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Sports Injury Patterns and Economic Consequences Before and During the COVID-19 Pandemic:A Comprehensive Study of Norwegian Sports From 2017 to 2020 Using Insurance Data
No full textUnderstanding injury rates and costs is crucial for targeted prevention, yet data across sports remain sparse. Furthermore, information on the impact of the COVID-19 pandemic on injuries across sports is limited. This study aimed to describe injury incidence rates, injured body regions, costs, and mean cost per 1000 athlete year across different sports before and during the COVID-19 pandemic. The study analyzed insurance data from licensed Norwegian athletes aged 13–50 years participating in football, handball, athletics, gymnastics, and swimming over a four-year period (2017–2020). Injury incidence rates, body region, costs, and mean cost per 1000 athlete year, as well as differences in injury rates between sports, sex, age groups, before and during the first year of the COVID-19 pandemic were analyzed. Over the full study period, the highest injury incidence rates were found in athletics, followed by handball, compared to football, gymnastics, and swimming. Lower extremity injuries accounted for the highest incidence rates and costs across sports. Surgical interventions in handball and football accounted for more than half of the costs. Over one fifth of injuries in gymnastics led to permanent medical impairment. During the first year of the COVID-19 pandemic, the number of licensed athletes and incidence rates decreased, except for athletics, which experienced an increase in both. The findings highlight the need for targeted injury prevention measures, particularly in athletics and for lower extremity injuries in handball and football. The fact that one in five injuries in gymnastics resulted in medical impairment is a cause for concern. The impact of the COVID-19 pandemic on sports participation and injury incidence underscores the influence of external factors on sports-related injuries.</p
Early clinical implementation and evaluation of an NLP-Based AI system for thrombophilia assessment using electronic health records
No full textBackground: Thrombophilia evaluation requires integration of biochemical findings with clinical history, much of which is embedded in unstructured electronic health record (EHR) text. Manual chart review is labour-intensive and prone to omissions. Natural language processing (NLP) offers a potential alternative by automatically identifying and highlighting relevant information to support more efficient and accurate assessments. Methods: We developed a transformer-based NLP model for thrombosis and integrated it with previously validated bleeding (transformer-based), anticoagulant, and antithrombotics (rule-based) models in an AI system that highlights key phrases in unstructured Danish EHRs to expedite clinician chart review. The system was implemented in routine clinical care to support thrombophilia evaluations. We retrospectively evaluated its performance based on 50 real-world EHRs reviewed by clinicians using the system. Eye-tracking was used to assess information-seeking behaviour during simulated reviews, and semi-structured interviews explored adoption potential post-implementation. Results: The thrombosis model achieved high sentence-level performance (sensitivity 98.8%, specificity 99.8%). In retrospective review, AI-assisted clinicians identified all previously documented findings, and identified additional relevant information in 68% of cases. Eye-tracking showed a 33% reduction in review time and improved identification of relevant content. Users adopted two distinct navigation styles: AI-guided scanning and manual scrolling, reflecting varied trust and cognitive strategies. Interviews revealed strong support for system accuracy and efficiency, with integration and training identified as key challenges. Conclusion: This evaluation highlights the potential of NLP tools to support clinical decision-making. Clear model design, sentence-level transparency, and user-centred evaluation are essential for safe and effective integration into clinical workflows.</p
Primary Antibody Deficiency in Patients With Chronic Rhinosinusitis:A Call for Immunologic Evaluation Prior to Biologic Therapy
