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1.	Willadsen, E., et al. (author) Inter-rater reliability in classification of canonical babbling status based on canonical babbling ratio in infants with isolated cleft palate randomised to Timing of Primary Surgery for Cleft Palate (TOPS) 2023 In: Clinical Linguistics & Phonetics. - : Informa UK Limited. - 0269-9206 .- 1464-5076. ; 37:1, s. 77-98 Journal article (peer-reviewed)abstract Canonical babbling (CB) is commonly defined as present when at least 15% of all syllables produced are canonical, in other words a canonical babbling ratio (CBR) >= 0.15. However, there is limited knowledge about inter-rater reliability in classification of CB status based on CBR and inter-rater differences in assessment of CBR. We investigated inter-rater reliability of experienced Speech Language Therapists (SLTs) on: classification of CB status based on CBR >= 0.15, CBRs and the total number of syllables per infant used to calculate CBR. Each infant (n = 484) was video-recorded at a clinical site in play interaction with their parent as part of the randomised controlled trial Timing of Primary Surgery for Cleft Palate. Each recording was subsequently assessed by three independent SLTs, from a pool of 29 SLTs. They assessed the recordings in real time. The three assessing SLTs agreed in classification of CB status in 423 (87.4%) infants, with higher complete agreement for canonical (91%; 326/358) than non-canonical (77%; 97/126). The average difference in CBR and total number of syllables identified between the SLT assessments of each infant was 0.12 and 95, respectively. This study provided new evidence that one trained SLT can reliably classify CB status (CBR >= 0.15) in real time when there is clear distinction between the observed CBR and the boundary (0.15); however, when the observed CBR approaches the boundary multiple SLT assessments are beneficial. Thus, we recommend to include assessment of inter-rater reliability, if the purpose is to compare CBR and total syllable count across infants or studies.
2.	Nilsson, Jonna, et al. (author) Associations of cardiorespiratory fitness and moderate-to-vigorous physical activity with latent cognitive abilities in older adults 2022 In: Psychology of Sport And Exercise. - : Elsevier. - 1469-0292 .- 1878-5476. ; 60, s. 102171-102171 Journal article (peer-reviewed)abstract It has been demonstrated that physical activity has a small but positive effect on cognition in old age, which suggests that it may be possible to alter the trajectory of age-related cognitive decline. However, our understanding of which aspects of physical activity that are important for modifying cognition remains incomplete. Adopting an exploratory approach in a sample of 115 healthy older adults (65–75 years), the present cross-sectional study used structural equation modelling to investigate the dissociable associations of physical activity (moderate-to-vigorous activity, derived from 7-day accelerometry) and cardiorespiratory fitness (VO2 max, derived from maximal treadmill ergometer test) with multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning). The results showed a significant positive association between fitness and working memory, when physical activity was statistically controlled for, and a positive association of similar point magnitude between physical activity and episodic memory, when fitness was statistically controlled for, although the latter association did not reach statistical significance. The results add to the foundation for a more careful investigation of the dissociable associations of moderate-to-vigorous physical activity and fitness with cognition in old age, and encourages future research to test the hypothesis that cardiorespiratory fitness benefits working memory via general cerebrovascular effects on grey matter volume, whilst moderate-to-vigorous physical activity benefits episodic memory via effects on neuroplastic processes.
3.	Yilmaz, Aylin, et al. (author) Upper Respiratory Tract Levels of Severe Acute Respiratory Syndrome Coronavirus 2 RNA and Duration of Viral RNA Shedding Do Not Differ Between Patients With Mild and Severe/Critical Coronavirus Disease 2019 2021 In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:1, s. 15-18 Journal article (peer-reviewed)abstract This study reports longitudinal viral RNA loads from the nasopharynx/throat in patients with mild and severe/critical coronavirus disease 2019 (COVID-19). We also investigated whether the duration of symptoms correlated with the duration of viral RNA shedding. A total of 56 patients were included. The highest viral loads occurred early after onset of symptoms. Neither the viral RNA loads in the upper respiratory tract nor the time to viral RNA clearance differed between patients with mild or severe/critical disease. There was a moderate correlation between number of days with symptoms and number of days with viral RNA shedding in patients with mild COVID-19.
