Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA.

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Outbreak of equine herpesvirus 4 (EHV-4) in Denmark: tracing patient zero and viral characterization.

BACKGROUND: Equine herpesvirus 4 (EHV-4) causes respiratory disease in horses, and the virus is considered endemic in the global equine population. However, outbreaks can occur when several horses are gathered in relation to shows, competitions, breeding units and at hospitals. In the spring year 2022, an EHV-4 outbreak occurred at the Large Animal Teaching Hospital, University of Copenhagen, Denmark. Nine horses were tested EHV-4 positive during the outbreak, which lasted approx. seven weeks. In addition, a tenth horse "Eq10" tested EHV-4 positive almost three weeks after the last of the outbreak horses tested positive. Detailed clinical registrations were obtained from all ten horses as well as their location and movement during hospitalization. Nasal swabs were obtained throughout the outbreak and tested by qPCR for EHV-4. Additionally, pre- and post-infection sera were tested for the presence of EHV-4 antibodies. Selected samples were characterized by partial and full genome sequencing. RESULTS: The most common clinical signs of the EHV-4 infected horses during this outbreak were pyrexia, nasal discharge, mandibular lymphadenopathy and increased lung sounds upon auscultation. Based on the locations of the horses, EHV-4 detection and antibody responses the most likely "patient zero" was identified as being "Eq1". Partial genome sequencing revealed that Eq10 was infected by another wild type EHV-4 strain, suggesting that the hospital was able to eliminate the outbreak by testing and reinforcing biosecurity measures. The complete genome sequence of the outbreak strain was obtained and revealed a closer relation to Australian and Japanese EHV-4 strains rather than to other European EHV-4 strains, however, very limited sequence data are available from Europe. CONCLUSION: The study illustrated the transmission of EHV-4 within an equine facility/hospital and provided new insights into the viral shedding, antibody responses and clinical signs related to EHV-4 infections. Finally, sequencing proved a useful tool in understanding the transmission within the hospital, and in characterizing of the outbreak strain.

Literary tastes are as heritable as other human phenotypes: Evidence from twins' library borrowing.

Social science research argues that differences in individuals' literary and cultural tastes originate in social environments. Yet, it might be that these differences are partly associated with genetic differences between individuals. To address this possibility, we use nation-scale registry data on library borrowing among Danish twins (N = 67,900) to assess the heritability of literary tastes. We measure literary tastes via borrowing of books of different genres (e.g., crime and biographical novels) and formats (physical, digital, and audio) and decompose the total variance in literary tastes into components attributable to shared genes (heritability), shared environments (social environment shared by siblings), and unique environments (social environments not shared by siblings). We find that genetic differences account for 45-70 percent of the total variance in literary tastes, shared environments account for almost none of the variance, and unique environments account for a moderate share. These results suggest that literary tastes are approximately as heritable as other human phenotypes (e.g., physical traits, cognition, and health). Moreover, heritability is higher for socioeconomically disadvantaged groups than for advantaged groups. Overall, our results suggest that research should consider the role of genetic differences in accounting for individual differences in literary and broader cultural tastes.

Magnetic Resonance Imaging Signs of Idiopathic Intracranial Hypertension.

