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Abstract 1. Attempts at determining the physiological basis of species’ differences, such as the ability to grow in deep shade, have been of limited success. However, this basis is fundamental to predicting species’ responses to rising atmospheric CO2 in the forest understorey. We linked a leaf photosynthesis and a tree architecture model to predict the effects of dynamic and steady state photosynthetic characteristics, crown architecture and elevated atmospheric CO2 concentration ([CO2]) on crown-level carbon gain (Acrown). Twenty-four-h Acrown was modelled for shade-tolerant Acer rubrum and shade-intolerant Liriodendron tulipifera saplings growing for three years in a forest understorey under ambient and elevated [CO2] in free-air CO2 enrichment. 2. Two factors best explained Acrown in ambient [CO2]: tree light environment and sapling allometry. Microsite light environment influenced carbon gain via daily photosynthetic photon flux (PFD), average diffuse PFD and sunfleck characteristics. Species differences in specific leaf area (SLA) and size-related biomass allocation to leaves affected the effective leaf area and hence Acrown. 3. At a common above-ground biomass, small saplings (100 g above-ground dry mass) of L. tulipifera had higher Acrown than A. rubrum samples due to larger SLA and greater biomass allocation to leaves. Larger saplings of the two species had similar Acrown due to greater carbon allocation to leaves with increasing plant size in A. rubrum vs L. tulipifera. For saplings > 800 g, Acrown was greater in A. rubrum than in L. tulipifera. Enhancement of Acrown by elevated [CO2] on sunny days was similar for both species. 4. Overall, though the shade-tolerant species had lower Acrown than the shade-intolerant species at a common small size, our results indicate that the relative performance of these species can reverse at larger sizes due to allocational differences. These results suggest that elevated [CO2] may accelerate competition for light between A. rubrum and L. tulipifera as these species grow larger in the understorey. [ABSTRACT FROM AUTHOR]

Focus group analysis, a qualitative research method involving group interviews, was used to explore resident physicians' experiences with older patients. Content analyses of three groups of resident physicians from five residency programs in an urban community identified several important themes in regard to caring for older patients and revealed strong emotional responses to caring for older patients. Implications for designing improved geriatrics curricula are presented. Residents emphasized the need for additional training in communication skills as well as broadening the scope of settings where geriatric education takes place. It is recommended that similar studies be conducted at other medical centers in order to better inform revisions in geriatric education. [ABSTRACT FROM AUTHOR]

Discussions about end of life care can be difficult for patients and practitioners. Numerous studies have demonstrated that dying patients often receive care that does not address their suffering adequately, partly due to inadequate physician-patient communication. An educational module was developed for graduate medical residents about the care of dying patients to improve their communication skills, particularly in the area of end life discussions with patients. The module contains didactic material as well as exercises to provide teacher and learners with a framework to explore personal and patient values, and how those values relate to medical decision making. Portions of module have also been utilized at seminars for social workers and nurses. [ABSTRACT FROM AUTHOR]

