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This study aims to evaluate the effectiveness of applying the evidence for preventing HSCT chemotherapy-induced OM in children and to elevate the nurses' compliance to the evidence. Methods: Following the clinical evidence practice application model of the Joanna Briggs Institute (JBI) evidence-Based Care Center. The process included reviewing literature, extracting evidence, identifying gaps, developing audit criteria, conducting a baseline audit, creating an action plan, implementing evidence-based interventions, and assessing outcomes. Results: After the evidence implementation, 6 out of 12 audit criteria with poor compliance are significantly improved, with statistically significant differences (P< 0.05). The incidence of OM decreases, with a statistically significant difference (66.6% vs 36.7%, P=0.02). The incidence of grade I, II, III, and IV OM also decreases (30% vs 23.3%, 23.3% vs 13.4%, 10% vs 0%, and 3.3% vs 0%). Ultimately, the standardized oral care practice routine and workflows to prevent OM were established. Conclusion: Bridging the gap between evidence and clinical practice can standardize nurse behavior, decrease the incidence of OM, and lower the OM severity in children undergoing HSCT. [ABSTRACT FROM AUTHOR]

Background and Objective: Olanzapine (OLZ) containing regimens are approved in adults for chemotherapy-induced nausea and vomiting (CINV) receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), and the same has not been approved in the pediatric population. In order to generate data regarding the efficacy and safety of OLZ as an adjunct to the standard of care (SoC) for CINV in pediatric patients receiving HEC/MEC, the review authors performed this systematic review and meta-analysis. Methods: A systematic literature search was performed through the databases Cochrane Library, Pub Med, and clinicaltrials.gov, from inception to September 2023, using keywords: "chemotherapy" and "olanzapine," "nausea" and "vomiting." Randomized clinical trials published in English that analyzed the efficacy and safety of olanzapine as an adjunct to SoC were included. The essential outcomes included in this study were the proportion of patients with no emesis in the acute and delayed phase, patients with no nausea in the acute and delayed phase, the proportion of patients requiring rescue medication, and the proportion of patients with reduced CNS arousal. Results: In the OLZ group, a greater number of patients had no emesis both in the acute and delayed phase (RR = 1.22; 95% CI = 1.09-1.37; P =.0004); and (RR = 1.23; 95% CI = 0.92-1.63; P =.16) respectively. Similarly, a higher number of patients showed no nausea both in the acute and delayed phase (RR = 1.08; 95% CI = 0.78-1.48; P =.66) and (RR = 1.12; 95% CI = 0.79-1.61; P =.52) respectively. The use of rescue medication was significantly less in the OLZ group (RR = 0.62; 95% CI = 0.42-0.91; P =.01). More patients experienced reduced CNS arousal in the OLZ group (RR = 2.97; 95% CI = 2.02-4.38; P <.0001). Conclusions: Olanzapine as an adjunct to the SoC may be effective in acute emesis, which may also reduce the use of rescue medication. Reduced CNS alertness was the significant adverse effect observed. For other endpoints, more studies are required to substantiate its role in CINV. [ABSTRACT FROM AUTHOR]

OBJECTIVES Literature is limited regarding ideal micafungin dosing in pediatric patients with hematologic malignancies receiving chemotherapy or hematopoietic stem cell transplantation. Micafungin is an intravenous echinocandin with activity against Candida and Aspergillus species and has a favorable safety profile compared with other antifungal classes. Our objective was to evaluate the breakthrough invasive fungal infection (IFI) rate in pediatric patients who received a prophylactic micafungin course at our institution. METHODS A single-center, retrospective study was conducted between January 1, 2011, and July 31, 2017, to determine the IFI rate in patients receiving micafungin prophylaxis. Patients with suspected IFI were evaluated for probable or proven infection based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group Consensus Group invasive fungal disease definitions. Statistical analyses were descriptive. RESULTS A total of 170 prophylactic micafungin courses from 129 unique patients ages <12 years at a median dose of 3 mg/kg daily were identified. The rate of probable or proven breakthrough IFIs was 2.4% as determined by clinical, radiologic, microbiologic, and histopathologic criteria. CONCLUSIONS A low rate of breakthrough IFI was seen with micafungin prophylaxis that is consistent with prior published adult hematopoietic stem cell transplantation studies. Micafungin was well tolerated, with liver function test elevations being transient in most cases and thought to be related to alternative factors. [ABSTRACT FROM AUTHOR]

Introduction: Many febrile neutropenia (FN) episodes are low risk (LR) for severe outcomes and can safely receive less aggressive management and early hospital discharge. Validated risk tools are recommended by the Children's Oncology Group to identify LR FN episodes. However, the complex dynamics of early hospital discharge and burdens faced by caregivers associated with the FN episode have been inadequately described. Methods: An adapted quality‐of‐life (QoL) survey instrument was administered by a convergent mixed methods design; qualitative and quantitative data from two sources, the medical record and the mixed methods survey instrument, were independently analyzed prior to linkage and integration. Code book was informed by conceptual framework; open coding was used. Mixed methods analysis used joint display of results to determine meta‐inferences. Results: Twenty‐eight patient–caregiver dyads participated with a response rate of 87%. Of the 27 FN episodes, 51.8% (14/27) were LR and 40.7% (11/27) had an early hospital discharge. The LR and early hospital discharge groups had higher mean QoL scores comparatively. Meta‐inferences are reciprocal influencers and expand the complex situation; FN negatively affects the entire family, and the benefits of hospital management were outweighed by risks and worsened symptoms, so an individualized approach to management and care at home was preferred. Conclusion: Early discharge of LR FN episodes positively impacts QoL, yet risk‐stratified management for FN is intricately complex. Optimal FN management should prioritize the patient's overall health; shared decision‐making is recommended and can improve care delivery. These results should be confirmed in a larger, more heterogeneous population. [ABSTRACT FROM AUTHOR]

The National Perinatal Association (NPA) is an interdisciplinary organization that strives to be a leading voice for perinatal care in the United States. Our diverse membership is comprised of healthcare providers, parents & caregivers, educators, and service providers, all driven by their desire to give voice to and support babies and families at risk across the country. Members of the NPA write a regular peer-reviewed column in Neonatology Today. [ABSTRACT FROM AUTHOR]

Background: Provision of paediatric palliative care for children with life-threatening or life-limiting conditions and their families is often complex. Guidelines can support professionals to deliver high quality care. Stakeholders expressed the need to update the first Dutch paediatric palliative care guideline with new scientific literature and new topics. This paper provides an overview of the methodology that is used for the revision of the Dutch paediatric palliative care guideline and a brief presentation of the identified evidence. Methods: The revised paediatric palliative care guideline was developed with a multidisciplinary guideline panel of 72 experts in paediatric palliative care and nine (bereaved) parents of children with life-threatening or life-limiting conditions. The guideline covered multiple topics related to (refractory) symptom treatment, advance care planning and shared-decision making, organisation of care, psychosocial care, and loss and bereavement. We established six main working groups that formulated 38 clinical questions for which we identified evidence by updating two existing systematic literature searches. The GRADE (CERQual) methodology was used for appraisal of evidence. Furthermore, we searched for additional literature such as existing guidelines and textbooks to deal with lack of evidence. Results: The two systematic literature searches yielded a total of 29 RCTs or systematic reviews of RCTs on paediatric palliative care interventions and 22 qualitative studies on barriers and facilitators of advance care planning and shared decision-making. We identified evidence for 14 out of 38 clinical questions. Furthermore, we were able to select additional literature (29 guidelines, two textbooks, and 10 systematic reviews) to deal with lack of evidence. Conclusions: The revised Dutch paediatric palliative care guideline addresses many topics. However, there is limited evidence to base recommendations upon. Our methodology will combine the existing evidence in scientific literature, additional literature, expert knowledge, and perspectives of patients and their families to provide recommendations. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread use of medical cannabis, little is known regarding the safety, efficacy, and dosing of cannabis products in children with cancer. The objective of this study was to systematically appraise the existing published literature for the use of cannabis products in children with cancer. Methods: This systematic review, registered with the International Prospective Register of Systematic Reviews (CRD42020187433), searched four databases: MEDLINE, Embase, PsycINFO, and the Cochrane Library. Abstracts and full texts were screened in duplicate. Data on types of cannabis products, doses, formulations, frequencies, routes of administration, indications, and clinical and demographic details as well as reported efficacy outcomes were extracted. Data on cannabinoid‐related adverse events were also summarized. Results: Out of 34,611 identified citations, 19 unique studies with a total of 1927 participants with cancer were included: eight retrospective chart reviews, seven randomized controlled trials, two open‐label studies, and two case reports. The included studies reported the use of various cannabis products for the management of symptoms. Cannabinoids were commonly used for the management of chemotherapy‐induced nausea and vomiting (11 of 19 [58%]). In controlled studies, somnolence, dizziness, dry mouth, and withdrawal due to adverse events were more commonly associated with the use of cannabinoids. Across all included studies, no serious cannabis‐related adverse events were reported. Conclusions: Although there is evidence to support the use of cannabis for symptom management, in children with cancer, there is a lack of rigorous evidence to inform the dosing, safety, and efficacy of cannabinoids. Because of the increasing interest in using cannabis, there is an urgent need for more research on medical cannabis in children with cancer. In the last 10 years, there has been an increase in the use of cannabis‐based products (both natural and synthetic cannabinoids) to help children with cancer‐related symptoms. This systematic review summarizes 19 studies related to the use of cannabinoids for the management of cancer‐related symptoms in children. The most common indication for the use of cannabinoids in the included studies was chemotherapy‐induced nausea and vomiting. A variety of cannabinoids were used: nabilone, Δ‐9‐tetrahydrocannabinol, dronabinol, and cannabidiol. The most common route of administration was oral with capsules as a formulation. [ABSTRACT FROM AUTHOR]

