AIM:To investigate the impact of different tourniquet pressures and application durations on venous diameter and compliance in children, in order to optimise conditions for peripheral intravenous catheter insertion. METHODS:This non-randomised clinical study included 21 healthy children aged 6-10 years. Vein diameter was measured using ultrasound. The force required to fully compress the vein was measured with a pressure-sensing device. Tourniquet pressures of 20-100 mmHg were applied for 60 s, with measurements every 10 s. Data were analyzed using non-parametric methods to assess changes over time and correlations between variables. RESULTS:Vein diameter changed significantly over time at all applied pressures. All tourniquet pressures showed a significant reduction in venous compliance. Substantial interindividual variation was observed in the pressure and timing that yielded optimal changes in vein diameter and compliance. Vein diameters ranged from 1 to 5 mm, with no consistent correlation with age or body weight. CONCLUSION:Paediatric tourniquet application markedly increases venous diameter and reduces venous compliance. The substantial interindividual variation in these responses motivates individualised rather than universal approaches. Future research should aim to develop practical techniques to assess and optimise venous conditions, thereby improving the success rate of paediatric intravenous catheter insertion.

OBJECTIVE:To explore the prevalence, risk factors, and impact of leukopenia among children treated with antiseizure medication (ASM) in a real-world setting. STUDY DESIGN:The most recent 198 pediatric (<18 years) patients treated with ASMs at Astrid Lindgren Children's Hospital were included in a retrospective cohort study. Clinical variables were collected from electronic medical records. Patients who did and did not develop leukopenia were compared. RESULTS:Ninety-seven (49%) patients developed at least 1 episode of leukopenia. Most episodes (180 [88%]) were mild (ie, lower normal limit - 3.0 × 109 cells/L) and no patient developed life-threatening leukopenia or died. Clinical actions (ie, ASM switch or tapering) were taken in only 9 (4%) episodes of leukopenia. The clinical impact was leukopenia symptoms in 7 (3%) episodes, and other blood cell cytopenias more frequently (62% vs 18%; P < .001) compared with children without leukopenia. The risk factors for developing leukopenia were dysfunction in other organ systems (eg, endocrinologic disorders, heart disease, or kidney disease), longer treatment duration, ASM combination treatments, and slightly older age (mean 11 vs 9 years, P = .03). Leukopenia was seen in treatments with almost all ASMs (ie, substances) with only a few significant differences between the groups. There was no difference in leukopenia incidence between older vs newer ASMs. CONCLUSIONS:Leukopenia is a far more common side-effect of ASMs than earlier described. However, this leukopenia is mostly asymptomatic and without complications. If mild leukopenia occurs, ASM discontinuation or adjustment may not be necessary.

Background: Families of children with cancer must obtain and understand knowledge and skills to care for their child’s oral drug treatment at home during a period of intense hospitalizations and while adjusting to the fact that their child has cancer. Aim: The aim of this study was to describe the experiences of parents handling oral anticancer drugs in a home setting. Methods: Parents of children with cancer were recruited from a pediatric oncology ward in Sweden to participate in an interview. The interviews were transcribed verbatim and subjected to qualitative content analysis. Results: We found the following categories and subcategories: parents’ views on the provided information - lack of, too little or contradictory information, and parents’ preferences for information delivery; safety over time; correct drug dose; and drug administration. As time passed, most parents adapted to their child’s illness, felt safer, and found it easier to take in and process any given information. Parents preferred information in different formats (written, movie clips and orally) and in their mother tongue. Many parents were aware of the importance of giving an accurate dose to their child and described the process of drug administration as overwhelming. Conclusions: Parents need to be provided with accurate, timely, nonconflicting and repeated information – in different forms and in their mother tongue – on how to handle oral anticancer drugs at home.