Importance: The magnetic resonance imaging (MRI) criteria currently used to diagnose idiopathic intracranial hypertension (IIH) are based on expert opinion and have limited accuracy. Additional neuroimaging signs have been proposed and used with contradictory results; thus, prospective evidence is needed to improve diagnostic accuracy. Objective: To provide evidence-based, accurate MRI signs for IIH diagnosis. Design, Setting, and Participants: This prospective cohort study was conducted from January 2018 to May 2021 with 3 validation cohorts at 2 Danish headache centers and with 3 independent international cohorts. Consecutive patients with suspected IIH were enrolled. Eligibility required the clinical suspicion of IIH, age 18 years or older, and written informed consent. The validation cohorts comprised patients with confirmed IIH from Austria and the US, and patients without IIH from the US. Data analysis was performed from December 2021 to August 2023. Exposure: Standardized diagnostic workup was performed to classify cases according to current criteria, and blinded evaluation of cerebral radiological diagnostics and papilledema was performed. Main Outcomes and Measures: The primary outcomes were MRI signs associated with IIH as assessed by univariate analyses. An MRI score estimating papilledema was calculated using machine learning. Internal validation of associations with lumbar puncture opening pressure and outcome and external validation of accuracy were performed in 3 cohorts. Results: Of 192 eligible patients (185 women [96.4%]; median [IQR] age, 28.0 [23.0-35.0] years), 110 were classified as having IIH, 4 as having probable IIH, and 1 as having suspected IIH without papilledema; 77 did not have IIH and served as controls, with corresponding age, sex, and weight. Papilledema at diagnosis was associated with perioptic subarachnoid space distension (56 patients [68.3%] vs 21 patients [41.2%]), posterior globe flattening (53 patients [66.3%] vs 10 patients [21.3%]), optic nerve disc protrusion (35 patients [30.4%] vs 2 patients [2.3%]), and transverse sinus venous stenosis (75 patients [79.8%] vs 29 patients [46.8%]). The papilledema-estimating MRI score showed optimal balance between sensitivity (49%) and specificity (87%) when 2 of the 3 latter signs were present and was associated with the lumbar puncture opening pressure and ophthalmological outcome. The score showed strong diagnostic accuracy in the external validation cohorts (587 patients; area under the receiver operating characteristic curve, 0.86) and outperformed the current (2013) diagnostic MRI criteria. Conclusions and Relevance: The findings of this cohort study of patients with IIH and controls suggest that an evidence-based MRI score including posterior globe flattening, optic nerve disc protrusion, and transverse sinus stenosis can estimate the presence of papilledema more accurately than the current diagnostic criteria.

Evaluation of North Sea saturation procedures through divers monitoring.

BACKGROUND: Saturation diving is a standard method of intervention for commercial diving during offshore operations. Current saturation procedures achieve a high level of safety with regards to decompression sickness but still put the divers under multiple stressors: 1) Environmental stress (long confinement, heat/cold, dense gases, high oxygen levels), 2) Work stress (muscular fatigue, psychological pressure, breathing equipment, etc.), 3) venous gas emboli associated with decompression, 4) Inflammation related to oxidative stress and microparticles. We present the results of a saturation divers monitoring campaign performed in the North Sea Danish sector, on the Tyra field, during 2022. The study was supported by TotalEnergies, the field operator, and performed by Boskalis Subsea Services, the diving contractor, onboard the diving support vessel Boka Atlantis. The objective was twofold: document the level of diving stress during saturation operations in the Danish sector, and compare the performances of two saturation procedures, the Boskalis and the NORSOK procedures. MATERIALS AND METHODS: Fourteen divers volunteered for the study. The monitoring package include weight and temperature measurements, psychomotor tests (objective evaluation) and questionnaires (subjective evaluation), Doppler bubble detection and bioimpedance. The results were presented in a radar diagram that provides a general view of the situation. RESULTS: The data were analysed along 3 dimensions: work and environmental, desaturation bubbles, oxidative stress and inflammation. The results showed little or no variations from the reference values. No bubbles were detected after excursion dives and the final decompression, except for two divers with a grade 1 after arriving at surface. No statistical difference could be found between the Boskalis and the NORSOK saturation procedures. CONCLUSIONS: At a depth of 40-50 msw corresponding to the Danish sector, the two saturation procedures monitored induce no or little stress to the divers. The divers know how to manage their diet, equilibrate their hydration and pace their effort. Data available on divers' post saturation period show a recovery over the 24-48 hours following the end of the decompression. Further research should focus on diving deeper than 100 msw where a greater stress can be anticipated.

Quantifying global redundant fisheries trade to streamline seafood supply chains.

Seafood plays an important role in sustainably feeding the world and is one of the most traded food products globally. However sustainability improvements are often focused on its production (e.g., aquaculture, fishing) rather than trade. Here, we quantify the magnitude and extent of global 'redundant two-way' seafood trade-the exchange of the same quantity of the same taxonomic species between two countries-to examine its prevalence and potential implications across the seafood supply chain. We focused on wild-caught seafood trade and found that redundant two-way trade has increased by 43%, between 2000 and 2015, making up 3.2% (7.7 Mt) of global seafood trade during that period. Although most countries were involved in redundant two-way seafood trade (111 of 212 analyzed), the majority occurred between five trade partners: Canada and the United States (15%), Germany and the Netherlands (11.8%); Denmark and Sweden (10.6%); Germany and Denmark (7.1%); and France and Norway (7%). Nearly 50% of redundant trade is made up of just four species including Atlantic herring, Atlantic cod, Skipjack tuna and Atlantic mackerel. While deficiencies in global seafood trade data mask seasonal and product heterogeneity, redundant trade could have implications for meeting conservation and sustainable development goals. Future research should build upon these findings to explore specific environmental, economic, and social implications associated with redundant two-way trade to benefit producers and consumers within the seafood supply chain.

