive overview of the quality of the evidence pertaining off-label drug use in children is lacking. The Dutch Pediatric Formulary (DPF) provides best evidence-based dosing guidelines for drugs used in children. For each drug-indication-age group combination-together compiling one record-we scored the highest available level of evidence: labeled use, systematic review or meta-analysis, randomized controlled trial (RCT), comparative research, noncomparative research, or consensus-based expert opinions. For records based on selected guidelines, the original sources were not reviewed. These records were scored as guideline. A total of 774 drugs were analyzed comprising a total of 6,426 records. Of all off-label records (n=2,718), 14% were supported by high quality evidence (4% meta-analysis or systematic reviews, 10% RCTs of high quality), 20% by comparative research, 14% by noncomparative research, 37% by consensus-based expert opinions, and 15% by selected guidelines. Fifty-eight percent of all records were authorized, increasing with age from 30% in preterm neonates (n=110) up to 64% in adolescents (n=1,630). Many have advocated that off-label use is only justified when supported by a high level of evidence. We show that this prerequisite would seriously limit available drug treatment for children as the underlying evidence is low across ages and drug classes. Our data identify the drugs and therapeutic areas for which evidence is clearly missing and could drive the global research agenda.

Considerations for determining the efficacy of new antiseizure medications in children age 1month to younger than 2 years.

Drug treatment for children with epilepsy should, ideally, be governed by evidence from adequate and well-controlled clinical studies. However, these studies are difficult to conduct, and so direct evidence supporting the informed use of specific drugs is often lacking. The Research Roundtable for Epilepsy (RRE) met in 2020 to align on an approach to therapy development for focal seizures in children age 1month <2 years of age. The RRE reviewed the regulatory landscape, epidemiology, seizure semiology, antiseizure medicine pharmacology, and safety issues applicable to this population. After reviewing evidence, the conclusion was that pediatric efficacy trials would be impracticable to conduct but a waiver of the regulatory requirement to conduct any study would lead to an absence of information to guide dosing in a critical population. Review of available data and discussion of RRE attendees led to the conclusion that the requirements for extrapolation of efficacy from older children down to infants from age 1month to <2 years old appeared to be met. After the RRE, the US Food and Drug Administration (FDA) approved brivaracetam for use in children with focal epilepsy above the age of 1month in August 2021 and lacosamide in October 2021, both based on the principle of extrapolation from data in older children. These recommendations should result in more rapid accessibility of antiseizure medications for infants.

Clinical Efficacy Evaluation of Psychological Nursing Intervention Combined with Drugs Treatment of Children with ADHD under Artificial Intelligence.

ADHD in children is one of the most common neurodevelopmental disorders. It is manifested as inattention, hyperactivity, impulsiveness, and other symptoms that are inconsistent with the developmental level in different occasions, accompanied by functional impairment in social, academic, and occupational aspects. At present, the treatment for children with ADHD is mainly based on psychological nursing intervention combined with drug therapy. Therefore, the actual efficacy evaluation of this treatment regimen is very important. Neural networks are widely used in smart medical care. This work combines artificial intelligence with the evaluation of clinical treatment effects of ADHD children and designs an intelligent model based on neural networks for evaluating the clinical efficacy of psychological nursing intervention combined with drug treatment of children with ADHD. The main research is that, for the evaluation of clinical treatment effect of ADHD in children, this paper proposes a 1D Parallel Multichannel Network (1DPMN), which is a convolutional neural network. The results show that network models can extract different data features through different channels and can achieve high accuracy evaluation of clinical efficacy of ADHD in children. On the basis of the model, performance is improved through the study of Adam optimizer to speed up the model convergence, adopts batch normalization algorithm to improve stability, and uses Dropout to improve the generalization ability of the network. Aiming at the problem of too many parameters, the 1DPMN is optimized through the principle of local sparseness, and the model parameters are greatly reduced.