No full textObjective: Chronic rhinosinusitis (CRS) is prevalent and causes a great negative impact on quality of life. Primary antibody deficiency (PAD) is highly prevalent with CRS compared to the background population. There are efficient treatment options to consider when CRS is a symptom of PAD. The condition seems to be underdiagnosed. Design: A prospective cohort study investigating adults with CRS for PAD. Results: One hundred and thirty-eight patients were included in the study. Mean age was 49 years. Twenty-nine (21%) had hypogammaglobulinemia. Nine of 83 (11%) patients had insufficient response to pneumovax polysaccharide vaccine, but insufficient clinical history for diagnosis of Specific Antibody Deficiency (SPAD). Four patients met the clinical criteria for PAD; one had Common Variable Immune Deficiency (CVID), one had IgA deficiency, and two had IgG subclass deficiency. No clinical characteristic was predictive of PAD, and severity of CRS was not indicative of hypogammaglobulinemia or insufficient vaccine response. Conclusion: Immunoglobulin testing should be a routine part of the diagnostic work-up in chronic rhinosinusitis before considering biologics, as primary antibody deficiency is an under-recognised but treatable cause of refractory disease.</p
The effects of paracetamol use during pregnancy on reproductive health and neurodevelopment
No full textParacetamol anses som sikkert at anvende under graviditet, og over halvdelen af alle gravide rapporterer om et forbrug. Udover den direkte brug som smertestillende middel, udsættes befolkningen indirekte gennem baggrundseksponering for paracetamol fra eksempelvis drikkevandet og for kemikaliet anilin, der omdannes til paracetamol i leveren. Eksponering for anilin sker gennem fødevarer, drikkevand, tobaksrøg og tekstiler. Biomonitoreringsstudier har vist, at paracetamol kan måles hos alle individer.Paracetamol passerer livmoderen, og studier peger på, at udsættelse for paracetamol underfosterstadiet kan påvirke både den reproduktive sundhed og den neurologiske udvikling. Eksperimentelle studier viser, at eksponering for paracetamol har antiandrogene egenskaber i fostre, sammenlignelige med visse hormonforstyrrende stoffer. Anogenital afstand (AGD),afstanden mellem anus og genitalier, er en biomarkør for antiandrogen aktivitet hos fostre, hvor kortere AGD er forbundet med reproduktionsforstyrrelser. AGD i spædbørn bruges som en tidlig markør for senere reproduktiv sundhed, men det er uklart, hvordan AGD udviklersig gennem barndommen, da eksisterende longitudinelle studier har fulgt børn op til 2-årsalderen. Kun få studier har undersøgt sammenhængen mellem mors paracetamolbrug under graviditeten og barnets AGD, med inkonsistente resultater. Androgener spiller også en rolle i fostrets neurologiske udvikling, men kun to studier har undersøgt sammenhængen mellem mors brug af paracetamol under graviditeten og barnets IQ, også her med modstridende resultater.Afhandlingen er baseret på data fra Odense Børnekohorte (OBK), et populationsbaseret prospektivt studie, hvor alle gravide kvinder bosiddende i Odense Kommune fra 2010 til2012 blev inviteret til at deltage, og 2.448 kvinder blev inkluderet. Kvinderne fik tilsendt trespørgeskemaer om medicinforbrug under graviditeten og afgav urinprøver vedsvangerskabsuge 28, hvoraf paracetamolkoncentrationer blev målt i 518 prøver. Børnene blev inviteret til kliniske undersøgelser ved 3 og 18 måneder samt ved 3, 5, 7 og 9 år, hvor AGD blev målt. IQ score ved 7 år blev vurderet af psykologer med et internationalt valideret måleredskab, Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V).Resultaterne viste, at AGD målt ved 3 måneder korrelerede med AGD på alle deefterfølgende alderstrin, og at kort AGD ved 3 måneder forudsagde kort AGD ved 9 år,særligt hos drenge, hvilket understøtter anvendelsen af AGD som en tidlig markør for senerereproduktiv sundhed. Over 65% af kvinderne rapporterede paracetamolbrug undergraviditeten. Paracetamolkoncentrationer blev påvist i alle urinprøver grundet indirekte eksponering, og 6% havde koncentrationer >4.000 ng/mL, hvilket indikerer nyligt brug indenfor de seneste 48 timer. Mors paracetamolbrug under graviditeten, både selvrapporteret og høje urinkoncentrationer, der indikerer nyligt brug, var associeret med små reduktioner iAGD hos både drenge og piger fra spædbarnsalder til 9 år. Derudover var morsparacetamolbrug under graviditeten associeret med lavere IQ ved 7 år. AGD og IQ varreduceret mest ved paracetamolkoncentrationer der indikerer nyligt brug, sandsynligvis fordidisse målinger omfatter kvinder med hyppigere brug, givet paracetamols korte halveringstid.Selvom reduktionerne i AGD og IQ var små på individniveau, kan den udbredte brug af paracetamol under graviditet (65% i OBK) have implikationer på befolkningsniveau. Reduceret AGD er forbundet med nedsat reproduktiv sundhed og selv små reduktioner i IQ kan ligeledes have