Invasive pulmonary aspergillosis remains a major cause of morbidity and mortality for immunocompromised children, particularly for patients with acute leukaemia and those undergoing haematopoietic stem cell transplantation. Timely diagnosis, using a combination of computed tomography (CT) imaging and microbiological testing, is key to improve prognosis, yet there are inherent challenges in this process. For CT imaging, changes in children are generally less specific than those reported in adults and recent data are limited. Respiratory sampling by either bronchoalveolar lavage or lung biopsy is recommended but is not always feasible in children, and serum biomarkers, including galactomannan, have important limitations. In this review we summarise the current paediatric data on available diagnostic tests for IPA and highlight key emerging diagnostic modalities with potential for future use. [ABSTRACT FROM AUTHOR]

This study aimed to optimize the dosing regimens of voriconazole (VRC) for pediatric patients after hematopoietic cell transplantation with different cytochrome P450 (CYP) 2C19 phenotypes and body weights, based on pharmacokinetic (PK)/pharmacodynamic (PD) analysis. The PK parameters of VRC were derived from previous literature. Combined with key factors affecting VRC, patients were categorized into 9 subgroups based on different CYP2C19 phenotypes (poor metabolizer/intermediate metabolizer, normal metabolizer, and rapid metabolizer/ultrarapid metabolizer) and typical body weights (15, 40, and 65 kg). Monte Carlo simulation was used to investigate dosing regimens for different groups. The area under the 24‐hour free drug concentration–time curve to the minimum inhibitory concentration (MIC) > 25 was used as the target value for effective treatment. The probability of target achievement and the cumulative fraction of response were determined on the basis of the assumed MICs and MICs distribution frequency of Aspergillus species and Candida species. When the MIC was ≤1 mg/L, 4 mg/kg every 12 hours was sufficient for optimal effects in groups 1‐3 and groups 5 and 6; however, 6 mg/kg every 12 hours was required for group 4, and 8 mg/kg every 12 hours was required for groups 7‐9. In empirical treatment, lower (2‐6 mg/kg every 12 hours) and higher (6‐12 mg/kg every 12 hours) dosing regimens were recommended for Candida spp. and Aspergillus spp., respectively. Our findings will assist in selecting appropriate dosing regimens of VRC for pediatric patients after hematopoietic cell transplantation with different CYP2C19 phenotypes and body weights. Clinically, it is better to continuously adjust the dosing on the basis of the therapeutic drug monitoring. [ABSTRACT FROM AUTHOR]

Background: Data from clinical trials of lumacaftor-ivacaftor (LUM-IVA) demonstrate improvements in lung clearance index (LCI) but not in FEV1 in children with Cystic Fibrosis (CF) aged 6–11 years and homozygous for the Phe508del mutation. It is not known whether LUM/IVA use in children can impact the progression of structural lung disease. We sought to determine the real-world impact of LUM/IVA on lung structure and function in children aged 6–11 years. Methods: This real-world observational cohort study was conducted across four paediatric sites in Ireland over 24-months using spirometry-controlled CT scores and LCI as primary outcome measures. Children commencing LUM-/IVA as part of routine care were included. CT scans were manually scored with the PRAGMA CF scoring system and analysed using the automated bronchus-artery (BA) method. Secondary outcome measures included rate of change of ppFEV1, nutritional indices and exacerbations requiring hospitalisation. Results: Seventy-one participants were recruited to the study, 31 of whom had spirometry-controlled CT performed at baseline, and after one year and two years of LUM/IVA treatment. At two years there was a reduction from baseline in trapped air scores (0.13 to 0.07, p = 0.016), but an increase from baseline in the % bronchiectasis score (0.84 to 1.23, p = 0.007). There was no change in overall % disease score (2.78 to 2.25, p = 0.138). Airway lumen to pulmonary artery ratios (AlumenA ratio) were abnormal at baseline and worsened over the course of the study. In 28 participants, the mean annual change from baseline LCI2.5 (-0.055 (-0.61 to 0.50), p = 0.85) measurements over two years were not significant. Improvements from baseline in weight (0.10 (0.06 to 0.15, p < 0.0001), height (0.05 (0.02 to 0.09), p = 0.002) and BMI (0.09 (0.03 to 0.15) p = 0.005) z-scores were seen with LUM/IVA treatment. The mean annual change from baseline ppFEV1 (-2.45 (-4.44 to 2.54), p = 0.66) measurements over two years were not significant. Conclusion: In a real-world setting, the use of LUM/IVA over two years in children with CF aged 6–11 resulted in improvements in air trapping on CT but worsening in bronchiectasis scores. Our results suggest that LUM/IVA use in this age group improves air trapping but does not prevent progression of bronchiectasis over two years of treatment. [ABSTRACT FROM AUTHOR]

Medicine use in children with cystic fibrosis (CF) is complicated by inconsistent pharmacokinetics at variance with the general population, a lack of research into this and its effects on clinical outcomes. In the absence of established dose regimens, therapeutic drug monitoring (TDM) is a clinically relevant tool to optimize drug exposure and maximize therapeutic effect by the bedside. In clinical practice though, use of this is variable and limited by a lack of expert recommendations. We aimed to review the use of TDM in children with CF to summarize recent developments, current recommendations, and opportunities for future directions. We searched PubMed for relevant publications using the broad search terms "cystic fibrosis" in combination with the specific terms "therapeutic drug monitoring (TDM)" and "children." Further searches were undertaken using the name of identified drugs combined with the term "TDM." Further research into the use of Bayesian forecasting and the relationship between exposure and response is required to personalize dosing, with the opportunity for the development of expert recommendations in children with CF. Use of noninvasive methods of TDM has the potential to improve accessibility to TDM in this cohort. [ABSTRACT FROM AUTHOR]

Rationale: Lumacaftor/ivacaftor (LUM/IVA) was shown to be safe and well tolerated in children 2 through 5 years of age with cystic fibrosis (CF) homozygous for F508del-CFTR in a Phase 3 open-label study. Improvements in sweat chloride concentration, markers of pancreatic function, and lung clearance index2.5 (LCI2.5), along with increases in growth parameters, suggested the potential for early disease modification with LUM/IVA treatment. Objective: To further assess the effects of LUM/IVA on CF disease progression in children 2 through 5 years of age using chest magnetic resonance imaging (MRI). Methods: This Phase 2 study had two parts: a 48-week, randomized, double-blind, placebo-controlled treatment period in which children 2 through 5 years of age with CF homozygous for F508del-CFTR received either LUM/IVA or placebo (Part 1) followed by an open-label period in which all children received LUM/IVA for an additional 48 weeks (Part 2). The results from Part 1 are reported. The primary endpoint was absolute change from baseline in chest MRI global score at Week 48. Secondary endpoints included absolute change in LCI2.5 through Week 48 and absolute changes in weight-for-age, stature-for-age, and body mass index–for-age z-scores at Week 48. Additional endpoints included absolute changes in sweat chloride concentration, fecal elastase-1 levels, serum immunoreactive trypsinogen, and fecal calprotectin through Week 48. The primary endpoint was analyzed using Bayesian methods, where the actual Bayesian posterior probability of LUM/IVA being superior to placebo in the chest MRI global score at Week 48 was calculated using a vague normal prior distribution; secondary and additional endpoints were analyzed using descriptive summary statistics. Results: Fifty-one children were enrolled and received LUM/IVA (n = 35) or placebo (n = 16). For the change in chest MRI global score at Week 48, the Bayesian posterior probability of LUM/IVA being better than placebo (treatment difference,,0; higher score indicates greater abnormality) was 76%; the mean treatment difference was 21.5 (95% credible interval, 25.5 to 2.6). Treatment with LUM/IVA also led to within-group numerical improvements in LCI2.5, growth parameters, and biomarkers of pancreatic function as well as greater decreases in sweat chloride concentration compared with placebo from baseline through Week 48. Safety data were consistent with the established safety profile of LUM/IVA. Conclusions: This placebo-controlled study suggests the potential for early disease modification with LUM/IVA treatment, including that assessed by chest MRI, in children as young as 2 years of age. [ABSTRACT FROM AUTHOR]