4.	Humayun, Jhangir, et al. (author) Systematic review of the healthcare cost of bronchopulmonary dysplasia. 2021 In: BMJ open. - : BMJ. - 2044-6055. ; 11:8 Journal article (peer-reviewed)abstract To determine the costs directly or indirectly related to bronchopulmonary dysplasia (BPD) in preterm infants. The secondary objective was to stratify the costs based on gestational age and/or birth weight.Systematic literature review.PubMed and Scopus were searched on 3 February 2020. Studies were selected based on eligibility criteria by two independent reviewers. Included studies were further searched to identify eligible references and citations.Two independent reviewers extracted data with a prespecified data extraction sheet, including items from a published checklist for quality assessment. The costs in the included studies are reported descriptively.Costs of BPD.The 13 included studies reported the total costs or marginal costs of BPD. Most studies reported costs during birth hospitalisation (cost range: Int$21392-Int$1 094509 per child, equivalent to €19103-€977397, in 2019) and/or during the first year of life. One study reported costs during the first 2years; two other studies reported costs later, during the preschool period and one study included a long-term follow-up. The highest mean costs were associated with infants born at extremely low gestational ages. The quality assessment indicated a low risk of bias in the reported findings of included studies.This study was the first systematic review of costs associated with BPD. We confirmed previous reports of high costs and described the long-term follow-up necessary for preterm infants with BPD, particularly infants of very low gestational age. Moreover, we identified a need for studies that estimate costs outside hospitals and after the first year of life.CRD42020173234.
5.	Stråvik, Mia, 1994, et al. (author) Maternal Intake of Cow's Milk during Lactation Is Associated with Lower Prevalence of Food Allergy in Offspring 2020 In: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:12, s. 1-19 Journal article (peer-reviewed)abstract Maternal diet during pregnancy and lactation may affect the propensity of the child to develop an allergy. The aim was to assess and compare the dietary intake of pregnant and lactating women, validate it with biomarkers, and to relate these data to physician-diagnosed allergy in the offspring at 12 months of age. Maternal diet during pregnancy and lactation was assessed by repeated semi-quantitative food frequency questionnaires in a prospective Swedish birth cohort (n = 508). Fatty acid proportions were measured in maternal breast milk and erythrocytes. Allergy was diagnosed at 12 months of age by a pediatrician specialized in allergy. An increased maternal intake of cow's milk during lactation, confirmed with biomarkers (fatty acids C15:0 and C17:0) in the maternal blood and breast milk, was associated with a lower prevalence of physician-diagnosed food allergy by 12 months of age. Intake of fruit and berries during lactation was associated with a higher prevalence of atopic eczema at 12 months of age. Our results suggest that maternal diet modulates the infant's immune system, thereby influencing subsequent allergy development.
6.	Möller, Marika, et al. (author) Cognitive dysfunction in post-COVID-19 condition : mechanisms, management, and rehabilitation 2023 In: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:5, s. 563-581 Research review (peer-reviewed)abstract The long-term effects of COVID-19 on cognitive function have become an area of increasing concern. This paper provides an overview of characteristics, risk factors, possible mechanisms, and management strategies for cognitive dysfunction in post-COVID-19 condition (PCC). Prolonged cognitive dysfunction is one of the most common impairments in PCC, affecting between 17% and 28% of the individuals more than 12 weeks after the infection and persisting in some cases for several years. Cognitive dysfunctions can be manifested as a wide range of symptoms including memory impairment, attention deficit, executive dysfunction, and reduced processing speed. Risk factors for developing PCC, with or without cognitive impairments, include advanced age, preexisting medical conditions, and the severity of acute illness. The underlying mechanisms remain unclear, but proposed contributors include neuroinflammation, hypoxia, vascular damage, and latent virus reactivation not excluding the possibility of direct viral invasion of the central nervous system, illustrating complex viral pathology. As the individual variation of the cognitive impairments is large, a neuropsychological examination and a person-centered multidimensional approach are required. According to the World Health Organization, limited evidence on COVID-19-related cognitive impairments necessitates implementing rehabilitation interventions from established practices of similar conditions. Psychoeducation and compensatory skills training are recommended. Assistive products and environmental modifications adapted to individual needs might be helpful. In specific attention- and working memory dysfunctions, cognitive training—carefully monitored for intensity—might be effective for people who do not suffer from post-exertional malaise. Further research is crucial for evidence-based interventions specific to COVID-19-related cognitive impairments.
