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Aim: Adolescence is a vulnerable period in cystic fibrosis, associated with declining lung function. This study described, implemented and evaluated a transition programme for adolescents.Methods: We conducted a single centre, nonrandomised and noncontrolled prospective programme at the cystic fibrosis centre at Copenhagen University Hospital Rigshospitalet from 2010 to 2011, assessing patients aged 12-18 at baseline and after 12 months. Changes implemented included staff training on communication, a more youth-friendly feel to the outpatient clinic, the introduction of youth consultations partly alone with the adolescent, and a parents' evening focusing on cystic fibrosis in adolescence. Lung function and body mass index (BMI) were measured monthly and adolescents were assessed for their readiness for transition and quality of life at baseline and 12 months.Results: We found that 40 (98%) of the eligible patients participated and youth consultations were successfully implemented with no dropouts. The readiness checklist score increased significantly over the one-year study period, indicating increased readiness for transfer and self-care. Overall quality of life, lung function and BMI remained stable during the study period.Conclusion: A well-structured transition programme for cystic fibrosis patients as young as 12 years of age proved to be both feasible and sustainable. [ABSTRACT FROM AUTHOR]

Advances in clinical genetic testing have led to increased insight into the human genome, including how challenging it is to interpret rare genetic variation. In some cases, the ability to detect genetic mutations exceeds the ability to understand their clinical impact, limiting the advantage of these technologies. Obstacles in genomic medicine are many and include: understanding the level of certainty/uncertainty behind pathogenicity determination, the numerous different variant interpretation‐guidelines used by clinical laboratories, delivering the certain or uncertain result to the patient, helping patients evaluate medical decisions in light of uncertainty regarding the consequence of the findings. Through publication of large publicly available exome/genome databases, researchers and physicians are now able to highlight dubious variants previously associated with different cardiac traits. Also, continuous efforts through data sharing, international collaborative efforts to develop disease‐gene‐specific guidelines, and computational analyses using large data, will indubitably assist in better variant interpretation and classification. This article discusses the current, and quickly changing, state of variant interpretation resources within cardiovascular genetic research, e.g., publicly available databases and ways of how cardiovascular genetic counselors and geneticists can aid in improving variant interpretation in cardiology. [ABSTRACT FROM AUTHOR]

Microscopy of stool samples is a labour-intensive and inaccurate technique for detection of intestinal parasites causing diarrhoea and replacement by PCR is attractive. Almost all cases of diarrhoea induced by parasites over a nine-year period in our laboratory were due to Giardia lamblia, Cryptosporidium species, or Entamoeba histolytica detected by microscopy. We evaluated and selected in-house singleplex real-time PCR (RT-PCR) assays for these pathogens in 99 stool samples from patients suspected of having intestinal parasitosis tested by microscopy. The strategy included a genus-specific PCR assay for C. parvum and C. hominis, with subsequent identification by a PCR that distinguishes between the two species. G. lamblia was detected in five and C. parvum in one out of 68 microscopy-negative samples. The performance of the in-house RT-PCR assays was compared to three commercially available multiplex test (MT-PCR) kit systems in 81 stool samples, collected in 28 microscopy-positive and 27 microscopy-negative samples from individuals suspected of intestinal parasitosis and in 26 samples from individuals without suspicion of parasitic infection. The in-house assays detected parasites in more samples from patients suspected of having parasitosis than did any of the kits. We conclude that commercial kits are targeting relevant parasites, but their performance may vary. [ABSTRACT FROM AUTHOR]

Unlabelled: Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo.Conclusion: This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge. [ABSTRACT FROM AUTHOR]

