Search

Aim: There is a lack of studies on paediatric triage systems. This study aimed to evaluate patient safety of the Gothenburg‐developed paediatric triage system West Coast System for Triage—Paediatric (WEST‐P). Method: This study was performed at the paediatric emergency department in Gothenburg, Sweden, October 2020 to April 2021. Included patients were double‐triaged with the WEST‐P, and the established Rapid Emergency Triage and Treatment System—Paediatrics (RETTS‐p). We compared the level of urgency between both systems to identify potentially undertriaged patients. Also, we assessed the patient safety according to clinical assessment at presentation, and pre‐defined criteria. Results: This study included 2290 (23%) of triaged patients (44% girls, median age: 5.0 years) during the study period. A higher number of patients triaged to low urgency in WEST‐P compared to RETTS‐p (p < 0.0001) was observed, and 497 cases with low WEST‐P and high RETTS‐p urgencies identified. Of these, 29 had a clinical assessment indicating high urgency. After patient safety assessment, seven (0.4%) were determined undertriaged by the new triage system WEST‐P. Conclusion: Our findings demonstrate a low risk of undertriage in the new WEST‐P. Thus, the WEST‐P has a high degree of patient safety when used in a paediatric emergency department. [ABSTRACT FROM AUTHOR]

The amount of research being performed in children, in particular pharmacological research, is lower than in adults, which is in direct contrast to the aims of the UN Convention on the Rights of the Child. A Pediatric Clinical Research Center (PCRC) has been established at Sahlgrenska University Hospital with the aim of supporting clinical research in children and adolescents. The number of inquiries and initiated clinical studies at PCRC has increased since the start in 2016. In addition, there is a need for regional and national infrastructures for paediatric clinical research and a national network for paediatric clinical studies. Conclusion: Sahlgrenska University Hospital has established an infrastructure to support paediatric research and to work with national networks and infrastructures. [ABSTRACT FROM AUTHOR]

Aim: There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden.Methods: A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs for paediatric clinical trials in Sweden. Questions regarding premises, competence, organisation, support for paediatric clinical trials and Good Clinical Practice Training were addressed.Results: In total, 137 individuals responded to the survey (109 doctors and 28 nurses). Overall, 61% of the respondents had previous experience of paediatric clinical trials. Some respondents had access to trial units, but only 34% had used the trial unit for support. Half of the responders were interested in recurrent paediatric Good Clinical Practice training. Doctors responded that clinical work often had to be prioritised and emphasised the need for research time.Conclusion: This study clearly shows the commitment for clinical trials among doctors and nurses involved in paediatric care in Sweden, but also that administrative, logistic and economic support in a sustainable setting and an expanded national collaboration are needed. [ABSTRACT FROM AUTHOR]

Aim: Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 μg/mL for procedural pain.Methods: Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3-34.1 weeks) and 2 μg/kg (n = 8, 27.4; 25.3-30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed.Results: The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15-31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman's r = -0.9, p < 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated.Conclusion: The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 μg/kg seems not effective for skin-breaking procedures. [ABSTRACT FROM AUTHOR]

AIMS Medication reviews by a third party have been introduced as a method to improve drug treatment in older people. We assessed whether this intervention reduces mortality and hospitalization for nursing home residents. METHODS Systematic literature searches were performed (from January 1990 to June 2012) in Medline, EMBASE, Cochrane Library, ProQuest Nursing & Allied Health Sources and Health Technology Assessment databases. We included randomized and nonrandomized controlled trials (RCTs and non-RCTs) of medication reviews compared with standard care or other types of medication reviews in nursing home residents. The outcome variables were mortality and hospitalization. Study quality was assessed systematically. We performed meta-analyses using random-effects models. RESULTS Seven RCTs and five non-RCTs fulfilled the inclusion criteria. The mean age of included patients varied between 78 and 86 years. They were treated with a mean of 4-12 drugs. The study quality was assessed as high (n = 1), moderate (n = 4) or low (n = 7). Eight studies compared medication reviews with standard care. In six of them, pharmacists were involved in the intervention. Meta-analyses of RCTs revealed a risk ratio (RR) for mortality of 1.03 [medication reviews vs. standard care; five trials; 95% confidence interval (CI) 0.85-1.23]. The corresponding RR for hospitalization was 1.07 (two trials; 95% CI 0.61-1.87). CONCLUSIONS Our findings indicate that medication reviews for nursing home residents do not reduce mortality or hospitalization. More research in the setting of controlled trials remains to be done in order to clarify how drug treatment can be optimized for these patients. [ABSTRACT FROM AUTHOR]