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Objective: Proper use of inhaled medications is essential for management of asthma, as inhaled therapies are recommended as first-line for both prevention and treatment of asthma symptoms. Optimizing adherence requires identifying and understanding multiple layers of systemic complexity to obtaining and using these therapies and offering specific solutions to address these barriers. Bronfenbrenner's socio-ecological model provides a framework for examining multilevel systems – both internal and external – that contribute to the management of childhood asthma. The four levels in this model consist of factors related to the individual, interpersonal relationships, organizational entities, and societal structures and rules. This narrative review identifies influences and factors related to asthma inhaler adherence by each level and offers evidence-based solutions to each obstacle.Data Sources: We conducted PubMed searches to identify relevant articles for barriers and solutions impacting asthma control at each level of the socio-ecological model.Study Selection: Common barriers to asthma control at each model level were identified. Pertinent studies for each barrier were identified and reviewed by the writing group for inclusion into the narrative review.Results: For each level of the socio-ecological model, three primary issues were identified based on the literature review. Approaches for addressing each issue in an evidence-based, systematic fashion are presented.Conclusion: Understanding the obstacles and potential interventions to achieve proper use of inhaled medications is a critical step necessary to develop and implement systematic solutions aimed at improving asthma control and morbidity for the more than 6 million affected children in the United States. [ABSTRACT FROM AUTHOR]

Rationale: A 24-week, phase 3, open-label study showed elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was safe and efficacious in children aged 6–11 years with cystic fibrosis (CF) and one or more F508del-CFTR alleles. Objectives: To assess long-term safety and efficacy of ELX/TEZ/ IVA in children who completed the pivotal 24-week phase 3 trial. Methods: In this phase 3, two-part (part A and part B), open-label extension study, children aged ≥6 years with CF heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) or homozygous for F508del (F/F genotype) who completed the 24-week parent study received ELX/TEZ/IVA based on weight. Children weighing,30 kg received ELX 100 mg once daily/TEZ 50 mg once daily/IVA 75 mg every 12 hours, whereas children weighing ≥30 kg received ELX 200 mg once daily/TEZ 100 mg once daily/IVA 150 mg every 12 hours (adult dose). The 96-week analysis of part A of this extension study is reported here. Measurements and Main Results: Sixty-four children (F/MF genotypes, n = 36; F/F genotype, n = 28) were enrolled and received one or more doses of ELX/TEZ/IVA. Mean (SD) period of exposure to ELX/TEZ/IVA was 93.9 (11.1) weeks. The primary endpoint was safety and tolerability. Adverse events and serious adverse events were consistent with common manifestations of CF disease. Overall, exposure-adjusted rates of adverse events and serious adverse events (407.74 and 4.72 events per 100 patient-years) were lower than in the parent study (987.04 and 8.68 events per 100 patient-years). One child (1.6%) had an adverse event of aggression that was moderate in severity and resolved after study drug discontinuation. From parent study baseline at Week 96 of this extension study, the mean percent predicted FEV1 increased (11.2 [95% confidence interval (CI), 8.3 to 14.2] percentage points), sweat chloride concentration decreased (262.3 [95% CI, 265.9 to 258.8] mmol/L), Cystic Fibrosis Questionnaire-Revised respiratory domain score increased (13.3 [95% CI, 11.4 to 15.1] points), and lung clearance index 2.5 decreased (22.00 [95% CI, 22.45 to 21.55] units). Increases in growth parameters were also observed. The estimated pulmonary exacerbation rate per 48 weeks was 0.04. The annualized rate of change in percent predicted FEV1 was 0.51 (95% CI, 20.73 to 1.75) percentage points per year. Conclusions: ELX/TEZ/IVA continued to be generally safe and well tolerated in children aged ≥6 years through an additional 96 weeks of treatment. Improvements in lung function, respiratory symptoms, and CFTR function observed in the parent study were maintained. These results demonstrate the favorable long-term safety profile and durable clinical benefits of ELX/TEZ/ IVA in this pediatric population. [ABSTRACT FROM AUTHOR]

Background: To assess the effectiveness of educational intervention to reduce the weight of school bags. Material and Methods: The study design was one group pre- and posttest experimental Research design. Place and Duration of Study: Government Senior Secondary School Dhanas, Chandigarh, and Shri Guru Harkrishan Model Senior Secondary School Sector-38D, Chandigarh (A private school) between July and November 2018. Names of the schools can be avoided. Total 760 students from selected sections nursery to 10th class of school were enrolled in the study. At baseline and end line weight of children, school bags and its content were weighed using weighing scale. Length of bag strap, breath of bag, torso of children, and their shoulders size were measured by measuring tape. Bag carrying style, posture, etc., were observed by observation checklist. Interviewed children (5th to 10th class) were using Nordic musculoskeletal questionnaire for musculoskeletal system assessment. Educational intervention was provided to the children for one month to reduce weight of school bag by teaching in assembly and displaying the charts in school. (Use of softbound thin textbooks, breaking thin books in 2-3 thin softbound books, use lightweight bag, pencil box, lunch box, and water bottles. Pack bag as per timetable.) Result: The result revealed that heavy school bags were carrying 69.7% children from government school and 80.2% from private school. Children carrying heavy bags reported musculoskeletal problems 5 times higher than their counterparts. After intervention, there was significant reduction in the weight of school bags (P < 0.001 as per paired t-test). Provide the weight of the bags before and after intervention in addition to the P value. Conclusion: Children carrying heavy bags were suffering from musculoskeletal problems. Intervention helped in reducing the weight of school bag. [ABSTRACT FROM AUTHOR]

During COVID-19, public health measures including masks and social distancing decreased viral upper respiratory infections (URI). Upper respiratory infections are the most common infectious etiology for low-risk pediatric febrile neutropenia (FN). This single-center, quasi-experimental, pre-post study was designed to understand the impact of public health measures on FN admissions and outcomes in the general pediatric oncology population during the COVID (March 2020–February 2021) vs. pre-COVID era (January 2018–February 2020) and their respective respiratory seasons (November–February). Episodes were risk-stratified using a tool recommended by the Children's Oncology Group. Descriptive and bivariate statistics were used to compare admission characteristics and outcomes. Comparing respiratory seasons, the Covid-era season had 60% fewer URI diagnoses (5/12), while high-risk episodes (63.6% [28/44] vs. 44.2% [23/52]) and intensive care admissions (18.2% [8/44] vs. 3.8% [2/52]) increased. Between eras, URIs were lower in the COVID-era (10.8% [16/148] vs. 19.9% [67/336]; p = 0.01), but admission characteristics and severe outcomes were not different. The impact of public health measures was most prominent during the respiratory season. Despite decreased incidence of URIs, the overall admission characteristics and severe outcomes were minimally impacted due to the brevity of respiratory seasons, but larger studies are warranted. [ABSTRACT FROM AUTHOR]