Clinical Study on Drug Treatment of Children with Tics

Clinical Study on Drug Treatment of Children with Tics

HGG-24. PRECLINICAL EFFICACY OF THE BRAIN PENETRANT CYCLIN-DEPENDENT KINASE INHIBITOR ZOTIRACICLIB IN PEDIATRIC DIFFUSE MIDLINE GLIOMAS

Children diagnosed with diffuse midline gliomas (DMG), including diffuse intrinsic pontine glioma (DIPG), have extremely poor outcomes with a median overall survival of 9–12 months from initial diagnosis. Standard-of-care is limited to focal radiation therapy, given the paucity of effective targeted therapies for DMG. To identify effective drugs for treatment of children diagnosed with DMG, we investigated the brain-penetrating multi cyclin-dependent kinase inhibitor Zotiraciclib (ZTR/TG02). ZTR has demonstrated encouraging response rates and a benign safety profile in phase 1 trials of adults with high-grade glioma. It is thought to achieve its anti-cancer activity mainly by transcription disruption, a previously described vulnerability of DMGs, by inhibiting multiple cyclin-dependent kinases 9 and 7 (CDK9, 7). We found that ZTR robustly reduces viability of different patient derived DMG cells in a dose-dependent manner, with a median IC50 of 201 nM across eight tested cell lines (range 11–1258 nM, 72 hrs). Consistently, we observed loss of RNA polymerase II phosphorylation after 24 hours of treatment, indicating effective CDK9 inhibition at low drug concentrations and after short incubation time. This effect was followed by depletion of short-lived proteins including MYC and the anti-apoptotic factor MCL-1. Putative biomarkers of response and resistance were identified in silico using DepMap data analysis. To assess the safety profile of ZTR, we exposed our zebrafish model to various drug concentrations and found the drug to be safe at IC50 molarity. Ongoing in vitro and in vivo studies evaluating the efficacy of ZTR in combination with promising combination therapies for more effective treatment of children with DMG are also underway.

A Rapid Review of Potential Drug Treatments for Children with COVID-19

The paediatric population constitutes a much smaller proportion of COVID-19 patients and seems to be less severely affected. However, the massive numbers of COVID-19 infections mean that many children require treatment in hospital. In the concerted and wide-ranging effort to discover a safe and effective treatment for COVID-19, paediatric involvement is necessary. This review aims to identify leading potential drug treatments and vaccines for COVID-19 that are being investigated with children involved. Clinicaltrials.gov, WHO Trial Registry Platform (ICTRP) and RAPS COVID-19 vaccine tracker webportals were searched for clinical trials in phase 3 that involved children below 15 years of age. Any preliminary results released were searched online. The review found 25 phase 3 drug trials with paediatric participants and 2 vaccine trials. No preliminary findings were found. Remdesivir appears to be a leading candidate drug treatment and 2 vaccines candidates, inactivated nCoV-19 (Sinopharm) and ChAdOx1 (Oxford University), are recruiting children in large phase 3 trials. No treatments are currently licensed for COVID-19 but results from numerous trials are eagerly awaited.

COVID-19 in Children and Neonates: A Comprehensive Review Article

Context: Novel coronavirus (COVID-19) has become a new public health crisis, posing a great threat to the people all around the world. We aimed to review the articles on COVID-19 in pediatric population to help physicians and other healthcare workers understand the importance of detecting silent disease carriers in this age group and stop further transmission to other healthy individuals and manage symptomatic patients based on the latest recommendations. Methods: We searched databases including PubMed, Scopus, Google Scholar, and Medline and reviewed 70 articles from December 2019 to mid-July 2020. Relevant articles about COVID-19 in children were included. Results: According to the latest reports, 1% - 5% of infected patients were under 19 years old. Death in this age group was rare but it can occur in children with severe disease. The overall course of disease -mainly pulmonary involvement- of the infected children tend to be milder than adults. This may be related to both host factors and exposure. The lab tests and computed tomography (CT) scan findings are nonspecific and milder compared to those in older ages. The cornerstone of COVID-19 management in pediatric group is supportive care. Of note, there is not any approved specific drug for treatment of children affected by COVID-19. Conclusions: COVID-19 disease characteristics in children are not yet fully established, which poses a significant problem for pediatric medical specialists. It should be considered that most children are asymptomatic or have mild symptoms. Critical cases, although uncommon, can occur especially in children with underlying diseases.