Adjusting the 15-method to Danish general practice: identification of barriers, facilitators, and user needs.

BACKGROUND: The 15-method is an opportunistic screening and brief intervention tool for alcohol-related problems in primary healthcare. A Danish feasibility study of the 15-method indicated that adjustments were needed to improve its contextual fit to Danish general practice. This adjustment process was conducted in two parts. The first part focused on identifying barriers, facilitators, and user needs for addressing alcohol using the 15-method. The second part will address the identified barriers and user needs to finalize a Danish version of the method. This study reports on part one of the adjustment process. METHODS: Semi-structured individual interviews and focus group interviews with healthcare professionals (n = 8) and patients (n = 5) from general practice in Denmark. Data analysis was conducted using thematic content analysis. The results were condensed into two focus areas that will form the basis for user workshops in part two of the adjustment process. RESULTS: The main barriers for addressing alcohol using the 15-method were patients and healthcare professionals not having the same agenda, having difficulty opening a conversation on alcohol, and workflow in the practices. Main facilitators included high interpersonal skills, taking the patient's perspective, and good routines and interdisciplinary work. Suggested adjustments and additions to the method included digitalization, visual icebreakers, quotes and examples, and development of a quick guide. The identified focus areas for user workshops were Communication and Material, and Integration to Workflows. CONCLUSION: Healthcare professionals found the opportunistic screening approach exemplified by the 15-method to be beneficial in identifying and addressing alcohol-related problems. They appreciate the method's structured framework that assists in presenting treatment options. Identified adjustment areas to the 15-method will lay the groundwork for future efforts to develop a finalized Danish version of the 15-method.

Nurses on shacking ground-A qualitative study of Danish dermatology and allergology nurses' experiences of relocation during the COVID-19 pandemic.

AIM: To investigate dermatology and allergology nurses' experiences of relocation from an outpatient clinic to a newly established COVID-19 infectious disease ward. DESIGN: A phenomenological-hermeneutical approach was applied. METHODS: Three focus groups with nurses were conducted from June to August 2020. Data were analysed in accordance with Ricoeur's theory of interpretation. RESULTS: The relocation represented a challenging period that involved uncertainty and evoked feelings of excitement and dedication towards the nursing profession. Nurses felt obligated to help; however, they also experienced that they did not have a say in the relocation. The placement on the infectious disease ward was characterized by adaptations in three areas: unfamiliar working environment, unfamiliar team competencies and inadequate nursing training. E-learning training was experienced as insufficient, as it did not enhance the nurses' specific competencies or confidence in caring for patients with COVID-19. CONCLUSION: The relocation of nurses from an outpatient clinic to a new COVID-19 infectious disease ward created a dilemma between nurses' sense of duty and their right to self-determination. A prompt relocation into a newly established unfamiliar field caused frustrations because there were no unspoken rules to rely on. Managers should take nurses' experiences and perceptions under careful consideration and strive for more involvement in future scenarios. PATIENT OR PUBLIC CONTRIBUTIONS: No patient or public contribution.

Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer's disease: a nationwide nested case-control study.

BACKGROUND: Patients with young onset Alzheimer's disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis. METHODS: In a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016-2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals. RESULTS: The study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05-1.31), increasing to 1.57 (95% CI 1.39-1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users. CONCLUSIONS: In this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD.

Inverse probability weighting for self-selection bias correction in the investigation of social inequality in mortality.