Background: Binaural auditory beat is an auditory illusion perceived when two different pure-tone sine waves with less than a 30 Hz difference are presented to a listener dichotically. Monaural beat stimulation is achieved by the superposition of amplitude-modulated signals of nearby frequencies to both ears simultaneously. Aim: The study aims to evaluate and compare anxiety level during restorative treatment using no music, monaural beats, and binaural auditory beats as audio distraction behavior guidance techniques in children aged 6-12 years. Settings and Design: Three-arm, parallel-group randomized study was conducted in the department of pediatric and preventive dentistry. Materials and Methods: The sample size of 45 participants was calculated and allocated into three groups as no music, monaural beats, and binaural auditory beats group. Teeth with Class I cavity in primary or permanent molars were prepared and restored. Anxiety was measured pre and postintervention using pulse oximeter and Venham's picture test. Statistical Analysis Used: Data obtained were analyzed with SPSS software version 20.0 and were carried out using one-way analysis of variance and dependent t-test and significance value < 0.05 was considered. Results: Binaural auditory beats and monaural beats showed a better reduction in anxiety levels as per Venham's picture test scores with statistically significant "P" value 0.0001 and 0.064, respectively. Likewise, binaural auditory beats showed better reduction in anxiety levels as per pulse rate scores with statistically significant "P" value 0.0001 as compared to conventional treatment technique. Conclusion: Binaural auditory beat was found to be the most effective followed by the monaural beat compared to the control group. Thus, binaural auditory beats and monaural beats can be used effectively as an essential aid to reduce anxiety in children. [ABSTRACT FROM AUTHOR]

Risk stratification of pediatric febrile neutropenia (FN) is an established concept, yet clinical risk tools misclassify nearly 5% of clinical standard-risk episodes with severe outcomes. The internal evaluation of a clinical risk tool before implementation has not been well-described. In this noninterventional cohort study, we evaluated a study decision rules (SDR) tool; a clinical risk tool with serial procalcitonin. The study standard-risk (SSR) group met clinical standard-risk criteria with two serial procalcitonin <0.4 ng/mL. The study high-risk (SHR) group met clinical high-risk criteria or clinical standard-risk with a procalcitonin ≥0.4 ng/mL. Descriptive and bivariate statistics compared the groups and outcomes. Clinical criteria alone identified 39.1% (238/608) standard-risk episodes; 5.9% (14/238) had severe events. Prospectively using the SDR, the SHR group encompassed 76.6% (92/120) of episodes; severe events occurred in 20% (3/15) of standard-risk episodes included due to elevated procalcitonin ≥0.4 ng/mL. The SHR group had more blood stream infections [21.7% (20/92) vs. 0% (0/28); P = 0.007] and intensive care admissions [13% (12/92) vs. 3.6% (1/28); P = 0.158]. In conclusion, the SDR with serial procalcitonin aided in identifying severe events in clinical standard-risk episodes, but analysis was limited. Institutions may consider similar internal evaluation methodology before FN episode risk stratification. [ABSTRACT FROM AUTHOR]

Management of pediatric Primary Spontaneous Pneumothorax (PSP) is controversial and based on guidelines on adults. Therapeutic strategies include: observation, needle aspiration, chest drain, or surgery. We aimed to assess: i) differences in the management of PSP in pediatric vs. adult departments; ii) risk of recurrence associated to each therapeutic choice; iii) management of "large" pneumothorax (i.e. >3cm at the apex on chest X-Ray); iv) role of CT scan in addressing the treatment. We reviewed all PSP treated at Pediatric Surgery Unit (PSU) and Thoracic Surgery Unit for adults (TSU) in a 10-year period (2011 to 2020). We included a total of 42 PSP: 30/42 1st episodes and 12/42 recurrences. Among the 30/42 1st episodes, 15/30 were managed in the PSU and 15/30 in the TSU. Observation was significantly most common among PSU patients (9/15, 60%) vs. TSU cases (1/15, 6.7%; p=0.005]. Chest drain placement was reduced in PSU (3/15, 20%) vs. TSU (12/15, 80%; p=0.002). Observational was associated with a reduced risk of recurrence (0/10, 0%) compared to chest drain (7/15, 46.7%; p=0.01). Management of 20/42 "large" pneumothorax was: 4/20 (20%) observation, 10/20 (50%) chest drain, 2/20 (10%) needle aspiration, 4/20 (20%) surgery. Twentythree/29 PSP (79.3%) underwent CT-scan after the first episode. Bullae were detected in 17/23 patients and 5/17 (29.4%) had seven episodes of recurrence. PSP patients treated by PSU were more likely to receive clinical observation. Those managed by TSU were mostly treated by chest drain. Observation seems an effective choice for clinically stable PSP, with low risk of recurrence at a mid-term follow-up. CT-scan seems not to detect those patients at higher risk of recurrence. [ABSTRACT FROM AUTHOR]

Rationale: The triple-combination regimen elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be safe and efficacious in children aged 6 through 11 years with cystic fibrosis and at least one F508del-CFTR allele in a phase 3, open-label, single-arm study. Objectives: To further evaluate the efficacy and safety of ELX/TEZ/IVA in children 6 through 11 years of age with cystic fibrosis heterozygous for F508del and a minimal function CFTR mutation (F/MF genotypes) in a randomized, double-blind, placebo-controlled phase 3b trial. Methods: Children were randomized to receive either ELX/TEZ/IVA (n = 60) or placebo (n = 61) during a 24-week treatment period. The dose of ELX/TEZ/IVA administered was based on weight at screening, with children <30 kg receiving ELX 100 mg once daily, TEZ 50 mg once daily, and IVA 75 mg every 12 hours, and children ⩾30 kg receiving ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 hours (adult dose). Measurements and Main Results: The primary endpoint was absolute change in lung clearance index2.5 from baseline through Week 24. Children given ELX/TEZ/IVA had a mean decrease in lung clearance index2.5 of 2.29 units (95% confidence interval [CI], 1.97-2.60) compared with 0.02 units (95% CI, -0.29 to 0.34) in children given placebo (between-group treatment difference, -2.26 units; 95% CI, -2.71 to -1.81; P < 0.0001). ELX/TEZ/IVA treatment also led to improvements in the secondary endpoint of sweat chloride concentration (between-group treatment difference, -51.2 mmol/L; 95% CI, -55.3 to -47.1) and in the other endpoints of percent predicted FEV1 (between-group treatment difference, 11.0 percentage points; 95% CI, 6.9-15.1) and Cystic Fibrosis Questionnaire-Revised Respiratory domain score (between-group treatment difference, 5.5 points; 95% CI, 1.0-10.0) compared with placebo from baseline through Week 24. The most common adverse events in children receiving ELX/TEZ/IVA were headache and cough (30.0% and 23.3%, respectively); most adverse events were mild or moderate in severity. Conclusions: In this first randomized, controlled study of a cystic fibrosis transmembrane conductance regulator modulator conducted in children 6 through 11 years of age with F/MF genotypes, ELX/TEZ/IVA treatment led to significant improvements in lung function, as well as robust improvements in respiratory symptoms and cystic fibrosis transmembrane conductance regulator function. ELX/TEZ/IVA was generally safe and well tolerated in this pediatric population with no new safety findings. [ABSTRACT FROM AUTHOR]

Pediatric acute myeloid leukemia (AML) is the second most common type of pediatric leukemia. Patients with AML are at high risk for several complications such as infections, typhlitis, and acute and long-term cardiotoxicity. Despite this knowledge, there are no definite supportive care guidelines as to what the best approach is to manage or prevent these complications. The NOPHO-DB-SHIP (Nordic-Dutch-Belgian-Spain-Hong-Kong-Israel-Portugal) consortium, in preparation for a new trial in pediatric AML patients, had dedicated meetings for supportive care. In this review, the authors discuss the available data and outline recommendations for the management of children and adolescents with AML with an emphasis on hyperleukocytosis, tumor lysis syndrome, coagulation abnormalities and bleeding, infection, typhlitis, malnutrition, cardiotoxicity, and fertility preservation. Improved supportive care has significantly contributed to increased cure rates. Recommendations on supportive care are an essential part of treatment for this highly susceptible population and will further improve their outcome. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate air leakage during invasive mechanical ventilation (IMV) in a pediatric intensive care unit (PICU) and explore potential risk factors. Methods: We conducted a retrospective cohort study of children who underwent IMV in a single-center PICU in a tertiary referral hospital. Air leakage risk factors and factors associated with an improved outcome were assessed. Results: A total of 548 children who underwent IMV were enrolled in this study. Air leakage occurred in 7.5% (41/548) of the cases in the PICU. Air leakage increased the duration of IMV and hospitalization time. Multivariate logistic regression analysis showed a higher risk of air leakage during IMV for PICU patients with acute respiratory dyspnea syndrome (ARDS) (OR = 4.38), a higher pediatric critical illness score (PCIS) (OR = 1.08), or a higher peak inspiratory pressure (PIP) (OR = 1.08), whereas the risk was lower for patients with central respiratory failure (OR = 0.14). The logistic model had excellent predictive power for air leakage, with an area under the curve of 0.883 and tenfold cross-validation. Patients aged between 1 and 6 years who were diagnosed with measles or pneumonia and had a low positive end-expiratory pressure (PEEP) or high PaO2/FiO2 ratio were associated with improved outcomes. Patients diagnosed with central respiratory failure or congenital heart diseases were associated with less desirable outcomes. Conclusions: Patients with ARDS, a higher PCIS at admission or a higher PIP were at higher risk of air leakage. [ABSTRACT FROM AUTHOR]

