A drug is granted a license for use after a thorough assessment of risks and benefits based on high‐quality scientific proof of its efficacy and safety. Many drugs that are relevant to children are ...not licensed for use in this population implying that a thorough assessment of risks and benefits in the pediatric population has not been made at all, implying a negative risk‐benefit balance in children, or implying insufficient information to establish the risk‐benefit balance. Use of drugs without positive assessment of risks and benefits exposes children to potential lack of efficacy, unknown toxicity, and harm. To aid guideline committees and individual prescribers, we here present a tutorial of the Benefit and Risk Assessment for Off‐label use (BRAvO) decision framework. This pragmatic framework offers a structured assessment of benefits and risks of off‐label drug use, including a clinical pharmacological based approach to age‐appropriate dose selection. As proof of concept and to illustrate the practical use, we have applied the framework to assess benefits and risks of off‐label use of ondansetron for gastroenteritis‐induced nausea and vomiting. The framework could also guide decisions on off‐label use in other special populations (e.g., pregnant women, elderly, obese, or critically ill patients) where off‐label drug use is frequent, thereby contributing to effective and safe pharmacotherapy.
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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.
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Most pediatric asthma guidelines offer evidence-based or best practice approaches to the management of asthma exacerbations but struggle with evidence-based approaches for severe acute asthma (SAA). ...We aimed to investigate current practices in children with SAA admitted to European pediatric intensive care units (PICUs), in particular, adjunct therapies, use of an asthma severity score, and availability of a SAA guideline. We designed a cross-sectional electronic survey across European PICUs. Thirty-seven PICUs from 11 European countries responded. In 8 PICUs (22%), a guideline for SAA management was unavailable. Inhaled beta-agonists and anticholinergics, combined with systemic steroids and IV MgSO
4
was central in SAA treatment. Seven PICUs (30%) used a loading dose of a short-acting beta-agonist. Eighteen PICUs (49%) used an asthma severity score, with 8 different scores applied. Seventeen PICUs (46%) observed an increasing trend in SAA admissions.
Conclusion
: Variations in the treatment of children with SAA mainly existed in the use of adjunct therapies and asthma severity scores. Importantly, in 22% of the PICUs, a SAA guideline was unavailable. Standardizing SAA guidelines across PICUs in Europe may improve quality of care. However, the limited number of PICUs represented and the data compilation method are constraining our findings.
What is Known:
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Recent reports demonstrate increasing numbers of children with SAA requiring PICU admission in several countries across the world.
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Most pediatric guidelines offer evidence-based approaches to the management of asthma exacerbations, but struggle with evidence-based approaches for SAA beyond these initial steps.
What is New:
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A large arsenal of adjunct therapies and 8 different asthma scores were used.
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In a large number of PICUs, a written guideline for SAA management is lacking.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Although sleep is frequently disrupted in the pediatric intensive care unit, it is currently not possible to perform real-time sleep monitoring at the bedside. In this study, spectral band powers of ...electroencephalography data are used to derive a simple index for sleep classification.
Retrospective study at Erasmus MC Sophia Children's Hospital, using hospital-based polysomnography recordings obtained in non-critically ill children between 2017 and 2021. Six age categories were defined: 6-12 months, 1-3 years, 3-5 years, 5-9 years, 9-13 years, and 13-18 years. Candidate index measures were derived by calculating spectral band powers in different frequent frequency bands of smoothed electroencephalography. With the best performing index, sleep classification models were developed for two, three, and four states via decision tree and five-fold nested cross-validation. Model performance was assessed across age categories and electroencephalography channels.
In total 90 patients with polysomnography were included, with a mean (standard deviation) recording length of 10.3 (1.1) hours. The best performance was obtained with the gamma to delta spectral power ratio of the F4-A1 and F3-A1 channels with smoothing. Balanced accuracy was 0.88, 0.74, and 0.57 for two-, three-, and four-state classification. Across age categories, balanced accuracy ranged between 0.83 and 0.92 and 0.72 and 0.77 for two- and three-state classification, respectively.