BACKGROUND: Empirical evaluation of inverse probability weighting (IPW) for self-selection bias correction is inaccessible without the full source population. We aimed to: (i) investigate how self-selection biases frequency and association measures and (ii) assess self-selection bias correction using IPW in a cohort with register linkage. METHODS: The source population included 17 936 individuals invited to the Copenhagen Aging and Midlife Biobank during 2009-11 (ages 49-63 years). Participants counted 7185 (40.1%). Register data were obtained for every invited person from 7 years before invitation to the end of 2020. The association between education and mortality was estimated using Cox regression models among participants, IPW participants and the source population. RESULTS: Participants had higher socioeconomic position and fewer hospital contacts before baseline than the source population. Frequency measures of participants approached those of the source population after IPW. Compared with primary/lower secondary education, upper secondary, short tertiary, bachelor and master/doctoral were associated with reduced risk of death among participants (adjusted hazard ratio [95% CI]: 0.60 [0.46; 0.77], 0.68 [0.42; 1.11], 0.37 [0.25; 0.54], 0.28 [0.18; 0.46], respectively). IPW changed the estimates marginally (0.59 [0.45; 0.77], 0.57 [0.34; 0.93], 0.34 [0.23; 0.50], 0.24 [0.15; 0.39]) but not only towards those of the source population (0.57 [0.51; 0.64], 0.43 [0.32; 0.60], 0.38 [0.32; 0.47], 0.22 [0.16; 0.29]). CONCLUSIONS: Frequency measures of study participants may not reflect the source population in the presence of self-selection, but the impact on association measures can be limited. IPW may be useful for (self-)selection bias correction, but the returned results can still reflect residual or other biases and random errors.

Perceptions of unilluminated occupations a survey of Danish occupational therapists.

BACKGROUND: In occupational therapy and -science positive aspects of occupation are highlighted. Recently, this discourse has been questioned, as it might leave out occupations - referred to as unilluminated occupations (UO) - that hold value to people, without fitting the positive ideal. AIM: To translate UO into Danish and to examine how occupational therapists (OTs) view and address UO. METHODS: A survey developed in USA was translated into Danish and distributed to OTs across Denmark. We added questions on the Danish wording of the concepts, including a content validity index (CVI). Data was subjected to a descriptive analysis. RESULTS: The respondents agreed that OTs must include examining the purpose and meaning of UO, however without having a responsibility to support performing these UO. The applied translation: high risk (risikable), unhealthy (usunde), unethical (uetiske), immoral (umoralske), and unacceptable (uacceptable) were deemed relevant in Danish, established by CVIs on 0.72-0.90. CONCLUSIONS AND SIGNIFICANCE: Although most respondents were positive towards examining and acknowledging clients' purpose and meaning of UO, no clear consensus when addressing UO in interventions was seen. Further research might shed light on ways to approach UO both in assessment and intervention. The Danish terms appeared relevant to encompass UO.

Screen Media Use and Mental Health of Children and Adolescents: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Excessive screen media use has been associated with poorer mental health among children and adolescents in several observational studies. However, experimental evidence supporting this hypothesis is lacking. Objective: To investigate the effects of a 2-week screen media reduction intervention on children's and adolescents' mental health. Design, Setting, and Participants: This prespecified secondary analysis of a cluster randomized clinical trial with a 2-week follow-up included 89 families (with 181 children and adolescents) from 10 Danish municipalities in the region of Southern Denmark. All study procedures were carried out in the home of the participants. Enrollment began on June 6, 2019, and ended on March 30, 2021. This analysis was conducted between January 1 and November 30, 2023. Intervention: Families were randomly allocated to a screen media reduction group or a control group. The 2-week screen media reduction intervention was designed to ensure a high level of compliance to the reduction in leisure-time screen media use. Participants allocated to the intervention group had to reduce their leisure-time screen media use to 3 hours per week or less per person and hand over smartphones and tablets. Main Outcomes and Measures: The main outcome was the between-group mean difference in change in total behavioral difficulties, measured by the Strengths and Difficulties Questionnaire at 2-week follow-up. Results were estimated using mixed-effects tobit regression models. Analyses were carried out as both intention to treat and complete case. Results: In the sample of 89 families including 181 children and adolescents (intervention group [45 families]: 86 children; mean [SD] age, 8.6 [2.7] years; 42 girls [49%]; control group [44 families]: 95 children; mean [SD] age, 9.5 [2.5] years; 57 girls [60%]), there was a statistically significant between-group mean difference in the total difficulties score, favoring the screen media reduction intervention (-1.67; 95% CI, -2.68 to -0.67; Cohen d, 0.53). The greatest improvements were observed for internalizing symptoms (emotional symptoms and peer problems; between-group mean difference, -1.03; 95% CI, -1.76 to -0.29) and prosocial behavior (between-group mean difference, 0.84; 95% CI, 0.39-1.30). Conclusions and Relevance: This secondary analysis of a randomized clinical trial found that a short-term reduction in leisure-time screen media use within families positively affected psychological symptoms of children and adolescents, particularly by mitigating internalizing behavioral issues and enhancing prosocial behavior. More research is needed to confirm whether these effects are sustainable in the long term. Trial Registration: ClinicalTrials.gov Identifier: NCT04098913.