Rationale: Chronic lung injury is common in sickle cell anemia (SCA) and worsens outcomes. Sensitive lung function tests might predict reversible disease that might benefit from therapeutic interventions. Objectives: To evaluate whether lung clearance index (LCI) (measuring global ventilation inhomogeneity), intraacinar ventilation inhomogeneity (Sacin), and conductive ventilation inhomogeneity (Scond) are more frequently abnormal than lung volumes in young people with SCA. Methods: Nitrogen multiple-breath washout, spirometry, and body plethysmography were cross-sectionally evaluated at steady state in subjects with SCA (hemoglobin SS) and healthy control subjects aged 8-21 years from London, United Kingdom. Results: Thirty-five patients (51% boys, mean ± SD age, 16.4 ± 3.5 yr) and 31 control subjects (48% boys; 16.2 ± 3.2 yr) were tested. There were significant differences between the study and control groups in mean LCI (mean difference, 0.42 units; 95% confidence interval [CI], 0.22 to 0.63; P = 0.0001), Sacin (mean difference, 0.014 units; 95% CI, 0.001 to 0.026; P = 0.04), forced expiratory volume in 1 second (FEV1) (mean difference, -0.79 z-scores; 95% CI, -1.28 to -0.30; P = 0.002), forced vital capacity (FVC) (mean difference, -0.80 z-scores; 95% CI, -1.28 to -0.31, P = 0.002), and total lung capacity (mean difference, -0.76 z-scores; 95% CI, -1.25 to -0.29, P = 0.002), but not in Scond and FEV1-to-FVC ratio. Whereas 29% (10 of 35) of patients had LCI > 95th percentile of control subjects, 23% (8 of 35) had abnormal FEV1 (<5th percentile of the reference population). Conclusions: LCI detected slightly more abnormalities than lung volumes in young people with SCA. Significant differences from control subjects in LCI and Sacin but not in Scond and FEV1-to-FVC ratio suggest that the lung function changes were most likely owing to patchy peripheral lung disease. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is the most common inherited disease in Caucasian populations, affecting around 50,000 patients in Europe and 30,000 in United States. A mutation in CF trans-membrane conductance regulator (CFTR) gene changes a protein (a regulated chloride channel), which is expressed in many tissues. Defective CFTR results in reduced chloride secretion and an overage absorption of sodium across the epithelia, leading to thickened secretions in organs such as pancreas and lung. Gradually, there have been considerable improvements in the survival of people with CF, thanks to substantial changes in specialized CF care and the discovery of new CFTR modulators drugs. Nevertheless, lung disease remains the most common cause of death. For these reasons improvement of sputum clearance is a major therapeutic aim in CF. So far, symptomatic mucolytic therapy is mainly based on inhalation of dornase alfa, hypertonic saline or mannitol, in combination with physiotherapy. The major component of mucus in CF is pus including viscous material such as polymerized DNA derived from degraded neutrophils. Dornase alfa cleaves the DNA released from the neutrophils and reduces mucous viscosity, and further prevent airway infections and damage to the lung parenchyma. In this review we will summarize the current knowledge on dornase alfa in the treatment of CF lung disease, especially highlighting the positive effect on lung clearance index, a sensitive measure of ventilation inhomogeneity. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 virus has infected more than 235 million people since it was accepted as a pandemic in March 2020. Although a milder disease is seen in the pediatric age group, the extent of lung damage and its long-term effects are still unknown. In this study, persistent respiratory symptoms and pulmonary function tests were investigated in children with COVID-19. Fifty children with a confirmed diagnosis of COVID-19 were included in the study. Patients were evaluated for ongoing respiratory symptoms and pulmonary function tests 3 months after infection. Patients with and without persistent symptoms were compared in terms of demographic, clinical, laboratory, and radiological characteristics and also disease severity. Three months after infection, persistent respiratory symptoms were found to be present in 28% of patients; cough, chest pain and tightness, dyspnea, and exertional dyspnea were the most common symptoms. Three patients had an obstructive deficit, and one had a restrictive deficit. Four patients had impaired diffusing capacity of the lungs for carbon monoxide (DLCO). A significant decrease in FEV1/FVC and an increase in lung clearance index were found in the patients with persistent respiratory symptoms. Persistent respiratory symptoms were present in 50% of patients who had severe disease and 12.5% with non-severe disease. DLCO was also significantly lower in the severe disease group. Conclusions: Our study suggests that the persistence of respiratory symptoms is not related to the severity of acute COVID-19 in children. The inflammatory process due to COVID-19 may continue regardless of its severity, and consequently, peripheral airways may be affected. What is Known: • As compared with adults, children with COVID-19 exhibit a milder disease course and lower mortality rates. However, due to the lack of follow-up studies on children, the long-term effects of their contracting the disease are unknown. What is New: • Although COVID-19 has been thought to have a milder course in children, respiratory system symptoms persist in approximately 30% of patients 3 months after infection. The persistent respiratory symptoms suggest that the inflammatory process due to COVID-19 may continue in some children, even if the clinical findings at admission are not severe, and that the peripheral airways may be affected accordingly. [ABSTRACT FROM AUTHOR]

Background: Dealing with the symptom burden of cancer diagnosis and treatment has led parents to seek different self-management strategies including Alternative and Complementary Medicine (CAM). The aim of this study was to perform a systematic review and meta-analysis about the use and effect of CAM modalities to treat adverse effects of conventional cancer treatment among children and young adults. Methods: Six scientific research databases were used to identify randomized controlled trials (RCTs) from 1990 to September 2020. Included studies investigated the use of CAM to treat cancer treatment related adverse effects in children and young adults compared to controls. Results: Twenty RCTs comprising 1,069 participants were included in this review. The included studies investigated acupuncture, mind–body therapies, supplements, and vitamins for chemotherapy-induced nausea and vomiting (CINV), oral mucositis, and anxiety among children and young adults who underwent conventional cancer treatment. Seven studies (315 participants) were included in the meta-analysis. The overall effect of CAM (including acupuncture and hypnosis only) on chemotherapy-induced nausea and/or vomiting and controls was statistically significant with a standard mean difference of -0.54, 95% CI [-0.77, -0.31] I2 = 0% (p < 0.00001). There was a significant difference between acupuncture and controls (n = 5) for intensity and/or episodes of CINV with an SMD -0.59, 95% CI [-0.85, -0.33] (p < 0.00001). No significant difference was found between hypnosis and controls (n = 2) for severity or episodes of CINV with an SMD -0.41, 95% CI [-1.09, 0.27] I2 = 41% (p = 0.19). Conclusion: Current evidence from this meta-analysis of randomized controlled trials shows that CAM, including acupuncture and hypnosis only, is effective in reducing chemotherapy-induced nausea and vomiting in children and young adults. More rigorous trials and long-term effects should be investigated if acupuncture and hypnosis are to be recommended for clinical use. [ABSTRACT FROM AUTHOR]

Background: Inhalation therapy is one of the cornerstones of the daily treatment regimen in patients with cystic fibrosis (CF). Recommendations regarding the addition of bronchodilators, especially salbutamol are conflicting due to the lack of evidence. New diagnostic measures such as multiple-breath washout (MBW) and functional magnetic resonance imaging (MRI) have the potential to reveal new insights into bronchodilator effects in patients with CF. Objective: The objective of the study was to comprehensively assess the functional response to nebulized inhalation with salbutamol in children with CF. Methods: Thirty children aged 6–18 years with stable CF performed pulmonary function tests, MBW, and matrix pencil-MRI before and after standardized nebulized inhalation of salbutamol. Results: Lung clearance index decreased (improved) by −0.24 turnover (95% confidence interval [CI]: −0.53 to 0.06; p = 0.111). Percentage of the lung volume with impaired fractional ventilation and relative perfusion decreased (improved) by −0.79% (CI: −1.99 to 0.42; p = 0.194) and −1.31% (CI: −2.28 to −0.35; p = 0.009), respectively. Forced expiratory volume (FEV1) increased (improved) by 0.41 z-score (CI: 0.24–0.58; p < 0.0001). We could not identify specific clinical factors associated with a more pronounced effect of salbutamol. Conclusions: There is a positive short-term effect of bronchodilator inhalation on FEV1 in patients with CF, which is independent of ventilation inhomogeneity. Heterogeneous response between patients suggests that for prediction of a therapeutic effect this should be tested by spirometry in every patient individually. [ABSTRACT FROM AUTHOR]