Background: Allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients is a potentially fatal inflammatory disease due to the dual-type immune response provoked by the fungal antigens. Despite serious side effects long-term treatment with corticosteroids is often required. Itraconazole has been reported to be a useful steroid-sparing agent. Methods: In a retrospective follow-up of 21 CF patients from a total of 250 treated once or twice within a five-year study period (1994–98), 9 patients were treated with systemic glucocorticosteroids in combination with itraconazole and 12 patients were treated with itraconazole (200–600 mg/day) as monotherapy. Results: During treatment the percentage of Aspergillus fumigatus (AF)-positive sputum cultures significantly reduced ( P < 0.05); precipitating antibodies to AF decreased significantly in all patients ( P < 0.05); forced expiratory volume (FEV 1) increased to pre-exacerbation level; total IgE levels decreased in 42% of patients on monotherapy and in 56% on combination therapy. Specific IgE (radioallergosorbant; RAST) level decreased in 6 of 21 patients. Eleven patients had transient increased levels of alanine transaminase (ALAT). One patient had isolated increase in alkaline phosphatase and another in aspartate transaminase (ASAT). Conclusions: High dose itraconazole as monotherapy or in combination with systemic glucocorticosteroids seems effective in CF patients with ABPA. No hepatotoxicity was observed during long-term therapy. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of allergic bronchopulmonary aspergillosis (ABPA) in cystic fibrosis (CF) patients may be difficult to establish because ABPA shares many characteristics with coexisting atopy or other lung infections in these patients. This study aimed to evaluate the sensitivity and specificity of various paraclinical parameters in the diagnosis of ABPA in patients with CF. Methods: Accumulated data from a 5‐year period in 238 CF patients were used to divide patients into two groups designated the ABPA group (n=26) and the non‐ABPA group (n=35). Patients in both groups were colonized with Aspergillus fumigatus, but only the ABPA group consistently demonstrated specific IgE antibodies and specific precipitins. Patients without A. fumigatus colonization were not assigned to either of these groups (n=177). By this selection as the true diagnosis, 10 patients were selected from the ABPA group and 10 patients from the non‐ABPA group. Results: The groups were comparable as to age, sex, lung function (P=0.6), and presence of chronic Pseudomonas aeruginosa infection (P>0.1). No significant difference between the groups in unspecific atopic parameters such as eosinophil count (P=0.9) or eosinophil cationic protein (ECP) in sputum, plasma, or serum (P=0.9, P=0.59, and P=0.9, respectively) was demonstrated. Total IgE was significantly higher in the ABPA group (P<0.01). The groups were comparable in skin prick test (SPT) positivity to a standard panel of aeroallergens (pollen, dander, molds, and mites) (P>0.2). Statistically significantly higher levels in the ABPA group were demonstrated in specific IgE to Af. (P<0.05), SPT positivity to Af. (P<0.02), and Af. precipitins (P<0.05). Histamine release (HR) to Af. tended to be higher (P=0.075) in the ABPA group. Specific IgE to Af. was determined by Magic Lite (ML), CAP, and Maxisorp (in‐house RAST). The CAP level was one to two classes higher than the ML level; however, the results were... [ABSTRACT FROM AUTHOR]

Aim: Knowledge about the clinical role that respiratory viruses play in infants and toddlers with cystic fibrosis (CF) remains limited. We determined the prevalence of respiratory viruses in routine respiratory secretion samples in children aged 0-3 years with CF. Associations with bacterial infections, respiratory tract symptoms and lung function were also explored., Methods: This prospective, longitudinal, single-centre study added viral polymerase chain reaction detection to the routine monitoring of CF lung disease at Copenhagen University Hospital, Denmark, from 1 July 2019 to 31 August 2020. The existing programme included monthly clinical assessments with endo-laryngeal suction for bacterial culturing and quarterly lung function testing., Results: We studied 19 children (11 males) with a median age of 1.8 (range 0.11-2.99) years. Viruses were detected in 86/193 (45%) samples. Rhinoviruses and enteroviruses were the most common (88%), followed by adenoviruses (9%), parainfluenza 1-3 (6%) and the respiratory syncytial virus (5%). A positive association was found between the annual incidence of viruses and bacteria, but there was no correlation with respiratory tract symptoms or lung function., Conclusions: Respiratory viruses were commonly detected in routine respiratory secretion samples. However, the results from this small study did not justify specific conclusions., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis., Methods: UTI was induced in 8-10 w female BALB/cJ-mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. In vitro bacterial growth (OD 600 ) was determined in urine from mice or from human volunteers., Results: Gel feeding increased urine output (1.40 ± 0.77 μL min -1 , p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg -1 , p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min -1 , osmolality: 1439 ± 473.5 mOsmol kg -1 ). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg -1 tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg -1 , p < 0.01). Correspondingly, the growth of E. coli was markedly reduced at osmolalities above 1200 mOsmol kg -1 compared to 600 mOsmol kg -1 and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL -1 , p < 0.01) compared to controls (24.65 ± 2.70 μg mL -1 )., Conclusion: Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake., (© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)