Short-term and long-term stroke risk following SARS-CoV-2 infection in relation to disease severity: a Danish national cohort study.

OBJECTIVES: Studies have reported high incidences of stroke in patients hospitalised with SARS-CoV-2, but the impact of disease severity is unexplored. We aimed to estimate the risk of incident ischaemic stroke in SARS-CoV-2 test-positive individuals compared with test-negative individuals stratified by disease severity during acute infection and post infection. DESIGN: A register-based cohort study. SETTING: A Danish nationwide study. PARTICIPANTS: All Danish adults who had PCR tests for SARS-CoV-2 performed between 1 March 2020 and 30 November 2021. Test-positive individuals were included at their first positive test. For individuals tested prior to 30 November 2021, we randomly sampled an index date from the distribution of test dates among SARS-CoV-2 test-positive individuals. Test-positive individuals were followed during the acute phase of infection (days 0-14) and post infection (180 days after the acute phase). Test-negative individuals were followed in equivalent time periods. PRIMARY AND SECONDARY OUTCOME MEASURES: Incident ischaemic stroke risk in SARS-CoV-2 test-positive individuals compared with test-negative individuals during acute infection and post infection. We calculated subdistribution HRs (SHR) with death as a competing risk using propensity score weighting as confounder control. The risk was stratified according to disease severity: community managed, hospitalised, or admission to the intensive care unit. RESULTS: Among 3 910 219 SARS-CoV-2 PRC-tested individuals, 356 421 test-positive and 3 067 456 test-negative individuals were included. A positive SARS-CoV-2 test was associated with an SHR of 3.32 (95% CI 2.60 to 4.25) overall for stroke compared with test negative in the acute phase. In the postinfection period, the risk of stroke remained increased in individuals hospitalised during the acute phase (SHR 1.85, 95% CI 1.45 to 2.37). Individuals with community-managed SARS-CoV-2 had no increased long-term risk of stroke (SHR 1.01, 95% CI 0.88 to 1.16). CONCLUSION: SARS-CoV-2 infection is associated with increased stroke risk. Disease severity seems to be an important factor. Individuals with community-managed SARS-CoV-2 had no increased stroke risk.

Pregnancy As Window of Opportunity? A Danish RCT on Physical Activity During Pregnancy.

Pregnancy is seen as a window of opportunity for health interventions, with the potential to produce long-term health changes for mother and child. The RCT FitMum investigates the effects of different regimes of physical activity during pregnancy. We suggest that rather than hitting a window of opportunity, the trial works in choreography with different timescapes through the processes of management of time. These timescapes are characterized by linear progression and futurity, alongside composite, complex time. We reconceptualize the intervention as a navigation of flows and passages in collective efforts, providing a situated and sustainable approach to interventions.

Making it Work: Everyday Life and Healthcare with Multiple Chronic Illnesses in Denmark.

A growing concern in clinical literature with the "treatment burden" of living with multimorbidity raises questions about how we can study and produce knowledge on the impact of health care. In this article, we draw on ethnographic material from fieldwork among people with multimorbidity in Denmark and recent theorization on "values" in health care, to show how an ongoing "trying out" and ways of "just getting on with it" are enacted in illness trajectories marked by multimorbidity. Our findings point to the importance of attending to the subject positions that particular healthcare relations and encounters make possible.

Deprescribing as a Way to Reduce Inappropriate Use of Drugs for Overactive Bladder in Primary Care (DROP): Protocol for a Cluster Randomized Controlled Trial With an Embedded Explanatory Sequential Mixed Methods Study.