Pharmacogenomics in Pediatric Oncology: Mitigating Adverse Drug Reactions While Preserving Efficacy.

Cancer is the leading cause of death in American children older than 1 year of age. Major developments in drugs such as thiopurines and optimization in clinical trial protocols for treating cancer in children have led to a remarkable improvement in survival, from approximately 30% in the 1960s to more than 80% today. Short-term and long-term adverse effects of chemotherapy still affect most survivors of childhood cancer. Pharmacogenetics plays a major role in predicting the safety of cancer chemotherapy and, in the future, its effectiveness. Treatment failure in childhood cancer-due to either serious adverse effects that limit therapy or the failure of conventional dosing to induce remission-warrants development of new strategies for treatment. Here, we summarize the current knowledge of the pharmacogenomics of cancer drug treatment in children and of statistically and clinically relevant drug-gene associations and the mechanistic understandings that underscore their therapeutic value in the treatment of childhood cancer.

Analysis of clinical characteristics and drug treatment of inflammatory bowel disease in children: a single center study

Objective: To analyze the clinical characteristics and efficacy of drug treatment in children with inflammatory bowel disease (IBD) at different ages of onset. Methods: The clinical data of 87 children with IBD admitted to Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2009 to December 2018 were collected. The patients were divided into four groups according to the age of onset: 0 -<2 years old group (36 cases), 2 -<6 years old group (10 cases), 6 -<10 years old group (12 cases) and 10 -<18 years old group (29 cases). The clinical manifestations, laboratory examination, endoscopic findings, pathologic and genetic changes, and treatment were compared among different age groups with chi-square test or Fisher's exact text. Results: (1) A total of 87 patients were diagnosed with IBD, including 50 Crohn's disease (CD) (57%), 25 ulcerative colitis (UC) (29%) and 12 unclassified inflammatory bowel disease (IBD-U) (14%). (2) Patients with fever accounted for 78% (28/36) and 8/10 in the 0 -<2 years old group and 2 -<6 years old group, respectively. Patients with abdominal pain and perianal diseases accounted for 6% (2/36) and 47% (17/36) in the 0 -<2 years old group, and their proportions were significantly different among the four groups (χ(2)=8.369, 40.317 and 13.130, all P<0.05). (3) Leukocytosis, thrombocytosis and anemia were more common in the 0-<2 years old group, seen in 72% (26/36), 31% (11/36) and 81% (29/36), respectively. There were significant differences in the changes of complete blood count among the four groups (χ(2)=21.919, 8.095 and 11.520, all P<0.05). (4) Colonic involvement accounted for 85% (17/20) in the 0 -<2 years old CD patients. While in the CD patients over 6 years old, 61% (14/23) had inflammation of ileum and colon, with a significant difference compared to that in patients under 6 years old (19% (5/27) , χ(2)=9.455, P=0.003). Also, the location of bowel inflammation among the four groups were significantly different (χ(2)=21.120, P<0.01). (5) Noncaseating granulomas were found in 15 (30%) CD patients, and crypt abscess was found in 11 (44%) UC patients. (6) Among the 24 patients whose genes were analyzed by high throughput sequencing, 12 had pathogenic single gene mutation. (7) There were 25 patients treated with total enteral nutrition. Among the 25 patients treated with thalidomide, 20 (80%) had clinical remission or partial remission. Among the 19 CD patients treated with infliximab (IFX), 14 had clinical remission at the 6(th) week of treatment, and the proportion of remission maintenance at the 30(th) week of treatment was 12/14. (8) The rate of clinical remission or partial remission was 64% (23/36) in the 0 -<2 years old group, 8/10 in the 2 -<6 years old group, 11/12 in the 6 -<10 years old group, and 83% (24/29) in the 10 -<18 years old group. Conclusions: The proportion of CD was higher than that of UC in this study. Infant onset inflammatory bowel disease was more likely to present with perianal lesions, and was usually associated with leukocytosis, thrombocytosis and anemia, and has high possibility of single gene mutation. IFX may be effective in treating CD.

