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Aim: There have been concerns about links between medication for attention deficit hyperactivity disorder (ADHD) and cardiac events in children and young people. Our aim was to identify any associations.

Method: This Swedish case–control study used national register data to identify individuals aged 5–30 years who received their first diagnosis of a cardiac arrest, arrhythmia, fainting or collapse in 2006–2018. Each case was matched with five controls, by age, sex and region. Associations between ADHD medication and cardiac events were assessed using adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Adjustments were made for concomitant medications and comorbidities, including congenital heart disease (CHD).

Results: We studied 112 605 cases (57.9% female), with a median age of 20 years (range 5–30), and 563 024 matched controls. Using ADHD medication was associated with cardiac events (aOR 1.63, 95% CI 1.47–1.81) across sexes and age groups. Undefined arrhythmias had the strongest association (aOR 2.66, 95% CI 2.27–3.13). Cardiac arrests and defined arrhythmias had no associations. Long-term medication was associated with an increased risk (aOR 1.20, 95% CI 1.12–1.28). CHD had no impact.

Conclusion: ADHD medication was associated with cardiac events, particularly undefined arrhythmias. CHD did not increase the risk.

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.

Children with congenital and acquired heart disease have an increased risk of thromboembolic events. There is a paucity of evidence on the optimal approach to thromboprophylaxis for this population, and the introduction of direct oral anticoagulants in recent years has led to significant variation in clinical practice. The aim of the study was to describe current practice in thromboprophylaxis prescribing amongst European Paediatric Cardiology units managing paediatric and congenital heart disease. A structured and approved online survey (SurveyMonkey.com) was developed for distribution to AEPC affiliated paediatric cardiology centres in Europe. Responses were received from 30 participants working in 27 Paediatric Cardiology centres across Europe. There is significant variation between participants in the approach to thromboprophylaxis in different patient cohorts, including functional single ventricle patients, post-cardiac catheterisation intervention/electrophysiology study, post-prosthetic valve insertion, cardiomyopathy/heart failure, and infective endocarditis. Differences were seen in the indications for thromboprophylaxis, as well as the agents used and the duration of treatment. Conclusion: There is significant variation in practice amongst participants in Europe. Further studies are required in order to develop evidence-based guidelines for clinical practice. (Table presented.)

The purpose of the study is to assess the prevalence of glucose disturbances (dysglycemia) in very low birth weight (VLBW) infants at 36 weeks postmenstrual age (PMA) using a continuous glucose monitoring (CGM) system and to identify possible risk factors for these disturbances. A prospective observational cohort study (VLBW Infants—Glucose and Hormonal Profiles over Time; LIGHT) included 35 VLBW infants admitted to a single tertiary neonatal intensive care unit during 2016–2019. Perinatal data were registered prospectively. CGM registration was performed at 36 weeks PMA for a period of 48 h. Protracted hyperglycemia and hypoglycemia were defined as > 30 min with glucose concentrations > 8 mmol/L or < 2.6 mmol/L, respectively. A total of 19,907 measurements were retrieved and analyzed. Protracted dysglycemia was found in 68.6% of infants, with 51% of infants experiencing hyperglycemia (4.5% of registration time) and 40% experiencing hypoglycemia (1.2% of registration time). Male sex was associated with longer time spent in hyperglycemia. Insulin treatment prior to 36 weeks PMA was associated with longer time spent in hypoglycemia. CGM values correlated strongly with capillary glucose measurements, and no values fell within clinically dangerous ranges.

Conclusion: Protracted dysglycemia is common in VLBW infants even at 36 weeks PMA. Identification of risk factors for dysglycemia might help delineate certain patients in need of careful monitoring of glucose concentrations even when nearing term age. CGM is a promising tool for glucose monitoring in the neonatal intensive care unit.

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.