7.	Amid Hägg, Shadi, et al. (author) The negative health effects of having a combination of snoring and insomnia 2022 In: JOURNAL OF CLINICAL SLEEP MEDICINE. - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 18:4, s. 973-981 Journal article (peer-reviewed)abstract Study Objectives: Insomnia and snoring are common sleep disorders. The aim was to investigate the association of having a combination of insomnia symptoms and snoring with comorbidity and daytime sleepiness. Methods: The study population comprised 25,901 participants (16-75 years, 54.4% women) from 4 Swedish cities, who answered a postal questionnaire that contained questions on snoring, insomnia symptoms (difficulties initiating and/or maintaining sleep and/or early morning awakening), smoking, educational level, and respiratory and nonrespiratory disorders. Results: Snoring was reported by 4,221 (16.2%), while 9,872 (38.1%) reported 1 insomnia symptom. A total of 2,150 (8.3%) participants reported both insomnia symptoms and snoring. The association with hypertension (adjusted odds ratio [OR], 1.4; 95% confidence interval [Cl], 1.2-1.6), chronic obstructive pulmonary disease (adjusted OR, 1.8; 95% CI, 1.3-2.4), asthma (adjusted OR, 1.9; 95% CI, 1.6-2.3), daytime sleepiness (adjusted OR, 7.9; 95% CI, 7.1-8.8), and the use of hypnotics (adjusted OR, 7.5; 95% CI, 6.1-9.1) was highest for the group with both insomnia symptoms and snoring. Conclusions: Participants with both snoring and insomnia run an increased risk of hypertension, chronic obstructive pulmonary disease, asthma, daytime sleepiness, and use of hypnotics. It is important to consider snoring in patients seeking medical assistance for insomnia and, vice versa, in patients with snoring inquiring about insomnia.
8.	Bengtsson, Caroline, et al. (author) Sinonasal outcome test-22 and peak nasal inspiratory flow : valuable tools in obstructive sleep apnoea 2020 In: Rhinology. - 0300-0729 .- 1996-8604. ; 58:4, s. 341-348 Journal article (peer-reviewed)abstract Background: Sinonasal complaints contribute to low adherence to continuous positive airway pressure (CPAP) treatment. We aimed to investigate sinonasal health in obstructive sleep apnoea (OSA) patients, using the sinonasal outcome test-22 (SNOT-22), and to analyse whether SNOT-22 is affected by CPAP adherence. We also aimed to investigate whether peak nasal inspiratory flow (PNIF) was able to predict adherence to CPAP. Methods:The study population comprised 197 OSA patients (60 females) initiating CPAP treatment The SNOT-22, PNIF and the Epworth Sleepiness Scale were assessed at baseline and follow-up. One-night polygraphy, the Hospital Anxiety and Depression Scale, peak expiratory flow and health-related issues were assessed at baseline. At follow-up, the patients were categorised into adherent (>4 hours/night) and non-adherent (<4 hours/night) to CPAP treatment. Results: The average time for following up CPAP treatment was (mean +/- SD) 24.0 +/- 23.9 days and it did not differ significantly between the groups.The SNOT-22 score was elevated among all OSA patients, 36.1 +/- 19.4.There was a larger improvement in the SNOT-22 score at follow-up among adherent CPAP users compared with non-adherent users (-10.4 +/- 13.9 vs. -3.2 +/- 15.4). A PNIF value of < 100 litres/min increased the risk of non-adherence to CPAP with an adjusted odds ratio (OR) of 2.40 ((95% CI 1.16-5.00)). Conclusions: The SNOT-22 was elevated in patients with OSA, indicating a considerable sinonasal disease burden.The SNOT-22 improved with good CPAP adherence. A low PNIF value was able to predict poor CPAP adherence. Both the SNOT-22 and PNIF can be valuable tools in the evaluation of OSA patients and in the management of CPAP treatment.