BackgroundThe shift of treatment of paediatric cancer patients to include more care at home puts a lot of pressure on health care professionals (HCPs) to prepare and train parents on safe and correct drug handling at home. Parents must take in and understand the information presented to them while coping with their own fear related to their child's cancer diagnosis. In Sweden, parents are expected to handle and manipulate oral anticancer drugs (OADs) in the home setting. There is however a lack of a standardized method to inform and educate parents on how to handle OADs in a correct way at home.AimTo describe parents' experiences of handling OADs at home after participating in an educational intervention.MethodEducational intervention in the present study aimed to improve parents' knowledge in key concepts that is, handling OADs at home by using information presented in different forms. Fifteen parents to 12 children with cancer were recruited from a paediatric oncology ward in Sweden to participate in an interview. The interviews were transcribed verbatim and subjected to qualitative content analysis.ResultsParents' experiences are presented in categories: Relieved stress, Awareness of own exposure, Facilitated my everyday life, Parents need continued support individually. The educational intervention resulted in both positive and negative feelings, increased awareness of drug exposure and correct drug handling at home. Practical training and information presented in different ways facilitated the process of drug handling. To handle the drug correctly at home parents requested to be trained and informed in the beginning of their child's oral drug treatment. In addition, parents requested to be individually approached by HCP to get answers to questions and concerns.ConclusionsThis educational intervention study shows promising results for the method used by HCPs to inform and educate parents on complicated topics such as handling OADs at home.

AIM:Studies on frequencies of manipulated medicines in paediatric care are common, but there is little knowledge of experiences of pharmacists and registered nurses in this area. The aim of this study was to explore registered nurses' and pharmacists' reasoning in the manipulation of medicines to paediatric inpatients.METHODS:Semistructured interviews with twelve registered nurses and seven pharmacists were performed at a Swedish paediatric university hospital. The interviews were transcribed verbatim and analysed using content analysis.RESULTS:Four major categories emerged from the analysis of the interviews: medicines management, knowledge, consulting others and organisation. Medicines management involved the process of drug handling, which is prescribing, reconstitution or manipulation and administration. Knowledge concerned both the knowledge base and how healthcare personnel seek information. Consulting others involved colleagues, registered nurses and pharmacists, between registered nurses, pharmacists and physicians and between registered nurses, pharmacists and caregivers. Organisation covered documentation, time and working environment.CONCLUSION:Both pharmacists and registered nurses stated that manipulation of medicines to paediatric patients was often necessary but felt unsafe due to lack of supporting guidelines. Pharmacists were natural members of the ward team, contributing with specific knowledge about medicines and formulations.

When reporting individual drug concentrations or proper pharmacokinetic data, it is important to adequately report the circumstances associated with sampling, storing, analysis methodology and pharmacokinetic modelling. If this is not done in sufficient detail it will be impossible to properly evaluate the validity of the results. The present text represents a suggested approach on what to report when you are contemplating to submit a manuscript to regional anesthesia and pain medicine, this to achieve relevant standards in this context.

Studies on frequencies of manipulated medicines in paediatric care are common, but there is little knowledge of experiences of pharmacists and registered nurses in this area. The aim of this study was to explore registered nurses' and pharmacists' reasoning in the manipulation of medicines to paediatric inpatients. Semistructured interviews with twelve registered nurses and seven pharmacists were performed at a Swedish paediatric university hospital. The interviews were transcribed verbatim and analysed using content analysis. Four major categories emerged from the analysis of the interviews: medicines management, knowledge, consulting others and organisation. Medicines management involved the process of drug handling, which is prescribing, reconstitution or manipulation and administration. Knowledge concerned both the knowledge base and how healthcare personnel seek information. Consulting others involved colleagues, registered nurses and pharmacists, between registered nurses, pharmacists and physicians and between registered nurses, pharmacists and caregivers. Organisation covered documentation, time and working environment. Both pharmacists and registered nurses stated that manipulation of medicines to paediatric patients was often necessary but felt unsafe due to lack of supporting guidelines. Pharmacists were natural members of the ward team, contributing with specific knowledge about medicines and formulations.

Background Lack of child-friendly dosage forms and strengths often leads to manipulation of medicines at hospital units or by caregivers in the home setting. One alternative to manipulating dosage forms is the use of extemporaneous preparations. In Sweden, these are produced according to good manufacturing practice by a few extemporaneous pharmacies. Objectives To compare frequencies of patients administered extemporaneous preparations in two separate years, 10 years apart. Methods This registry-based study describes and compares the frequency of extemporaneous oral preparations administered to paediatric patients in 2009 and 2019 at a Swedish university hospital. The study included 117 023 oral administrations (to 4905 patients) and 128 638 oral administrations (to 4718 patients) from 2009 and 2019, respectively. Results The frequency of inpatients administered one or more extemporaneous preparations increased from 22% in 2009 to 40% in 2019 (p<0.0001). The increase was observed in all age groups. The use of some active pharmaceutical ingredients increased (eg, captopril, clonidine, hydrocortisone, melatonin and propranolol), and some active pharmaceutical ingredients decreased between the study years (eg, midazolam and sildenafil). Conclusions The introduction of new authorised products has decreased the need for manipulation or extemporaneous preparations in some therapeutic groups. There remains, however, a pronounced lack of commercially available child-friendly dosage forms and suitable strengths enabling safe administration of medicines to children, indicated by the large percentage of patients receiving at least one extemporaneous preparation.