Aim: To describe glucose homeostasis disturbances (dysglycaemia) in very low-birthweight infants (<1500 g) during the admission period and explore associated risk factors., Methods: The LIGHT (very low-birthweight infants - glucose and hormonal profile over time) study was a prospective observational cohort study that included 49 very low-birthweight infants admitted to the tertiary neonatal intensive care unit in Umeå, Sweden, during 2016-2019. All glucose concentrations (n = 3515) sampled during the admission period were registered., Results: Hyperglycaemia >10 mmol/L and hypoglycaemia <2.6 mmol/L were registered in 63% and 55% of the infants, respectively. Onset of dysglycaemia occurred almost exclusively in the first postnatal week. Hyperglycaemia followed 15% of corticosteroid doses given; all were preceded by pre-existing hyperglycaemia. Pre-existing hyperglycaemia was found in 66.7% of hyperglycaemic infants who received inotrope treatment. Upon commencement, 72.5% of antimicrobial treatments given were neither preceded nor followed by hyperglycaemia., Conclusion: Dysglycaemia was common in very low-birthweight infants. Daily means of glucose concentrations seemed to follow a postmenstrual age-dependent pattern, decreasing towards term age suggesting a postmenstrual age-dependent developmental mechanism. The primary mechanism causing hyperglycaemia was independent of sepsis, and corticosteroid and inotrope treatments. No hypoglycaemia was registered during ongoing insulin treatment., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Introduction: Patients with congenital heart disease (ConHD) are at increased risk for adverse cardiac events. Predicting long-term outcomes and guidance of patient management might benefit from a range of (new) biomarkers. This is a rapidly evolving field with potentially large consequences for clinical decision making. With a systematic review of available biomarkers in ConHD we identified the clinical role of these markers, knowledge gaps and future research directions., Methods: We systematically reviewed the literature on associations between blood biomarkers and outcome measures (mortality or composite adverse outcomes in patients with ConHD., Results: The inclusion criteria were met by 102 articles. Biomarkers assessed in more than 3 studies are discussed in the main text, those studied in 3 or less studies are summarized in the supplement. Thus, we discuss 15 biomarkers from 92 studies. These biomarkers were studied in 32,399 / 10,735 patients for the association with mortality and composite adverse outcomes, respectively. Biomarkers that were studied most and had statistically significant associations with mortality or composite adverse outcomes were (NT-pro)BNP, MELD-XI score, Hs-CRP, creatinine, albumin and sodium. Most of these biomarkers are involved in intracardiac processes associated with inflammation or are markers of renal function., Conclusion: For (NT-pro)BNP, clinical value for prediction of mortality and composite adverse outcomes in adult and paediatric ConHD has been shown. For MELD-XI, hs-CRP, albumin, creatinine, sodium, RDW, and GDF-15, correlations with mortality and composite adverse outcomes have been demonstrated in patient groups with mixed types of ConHD, but clinical utility needs additional exploration., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The aim of this study was to assess cardiac event incidence and trends by sex and age in young patients on psychopharmacological treatment in Sweden., Methods: This nationwide incidence study encompassed data from Swedish registers (2006-2018). Patients aged 5-30 years were exposed to one or more psychotropic medications (attention deficit hyperactivity disorder medications, antihistamines, selective serotonin reuptake inhibitors, other antidepressants, anxiolytics, antipsychotics, hypnotics/sedatives). Annual incidences, trends and mean incidences of cardiac events (cardiac arrest, arrhythmias, fainting/collapse, sudden death) and recurrent events were calculated., Results: Among those exposed (n = 875 430, 2 647 957 patient-years, 55% female), 26 750 cardiac events were identified. The mean annual incidence of cardiac events and first-ever events were 0.99% and 0.80%, respectively, showing significant upward annual trends of 4.26% and 2.48%, respectively (P < .001). The highest incidences were among females aged 15-19 years (1.50%) and those exposed to polypharmacy (1.63%), anxiolytics (1.53%) or antihistamines (1.27%). The mean annual incidences of cardiac arrest and arrythmias, for both sexes, were 0.01% and 0.51%, respectively. Fainting/collapse accounted for about half of all events, occurring more often in females. The pattern of rising annual incidence remained after excluding fainting/collapse. In all, 21.1% of events were recurrent. Death, including sudden death, occurred in 13 patients., Conclusions: The mean annual incidence of cardiac events among young patients receiving psychopharmacological treatment was low, 0.99%, with an upward trend of 4.26% annually. Incidence was highest in adolescent females and patients exposed to polypharmacy. Our study highlights the need for more knowledge regarding the possible association between exposure to psychopharmacological treatment and cardiac events., (© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Aim: Psychotropic medication can contribute to arrhythmia and identifying individuals at risk is crucial. This Swedish study compared the corrected QT (QTc) intervals of adolescents on psychotropic medication with unmedicated controls, when supine and after rising rapidly., Methods: The study was carried out at Östersund County Hospital in March 2022 and February to March 2023. It comprised 16 cases, aged 10-17 years and 28 controls. QTc intervals were measured with electrocardiography and calculated using Bazett's and Fridericia's formulas. Univariate and multiple linear regressions were used to assess differences in QTc intervals between the cases and controls and across sex, age and body mass index., Results: The mean QTc interval when supine, calculated with Bazett's formula, was longer for the adolescents on psychotropic medication than the controls (p = 0.046). The same was true for the mean QTc interval after rising rapidly from the supine position, calculated with both Bazett's formula (p = 0.009) and Fridericia's formula (p = 0.007). Mean QTc intervals varied by sex and age groups. Psychotropic medication prolonged QTc intervals, particularly in girls., Conclusion: Longer QTc intervals were found in adolescents on psychotropic medication, particularly after rising rapidly from the supine position., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Atrial septal defect secundum is a common type of congenital heart defect and even more common among children born premature. The aim of this study was to assess premature birth as a potential associated risk factors for cardiac morbidity in children with isolated ASD II. In this retrospective national registry-based case-control study all children born in Sweden between 2010 and 2015 with an isolated ASD II diagnosis were included. Association between premature birth and cardiac morbidity in children with isolated ASD II was assessed by different outcomes-models using conditional logistic regression and adjustments were made for confounding factors. Overall, 11% of children with an isolated ASD II received treatment for heart failure. Down syndrome was the only independent risk factors for associated with cardiac morbidity in children with ASD II (OR = 2.25 (95%CI 1.25-4.07). Preterm birth in children was not associated with an increased risk of ASD II cardiac morbidity., (© 2024. The Author(s).)