9.	Bjornsdottir, E., et al. (author) Are symptoms of insomnia related to respiratory symptoms? Cross-sectional results from 10 European countries and Australia 2020 In: BMJ Open. - : BMJ. - 2044-6055. ; 10:4 Journal article (peer-reviewed)abstract Objectives To compare the prevalence of different insomnia subtypes among middle-aged adults from Europe and Australia and to explore the cross-sectional relationship between insomnia subtypes, respiratory symptoms and lung function. Design Cross-sectional population-based, multicentre cohort study. Setting 23 centres in 10 European countries and Australia. Methods We included 5800 participants in the third follow-up of the European Community Respiratory Health Survey III (ECRHS III) who answered three questions on insomnia symptoms: difficulties falling asleep (initial insomnia), waking up often during the night (middle insomnia) and waking up early in the morning and not being able to fall back asleep (late insomnia). They also answered questions on smoking, general health and chronic diseases and had the following lung function measurements: forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio. Changes in lung function since ECRHS I about 20 years earlier were also analysed. Main outcome measures Prevalence of insomnia subtypes and relationship to respiratory symptoms and function. Results Overall, middle insomnia (31.2%) was the most common subtype followed by late insomnia (14.2%) and initial insomnia (11.2%). The highest reported prevalence of middle insomnia was found in Iceland (37.2%) and the lowest in Australia (22.7%), while the prevalence of initial and late insomnia was highest in Spain (16.0% and 19.7%, respectively) and lowest in Denmark (4.6% and 9.2%, respectively). All subtypes of insomnia were associated with significantly higher reported prevalence of respiratory symptoms. Only isolated initial insomnia was associated with lower FEV1, whereas no association was found between insomnia and low FEV1/FVC ratio or decline in lung function. Conclusion There is considerable geographical variation in the prevalence of insomnia symptoms. Middle insomnia is most common especially in Iceland. Initial and late insomnia are most common in Spain. All insomnia subtypes are associated with respiratory symptoms, and initial insomnia is also associated with lower FEV1.
10.	Michelet, Mona, et al. (author) Associations between unmet needs for daytime activities and company and scores on the Neuropsychiatric Inventory-Questionnaire in people with dementia : a longitudinal study 2021 In: Aging & Mental Health. - : Informa UK Limited. - 1360-7863 .- 1364-6915. ; 26:4, s. 725-734 Journal article (peer-reviewed)abstract OBJECTIVES To examine prospectively the association between unmet needs for daytime activities and company and behavioural and psychological symptoms of dementia.METHODS We included 451 people with mild or moderate dementia, from eight European countries, who were assessed three times over 12 months. Unmet needs were measured with the Camberwell Assessment of Need for the Elderly. Three sub-syndromes of the Neuropsychiatric Inventory-Questionnaire were regressed, one-by-one, against unmet needs for daytime activities and company, adjusting for demographic and clinical-functional covariates.RESULTS Unmet needs for daytime activities were associated with more affective symptoms at baseline, six and twelve months, mean 0.74 (p < 0.001), 0.76 (p < 0.001) and 0.78 (p = 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.39 points, p = 0.007) and at six months follow-up (mean 0.31 points, p = 0.006). Unmet needs for company were associated with more affective symptoms at baseline, six and twelve months, mean 0.44 (p = 0.033), 0.67 (p < 0.001) and 0.91 (p < 0.001) points higher score respectively, and with more psychotic symptoms at baseline (mean 0.40 points, p = 0.005) and at six months (mean 0.35 points, p = 0.002) follow-up.CONCLUSION Interventions to reduce unmet needs for daytime activities and company could reduce affective and psychotic symptoms in people with dementia.
11.	Sigurðardóttir, E. S., et al. (author) Female sex hormones and symptoms of obstructive sleep apnea in European women of a population-based cohort 2022 In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17 Journal article (peer-reviewed)abstract Background The prevalence of obstructive sleep apnea is higher in women after menopause. This is suggested to be a result of an altered sex hormone balance but has so far not been confirmed in a population-based study. Objective To investigate whether serum concentration of estrogens and progesterone are associated with the prevalence of sleep apnea symptoms in middle-aged women of the general population. Methods We analyzed data from 774 women (40–67 years) from 15 study centers in seven countries participating in the second follow-up of the European Community Respiratory Health Survey (2010–2012). Multiple logistic regression models were fitted with self-reported symptoms of sleep apnea as outcomes and serum concentrations of various estrogens and progesterone as predictors. All analyses were adjusted for relevant covariates including age, BMI, education, study center, smoking habits, and reproductive age. Results Among all included women, a doubling of serum concentrations of estrone and progesterone was associated with 19% respectively 9% decreased odds of snoring. Among snorers, a doubling of the concentrations of 17β-estradiol, estrone and estrone 3-sulfate was associated with 18%, 23% and 17% decreased odds of breathing irregularly, and a doubling of the progesterone concentration was further associated with 12% decreased odds of waking up suddenly with a chocking sensation. Other evaluated associations were not statistically significant. Conclusions Middle-aged women with low serum estrogen and progesterone levels are more likely to snore and report symptoms of obstructive sleep apnea.