We propose an interpretable and generalizable sleep index derived from single-channel electroencephalography for automated sleep monitoring at the bedside in non-critically ill children ages 6 months to 18 years, with good performance for two- and three-state classification.
van Twist E, Hiemstra FW, Cramer ABG, et al. An electroencephalography-based sleep index and supervised machine learning as a suitable tool for automated sleep classification in children.
. 2024;20(3):389-397.
Purpose
Sedatives administered to critically ill children should be titrated to effect, because both under- and oversedation may have negative effects. We conducted a systematic review to examine ...reported incidences of under-, optimal, and oversedation in critically ill children receiving intensive care.
Methods
A systematic literature search using predefined criteria was performed in PubMed and Embase to identify all articles evaluating level of sedation in PICU patients receiving continuous sedation. Two authors independently recorded: study objective, study design, sample size, age range, details of study intervention (if applicable), sedatives used, length of sedation, sedation scale used, and incidences of optimal, under-, and oversedation as defined in the studies.
Results
Twenty-five studies were included. Two studies evaluated sedation level as primary study outcome; the other 23 as secondary outcomes. Together, these studies investigated 1,163 children; age range, 0–18 years. Across studies, children received many different sedative agents and sedation level was assessed with 12 different sedation scales. Optimal sedation was ascertained in 57.6 % of the observations, under sedation in 10.6 %, and oversedation in 31.8 %.
Conclusions
This study suggests that sedation in the PICU is often suboptimal and seldom systematically evaluated. Oversedation is more common than undersedation. As oversedation may lead to longer hospitalization, tolerance, and withdrawal, preventing oversedation in pediatric intensive care deserves greater attention.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Innovative and sustainable sampling strategies for bioanalytical quantification of drugs and metabolites have gained considerable interest. Scavenging can be stratified as a sustainable sampling ...strategy using residual material because it aligns with the green principles of waste reduction and sampling optimization. Scavenged sampling includes all biological fluids' (eg, blood, liquor, and urine) leftover from standard clinical care. This review elaborates on the past and current landscape of sustainable sampling within therapeutic drug monitoring, with a focus on scavenged sampling.
In February 2021, 4 databases were searched to assess the literature on the clinical use of innovative and sustainable sampling techniques without applying publication date restrictions. Studies reporting the clinical use of scavenged blood sampling and bridging studies of scavenged sampling and normal blood sampling were eligible for inclusion.
Overall, 19 eligible studies concerning scavenged sampling were identified from 1441 records. Scavenged sampling is mainly applied in the pediatric population, although other patient groups may benefit from this strategy. The infrastructure required for scavenged sampling encounters several challenges, including logistic hurdles, storage and handling conditions, and documentation errors. A workflow is proposed with identified opportunities that guide the implementation of scavenged sampling.
This review presents current evidence on the clinical use of scavenged sampling strategies. Scavenged sampling can be a suitable approach for drug quantification to improve dosage regimens, perform pharmacokinetic studies, and explore the value of therapeutic drug monitoring without additional sample collection.
Objectives
To prospectively evaluate quality of life (QoL) and psychosocial outcomes in children with severe acute asthma (SAA) after pediatric intensive care (PICU) admission compared to children ...with SAA who were admitted to a general ward (GW). In addition, we assessed posttraumatic stress (PTS) and asthma‐related QoL in the parents.
Methods
A preplanned follow‐up of 3 to 9 months of our nationwide prospective multicenter study, in which children with SAA admitted to a Dutch PICU (n = 110) or GW (n = 111) were enrolled between 2016 and 2018. Asthma‐related QoL, PTS symptoms, emotional and behavioral problems, and social impact in children and/or parents were assessed with validated web‐based questionnaires.
Results
We included 100 children after PICU and 103 after GW admission, with a response rate of 50% for the questionnaires. Median time to follow‐up was 5 months (range: 1‐12 months). Time to reach full schooldays after admission was significantly longer in the PICU group (mean of 10 vs 4 days, P = .001). Parents in the PICU group reported more PTS symptoms (intrusion P = .01, avoidance P = .01, arousal P = .02) compared to the GW group.