Induction of Glutathione Transferases and NAD(P)H Quinone Dehydrogenase 1 in Rats Dosed with Dichloroacetate

Dichloroacetate (DCA) is an investigational drug for treatment of children and adults with genetic or acquired mitochondrial diseases and cancer. The pharmacokinetics and dynamics of DCA vary by subject age. For example, the chronic use of DCA in adults is associated with the development of reversible peripheral neuropathy, a side effect that is seldom observed in children, who metabolize DCA more quickly. The dechlorination of DCA to its inactive metabolite, glyoxylate, is catalyzed by maleylacetoacetate isomerase/glutathione transferase zeta 1 (MAAI/GSTZ1). GSTZ1 is also critical in tyrosine catabolism through trans‐isomerization of maleylacetoacetate (MAA) and maleylacetone (MA). However, DCA causes mechanism‐based inactivation of GSTZ1, resulting in inhibition of both DCA metabolism and isomerization of MAA and MA. The resulting tissue accumulation of DCA, MAA, and MA may be a mechanism of toxicity. Studies in GSTZ1(−/−) mice showed induction of antioxidant enzymes and GSTs A1/A2, M1 and M5, as well as an increase in the GSSG:GSH ratio, suggesting that GSTZ1 deficiency causes oxidative stress. In this study, we determined if loss of the expression and activity of GSTZ1 in rat tissues following multiple DCA dosages that mimicked therapy resulted in similar effects. Adult (52 wk) female Sprague Dawley rats (8 per group) and young (4 wk) male and female Sprague Dawley rats (4 per group) were dosed with sodium DCA (100 mg/kg) or sodium acetate (100 mg/kg) by oral gavage daily for 8 consecutive days. On the 9th day, rats were euthanized, livers were removed and cytosolic and mitochondrial subcellular fractions were prepared. Protein expression was assessed by Western blot using antibodies to A, M, P, T and O‐class GSTs and to NAD(P)H quinone dehydrogenase 1 (NQO1), gamma‐glutamylcysteine ligase complex (GCLC), and glutathione synthetase (GSS). GSH and GSSG levels were measured by LC/MS/MS. Enzyme activity was measured in hepatic cytosol using 1‐chloro‐2,4‐dinitrobenzene (CDNB), 1,2‐dichloro‐4‐nitrobenzene (DCNB), and 2,6‐dichloroindophenol (DCPIP) as substrates. In comparison to acetate‐treated controls, GST activities with CDNB and DCNB were higher in DCA‐treated rats irrespective of age (p &lt; 0.05), as was the relative expression of GSTA1/A2 (p &lt; 0.01), whereas DCA‐treated adults displayed higher levels of GSTM1 (p &lt; 0.05) and GSTO1 (p &lt; 0.05). Changes in the expression of P and T‐class GSTs following multiple doses of DCA were not observed for either group. NQO1 expression and activity were higher in juveniles after DCA dosing (p &lt; 0.05). GSH concentrations were increased by DCA in adults but the GSH:GSSG ratio was not changed. Levels of GCLC and GSS were higher and lower, respectively, in adults treated with DCA. We conclude that DCA‐mediated depletion of GSTZ1 causes oxidative stress and promotes the induction of antioxidant enzymes that may vary between age groups. These findings will be important when interpreting outcomes of ongoing clinical trials of DCA in children and adults.Support or Funding InformationSupported in part by NIH RO1‐GM099871.

Progress in drug treatment for children with bronchial asthma

Pharmacotherapy is the main part of management of bronchial asthma in children.However, due to the heterogeneity of bronchial asthma, some patients are poorly controlled despite regular medication.Thus new drug and technologies need to be explored.With deep understanding of the pathogenesis of bronchial asthma, a lot of new drugs were available to asthmatic patients, especially the targeted drugs dominated by monoclonal antibodies, which have become the hot spot of bronchial asthma treatment. Key words: Children; Bronchial asthma; Drug

Results of a multicenter study on the efficacy of cortexin in treatment of cognitive dysfunction in children