12.	Wackernagel, Dirk, et al. (author) Enteral supplementation with arachidonic and docosahexaenoic acid and pulmonary outcome in extremely preterm infants 2024 In: Prostaglandins Leukotrienes and Essential Fatty Acids. - 0952-3278 .- 1532-2823. ; 201 Journal article (peer-reviewed)abstract Enteral supplementation with arachidonic acid (AA) and docosahexaenoic acid (DHA) in extremely preterm infants has shown beneficial effects on retinopathy of prematurity and pulmonary outcome whereas exclusive DHA supplementation has been associated with increased pulmonary morbidity. This secondary analysis evaluates pulmonary outcome in 204 extremely preterm infants, randomized to receive AA (100 mg/kg/day) and DHA (50 mg/kg/day) enterally from birth until term age or standard care. Pulmonary morbidity was primarily assessed based on severity of bronchopulmonary dysplasia (BPD). Serum levels of AA and DHA during the first 28 days were analysed in relation to BPD. Supplementation with AA:DHA was not associated with increased BPD severity, adjusted OR 1.48 (95 % CI 0.85–2.61), nor with increased need for respiratory support at post menstrual age 36 weeks or duration of oxygen supplementation. Every 1 % increase in AA was associated with a reduction of BPD severity, adjusted OR 0.73 (95 % CI 0.58–0.92). In conclusion, in this study, with limited statistical power, enteral supplementation with AA:DHA was not associated with an increased risk of pulmonary morbidity, but higher levels of AA were associated with less severe BPD. Whether AA or the combination of AA and DHA have beneficial roles in the immature lung needs further research.
13.	Forsberg, Gustaf, et al. (author) Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden 2024 In: Acta Anaesthesiologica Scandinavica. - : John Wiley & Sons. - 0001-5172 .- 1399-6576. ; 68:2, s. 226-235 Journal article (peer-reviewed)abstract Background: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality.Methods: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI.Results: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves.Conclusion: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.
14.	Hårdstedt, Maria, 1971-, et al. (author) Swimming-Induced Pulmonary Edema : Diagnostic Criteria Validated by Lung Ultrasound 2020 In: Chest. - : American College of Chest Physicians. - 0012-3692 .- 1931-3543. ; 158:4, s. 1586-1595 Journal article (peer-reviewed)abstract BACKGROUND: Despite the increasing popularity of open water swimming worldwide, swimming-induced pulmonary edema (SIPE) is a poorly recognized condition lacking established diagnostic criteria.RESEARCH QUESTION: The aim of this study was to identify diagnostic criteria of SIPE during a large open water swimming event.STUDY DESIGN AND METHODS: In this cross-sectional study, 17,904 individuals swam 1,000, 1,500, or 3,000 m in cold open water during Sweden's largest open water swimming event in 2018 and 2019. Of 166 swimmers seeking medical attention for acute respiratory symptoms, 160 were included in the study. Medical history, symptoms, and clinical findings were collected. On-site lung ultrasound (LUS) was performed to verify pulmonary edema.RESULTS: Pulmonary edema was confirmed by LUS in 102 patients (64%); findings were unilateral in 11 (7%). Peripheral oxygen saturation was identified as a strong independent diagnostic test for pulmonary edema, with ≤ 95% as the suggested cut off based on receiver-operating characteristic curve analysis (area under the curve, 0.893; P < .0001). Crackles on lung auscultation, predominantly over the anterior chest, identified 88% of patients with edema. Peripheral oxygen saturation ≤ 95% or auscultation findings of crackles identified pulmonary edema with a sensitivity of 97% and a specificity of 86%. A specificity of 98% and a positive predictive value of 99% for LUS-verified pulmonary edema were reached if patients presented with both oxygen saturation ≤ 95% and auscultation of crackles.INTERPRETATION: We suggest a clinical algorithm for diagnosis of SIPE for swimmers with acute respiratory symptoms during swimming in cold open water. Novel features of focally distributed edema in the anterior parts of the lungs, sometimes unilateral, add to this unique dataset of an underreported condition.