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Background: Paediatric acute respiratory distress syndrome (PARDS) is a manifestation of severe, life-threatening lung injury necessitating mechanical ventilation with mortality rates ranging up to 40-50%. Neuromuscular blockade agents (NMBAs) may be considered to prevent patient self-inflicted lung injury in PARDS patients, but two trials in adults with severe ARDS yielded conflicting results. To date, randomised controlled trials (RCT) examining the effectiveness and efficacy of NMBAs for PARDS are lacking. We hypothesise that using NMBAs for 48 h in paediatric patients younger than 5 years of age with early moderate-to-severe PARDS will lead to at least a 20% reduction in cumulative respiratory morbidity score 12 months after discharge from the paediatric intensive care unit (PICU).Methods: This is a phase IV, multicentre, randomised, double-blind, placebo-controlled trial performed in level-3 PICUs in the Netherlands. Eligible for inclusion are children younger than 5 years of age requiring invasive mechanical ventilation with positive end-expiratory pressure (PEEP) ≥ 5 cm H2O for moderate-to-severe PARDS occurring within the first 96 h of PICU admission. Patients are randomised to continuous infusion of rocuronium bromide or placebo for 48 h. The primary endpoint is the cumulative respiratory morbidity score 12 months after PICU discharge, adjusted for confounding by age, gestational age, family history of asthma and/or allergy, season in which questionnaire was filled out, day-care and parental smoking. Secondary outcomes include respiratory mechanics, oxygenation and ventilation metrics, pulmonary and systemic inflammation markers, prevalence of critical illness polyneuropathy and myopathy and metrics for patient outcome including ventilator free days at day 28, length of PICU and hospital stay, and mortality DISCUSSION: This is the first paediatric trial evaluating the effects of muscular paralysis in moderate-to-severe PARDS. The proposed study addresses a huge research gap identified by the Paediatric Acute Lung Injury Consensus Collaborative by evaluating practical needs regarding the treatment of PARDS. Paediatric critical care practitioners are inclined to use interventions such as NMBAs in the most critically ill. This liberal use must be weighed against potential side effects. The proposed study will provide much needed scientific support in the decision-making to start NMBAs in moderate-to-severe PARDS.Trial Registration: ClinicalTrials.gov NCT02902055 . Registered on September 15, 2016. [ABSTRACT FROM AUTHOR]

Infections are still one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper was the presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation with Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing (European Conference on Infections in Leukemia (ECIL) and European Society of Blood and Marrow Transplantation (EBMT) guidelines, as well as the results of a survey performed among all Polish transplant centers, were the background material for the working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on the principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented. [ABSTRACT FROM AUTHOR]

Tremor, as in our case, is also reported.2,4 The differential diagnosis of tremor caused by metoclopramide is acute cerebellar ataxia/acute cerebellitis (ACA/AC), which is often accompanied by prodromal viral infections. Although long-term use and overdose have been reported as risk factors for its development, even a single dose of metoclopramide can cause substantial motor symptoms, as in our case.3 Treatment of metoclopramide-induced tremor is supportive. Keywords: metoclopramide; tremor; children EN metoclopramide tremor children 987 989 3 10/13/22 20221001 NES 221001 Metoclopramide is a dopamine receptor antagonist that, despite no evidence to support its use in children with acute gastroenteritis,1 is frequently used for the symptomatic treatment of nausea and vomiting in pediatric acute gastroenteritis in Japan, where ondansetron and other serotonin receptor agonists are not approved for this condition. [Extracted from the article]

La lesión pulmonar crónica, un rasgo común en pacientes con anemia falciforme (SCA), suele agravar la condición del paciente. Contar con pruebas de función pulmonar sensitivas podría ayudarnos a predecir cuándo la enfermedad podría revertirse mediante intervenciones terapéuticas apropiadas. En este trabajo se determinó la frecuencia con que el índice de depuración pulmonar (LCI) (que mide la inhomogeneidad en la ventilación global), la inhomogeneidad en la ventilación intraacinar (Sacin) y la inhomogeneidad en la ventilación conductiva (Scond) presentan valores anormales en pacientes jóvenes con SCA, con el objetivo de evaluar la utilidad de estos parámetros al valorar la lesión pulmonar, en comparación con los volúmenes pulmonares, actualmente empleados en el diagnóstico. En este estudio se analizaron los resultados de múltiples lavados respiratorios con nitrógeno, espirometría y pletismografía corporal, de manera transversal y en estado estacionario, en pacientes con SCA (con hemoglobina SS) y en sujetos sanos con edades entre 8 y 21 años, residentes en Londres, Reino Unido. En total se analizaron 35 pacientes (51% varones, 16.4 ± 3.5 años) y 31 sujetos control (48% varones, 16.2 ± 3.2 años). Se encontraron diferencias significativas entre el grupo de estudio y el de control en el LCI medio, la Sacin, el volumen espiratorio forzado en 1 segundo (FEV1), la capacidad vital forzada (CVF) y la capacidad pulmonar total, pero no en Scond ni en la relación entre VEF1 y CVF. Es interesante que 29% de los pacientes mostraron valores anormales en el LCI, mientras que sólo 23% (8 de 35) tenían un VEF1 anormal. El LCI permitió detectar un número ligeramente mayor de anomalías que los volúmenes pulmonares en jóvenes con SCA. El hallazgo de diferencias significativas en el LCI y Sacin con respecto a los controles, pero no en Scond ni en la relación entre el VEF1 y la CVF, sugiere la presencia de una enfermedad pulmonar periférica con patrón en parches. [ABSTRACT FROM AUTHOR]

Clostridioides difficile infection is very common in immunocompromised children. Management is confounded by frequent asymptomatic colonization, multiple alternative etiologies for gastrointestinal symptoms, and high rates of relapse. Important considerations include indications for testing, appropriate choice of diagnostic tests, antibiotic therapy for initial and subsequent episodes, and primary and secondary prevention. [ABSTRACT FROM AUTHOR]

Background Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β- d -glucan (BDG) assay in children with AML receiving antifungal prophylaxis. Methods Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC). Results Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1–43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%. Conclusions The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged. [ABSTRACT FROM AUTHOR]

Purpose: To (1) describe and compare, across all eligible guidelines, recommendations that address any aspect of clinical assessment or management of anxiety and distress experienced by children and adolescents undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT), and (2) assess guideline characteristics that influence identified recommendations. Methods: We searched five databases for relevant guidelines and conducted a grey literature search. Guidelines had to refer to children 0–18 years old who were undergoing cancer treatment or HSCT, describe any aspect of clinical assessment or management of symptoms of anxiety and distress, and be publicly accessible and published in English on or after 2000. Results: We identified 118 guidelines on pediatric cancer of which 13 mentioned clinical assessment or management of anxiety and distress. Six contained ≥ 1 recommendation addressing assessments of symptoms of which only two recommended specific screening instruments. Ten contained ≥ 1 recommendation addressing interventions for symptoms, of which six described specific interventions such as distraction and medication. Psychologists and nurses were the most common panel members and three guideline panels included a patient advocate. Only two guidelines received overall quality ratings > 80.0%. Conclusion: We identified no guidelines that were specific to clinical assessment or management of anxiety and distress among children and adolescents undergoing cancer treatment or HSCT, and thus, clinicians lack evidence-informed guidance on how to manage these specific symptoms. Future research should establish high-quality guidelines that offer recommendations specific to clinical assessment and management of anxiety and distress in pediatric oncology and HSCT. [ABSTRACT FROM AUTHOR]