Aim: Clinical trials and the need for new treatments were recently listed among the most important factors for child health. The aim of the present study was to describe some of our experiences with budget preparations in paediatric clinical trials. Methods: We selected 10 trials sponsored by the pharmaceutical industry at the Pediatric Clinical Research Center at Sahlgrenska University Hospital in Gothenburg, Sweden. We compared the sponsor's initial budget (budget proposal from the sponsor), with the final budget (negotiated and agreed between sponsor and site) and identified areas where discrepancies may arise. Results: The mean difference in total budget amount between the initial budget and the final budget was +60% (mean 59%, range 31%–139%). The costs for preparation of the clinical trial, time spent for study activities and costs for examinations were identified as key budget items for these differences. Conclusion: Our findings indicate that a substantial part of the trial‐related costs would not be covered by the sponsor, had the initial budget been accepted. A thorough review and budget negotiation, as well as to have a dedicated team member for this task, are essential to ensure equitable responsibility for the study‐related costs and to avoid discontinuation of trials. [ABSTRACT FROM AUTHOR]

Background: Approximately one third of thromboembolic (TE) events are related to obesity, but to which extent elevated body mass index (BMI) during the distinct periods of childhood and puberty contributes is not known. We aimed to evaluate the impact of high BMI during childhood and puberty for the risk of adult venous and arterial thromboembolic events (VTE, ATE, respectively) in men. Methods: We included 37,672 men from the BMI Epidemiology Study (BEST) Gothenburg with data on weight and height in childhood, young adult age, and on pubertal BMI change. Information on outcomes (VTE [n = 1683], ATE [n = 144], or any first TE event [VTE or ATE; n = 1780]) was retrieved from Swedish national registers. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regressions. Results: Both BMI at 8 years of age and the pubertal BMI change were associated with VTE, independently of each other (BMI at 8: HR 1.06 per standard deviation [SD] increase, 95% CI, 1.01;1.11; pubertal BMI change: HR 1.11 per SD increase, 95% CI, 1.06;1.16). Individuals with normal weight during childhood followed by young adult overweight (HR 1.40, 95% CI, 1.15;1.72), and individuals with overweight at both childhood and young adult age (HR 1.48, 95% CI, 1.14;1.92), had a significantly increased risk of VTE in adult life, compared with the normal weight reference group. Individuals with overweight in childhood and in young adult age had increased risk of ATE and TE. Conclusion: Young adult overweight was a strong determinant, and childhood overweight a moderate determinant, of the risk of VTE in adult men. [ABSTRACT FROM AUTHOR]

Children frequently respond differently to therapies compared to adults. Differences also exist between paediatric age groups for pharmacokinetics and pharmacodynamics in both efficacy and safety. Paediatric pharmacovigilance requires an understanding of the unique aspects of children with regard to, for example, drug response, growth and development, clinical presentation of adverse drug reactions (ADRs), how they can be detected and population‐specific factors (e.g., more frequent use of off‐label/unlicensed drugs). In recognition of these challenges, a group of experts has been formed in the context of the conect4children (c4c) project to support paediatric drug development. This expert group collaborated to develop methodological considerations for paediatric drug safety and pharmacovigilance throughout the life‐cycle of medicinal products which are described in this article. These considerations include practical points to consider for the development of the paediatric section of the risk management plan (RMP), safety in paediatric protocol development, safety data collection and analysis. Furthermore, they describe the specific details of post‐marketing pharmacovigilance in children using, for example, spontaneous reports, electronic health care records, registries and record‐linkage, as well as the use of paediatric pharmacoepidemiology studies for risk characterisation. Next the details of the assessment of benefit–risk and challenges related to medicinal product formulation in the context of a Paediatric Investigation Plan (PIP) are presented. Finally, practical issues in paediatric signal detection and evaluation are included. This paper provides practical points to consider for paediatric pharmacovigilance throughout the life‐cycle of medicinal products for RMPs, protocol development, safety data collection and analysis and PIPs. [ABSTRACT FROM AUTHOR]

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease‐ and/or target organ‐specific examples. Identifying and testing PD targets and effects in special populations, and application of age‐ and/or population‐specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD‐related as well as drug safety‐related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development. [ABSTRACT FROM AUTHOR]