15.	Voss, Erica A, et al. (author) Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study. 2023 In: EClinicalMedicine. - 2589-5370. ; 58 Journal article (peer-reviewed)abstract Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population.A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases.Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism.Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term.None.
16.	Brew, Bronwyn K., et al. (author) Paediatric asthma and non-allergic comorbidities : A review of current risk and proposed mechanisms 2022 In: Clinical and Experimental Allergy. - Stockholm : Wiley-Blackwell Publishing Inc.. - 0954-7894 .- 1365-2222. ; 15:9, s. 1035-1047 Research review (peer-reviewed)abstract It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
17.	Vasileiadou, Styliana, et al. (author) Low agreement between Swedish national registers and parental questionnaires on allergic rhinitis 2023 In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - 1399-3038. ; 34:11 Journal article (peer-reviewed)abstract Allergic rhinitis (AR) has been well documented using questionnaire-based studies. Here, we examine the agreement between parental-reported data during childhood with the emphasis on 12-year-olds and data from two national Swedish registers to determine whether register data on AR can supplement or replace questionnaire data.Data were collected from a prospective, longitudinal cohort study of children born in western Sweden in 2003. Parental questionnaires were filled out at 6months and one, four, eight, and 12years of age. A total of 3634 children were linked to the Swedish Prescribed Drug Register (SPDR) and the National Patient Register (NPR) using personal identity numbers. The agreement between the register and questionnaire data was estimated using Cohen's kappa with 95% confidence intervals.According to the SPDR, 9.9% (n=360/3634) of the children were dispensed specific AR medication at 11-13years of age compared with the 12years questionnaire where 23% reported AR medication use during the last 12months. The overall agreement between questionnaire and SPDR data on AR medication was slight (kappa 0.05). At 11-12years, 1.8% (n=65/3634) of the children received an outpatient AR diagnosis in the NPR, while 10% reported doctor-diagnosed AR in the questionnaire. The overall agreement between questionnaire and NPR data on AR diagnosis was slight (kappa 0.16).There was poor agreement between questionnaire and register data regarding AR and dispensed medication. Explanations could include over-the-counter drugs and diagnosis in primary care, which are not included in the registers.
18.	Dutta, Nikita, 1992, et al. (author) Combinatory analysis of immune cell subsets and tumor-specific genetic variants predict clinical response to PD-1 blockade in patients with non-small cell lung cancer 2023 In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 12 Journal article (peer-reviewed)abstract Immunotherapy by blocking programmed death protein-1 (PD-1) or programmed death protein-ligand1 (PD-L1) with antibodies (PD-1 blockade) has revolutionized treatment options for patients with non-small cell lung cancer (NSCLC). However, the benefit of immunotherapy is limited to a subset of patients. This study aimed to investigate the value of combining immune and genetic variables analyzed within 3-4 weeks after the start of PD-1 blockade therapy to predict long-term clinical response.Blood collected from patients with NSCLC were analyzed for changes in the frequency and concentration of immune cells using a clinical flow cytometry assay. Next-generation sequencing (NGS) was performed on DNA extracted from archival tumor biopsies of the same patients. Patients were categorized as clinical responders or non-responders based on the 9 months' assessment after the start of therapy.We report a significant increase in the post-treatment frequency of activated effector memory CD4+ and CD8+ T-cells compared with pre-treatment levels in the blood. Baseline frequencies of B cells but not NK cells, T cells, or regulatory T cells were associated with the clinical response to PD-1 blockade. NGS of tumor tissues identified pathogenic or likely pathogenic mutations in tumor protein P53, Kirsten rat sarcoma virus, Kelch-like ECH-associated protein 1, neurogenic locus notch homolog protein 1, and serine/threonine kinase 11, primarily in the responder group. Finally, multivariate analysis of combined immune and genetic factors but neither alone, could discriminate between responders and non-responders.Combined analyses of select immune cell subsets and genetic mutations could predict early clinical responses to immunotherapy in patients with NSCLC and after validation, can guide clinical precision medicine efforts.