To study the efficacy and tolerability of cortexin in the treatment of cognitive dysfunction in children. Material and methods: The study included 635 patients, aged 3–7 years. Patients were divided into 4 clinical groups: group 1 (269 children with attention deficit hyperactivity disorder (ADHD)), group 2 (215 children with speech delay), group 3 (82 patients with the consequences of a perinatal lesion of the central nervous system), group 4 (69 patients with asthenic/neurotic syndrome). Attention, visual memory and thinking were assessed before and after treatment. Standard treatment of cortexin, including 10 intramuscular injections, was used. Results and conclusion: The reliable effect of cortexin on cognitive impairment was shown. The best response to treatment was observed in patients with ADHD, aged 3–4 years, in particular on the tests measuring thinking. The tolerability of cortexin was good. It has been concluded that cortexin is an effective drug for treatment of children with ADHD, speech delay and consequences of a perinatal lesion of the central nervous system.

Results of a multicenter study on the efficacy of cortexin in treatment of cognitive dysfunction in children

To study the efficacy and tolerability of cortexin in the treatment of cognitive dysfunction in children. The study included 635 patients, aged 3-7 years. Patients were divided into 4 clinical groups: group 1 (269 children with attention deficit hyperactivity disorder (ADHD)), group 2 (215 children with speech delay), group 3 (82 patients with the consequences of a perinatal lesion of the central nervous system), group 4 (69 patients with asthenic/neurotic syndrome). Attention, visual memory and thinking were assessed before and after treatment. Standard treatment of cortexin, including 10 intramuscular injections, was used. The reliable effect of cortexin on cognitive impairment was shown. The best response to treatment was observed in patients with ADHD, aged 3-4 years, in particular on the tests measuring thinking. The tolerability of cortexin was good. It has been concluded that cortexin is an effective drug for treatment of children with ADHD, speech delay and consequences of a perinatal lesion of the central nervous system.

Pathogens and drug susceptibility test of septic arthritis of hip in children

Objective To study the pathogens and their drug susceptibility of septic arthritis of hip in children. Methods Prior to the antibiotic treatment, pus was extracted for bacterial culture under aseptic operation. The pathogenic bacterium was identified and drug susceptibility was analyzed using a fully automated bacterial identification/drug susceptibility system. Results A total of 68 pathogens were isolated, in which 42 were Gram-positive bacteria, 23 were Gram-negative bacteria and 3 were fungi. The results showed differences in the bacterial types of hip septic arthritis in children with different ages (5 days to 13 years). For newborns (less than 1 month), the most common pathogen was Klebsiella pneumoniae; for the ages of 1 month to 13 years old, the most common pathogen was Staphylococcus aureus. The results of drug susceptibility tests showed that Gram-positive bacteria were highly susceptible to vancomycin, teicoplanin and linezolid; the resistance of Staphylococcus aureus to penicillin was up to 96%; and Klebsiella pneumoniae, Escherichia coli, Haemophilus influenzae, Enterobacter cloacae and Salmonella were highly sensitive to meropenem and imipenem. Conclusion In the antimicrobial drug treatment of children with hip septic arthritis, the etiology sample should be collected for drug susceptibility analysis. Empirical drug therapy strategy should be applied in the absence of the analysis results. Sensitive antibiotic drug therapy should be used after obtaining reliable etiological diagnosis and drug susceptibility results, and simultaneously taking the age into consideration. Key words: Children; Hip joint; Septic arthritis; Drug resistance; Antibiotic; Drug susceptibility test

Management of Pregnant Women and Children: Focusing on Preventing Mother-to-Infant Transmission.

Hepatitis B virus (HBV) immunization has been effectively preventing chronic HBV infection with >90% efficacy in countries with universal neonatal immunization. Perinatal mother-to-infant transmission of HBV remains the major cause of chronic HBV infection despite immunization. Maternal hepatitis B e-antigen (HBeAg) and high viral load have been noted to be the most important risk factors for transmission. In recent years, short-term antiviral therapy for pregnant women in the third trimester has been shown to be highly effective in reducing 90% of vaccine failure in children. It is important to monitor maternal aminotransferase elevations postpartum. Long-term outcome of mothers and children is needed and awaits further investigations. Despite the above-mentioned preventive measures, it is also important to monitor high-risk children at 1 year of age with hepatitis B surface antigen and anti-hepatitis B to identify those with chronic HBV infection. Most of the children with chronic HBV infection were in the immune-tolerant phase. The goals for antiviral treatment in children are to reduce severity of liver injury, achieve HBeAg seroconversion, and prevent development of liver fibrosis and cancer. Studies on antiviral therapy are undergoing to elucidate the optimal indication and drug treatment for children. The ideal future goal of treatment is to eradicate chronic HBV infection globally.