Background: In adults with rheumatic diseases pulmonary complications are relevant contributors to morbidity and mortality. In these patients diffusion capacity for CO (DLCO) is an established method to detect early pulmonary impairment. Pilot studies using DLCO indicate that early functional pulmonary impairment is present even in children with rheumatic disease albeit not detectable by spirometry and without clinical signs of pulmonary disease. Since the lung clearance index (LCI) is also a non-invasive, feasible and established method to detect early functional pulmonary impairment especially in children and because it requires less cooperation (tidal breathing), we compared LCI versus DLCO (forced breathing and breath-holding manoeuvre) in children with rheumatic diseases. Findings: Nineteen patients (age 9–17 years) with rheumatic disease and no clinical signs of pulmonary disease successfully completed LCI and DLCO during annual check-up. In 2 patients LCI and DLCO were within physiological limits. By contrast, elevated LCI combined with physiological results for DLCO were seen in 8 patients and in 9 patients both, the LCI and DLCO indicate early functional pulmonary changes. Overall, LCI was more sensitive than DLCO to detect early functional pulmonary impairment (p = 0.0128). Conclusions: Our findings suggest that early functional pulmonary impairment is already present in children with rheumatic diseases. LCI is a very feasible and non-invasive alternative for detection of early functional pulmonary impairment in children. It is more sensitive and less cooperation dependent than DLCO. Therefore, we suggest to integrate LCI in routine follow-up of rheumatic diseases in children. [ABSTRACT FROM AUTHOR]

Purpose of Review: Prior invasive fungal infection (IFI) in children with malignancies was considered a contraindication for hematopoietic stem cell transplant (HSCT). This review summarizes the current evidence in safety of allogeneic HSCT with prior IFI in children. Recent Findings: In adult population, some studies have shown that pre-transplant IFI should not be considered a contraindication to allogeneic HSCT, but, in the pediatric population, there is limited information about safety of HSCT in children with prior IFI. Summary: Epidemiological studies in adults with prior IFI show that allogeneic HSCT is safe. There is no sub-analysis in children within these databases. Studies evaluating risk factors for developing IFI in children with allogeneic HSCT have not found that prior IFI is associated with the reactivation of the fungal infection. A proper control of IFI, the correct choice of conditioning regimen, and secondary prophylaxis make allogeneic HSCT feasible in children with prior IFI. There is an urgency of studies in children evaluating other outcomes to establish HSCT safety in children with prior IFI. [ABSTRACT FROM AUTHOR]

For infants, children, and adolescents with progressive advanced lung disease, lung transplantation represents the ultimate therapy option. Fortunately, outcomes after pediatric lung transplantation have improved in recent years now producing good long‐term outcomes, no less than comparable to adult lung transplantation. The field of pediatric lung transplantation has rapidly advanced; thus, this review aims to update on important issues such as transplant referral and assessment, and extra‐corporal life support as "bridge to transplantation". In view of the ongoing lack of donor organs limiting the success of pediatric lung transplantation, donor acceptability criteria and surgical options of lung allograft size reduction are discussed. Post‐transplant, immunosuppression is vital for prevention of allograft rejection; however, evidence‐based data on immunosuppression are scarce. Drug‐related side effects are frequent, close therapeutic drug monitoring is highly advised with an individually tailored patient approach. Chronic lung allograft dysfunction (CLAD) remains the Achilles' heel of pediatric lung transplant limiting its long‐term success. Unfortunately, therapy options for CLAD are still restricted. The last option for progressive CLAD would be consideration for lung re‐transplant; however, numbers of pediatric patients undergoing lung re‐transplantation are very small and its success depends highly on the optimal selection of the most suitable candidate. [ABSTRACT FROM AUTHOR]

Background: Objectives were to build a machine learning algorithm to identify bloodstream infection (BSI) among pediatric patients with cancer and hematopoietic stem cell transplantation (HSCT) recipients, and to compare this approach with presence of neutropenia to identify BSI.Methods: We included patients 0-18 years of age at cancer diagnosis or HSCT between January 2009 and November 2018. Eligible blood cultures were those with no previous blood culture (regardless of result) within 7 days. The primary outcome was BSI. Four machine learning algorithms were used: elastic net, support vector machine and two implementations of gradient boosting machine (GBM and XGBoost). Model training and evaluation were performed using temporally disjoint training (60%), validation (20%) and test (20%) sets. The best model was compared to neutropenia alone in the test set.Results: Of 11,183 eligible blood cultures, 624 (5.6%) were positive. The best model in the validation set was GBM, which achieved an area-under-the-receiver-operator-curve (AUROC) of 0.74 in the test set. Among the 2236 in the test set, the number of false positives and specificity of GBM vs. neutropenia were 508 vs. 592 and 0.76 vs. 0.72 respectively. Among 139 test set BSIs, six (4.3%) non-neutropenic patients were identified by GBM. All received antibiotics prior to culture result availability.Conclusions: We developed a machine learning algorithm to classify BSI. GBM achieved an AUROC of 0.74 and identified 4.3% additional true cases in the test set. The machine learning algorithm did not perform substantially better than using presence of neutropenia alone to predict BSI. [ABSTRACT FROM AUTHOR]

While the benefits of regular participation in physical activity in children and young people are clear, misconceptions have developed about the possible negative effects and potential complications of exercise on long-term conditions such as epilepsy, asthma and diabetes. Over the last decade evidence has emerged supporting the positive impact that physical activity has on long-term conditions. Previous concerns were raised about the risks of hypoglycaemia in children with type 1 diabetes mellitus (T1DM) thus limiting participation in sports. Importantly, physical activity improves the metabolic profile, bone mineral density, cardiorespiratory fitness and insulin sensitivity while lowering mortality risk in children with T1DM. Children with asthma were prevented from doing exercise due to concerns about precipitating an acute asthmatic episode. To the contrary, physical activity interventions have consistently shown an increase in cardiovascular fitness, physical capacity, asthma-free days and quality of life in childhood asthmatics. Children with epilepsy are often excluded from sports due to concerns relating to increased seizure frequency, yet evidence suggests that this is not the case. The evidence supporting physical activity in childhood survivors of cancer is growing but still primarily confined to patients with acute lymphoblastic leukaemia. Participation in sports and physical activity also reduces mental health problems developing in adolescence. While further research is required to investigate benefits of physical activity on specific aspects of long-term conditions in children, in general this group should be advised to increase participation in sports and exercise as a means of improving long-term physical and mental health. [ABSTRACT FROM AUTHOR]

Background: Antineoplastic-induced nausea and vomiting (AINV) is a treatment-related issue that can have significant negative influences on the cancer patient's quality of life. Assessment of nausea is challenging in children as few studies include the perception of nausea as an outcome, and the severity is rarely evaluated with the use of a validated instrument. We describe our experience of integrating an AINV tool into patient care at the Alberta Children's Hospital. Procedure: The Pediatric Nausea Assessment Tool (PeNAT) was adapted to create a standardized tool that could be used by the clinical pharmacists for AINV assessment. From February to August 2017, 74 patients receiving 217 cycles of highly or moderately emetogenic chemotherapy (HEC or MEC) were eligible to use the AINV tool. Patients that completed the AINV tool were contacted to complete a satisfaction survey. Results: AINV tool uptake was low: 47 (22%) eligible chemotherapy cycles utilized the tool (24 (32%) and 23 (16%) cycles of HEC and MEC, respectively, (p < 0.01)). Ifosfamide-containing cycles received the highest nausea ratings, with nausea severity correlated with agent emetogenicity. Mean nausea rating was 2.07 versus 1.76 for patients receiving HEC or MEC, respectively. Clinical pharmacists performed 1.24 AINV interventions per day. Patient satisfaction with AINV care overall was high; however, 51% of patients indicated that the tool led to no changes in nausea symptoms. Conclusions: AINV tool uptake was low with limited value in improving outcomes. Incorporation of nausea assessment into the electronic health record and potential use of a mobile application may improve uptake. [ABSTRACT FROM AUTHOR]

Purpose: Investigation of the current practice of diagnostics and treatment in pediatric cancer patients with febrile neutropenia. Methods: On behalf of the German Society for Pediatric Oncology and Hematology and the German Society for Pediatric Infectious Diseases, an Internet-based survey was conducted in 2016 concerning the management of febrile neutropenia in pediatric oncology centers (POC). This survey accompanied the release of the corresponding German guideline to document current practice before its implementation in clinical practice. Results: In total, 51 POCs participated (response rate 73%; 43 from Germany, and 4 each from Austria and Switzerland). Identified targets for antimicrobial stewardship concerned blood culture diagnostics, documentation of the time to antibiotics, the use of empirical combination therapy, drug monitoring of aminoglycosides, the time to escalation in patients with persisting fever, minimal duration of IV treatment, sequential oral treatment in patients with persisting neutropenia, indication for and choice of empirical antifungal treatment, and the local availability of a pediatric infectious diseases consultation service. Conclusion: This survey provides useful information for local antibiotic stewardship teams to improve the current practice referring to the corresponding national and international guidelines. [ABSTRACT FROM AUTHOR]