19.	Johansson, I, et al. (author) PD-1 inhibitor therapy of basal cell carcinoma with pulmonary metastasis. : PD-1 inhibition in basal cell carcinoma 2022 In: Journal of the European Academy of Dermatology and Venereology. - : Wiley. - 1468-3083 .- 0926-9959. ; 36:Suppl 1, s. 70-73 Journal article (peer-reviewed)abstract Basal cell carcinoma (BCC) may be challenging to differentiate from basaloid squamous cell carcinoma (bSCC), both clinically and histologically. BCC constitutes one of the most common tumours and metastatic behaviour is extremely rare. In contrast, bSCC is a rare entity with an increased propensity for distant metastasis. If these conditions develop into inoperable metastatic disease, the therapeutic alternatives are different, but the use of PD-1 inhibitors may be a valid option for both. Here, we report a case with complex histology with a component initially classified as bSCC with lung metastases and treated with the PD-1 inhibitor cemiplimab resulting in radiological and clinical responses. Re-examination of the lung biopsy using routine histomorphology in combination with immunohistochemical staining for cytokeratin 14, cytokeratin17 and BerEp4 has, however, revealed a histopathological pattern of BCC, which is in concordance with a similar analysis of the cutaneous primary tumour in the face that the patient underwent surgery for more than 5years earlier.
20.	Baldanzi, Gabriel, et al. (author) OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study 2023 In: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516 Journal article (peer-reviewed)abstract BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
21.	Celik, Y., et al. (author) Association of Excessive Daytime Sleepiness with the Zung Self-Rated Depression Subscales in Adults with Coronary Artery Disease and Obstructive Sleep Apnea 2021 In: Diagnostics. - : MDPI AG. - 2075-4418. ; 11:7 Journal article (peer-reviewed)abstract Excessive daytime sleepiness (EDS) is a factor associated with both obstructive sleep apnea (OSA) and depressive symptoms. Continuous positive airway pressure (CPAP) treatment may decrease EDS in adults with OSA; however, the modulatory role of depressive symptoms on the improvement of EDS is not known. We aimed to explore the association between subscales of the Zung Self-rated Depression Scale (SDS) and Epworth Sleepiness Scale (ESS) over a 2-year period in coronary artery disease (CAD) patients with OSA. This was a post-hoc analysis of the RICCADSA cohort, in which 399 adults with CAD (155 sleepy OSA [apnea-hypopnea index >= 15/h] and ESS score >= 10, who were offered CPAP; and 244 nonsleepy OSA [ESS < 10]), randomized to CPAP [n = 122] or no-CPAP [n = 122]) were included. Three factors were extracted from the Zung SDS, based on the principal component analysis: F1, cognitive symptoms and anhedonia; F2, negative mood; and F3, appetite. In a mixed model, the ESS score decreased by 3.4 points (p < 0.001) among the sleepy OSA phenotype, which was predicted by the decline in the F2, but not in the F1 and F3 scores. The fixed effects of time were not significant in the nonsleepy OSA groups, and thus, further analyses were not applicable. Additional within-group analyses showed a significant decrease in all subscales over time both in the sleepy and nonsleepy OSA patients on CPAP whereas there was a significant increase in the nonsleepy OSA group randomized to no-CPAP. We conclude that the improvement in negative mood symptoms of depression, but not changes in cognitive symptoms and anhedonia as well as appetite, was a significant predictor of decline in the ESS scores over a 2-year period in this CAD cohort with sleepy OSA on CPAP treatment.