AbstractAimThe aim of this study was to describe the experiences of parents handling oral anticancer drugs in a home setting.MethodsParents of children with cancer were recruited from a paediatric oncology ward in Sweden to participate in an interview. The interviews were transcribed verbatim and subjected to qualitative content analysis.ResultsWe found the following categories and subcategories: parents’ views on the provided information—lack of, too little or contradictory information, and parents’ preferences for information delivery; safety over time; correct drug dose; and drug administration. As time passed, most parents adapted to their child's illness, felt safer and found it easier to take in and process any given information. Parents preferred information in different formats (written, movie clips and orally) and in their mother tongue. Many parents were aware of the importance of giving an accurate dose to their child and described the process of drug administration as overwhelming.ConclusionParents need to be provided with accurate, timely, nonconflicting and repeated information—in different forms and in their mother tongue—on how to handle oral anticancer drugs at home.

This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month–18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results show a decrease in the manipulation of both oral and rectal medicines to paediatric patients in 2019 compared to 2009. Even though this implies a safer practice, there is still a pronounced lack of child-friendly dosage forms and suitable strengths enabling the safe administration of medicines to sick children.

Background Survival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants. Methods Twenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured. Results The CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18–24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development. Conclusion Our data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.

Perinatal asphyxia, resulting in hypoxic-ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long-term outcomes. We prospectively enrolled 18-term born infants with HIE and 10-term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain-derived and inflammation associated proteins in their CSF. Increased CSF concentrations of several brain-specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha-II spectrin. The functional proteins included energy-related proteins like neuron-specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE. Brain-specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.

1 Risks for death after admission to pediatric intensive care 2 (PICU) a comparison with the general population 3 4 Tova Hannegård Hamrin MD, PhD1,3, Staffan Eksborg PhD1,2 5 (1) Pediatric Perioperative Medicine and Intensive Care, Astrid Lindgren Children's 6 Hospital, Karolinska University Hospital Solna, Stockholm, Sweden. 7 (2) Childhood Cancer Research Unit, Department of Women’s and Children's Health, 8 Karolinska Institutet, Astrid Lindgren Children's Hospital, Barnläkemedelsgruppen, 9 Karolinska University Hospital Solna, Stockholm, Sweden. 10 (3) Department of Physiology and Pharmacology, Section of Anesthesiology and 11 Intensive Care, Karolinska Institutet, Astrid Lindgren Children's Hospital, Karolinska 12 University Hospital Solna, Stockholm, Sweden. 13 Corresponding author: Tova Hannegård Hamrin (THH) 14 E-mail: tova.hannegard-hamrin@regionstockholm.se 15 16 . CC-BY 4.0 International license It is made available under a perpetuity. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint The copyright holder for this this version posted March 10, 2022. ; https://doi.org/10.1101/2022.03.09.22272138 doi: medRxiv preprint

Aim Perinatal asphyxia, resulting in hypoxic-ischaemic encephalopathy (HIE), has been associated with high mortality rates and severe lifelong neurodevelopmental disabilities. Our aim was to study the association between the proteomic profile in cerebrospinal fluid (CSF) and the degree of HIE and long-term outcomes. Methods We prospectively enrolled 18-term born infants with HIE and 10-term born controls between 2000 and 2004 from the Karolinska University Hospital. An antibody suspension bead array and FlexMap3D analysis was used to characterise 178 unique brain-derived and inflammation associated proteins in their CSF. Results Increased CSF concentrations of several brain-specific proteins were observed in the proteome of HIE patients compared with the controls. An upregulation of neuroinflammatory pathways was also noted and this was confirmed by pathway analysis. Principal component analysis revealed a gradient from favourable to unfavourable HIE grades and outcomes. The proteins that provided strong predictors were structural proteins, including myelin basic protein and alpha-II spectrin. The functional proteins included energy-related proteins like neuron-specific enolase and synaptic regulatory proteins. Increased CSF levels of 51 proteins correlated with adverse outcomes in infants with HIE. Conclusion Brain-specific proteins and neuroinflammatory mediators in CSF may predict HIE degrees and outcomes after perinatal asphyxia.