Objective: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period., Design: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study., Setting: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden., Patients: 48 infants born <1500 g (VLBW) during 2016-2019., Outcome Measures: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks., Results: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period., Conclusions: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Exercise-induced laryngeal obstruction (EILO) is diagnosed by the continuous laryngoscopy during exercise (CLE) test. Whether or how much CLE test scores vary over time is unknown. This study aimed to compare CLE test scores in athletes over time, irrespective of respiratory symptoms and grade of laryngeal obstruction., Methods: Ninety-eight athletes previously screened for EILO were invited for a follow-up CLE test irrespective of CLE scores and respiratory symptoms. Twenty-nine athletes aged 16-27 did a follow-up CLE test 3-23 months after the baseline test. Laryngeal obstruction at the glottic and supraglottic levels was graded by the observer during exercise, at baseline and follow-up, using a visual grade score (0-3 points)., Results: At baseline, 11 (38%) of the 29 athletes had moderate laryngeal obstruction and received advice on breathing technique; among them, 8 (73%) reported exercise-induced dyspnea during the last 12 months. At follow-up, 8 (73%) of the athletes receiving advice on breathing technique had an unchanged supraglottic score. Three (17%) of the 18 athletes with no or mild laryngeal obstruction at baseline had moderate supraglottic obstruction at follow-up, and none of the 3 reported exercise-induced dyspnea., Conclusions: In athletes with repeated testing, CLE scores remain mostly stable over 3-24 months even with advice on breathing technique to those with EILO. However, there is some intraindividual variability in CLE scores over time., Trial Registration: ISRCTN, ISRCTN60543467, 2020/08/23, retrospectively registered, ISRCTN - ISRCTN60543467: Investigating conditions causing breathlessness in athletes., (© 2023. The Author(s).)

Background and Objectives: Despite decades of new policy guidelines and mandatory training modules, sexual harassment (SH) and gender bias (GB) continue in academic medicine. The hierarchical structure of medical training makes it challenging to act when one experiences or witnesses SH or GB. Most trainings designed to address SH and GB are driven by external mandates and do not utilize current educational techniques. Our goal was to design training that is in-person, active, and directed toward skills development., Methods: Our academic family medicine (FM) department began by surveying our faculty and residents about their lived experiences of SH and GB. We used these data, incorporating principles of adult learning, to deliver voluntary, experiential, interactive workshops throughout 2019. The workshops took place during faculty development meetings and an annual retreat. We used interactive techniques that included case-based and Theater of the Oppressed formats., Outcomes: Eighty percent of faculty and residents participated in at least one of our voluntary training sessions. In April of 2020, we administered a retrospective, pre/postsurvey on confidence in recognizing, responding to, and reporting SH and GB. We found significant improvements in all domains surveyed; many participants reported using the skills in the 6 months prior to completing the surveys., Conclusion: We demonstrated that voluntary, interactive training sessions using the recommendations of the National Academies of Science Engineering and Medicine Report on the Sexual Harassment of Women improve participants' reported confidence in recognizing, responding to, and reporting SH and GB in one academic FM department. This training intervention is practical and can be disseminated and implemented in many settings.