PRS53 - Current Practice of Drug Treatment In Children with ILD: First Insights From The Child-Eu Registry

PRS53 - Current Practice of Drug Treatment In Children with ILD: First Insights From The Child-Eu Registry

Antiepileptic Drug Treatment in Children with Epilepsy.

Most children with new-onset epilepsy achieve seizure freedom with appropriate antiepileptic drugs (AEDs). However, nearly 20 % will continue to have seizures despite AEDs, as either monotherapy or in combination. Despite the growing market of new molecules over the last 20 years, the proportion of drug-resistant epilepsies has not changed. In this review, we report the evidence of efficacy and safety based on phase III randomized controlled clinical trials (RCTs) of AEDs currently used in the paediatric population. We conducted a literature search using the PubMed database and the Cochrane Database of Systematic Reviews. We also analysed the RCTs of newer AEDs whose efficacy in adolescents and adults might suggest possible use in children. Most of the phase III trials on AEDs in children have major methodological limitations that considerably limit meaningful conclusions about comparative efficacy between old and new molecules. Since the efficacy of new drugs has only been reported versus placebo, the commonly held opinion that new and newer AEDs have a better safety profile than old ones does not appear to be supported by evidence. Despite limited solid evidence, pharmacological management has improved over the years as a consequence of increased awareness of some degree of specificity of treatment in relation to different epilepsy syndromes and attention to adverse events. Future research should be directed taking these factors, as well as the diversity of epilepsy, into consideration.

Antiepileptic drug treatment in children

Antiepileptic drug treatment in children

The relationship between paroxysmal EEG abnormalities and anti-epileptic drug treatment in children with developmental disorders

The relationship between paroxysmal EEG abnormalities and anti-epileptic drug treatment in children with developmental disorders

Study on the treatment of children dependent on network game of psychological intervention combined with drug

Objective To study the curative effect of psychological intervention combined with drug treatment of children addicted to the network game. Methods One hundred and twelve children addicted to the network game were selected, who were admitted to the outpatient department of the Second Affiliated Hospital of Xinxiang Medical University from Feb.2009 to Oct.2013 were selected, according to the admission time sequence, they were randomly divided into drug treatment group, psychological intervention group(as control group) and psychological intervention combined with drug therapy group(test group). Each of the control groups had 38 cases of patients, while treatment group had 36 cases.Drug treatment group was treated with oral Fluoxetine Hydrochloride Capsules 10 mg, 1 time/d; the psychological intervention group was given the general psychological conversation, until discharged from the hospital; the test group adopted the cognitive restructuring, imagine the debate, self suggestion, remind yourself of cognitive therapy and behavior contract, behavior reinforcement, behavior extinction, aversive stimulus, self-regulation of behavior therapy combined with drug therapy.Respectively, before treatment, 2 weeks, 4 weeks and 8 weeks after the end of the treatment, Chinese Internet Addiction Scale, Coping Style Questionnaire (CSQ) and symptom checklist 90 (SCL-90) of each factor were evaluated. Results By the end of the 2 weeks and 8 weeks after the treatment, CIAS scores in the treatment group were significantly lower than that in drug therapy and psychological intervention group, the differences were statistically significant (t=2.49, 2.03, all P 0.05). Comparison of the SCL-90 score between the test group and the 2 control groups, the differences were statistically significant (t=5.05, 4.31, all P 0.05). Conclusions Psycholoical intervention therapy including cognitive therapy, behavior therapy combined with drug treatment have good effect on children's addiction to Web games. Key words: Network game on; Psychological intervention; Drug treatment; Child