Several of the requirements for obtaining a medical degree according to the Swedish Higher Education Ordinance illustrate the scientific basis of the profession, and systematic reviews as well as health technology assessments (HTA) constitute cornerstones in evidence-based medicine. In this study, medical students' experience of scientific education related to the profession was explored, and their knowledge achieved was sampled by five multiple-choice questions (MCQ). A total of 433 out of 641 students attending the final semester in six medical schools in Sweden participated (response rate: 68%). Most of them experienced that a majority of the scientifically related learning outcomes for the medical degree had been adequately examined. Regarding the steps of a systematic review, 60% stated that they had been trained to define a specific research question, 64% to find relevant literature according to such a specific research question, 72% to assess scientific articles according to a checklist, 40% to compile results from several studies, and 35% to assess the certainty of evidence according to GRADE. Only 6% stated that they had received education regarding HTA, a factor that was strongly associated with students' perception that they had obtained adequate skills regarding how patient work is based on scientific evidence (adjusted odds ratio [OR] 14.1; 95% CI 1.80-110). Such an association was also found for credit-awarded hands-on evidence-related learning activities during clinical courses (OR 2.72; 95% CI 1.02-7.24). The median student answered 3 of 5 MCQs correctly. The results of a case/control study, a forest plot, and the concept of cost-effectiveness were frequently interpreted erroneously. In conclusion, several aspects of the scientific basis for professional life as a medical doctor seem to be well covered in the medical degree program, whereas others deserve increased attention.

Totalt 433 termin 11-studenter vid 6 lärosäten svarade på hur läkarprogrammet förberett dem för evidensbaserat patientarbete.

Drygt 7 av 10 uppgav att de fått träna på att granska vetenskapliga artiklar enligt mall, men färre att de tränat på andra moment i en systematisk översikt.

Medianstudenten hade 3 av 5 rätt på kunskapsfrågor relaterade till HTA, men en fall–kontrollstudie, ett skogsdiagram  och begreppet kostnadseffektivitet tolkades ofta på fel sätt.

Undervisning i HTA samt poänggivande moment i tillämpad evidensbaserad medicin under kliniska terminer var förknippade med upplevelsen att läkarprogrammet gett tillräcklig färdighet i hur man baserar patientarbete på vetenskap.

Objective: To explore teaching- and assessment-related factors that predict medical students' perceived attainment of sufficient skills to incorporate scientific evidence into patient care.

Methods: An anonymous questionnaire was distributed to final-semester students in six medical programs in Sweden. The students were asked to rate statements concerning the extent to which 11 national degree outcomes related to the scientific basis of medicine (scholarly degree outcomes) had been adequately assessed during the program; their perceived preparedness for evidence-based patient care; and training during the program regarding the components of a systematic review/health technology assessment (HTA).

Results: In total, 433 students (median age: 25 years [interquartile range: 24-28], 59% female) participated in the study (response rate: 68%). A multivariate analysis indicated that experienced adequate assessment on a single scholarly degree outcome (i.e., "Demonstrate knowledge of the scientific foundation of medicine and insight into current research as well as knowledge of the link between science and proven experience") predicted the students' perception of having developed sufficient skills in incorporating scientific evidence into patient care (odds ratio: 6.17 [95% confidence interval: 3.10; 12.3]). The educational content predictors of this perception included the teaching of HTA (11.3 [1.44; 89.5]) and training regarding two components of a systematic review/HTA: appraising scientific articles using checklists (2.46 [1.23; 4.90]) and assessing organizational aspects related to the introduction/withdrawal of a health technology (2.65 [1.05; 6.67]). The presence of hands-on, credit-bearing, evidence-based medicine (EBM)-related learning activities during clinical courses was also predictive (4.68 [1.69; 13.0]).

Conclusions: This study highlights important educational activities that prepare medical students to incorporate scientific evidence into patient care: (i) adequate assessment of key content regarding scholarly outcomes, including the scientific foundation of medicine; (ii) learning activities about HTA and the systematic review process; and (iii) hands-on application of EBM-related learning activities integrated into clinical courses.

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.

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.

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.