COVID-19 has ravished the world, with secondary consequences that are not yet possible to estimate. WHO and the European Extracorporeal Life Support Organization (ELSO) recommended extracorporeal membrane oxygenation (ECMO) early in the pandemic, according to the standard criteria. In March, 2020, the EuroELSO survey was established to report the use of ECMO and outcomes in patients with COVID-19 once per week.1

Background: The aim of this study was to use Body Surface Area (BSA) data calculated with the Mosteller equation to test potential new equations that estimate BSA using Body Weight (BW) alone in children aged 0–18 years.Mosteller’s equation, the golden standard at our hospital, was used to calculate the BSA in infants and children aged 0–18 years using BW and height data from 27,440 hospital visits by 20,635 patients over one year. Methods: The best fit of three nonlinear regression equations (third-order polynomial, Meeh-type, and modified Boyd self-adjusting-type) to a plot of the calculated Mosteller BSA values versus BW was then investigated. The correlation between the BSA values estimated by these equations and the Mosteller BSA values was established by the Spearman rank correlation test. Bias and precision were evaluated as outlined by Sheiner and Beal. Measured and estimated BSA values were compared using the Eksborg plot. Results: The estimated BSA values from all three equations and the BSA values from the Mosteller equation were closely correlated (P < .0001). The third-order polynomial and Meeh-type equations overestimated BSA by 0.13% and 0.40%, respectively, while the Boyd self-adjusted-type equation underestimated BSA by 0.060%. For the entire pediatric population, the best fit was obtained with the Meeh-type equation: 99.2% of the Meeh/Mosteller BSA ratios were within the range of 0.9–1.1 when compared with 98.3% and 97.2% for the polynomial and Boyd-type equations, respectively. Conclusion: A single Meeh-type equation can be used to predict the results of Mosteller equation when H is not available with high precision and accuracy in children aged 0–18 years, including term neonates. We now plan to include the results of this study in CPOE systems in Sweden to improve drug dosage in all children.

Objectives: Data on long-term survival in children after interhospital transport to a PICU are scarce. The main objective was to investigate short- and long-term outcome after acute interhospital transport to a PICU for different age and risk stratification groups. Secondary aims were to investigate whether neonatal patients would have higher mortality and be more resource demanding than older patients. Design: Single-center, retrospective cohort study. Setting: Specialist pediatric transport team and a tertiary PICU in Sweden. Patients: Critically ill children 0-18 years old, acutely transported by a specialist pediatric transport team to a PICU in Sweden (January 1. 2008, to December 31, 2016). Interventions: None. Measurements and Main Results: A total of 401 acute transport events were included. Overall mortality was 15.7% with a median follow-up time of 3.4 years (range, 0-10.2 yr). Median predicted death rate was 4.9%. There was no mortality during transport. Cumulative mortality almost doubled within the first 6 months after PICU discharge, from 6.5% to 12.0%. Of late deaths, 66.7% occurred in the risk stratification group predicted death rate 0-10%, and 95% suffered from severe comorbidity. There were no deaths after PICU discharge in the neonatal group. Cumulative mortality in multiple transported patients was 36.4%. Conclusions: This is the first report on long-term survival after acute pediatric interhospital transport. For the entire cohort, there was significant mortality after PICU discharge, especially in multiple transported patients. In contrast, survival in the subgroup of neonatal patients was high after PICU discharge.

Higher chloroquine doses can effectively treat up to 93 to 96% of malaria infections caused by Plasmodium falciparum carrying the resistance-conferring chloroquine resistance transporter ( pfcrt ) 76T allele. The tolerability of 50 (double the standard dose) and 70 mg/kg total chloroquine doses were assessed in this study. Fifteen 4- to 8-year-old children with uncomplicated malaria were given 10 mg/kg of chloroquine twice daily for 2 days and 5 mg/kg twice daily on the third day.