BACKGROUND: Potentially inappropriate medication remains a significant concern in general practices, particularly in the context of overactive bladder (OAB) treatment for individuals aged 65 years and older. This study focuses on the exploration of alternative options for treating OAB and the deprescribing of anticholinergic drugs commonly used in OAB. The research aims to comprehensively evaluate the efficiency of deprescribing through a mixed methods approach, combining quantitative assessment and qualitative exploration of perceptions, experiences, and potential barriers among patients and health care personnel. OBJECTIVE: This study aims to evaluate the efficiency and safety of the intervention in which health care staff in primary care encourage patients to participate in deprescribing their drugs for OAB. In addition, we aim to identify factors contributing to or obstructing the deprescribing process that will drive more informed decisions in the field of deprescribing and support effective and safe treatment of patients. METHODS: The drugs for overactive bladder in primary care (DROP) study uses a rigorous research design, using a randomized controlled trial (RCT) with an embedded sequential explanatory mixed methods approach. All general practices within the North Denmark Region will be paired based on the number of general practitioners (GPs) and urban or rural locations. The matched pairs will be randomized into intervention and control groups. The intervention group will receive an algorithm designed to guide the deprescribing of drugs for OAB, promoting appropriate medication use. Quantitative data will be collected from the RCT including data from Danish registries for prescription analysis. Qualitative data will be obtained through interviews and focus groups with GPs, staff members, and patients. Finally, the quantitative and qualitative findings are merged to understand deprescribing for OAB comprehensively. This integrated approach enhances insights and supports future intervention improvement. RESULTS: The DROP study is currently in progress, with randomization of general practices underway. While they have not been invited to participate yet, they will be. The inclusion of GP practices is scheduled from December 2023 to April 2024. The follow-up period for each patient is 6 months. Results will be analyzed through an intention-to-treat analysis for the RCT and a thematic analysis for the qualitative component. Quantitative outcomes will focus on changes in prescriptions and symptoms, while the qualitative analysis will explore experiences and perceptions. CONCLUSIONS: The DROP study aims to provide an evidence-based intervention in primary care that ensures the deprescription of drugs for OAB when there is an unfavorable risk-benefit profile. The DROP study's contribution lies in generating evidence for deprescribing practices and influencing best practices in health care. TRIAL REGISTRATION: ClinicalTrials.gov NCT06110975; https://clinicaltrials.gov/study/NCT06110975. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56277.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort.

BACKGROUND: The prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth. METHODS: We analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features. RESULTS: We detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e - 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels. CONCLUSIONS: Cyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

Exploring the course of functional somatic symptoms (FSS) from pre- to late adolescence and associated internalizing psychopathology - an observational cohort-study.

BACKGROUND: Functional somatic symptoms (FSS), which commonly cannot be attributed to well-defined organic pathology, often co-occur with internalizing psychopathology and fluctuate throughout different life stages. We examined FSS courses throughout adolescence, and the association between preadolescent FSS, FSS severity and internalizing psychopathology at late adolescence. METHODS: Data from the Copenhagen Child Cohort (CCC2000) were utilized from assessments at ages 11-12 years (preadolescence; T0) and 16-17 years (late adolescence; T1). Self-report questionnaire and interview data on FSS, internalizing psychopathology, chronic medical conditions, and sociodemographic data from Danish national registers were available for 1285 youths. FSS courses were categorized into persistent (high FSS at T0 & T1), remission (high FSS only at T0), incident (high FSS only at T1) or no FSS (no FSS at T0 & T1). Multiple linear and multinomial logistic regressions were conducted to investigate the FSS/psychopathology association. RESULTS: 1.8% of adolescents fell into the persistent FSS course group throughout adolescence. Higher preadolescent FSS predicted FSS (b = 0.07, p < .001), anxiety (b = 0.05, p < .001) and depression (b = 0.06, p < .001) at age 16/17, even after controlling for sex, parental education, a chronic medical condition and internalizing psychopathology in preadolescence. Persistent, incident, and remittent FSS courses were associated with significantly higher mean levels of anxiety and depression compared to the reference group (no FSS). CONCLUSIONS: FSS during pre- and late adolescence might increase and co-occur with anxiety and depression throughout adolescence, potentially due to shared underlying risk factors and processes.