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost‐effectiveness of a new children's treatment has several non‐trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to present prevalence data for overweight and obesity across school age in a large, recent, population‐based cohort of children in Gothenburg, Sweden. Methods: We included 66,807 children (48.5% girls) aged 5–18.9 years who had their height and weight measured in school health care 2015–2018. The BMI values were categorised according to the age‐dependent cut‐offs for overweight and obesity from the International Obesity Task Force (IOTF). Results: Overall, the prevalence of overweight and obesity for girls and boys was 18.1% and 18.0%, respectively. We observed increasing proportions of overweight (girls 11.5–17.1% and boys 8.4–17.4%) and obesity (girls 3.0–4.2% and boys 2.7–6.1%) with increasing age (p < 0.001 for trend in both sexes). Moreover, girls had higher prevalence of overweight during ages 5.0 to 8.9 years compared with boys (p < 0.001), while boys had higher prevalence of obesity 15.0–18.9 years compared with girls (p < 0.001). Conclusion: In conclusion, we demonstrate increasing prevalence of overweight and obesity across the entire school age range, as well as differences in prevalences between boys and girls, in a population‐based sample of 67,000 children in Gothenburg city, Sweden. Continuous monitoring of schoolchildren, together with effective preventive measures, is crucial to curb the obesity epidemic and its consequences. [ABSTRACT FROM AUTHOR]

Background: The role of pubertal BMI change in adult‐onset concomitant asthma and allergic rhinitis is unknown. Objective: We investigated the association of childhood and young adult BMI, and pubertal BMI changes with adult‐onset asthma, allergic rhinitis, and concomitant asthma and rhinitis in Swedish men. Methods: The BMI Epidemiology Study in Gothenburg, Sweden, comprised of height and weight measures taken from school health records (6.5‐9.5 years) and during military conscription (17.5‐22 years) for all men born 1945‐1961 (n = 37 652). Age‐adjusted childhood BMI centred at 8 years and young adult BMI at 20 years were linked to high quality data on asthma and allergic rhinitis diagnoses from the Swedish National Patient Register. Findings: High BMI (4th quartile vs the two median quartiles) at 8 years was associated with increased risk of concomitant asthma and allergic rhinitis (HR 1.45; 95% CI 1.00‐2.11). Overweight (HR 1.45; 95% CI 1.12‐1.89) and obesity (HR 1.95; 95% CI 1.08‐3.54) at 20 years were associated with increased risk of asthma without concomitant allergic rhinitis as main or auxiliary diagnosis. Pubertal BMI change showed a non‐linear association, so that both low (1st quartile vs the two median quartiles) and high pubertal BMI changes were associated with increased risk of asthma (low: HR 1.36; 95% CI 1.11‐1.68; high: HR 1.32; 95% CI 1.07‐1.63) and asthma without concomitant allergic rhinitis (low: HR 1.33; 95% CI 1.04‐1.69; high: HR 1.36; 95% CI 1.07‐1.74) as a main diagnosis. Conclusions and Clinical Relevance: Both low and high pubertal BMI changes are predictors of adult‐onset asthma in men, particularly asthma without concomitant allergic rhinitis. Primary prevention of adult‐onset asthma requires monitoring of changes in BMI during puberty. [ABSTRACT FROM AUTHOR]

Most patients with the syndrome &rbline;esistance to &tbline;hyroid &hbline;ormone (RTH) express a mutant thyroid hormone receptor β (TRβ) with transdominant negative transcriptional effects. Since no patient with a mutant TRα has been identified, we introduced a point mutation into the mouse thyroid hormone receptor (TRα1) locus originally found in the TRβ gene, that reduces ligand binding 10-fold. Heterozygous 2- to 3-week- old mice exhibit a severe retardation of post-natal development and growth, but only a minor reduction in serum thyroxine levels. Homozygous mice died before 3 weeks of age. Adult heterozygotes overcome most of these defects except for cardiac function abnormalities, suggesting that other factors compensate for the receptor defect. However, the additional deletion of the TRβ gene in this mouse strain caused a 10-fold increase in serum thyroxine, restored hormonal regulation of target genes for TRs, and rescued the growth retardation. The data demonstrate a novel array of effects mediated by a dominant negative TRα1, and may provide important clues for identification of a potentially unrecognized human disorder and its treatment. [ABSTRACT FROM AUTHOR]