samfundsmæssige konsekvenser i form af lavere uddannelsesniveau, reduceret arbejdsmarkedstilknytning og dårligere helbred. Disse resultater peger på et behov for øget opmærksomhed på de potentielle langsigtede konsekvenser af mors paracetamolbrug under graviditet. I situationer uden en medicinsk indikation bør ikke-farmakologiskeinterventioner overvejes.Paracetamol is widely considered safe during pregnancy, and more than half of pregnant women use it. Besides its direct use as an analgesic, the general population is indirectly exposed through other pathways, including background exposure to paracetamol itself e.g.,through drinking water, and to the chemical aniline, which is metabolised to paracetamol in the human body. Aniline exposure can occur through food, drinking water, tobacco smoke, textiles, and cosmetics. Biomonitoring studies have shown that paracetamol is detectable in all individuals. Paracetamol crosses the placenta barrier, and recent evidence suggests that exposure during fetal life adversely affects reproductive health and neurodevelopment. Experimental studies indicate that paracetamol exposure has antiandrogenic properties during fetal life, comparable to certain endocrine-disrupting chemicals. Anogenital distance (AGD), the distance between the anus and the genitalia, is a biomarker for antiandrogenic prenatal exposure, where shorter AGD is associated with reproductive conditions. AGD in infancy is used as an early marker of later reproductive health, but its development during childhood remains unknown, as existing longitudinal studies have only followed children up to 2 years of age. Few studies have examined the association between maternal paracetamol use during pregnancy and AGD in infants, with inconsistent findings. Androgens also play a role in neurodevelopment in the fetus, but only two studies have investigated the association between maternal paracetamol use during pregnancy and child IQ, with inconsistent results. This thesis was assessed based on data from the Odense Child Cohort (OCC), a populationbased prospective study, in which all pregnant women residing in the municipality of Odense, Denmark, from 2010 to 2012 were invited to participate. In total, 2,448 mother-child pairs were included. All pregnant women were asked to complete two questionnaires during pregnancy and one after delivery. Maternal urine samples were collected at gestational week28, and urinary paracetamol concentrations were measured in 518 urine samples. Children were invited for clinical examinations at 3 and 18 months, and at 3, 5, 7, and 9 years, where AGD was measured. At age 7, trained psychologists assessed IQ scores using a shortened Danish version of the internationally validated Wechsler Intelligence Scale for Children, Fifth Edition (WISC-V).The findings showed that AGD measured at 3 months was correlated with AGD at all subsequent ages, and that short AGD in infancy predicted short AGD at age 9, particularly in boys, supporting its use as an early marker of later reproductive health. Approximately65% of women reported paracetamol use during pregnancy. Paracetamol concentrations were detected in all urine samples, reflecting background exposure, and 6% had concentrations >4000 ng/mL, indicating recent use within the past 48 hours. Paracetamol use during pregnancy, both self-reported and high urinary concentrations indicating recent use, was associated with modest reductions in AGD in both boys and girls from infancy to 9 years of age. Similarly, paracetamol use during pregnancy was associated with a tendency towards reductions in child IQ at 7 years of age. For both outcomes, AGD and IQ, the largest reductions were observed for high maternal urinary concentrations, indicating recent use, likely because such measurements capture women with more frequent or even daily use, given the short half-life of paracetamol.Although reductions in AGD and IQ were small at the individual level, the widespread use of paracetamol during pregnancy (65% in OCC) may have important implications at a population level. Shorter AGD is associated with reduced reproductive health, and small reductions in IQ may affect society through lower educational attainment, reduced labour market participation, and poorer health. These findings highlight the need for increased awareness of the potential long-term impacts of paracetamol use during pregnancy, and insituations where there is no absolute indication for use, non-pharmacological interventions should be considered
A quantitative size stability metrics for long-acting suspensions and its prediction with machine learning