Aim: The use of pulmonary vasodilator therapy in children born preterm is largely unknown. Our aim was to map prescription patterns in children with bronchopulmonary dysplasia in Sweden., Methods: This was a descriptive national registry-based study of children <7 years who had been prescribed a pulmonary vasodilator during 2007-2017, were born preterm and classified as having bronchopulmonary dysplasia. Information on prescriptions, patient characteristics and comorbidities were retrieved from the Swedish Prescribed Drug Register and linked to other national registers., Results: The study included 74 children, 54 (73%) born at 22-27 weeks' gestation and 20 (27%) at 28-36 weeks. Single therapy was most common, n = 64 (86.5%), and sildenafil was prescribed most frequently, n = 69 (93%). Bosentan, iloprost, macitentan and/or treprostinil were used mainly for combination therapies, n = 10 (13.5%). Patent ductus arteriosus or atrial septal defect were present in 29 (39%) and 25 (34%) children, respectively, and 20 (69%) versus 3 (12%) underwent closure. Cardiac catheterisation was performed in 19 (26%) patients. Median duration of therapy was 4.6 (1.9-6.8, 95% CI) months. Mortality was 9%., Conclusion: Preterm children with bronchopulmonary dysplasia were prescribed pulmonary vasodilators, often without prior catheterisation. Sildenafil was most commonly used. Diagnostic tools, effects, and drug safety need further evaluation., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Pulmonary vasodilator therapy is still often an off-label treatment for pulmonary hypertension in children. The aim of this nationwide register-based study was to assess patient characteristics and strategies for pulmonary vasodilator therapy in young Swedish children. Prescription information for all children below seven years of age at treatment initiation, between 2007 and 2017, was retrieved from the National Prescribed Drug Register, and medical information was obtained by linkage to other registers. All patients were categorized according to the WHO classification of pulmonary hypertension. In total, 233 patients had been prescribed pulmonary vasodilators. The treatment was initiated before one year of age in 61% (N = 143). Sildenafil was most common (N = 224 patients), followed by bosentan (N = 29), iloprost (N = 14), macitentan (N = 4), treprostinil (N = 2) and riociguat (N = 2). Over the study period, the prescription rate for sildenafil tripled. Monotherapy was most common, 87% (N = 203), while 13% (N = 20) had combination therapy. Bronchopulmonary dysplasia (N = 82, 35%) and/or congenital heart defects (N = 156, 67%) were the most common associated conditions. Eight percent (N = 18) of the patients had Down syndrome. Cardiac catheterization had been performed in 39% (N = 91). Overall mortality was 13% (N = 30) during the study period. This study provides an unbiased overview of national outpatient use of pulmonary vasodilator therapy in young children. Few cases of idiopathic pulmonary arterial hypertension were found, but a large proportion of pulmonary hypertension associated with congenital heart defects or bronchopulmonary dysplasia. Despite treatment, mortality was high, and additional pediatric studies are needed for a better understanding of underlying pathologies and evidence of treatment effects., (© The Author(s) 2021.)

Background and Aims: Clinical support systems are widely used in pediatric care. The aim of this study was to assess the support for drug treatments used at pediatric cardiac wards and intensive care units in Sweden., Methods: Drug information, such as type of drug, indication, dose, and route of administration, for all in-hospital pediatric cardiac patients, was included in the study. Treatments were classified as either on-label (based on product information) or off-label. Support for off-label treatment was stratified by the use of clinical support systems (the national database on drugs, local, or other clinical experience guidelines)., Results: In all, 28 patients were included in the study. The total number of drug treatments was 233, encompassing 65 different drugs. Overall, 175 (75%) treatments were off-label. A majority of off-label drug treatments were supported by other sources of information shared by experts. A total of 7% of the drug treatments were used without support., Conclusion: Off-label drug treatment is still common in Swedish pediatric cardiac care. However, the majority of treatments were supported by the experience shared in clinical support systems., Key Points: Seventy-five percent of all prescriptions in pediatric cardiology care were off-label.A majority of patients received three or more drug treatments off-label.Use of clinical support systems and guidelines was common, but in 7% of all drug treatments, no support was found for the chosen treatment., Competing Interests: The authors have no conflicts of interest to declare., (© 2021 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