Aesthetic and moral evaluations engage appetitive and defensive emotions. While the role played by pleasure in positive aesthetic and moral judgements has been extensively researched, little is known about how defensive emotions influence negative aesthetic and moral judgements. Specifically, it is unknown which defensive emotions such judgements tap into, and whether both kinds of judgement share a common emotional root. Here, we investigated how participants' individual sensitivity to disgust, fear, anger and sadness predicted subjective judgements of aesthetic and moral stimuli. Bayesian modelling revealed that participants who were more sensitive to anger and fear found conventional and moral transgressions more wrong. In contrast, participants who were more sensitive to disgust disliked asymmetrical geometric patterns and untidy rooms more. These findings suggest that aesthetic and moral evaluations engage multiple defensive emotions, not just disgust, and that they may rely on different defensive emotions as part of their computational mechanism., (© 2022 The Authors. British Journal of Psychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

Aim: As no data to our knowledge exist, the aim of the study was to describe the national prevalence and characteristics of Danish children and adolescents with severely impaired lung function., Methods: We performed a descriptive, cross-sectional Danish multi-centre study. Children and adolescents between 6 and 18 years old demonstrating severely impaired lung function from 2015 to 2018, defined by forced expiratory volume in 1 second (FEV 1 ) <60% or who had lung transplantation, were eligible for inclusion., Results: This study included 113 children with a mean age (standard deviation) of 12.9 years (3.5 years). The prevalence of severely impaired lung function was approximately 13 in 100,000. The mean (standard deviation) FEV 1 was 46.1% (10.1%) of predicted, and z-score was -4.5 (0.8). The most frequent diagnosis was cystic fibrosis (20.4%), followed by asthma (19.5%) and bronchiolitis obliterans (16.8%), while almost 25% had different elements of airway malformations or non-pulmonary conditions. Two adolescents with cystic fibrosis underwent lung transplantation., Conclusion: The estimated prevalence of severely impaired lung function in Danish children and adolescents was low, and extremely, few children underwent lung transplantation. The most frequent diagnosis was cystic fibrosis, while almost 25% had different elements of airway malformations or non-pulmonary conditions, which may require clinical attention., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Gastrointestinal (GI) symptoms are often reported by CF patients. Despite a proven relation to exocrine pancreatic insufficiency (PI), it remains unclear whether GI symptoms are related to the timing of pancreatic enzyme replacement therapy (PERT). Whereas most international recommendations suggest administration of PERT at the beginning of meals, it has not been studied whether such a proceeding is associated with lower burden of symptoms., Methods: Thirty CF patients aged 0-17 years of age with PI were randomised to four weeks of PERT prior to meals followed by four weeks of PERT after meals or vice versa. Using the CF-specific validated CFAbd-Score, abdominal pain, dysfunctional bowel habits and Quality of Life (QoL) related to GI symptoms were assessed in relation to the timing of PERT. Data were analysed using a linear mixed model., Results: There was no significant difference regarding abdominal pain, bowel habits or QoL related to GI symptoms when timing of PERT was changed from prior to after meals., Conclusion: No significant difference was found when administration mode of PERT changed from prior to after meals or vice versa. However, after an individual assessment, some patients may profit from changing administration mode of PERT from prior to after meals., (© 2021 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: Denmark has a high standard cystic fibrosis care. However, newborn screening was not implemented until 2016. This article describes the clinical status of cystic fibrosis patients at time of diagnosis prior to newborn screening., Methods: Patients diagnosed with cystic fibrosis in Denmark in 2010-2014 were reviewed using the Danish Cystic Fibrosis Registry as well as patient files. Parameters collected were age at diagnosis, gender, weight, height, forced expiratory volume at 1 second, cystic fibrosis transmembrane regulator-genotype, lung bacteriology at diagnosis and previous diagnoses., Results: A total of 63 patients were diagnosed in the study period. The most typical pre-cystic fibrosis diagnoses were asthma and pneumonia. The median age at diagnosis was 1.4 years for the pancreatic insufficient and 27.3 years for the pancreatic sufficient patients. Of the pancreatic insufficient patients, 21% had moderate to severe malnutrition with BMI below minus 2 SD and 40% had moderate to severe stunting with height below minus 2 SD., Conclusion: Diagnosis was delayed considerably compared to diagnosis by newborn screening in other countries. Many cystic fibrosis patients diagnosed due to clinical symptoms were moderately to severely underweight or stunted at diagnosis., (©2019 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)