No full textDefining suspension stability can be extremely complex, but beyond critical during the formulation development of nano- and microsuspensions intended for long-acting injectables. As of now, the current practice is based on the trial-and-error approach to determine suitable stabilizers and corresponding stabilization concentrations to allow size reduction due to proper wetting while minimizing particle agglomeration or crystal growth by Ostwald ripening during storage, making the definition of suspension stability subjective in the existing literature. The present study proposed a quantitative measurement of the suspension stability (i.e., suspension stability index (SSI)) defined by two coefficients of variation from the suspension population median, i.e., D50CV, and distribution, i.e., SpanCV, over 28 days of storage under accelerated conditions. Various predictive models for SSI were constructed with a defined threshold for the D50CV and SpanCV where the support vector classification (SVC) model was found to hold the best performance based on a 5-fold cross-validated accuracy of 0.82 and F1 score of 0.82 while also having a good transferability. Critical factors that impacted the SSI included the stabilizer type and its corresponding concentration while the drug compound was found to interact with multiple parameters with the exception of the bead size. Overall, the presented quantitative metric of suspension stability based on the SSI could potentially contribute to a more comparable investigation of suspension stability during formulation development by using the classification model from the presented dataset as a screening tool.</p
Neutralizing the odds:Biomechanical protection by adiposity offsets physiological burden to explain the trauma ’obesity-paradox’
No full textBackground The global rise in obesity presents a complex challenge in trauma care, characterized by the "Obesity Paradox." This study aimed to evaluate the biomechanical protection hypothesis and its influence on initial injury severity and clinical outcome in severely injured patients. Methods This retrospective study analyzed 1549 adult trauma patients (ISS≥9) divided into Non-Obese (NO, BMI<30) and Obese (OB, BMI≥30) cohorts. Primary endpoints included ISS, regional AIS scores, and mortality. Secondary endpoints included physiological burden (SAPS II) and resource utilization (LOS, ICU LOS). Group differences were analyzed and the independent effect of BMI on mortality, adjusting for Age, ISS, and ASA status assessed. Results The OB cohort was significantly older and presented higher pre-existing comorbidity. Supporting the cushioning effect, OB patients exhibited a significantly lower overall ISS (p=0.035) and lower regional AIS scores for the Head/Neck (p=0.008) and Abdomen/Pelvis (p=0.036). OB patients suffered greater morbidity however, with higher SAPS II scores (p<0.001) and longer total LOS (p=0.005) and ICU LOS (p=0.021). Despite this morbidity and their lower ISS, in-hospital mortality was comparable between groups (p=0.728). Multivariate analysis confirmed that Age and ISS were strong, independent mortality predictors (OR>1.08, p<0.001), while BMI itself was not a significant independent predictor (OR1.036, p=0.119). Conclusions Our findings strongly suggest that the "Obesity Paradox" in major trauma is not a mere statistical anomaly, but a reproducible phenomenon with a distinct mechanistic explanation: Biomechanical protection which results in a lower ISS, neutralizes the increased physiological and comorbidity burden of the obese state.</p
Attenuating ETEC virulence using a heat-labile enterotoxin-blocking binding protein
No full textBacterial enteric pathogens are major contributors to the global burden of diarrheal diseases and the associated consequences for human health including malnutrition, growth stunting, morbidity, and mortality. While mortality from diarrhea has decreased, incidence remains high, and better interventions for preventing disease are needed. Single-domain antibodies (i.e., VHHs), functioning as target-binding proteins in the gastrointestinal tract, have been proposed as a potential approach to mitigate bacterial pathogenesis. Here, we describe a mitigation strategy where precision binding of a bivalent VHH to the receptor-binding B-pentamer of heat-labile enterotoxin aggregates the AB5 toxin and impairs enterotoxigenic Escherichia coli colonization in a flow chamber model simulating the human intestine. The VHH construct also binds to the structurally similar cholera toxin and effectively abrogates its intestinal cell cytotoxicity in vitro. Based on these results, we believe that targeting virulence could emerge as a new strategy for the management of bacterial enteric pathogens, supporting gut health in at-risk populations alongside vaccination campaigns or in populations without access to vaccines.</p