22.	Engström, Gunnar, et al. (author) Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications 2024 In: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49 Journal article (peer-reviewed)abstract Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
23.	Gunduz, C., et al. (author) Long-term positive airway pressure therapy is associated with reduced total cholesterol levels in patients with obstructive sleep apnea: data from the European Sleep Apnea Database (ESADA) 2020 In: Sleep Medicine. - : Elsevier BV. - 1389-9457. ; 75, s. 201-209 Journal article (peer-reviewed)abstract Background and aim: Obstructive sleep apnea (OSA) is an independent risk factor for dyslipidemia. The current study examined the effects of positive airway pressure (PAP) treatment on lipid status in the European Sleep Apnea Database (ESADA). Methods: The prospective cohort study enrolled 1564 OSA subjects (74% male, mean age 54 ± 11y, body mass index (BMI) 32.7 ± 6.6 kg/m2 and apnea-hypopnea index (AHI) 40.3 ± 24.4 n/h) undergoing PAP therapy for at least three months (mean 377.6 ± 419.5 days). Baseline and follow-up total cholesterol (TC) from nine centers were analyzed. Repeated measures and logistic regression tests (adjusted for age, sex, weight changes, lipid lowering medication, PAP compliance, and treatment duration) were used to compare changes in TC concentration. Incident risk for a coronary heart disease event (CHD) was used to compute a Framingham CHD risk score (estimated from age, BMI, blood pressure, and TC). Results: Adjusted means of TC decreased from 194.2 mg/dl to 189.3 mg/dl during follow-up (p = 0.019). A clinically significant (10%) reduction of TC at PAP follow-up was observed in 422 patients (27%). Duration of PAP therapy was identified as independent predictor for TC reduction, which implies an approximately 10% risk reduction for incident CHD events (from 26.7% to 24.1% in men and from 11.2% to 10.1% in women, p < 0.001 respectively). Conclusion: This observational study demonstrates a reduction of TC after long-term PAP treatment. The close association between TC concentration and cardiovascular (CV) mortality suggests that identification and treatment of OSA may have a beneficial effect on overall CV risk due to this mechanism. This possibility needs to be evaluated in prospective randomized studies. © 2020 Elsevier B.V.
24.	Javaheri, S., et al. (author) Obstructive sleep apnea and stroke: The mechanisms, the randomized trials, and the road ahead 2022 In: Sleep Medicine Reviews. - : Elsevier BV. - 1087-0792. ; 61:February Journal article (peer-reviewed)abstract When considered separately from cardiovascular disease, stroke is the third leading cause of death in the U.S. and is the leading cause of long-term disability in adults. New approaches that can be offered to the majority of ischemic stroke patients, can be continued throughout post-stroke care, can limit stroke severity, and can complement or even enhance rehabilitation, would transform ischemic stroke recovery. The treatment of obstructive sleep apnea (OSA) in patients with acute ischemic stroke may represent one such approach. This manuscript reviews the epidemiologic studies of the bidirectional association between OSA and stroke, and the mechanisms and molecular signatures of OSA leading to transient ischemic attack and stroke as well as the randomized controlled trials and observational cohort studies examining continuous positive airway treatment efficacy on the impact of stroke outcomes. Finally, the insights these studies provide on future research are also discussed. © 2021 Elsevier Ltd
25.	Kjellström, Barbro, et al. (author) Adherence to disease-specific drug treatment among patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension 2020 In: European Respiratory Journal Open Research. - Sheffield : European Respiratory Society (ERS). ; 6:4 Journal article (peer-reviewed)abstract Background: Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong treatment. The aim of the present study was to investigate adherence to disease-specific treatment in patients with PAH or CTEPH. Methods: The study comprised an adult population diagnosed with PAH (n=384) or CTEPH (n=187) alive in 2016-2017. The study utilised three registries: the Swedish PAH registry, the National Board of Health and Welfare, and Statistics Sweden. Withdrawals from pharmacies of disease-specific oral treatments were studied. Adherence was assessed as: 1) Number of days covered defined as the difference between the total number of daily dosages dispensed and the total number of days covered; and 2) Manual assessment by two persons that independently reviewed each patient's prescription fill history to detect anomalies or patterns of deteriorating or improving adherence over time. Results: The mean age was 61±16 years, 61% were female and mean time since diagnosis was 4.6 years. Adherence was 62% using the Number of days covered method and 66% by the Manual assessment method. Drug-specific adherence varied from 91% for riociguat to 60% for sildenafil. Good adherence was associated with shorter time since diagnosis in patients with PAH and with lower number of concomitant other chronic treatments in patients with CTEPH. Age, sex, socioeconomic status or number of pulmonary hypertension (PH) treatments were not associated with adherence. Conclusion: Adherence to oral disease-specific treatment was 60-66% and associated with time since diagnosis and number of concomitant chronic treatments. Sex, age or socioeconomic factors did not affect adherence.

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