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., (© 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Syncope is a common and often benign disorder presenting at the pediatric emergency department. Long-QT syndrome may be presented with syncope, ventricular arrhythmias or sudden death and is vital to exclude as an underlying cause in children presented with syncope. Few studies have assessed QTc in relation to body posture in children. In this study, we assessed the QTc interval while laying down and during active standing in children with known long-QT syndrome compared to healthy controls., Methods: Children aged 1-18 years with long-QT syndrome (N = 17) matched to two healthy controls (N = 34) were included in this case-control study. The ECG standing was performed immediately after the ECG in the supine position. The QTc interval and QTc-difference by changing the body position were calculated., Results: All children with long-QT syndrome were treated with propranolol. QTc was prolonged among long-QT syndrome children while lying down and when standing up, compared to controls. A prolongation of QTc appeared when standing up for both cases and controls. There was no significant difference in QTc increase between the groups. A QTc over 440 ms was observed among four cases lying down and in eight cases while standing, but not in any of the controls. The standing test with a cut-off of 440 ms showed a sensitivity of 47% and a specificity of 100% for case-status in our study., Conclusion: QTc measured on ECG when rapidly rising up is prolonged in both healthy and LQTS children. More importantly, it prolongs more in children with LQTS and increases in pathological levels.

Introduction: Secundum atrial septal defect is one of the most common congenital heart defects. Previous paediatric studies have mainly addressed echocardiographic and few clinical factors among children associated with adverse events. The aim of this study was to identify neonatal and other clinical risk factors associated with adverse events up to one year after closure of atrial septal defect., Methods: This retrospective case-control study includes children born in Sweden between 2000 and 2014 that were treated surgically or percutaneously for an atrial septal defect. Conditional logistic regression was used to evaluate the association between major and minor adverse events and potential risk factors, adjusting for confounding factors including prematurity, neonatal sepsis, neonatal general ventilatory support, symptomatic atrial septal defects, and pulmonary hypertension., Results: Overall, 396 children with 400 atrial septal defect closures were included. The median body weight at closure was 14.5 (3.5-110) kg, and the median age was 3.0 (0.1-17.8) years. Overall, 110 minor adverse events and 68 major events were recorded in 87 and 49 children, respectively. Only symptomatic atrial septal defects were associated with both minor (odds ratio (OR) = 2.18, confidence interval (CI) 95% 1.05-8.06) and major (OR = 2.80 CI 95% 1.23-6.37) adverse events., Conclusion: There was no association between the investigated neonatal comorbidities and major or minor events after atrial septal defect closure. Patients with symptomatic atrial septal defects had a two to four times increased risk of having a major event, suggesting careful management and follow-up of these children prior to and after closure.

An asymptomatic Atrial Septal Defect (ASD) is often closed at the age of 3-5 years using a transcatheter or surgical technique. Symptomatic ASD or ASD associated with pulmonary hypertension (PHT) may require earlier closure, particularly in combination with other non-cardiac risk factors for PHT, but the indications for early closure and the potential risk for complications are largely unknown. The aim of this study was to assess risk factors for needing ASD closure during the first and second years of life. This case-control study included all children treated with surgical or percutaneous ASD closure between 2000 and 2014 at two out of three pediatric heart centers in Sweden. "Cases" were children with ASD closure at ≤1 or ≤2 years of age. Clinical data were retrieved from medical journals and national registries. Overall, 413 children were included. Of these, 131 (32%) were ≤2 years, and 50 (12%) were ≤1 year. Risk factors associated with a ≤2 years ASD closure were preterm birth, OR = 2.4 (95% CI: 1.5-3.9); additional chromosomal abnormalities, OR = 3.4 (95% CI: 1.8-6.5); pulmonary hypertension, OR = 5.8 (95% CI: 2.6-12.6); and additional congenital heart defects, OR = 2.6 (95% CI: 1.7-4.1). These risk associations remained after adjustments for confounding factors, such as need for neonatal respiratory support, neonatal pulmonary diseases, neonatal sepsis, additional congenital heart defects (CHD) and chromosomal abnormalities. ASD size:body weight ratio of 2.0, as well as a ratio of 0.8 (upper and lower limit of the ASD size:body weight ratios), was associated with increased risk of an early ASD closure. Risk factors such as very premature birth, very low birth weight, congenital, and chromosomal abnormalities, neonatal pulmonary disease and need for ventilation support, as well as pulmonary hypertension, were associated with very early (<1 year of age) ASD closure. Several independent neonatal risk factors were associated with an increased risk of early ASD closure at 2 and at 1 year of age. An ASD size:body weight ratio is a poor predictor for indications for ASD closure., (Copyright © 2020 Tanghöj, Liuba, Sjöberg and Naumburg.)