MTX is the medication most commonly used for antirheumatic treatment in juvenile idiopathic arthritis. It has high efficacy, is usually well tolerated and has an excellent safety profile. However, frequently intolerance symptoms develop that manifest as nausea, feelings of disgust or abdominal complaints prior to or directly after administration of the medication. No obvious toxicity is causing these intolerance symptoms, but symptoms are strictly limited to MTX and not transferred to other medications. MTX intolerance causes a significant reduction of quality of life in affected patients, frequently puts the treating physician in difficult situations regarding treatment choice, and may lead to uncomfortable decisions whether or not to stop an otherwise effective drug. Conventional countermeasures such as antiemetics, change of route from subcutaneous to oral or vice versa, or taste masking usually have only a limited effect. In this review, we present the current knowledge on MTX intolerance, its clinical picture and commonly employed strategies. We also consider newer behavioural treatment strategies that may offer a more effective symptom control. [ABSTRACT FROM AUTHOR]

Objective: To explore the extent to which micronutrient deficiencies (MND) affect children's health-related quality of life (HRQoL), using vitamin D deficiency (VDD) as a case study.Design: Proxy valuation study to estimate the impact of VDD on the HRQoL of younger (0-4 years) and older (>4 years) children. We used the Child Health Utility 9 Dimension (CHU9D) questionnaire to estimate HRQoL for children within six VDD-related health states: 'hypocalcaemic cardiomyopathy', 'hypocalcaemic seizures', 'active rickets', 'bone deformities', 'pain and muscle weakness' and 'subclinical VDD'.Setting: Sampling was not restricted to any particular setting and worldwide experts were recruited.Participants: Respondents were paediatric bone experts recruited through network sampling.Results: Thirty-eight experts completed the survey. The health state with the largest detrimental impact (mean score (se)) on children's HRQoL was hypocalcaemic cardiomyopathy (0·47 (0·02)), followed by hypocalcaemic seizures (0·50 (0·02)) and active rickets (0·62 (0·02) in young children; 0·57 (0·02) in older children). Asymptomatic VDD had a modest but noticeable negative impact on HRQoL, attributed mostly to tiredness in both age groups and pain in the older paediatric population.Conclusions: Elicitation of HRQoL from clinical experts suggests a negative impact of VDD on HRQoL, even if there is no recognizable clinical manifestation. HRQoL data from populations of patients with MND will inform public health policy decisions. In some settings, routine collection of HRQoL data alongside national nutrition surveys may help capture the full burden of MND and prioritize resources towards effective prevention. [ABSTRACT FROM AUTHOR]

Vitamin D is mainly made in the skin following exposure to sunlight but can also be taken in via specific natural or fortified food sources. It is essential for intestinal calcium absorption and thereby bone mineralisation. Deficiency in vitamin D, or low dietary calcium intake, therefore results in defective bone mineralisation causing osteomalacia in children and adults and rickets in growing children. The leading causes of rickets and osteomalacia worldwide are solar vitamin D deficiency and/or nutritional calcium deficiency. Long-standing severe vitamin D deficiency can lead to craniotabes, large fontanelle, leg bowing, stunted growth and obstructed labour. The deficient state in the infant is almost always acquired from the mother. Therefore, robust antenatal and infant vitamin D supplementation programmes are obligatory to prevent complications. Conversely, lack of programme monitoring and conflicting recommendations can lead to confusion among healthcare professionals and poor uptake in the population. Factors shown to improve adherence to supplementation include universal supplementation of breast- and bottle-fed infants, monitoring supplementation at antenatal/postnatal healthcare visits, providing information to families at discharge from the neonatal unit and financial family support. [ABSTRACT FROM AUTHOR]

Purposes of Study: analysis and measurement of incidence and to show clinical factors that association vitamin D deficiency in children between < 1 year - 11 years old. Design and Method: This study is prospective, total children 172 with 108 male and 64 female. Age group of children extend from <1-11 years old and planned into four groups: < 1, 1-3, 4-7, 8-11 years old. Serum 25-OHD assay, serum calcium and alkaline phosphatase were measured. Vitamin D deficiency were arrange into three groups according to severity of vitamin D as following : mild vitamin D deficiency is 20-30 ng/ml, moderate vitamin D deficiency is 10-20 ng/ml and severe vitamin D deficiency is< 10 ng/ml. Results: Among 172 children, 95 of children were healthy, 77 children had vitamin D deficiency. 25-OHD deficiency showed 16.8%, 38.9% and 44.2% in mild, moderate and severe cases respectively. Age of children was older age (5.59±3.42) in vitamin D deficiency. Mean vitamin D deficiency is much lower with highly significant association (P value = 0.00) in compare to normal children. Male gender were predominant in normal and deficient vitamin D respectively but with independence association. Serum calcium and alkaline phosphatase measurement showed hypocalcaemia with elevated level of alkaline phosphatase in vitamin D deficiency and both of them had highly significant difference (P value = 0.00). Conclusion: Vitamin D deficiency is very common (44.76%) in age group between <1-11 years old and severe vitamin D deficiency (< 10 ng/ml) is the commonest vitamin D deficiency (44.2%) specially older age group (8-11years). vitamin D deficiency is associated with significant hypocalcaemia and elevated alkaline phosphatase. [ABSTRACT FROM AUTHOR]

Purpose: We developed a pharmacokinetic model of intravenous sildenafil in newborns with congenital diaphragmatic hernia (CDH) to achieve a target plasma concentration of over 50 μg/l. Methods: Twenty-three CDH newborns with pulmonary hypertension (64 blood samples) received intravenous sildenafil. Patients received a loading dose of 0.35 mg/kg (IQR 0.16 mg/kg) for 3 h, followed by a continuous infusion of 1.5 mg/kg/day (IQR 0.1 mg/kg/day). For model development, non-linear mixed modeling was used. Inter-individual variability (IIV) and inter-occasion variability were tested. Demographic and laboratory parameters were evaluated as covariates. Normalized prediction distribution errors (NPDE) and visual predictive check (VPC) were used for model validation. Results: A two-compartment disposition model of sildenafil and a one-compartment disposition model of desmethyl sildenafil (DMS) was observed with IIV in sildenafil and DMS clearance and volume of distribution of sildenafil. NPDE and VPC revealed adequate predictability. Only postnatal age increased sildenafil clearance. This was partly compensated by a higher DMS concentration, which also has a therapeutic effect. In this small group of patients, sildenafil was tolerated well. Conclusions: This model for sildenafil in CDH patients shows that concentration-targeted sildenafil dosing of 0.4 mg/kg in 3 h, followed by 1.6 mg/kg/day continuous infusion achieves appropriate sildenafil plasma levels. [ABSTRACT FROM AUTHOR]

Summary: Background: Epidemiology and management practices of invasive fungal diseases (IFD) after allogeneic haematopoietic stem cell transplantation (HSCT) are a subject of constant change. We investigated the contemporary incidence, diagnostics, antifungal management and outcome at a major paediatric transplant centre in Germany. Methods: The single‐centre retrospective observational study included all paediatric allogeneic HSCT patients (pts) transplanted between 2005 and 2015. Patient‐related data were assessed up to 365 days post‐transplant. The primary endpoint was the incidence of possible, probable and proven IFDs. Secondary endpoints included diagnostics and antifungal treatment; analysis of risk factors; and overall survival with the last follow‐up in January 2017. Results: A total of 221 first (196), second (21) or third (4) procedures were performed in 200 pts (median age: 9 years, range, 0.5‐22) for leukaemia/lymphoma (149) and non‐malignant disorders (72). Prophylaxis was administered in 208 HSCT procedures (94%; fluconazole, 116, mould‐active agents, 92). At least one computed tomography scan of the chest was performed in 146, and at least one galactomannan antigen assay in 60 procedures. There were 15 cases of proven (candidemia, 4; aspergillosis, 4) or probable (aspergillosis, 7) IFDs, accounting for an incidence rate of 6.8%. Overall mortality at last follow‐up was 30%; the occurrence of proven/probable IFDs was associated with a reduced survival probability (P <.001). Conclusion: Morbidity and mortality from IFDs at our institution were consistent with data reported from other centres. Utilisation of healthcare resources for prevention, diagnosis and management of IFDs was considerable. [ABSTRACT FROM AUTHOR]

The article highlights comment on the study that examines risk factors for chemotherapy-induced nausea (CIN) in children with cancer. It critiques the study's sample size calculation, methodology, anti-emetic regime, design, and model construction, suggesting that the results may be unreliable and cautioning against over interpretation.