Conclusion
No significant differences were found between PICU and GW children on self‐reported outcome domains, except for the time to reach full schooldays. PICU parents reported PTS symptoms more often than the GW group. Therefore, monitoring asthma symptoms and psychosocial screening of children and parents after PICU admission should both be part of standard care after SAA. This should identify those who are at risk for developing PTSD, to timely provide appropriate interventions.
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Introduction In pursuing optimal health care, an adequate medical workforce is crucial. However, many countries are struggling with a misalignment of students' specialty preferences and societal ...needs regarding the future medical workforce. In order to bridge this gap, it is relevant to gain a better understanding of the medical career choice processes. We explored career orientations among medical students in the Netherlands and their implications for future career choices. Methods We used Q-methodology, a hybrid qualitative-quantitative method, to explore career orientations of medical students. Medical students from two universities in the Netherlands, varying in year of progression of medical school, ranked 62 statements with regard to importance for their future career choice. Participants explained their ranking in an interview and completed a questionnaire regarding demographics. Using by-person factor analysis we identified groups of individuals with similar orientations. Results Twenty-four students participated in this study, resulting in three distinct orientations towards future careers: a first career orientation that highly values lifelong self-development; a second that values work-life balance, and a third that was more concerned with achievement and recognition of their work. Conclusion Medical students' career orientations differed in the importance of challenge, work-life balance, and need for recognition. This knowledge can help to design interventions to shift career choices of medical students closer towards future needs in society. Offering career coaching to students that challenges them to explore and prioritise their values, needs and motivations, for example using the materials form this study as a tool, and stimulates them to consider specialties accordingly, could be a promising strategy for guiding students to more long-term satisfying careers.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Unraveling the medical residency selection game Gennissen, Lokke M.; Stegers-Jager, Karen M.; de Graaf, Jacqueline ...
Advances in health sciences education : theory and practice,
03/2021, Volume:
26, Issue:
1
Journal Article
Peer reviewed
Open access
The diversity of modern society is often not represented in the medical workforce. This might be partly due to selection practices. We need to better understand decision-making processes by selection ...committees in order to improve selection procedures with regard to diversity. This paper reports on a qualitative study with a socio-constructivist perspective conducted in 2015 that explored how residency selection decision-making occurred within four specialties in two regions in the Netherlands. Data included transcripts of the decision-making meetings and of one-on-one interviews with committee members before and after the group decision-making meetings. Candidates struggled to portray themselves favorably as they had to balance playing by the rules and being authentic; between fitting in and standing out. Although admissions committees had a welcoming stance to diversity, their practices were unintentionally preventing them from hiring underrepresented minority (URM) candidates. While negotiating admissions is difficult for all candidates, it is presumably even more complicated for URM candidates. This seems to be having a negative influence on attaining workforce diversity. Current beliefs, which make committees mistakenly feel they are acting fairly, might actually justify biased practices. Awareness of the role of committee members in these processes is an essential first step.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Aims
Inflammation and organ failure have been reported to have an impact on cytochrome P450 (CYP) 3A‐mediated clearance of midazolam in critically ill children. Our aim was to evaluate a previously ...developed population pharmacokinetic model both in critically ill children and other populations, in order to allow the model to be used to guide dosing in clinical practice.
Methods
The model was evaluated externally in 136 individuals, including (pre)term neonates, infants, children and adults (body weight 0.77–90 kg, C‐reactive protein level 0.1–341 mg l–1 and 0–4 failing organs) using graphical and numerical diagnostics.
Results
The pharmacokinetic model predicted midazolam clearance and plasma concentrations without bias in postoperative or critically ill paediatric patients and term neonates median prediction error (MPE) <30%. Using the model for extrapolation resulted in well‐predicted clearance values in critically ill and healthy adults (MPE <30%), while clearance in preterm neonates was over predicted (MPE >180%).
Conclusion
The recently published pharmacokinetic model for midazolam, quantifying the influence of maturation, inflammation and organ failure in children, yields unbiased clearance predictions and can therefore be used for dosing instructions in term neonates, children and adults with varying levels of critical illness, including healthy adults, but not for extrapolation to preterm neonates.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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