Clinical utility of longitudinal ctDNA monitoring by multiplex MS-ddPCR for risk stratification and follow-up in rectal cancer
No full textIntroduction: Personalized treatment strategies in rectal cancer aim to balance escalation and de-escalation based on recurrence risk. Accurately identifying which patients will benefit from each approach is essential for optimizing outcomes and guiding follow-up. However, current clinical methods lack the precision needed to reliably predict response and long-term prognosis. Methods: In this feasibility study, we evaluated the prognostic utility of a novel methylation-specific droplet digital PCR (MS-ddPCR) multiplex assay in 56 patients with locally advanced rectal cancer (LARC) undergoing neoadjuvant treatment (nT) and surgery. Circulating tumor DNA (ctDNA) was analyzed at four time points (baseline, during nT, preoperatively, 6 months post-surgery). Associations between ctDNA status and dynamics with tumor regression grade (TRG), disease recurrence, and overall survival (OS) were assessed using receiver operating characteristics (ROC) analyses and survival statistics. Results: ctDNA was detected in 59% of the patients at baseline. Preoperative ctDNA had limited discriminative value for pathologic response, AUC 0.60 (95% CI 0.45–0.76). In contrast, ctDNA positivity 6 months postoperatively was strongly associated with recurrence within 2 years following surgery, AUC 0.96 (95% CI, 0.91–1.00). CtDNA positivity 6 months post-surgery was associated with inferior 2-year DFS (38% vs 94%, p for log-rank < 0.001) and 3-year OS (63% vs 100%, p for log-rank < 0.001). Conclusion: With this MS-ddPCR assay, preoperative ctDNA showed limited prognostic value, whereas ctDNA 6 months postoperatively was strongly associated with recurrence and overall survival. The absence of an immediate postoperative sample limited assessment of early molecular response—a time point critical for guiding treatment decisions and follow-up strategies—underscoring the need for earlier sampling in future studies to optimize ctDNA-guided management. Given the small cohort and exploratory design, these findings are hypothesis-generating and support further validation of the assay in larger, prospective trials.</p
Assessing adult attachment after out-of-hospital cardiac arrest:an exploratory analysis and construct validation of the ECR-RS
No full textAim To explore the construct validity of the ‘Experience in Close Relationships – Relationship Structures’-questionnaire (ECR-RS) in a population of out-of-hospital cardiac arrest (OHCA) survivors. Objectives were to (i) describe item- and scale-level response patterns, and (ii) evaluate the preliminary construct validity of the ECR-RS, including its dimensional (structural), known-groups, and convergent validity. Methods An exploratory cross-sectional validation study, with OHCA survivors completing the ECR-RS, Hospital Anxiety and Depression Scale (HADS), and the mental health component from the Short Form-12 (SF-12 MCS) three months post- arrest. Descriptive statistics and floor/ceiling analyses were performed. Dimensional validity was assessed using response distribution patterns and exploratory factor analysis (EFA), followed by reliability using Cronbach’s α ́s. Known-group validity was tested using a priori hypotheses, Spearman’s correlations, and Mann-Whitney U tests. Convergent validity was evaluated by correlating ECR-RS total scores with HADS and SF-12 MCS. Results Among 123 survivors (median age 59.9 years, 84 % male), ECR-RS total scores were low on both subscales and floor effects were observed at scale level (31 % for avoidant and 72 % for anxious attachment). EFA supported the expected two-factor structure, though item 4–6 showed poor loadings/cross-loadings. Internal consistency was acceptable (total scale Cronbach’s α = 0.88) and improved when problematic items were excluded. Known-group hypotheses were not supported. Anxious attachment correlated moderately with symptoms of anxiety and depression and was inversely correlated with mental health scores. Conclusion The ECR-RS demonstrated partial construct validity among OHCA survivors, but item-level inconsistencies and pronounced floor effects limit its utility. Findings highlight the need for a revised instrument better suited to post-cardiac arrest relational and psychological dynamics.</p