Missingness mechanisms and generalizability of patient reported outcome measures in colorectal cancer survivors - assessing the reasonableness of the "missing completely at random" assumption.

BACKGROUND: Patient-Reported Outcome Measures (PROM) provide important information, however, missing PROM data threaten the interpretability and generalizability of findings by introducing potential bias. This study aims to provide insight into missingness mechanisms and inform future researchers on generalizability and possible methodological solutions to overcome missing PROM data problems during data collection and statistical analyses. METHODS: We identified 10,236 colorectal cancer survivors (CRCs) above 18y, diagnosed between 2014 and 2018 through the Danish Clinical Registries. We invited a random 20% (2,097) to participate in a national survey in May 2023. We distributed reminder e-mails at day 10 and day 20, and compared Initial Responders (response day 0-9), Subsequent Responders (response day 10-28) and Non-responders (no response after 28 days) in demographic and cancer-related characteristics and PROM-scores using linear regression. RESULTS: Of the 2,097 CRCs, 1,188 responded (57%). Of these, 142 (7%) were excluded leaving 1,955 eligible CRCs. 628 (32%) were categorized as initial responders, 418 (21%) as subsequent responders, and 909 (47%) as non-responders. Differences in demographic and cancer-related characteristics between the three groups were minor and PROM-scores only marginally differed between initial and subsequent responders. CONCLUSION: In this study of long-term colorectal cancer survivors, we showed that initial responders, subsequent responders, and non-responders exhibit comparable demographic and cancer-related characteristics. Among respondents, Patient-Reported Outcome Measures were also similar, indicating generalizability. Assuming Patient-Reported Outcome Measures of subsequent responders represent answers by the non-responders (would they be available), it may be reasonable to judge the missingness mechanism as Missing Completely At Random.

Incidence and survival of primary metastatic breast cancer in Denmark; implication of breast cancer screening, classification, and staging practice.

BACKGROUND: Primary metastatic breast cancer (pMBC) accounts for 5-10% of annual breast cancers with a median survival of 3-4 years, varying among subtypes. In Denmark, the incidence of breast cancer increased until 2010, followed by a stabilisation. Several factors influencing pMBC incidence and survival, including screening prevalence, staging methods, and classification standards, remain pivotal but inadequately documented. MATERIAL AND METHOD: This retrospective observational study involving pMBC patients diagnosed between 2000 and 2020 encompassed all Danish oncology departments. Data from the Danish Breast Cancer Group database and the National Patient Register included diagnosis specifics, demographics, treatment, and follow-up. RESULTS: Between 2000 and 2020, 3,272 patients were diagnosed with pMBC, a rise from 355 patients in 2000-2004 to 1,323 patients in 2015-2020. The increase was particularly observed in patients aged 70 years or older. Changes in tumour subtypes were observed, notably with a rise in human epidermal growth factor receptor 2 (HER2)-positive cases but a steady distribution of estrogen receptor (ER) status. Diagnostic practices changed over the two decades, with 6% evaluated with PET/CT (positron emission tomography-computed tomography) or CT (computed tomography) with a bone evaluation in 2000-2004 and 65% in 2015-2020. Overall survival (OS) improved from 23 months in 2000-2004 to 33 months in 2015-2020. In patients with ER-positive and HER2-positive disease, the multivariable model showed improved survival by year of diagnosis, and further, patients with ER-negative/HER2-negative disease fared worse the first 2 years after diagnosis. INTERPRETATION: Our study delineates changes in the treatment and survival of pMBC over two decades. Stage migration, screening introduction, and changes in registration practice, however, prevent a valid assessment of a possible causal relationship.

Treatment-related mortality among children with cancer in Denmark during 2001-2021.

BACKGROUND: Survival of children with cancer has markedly improved over recent decades, largely due to intensified treatment regimes. The intensive treatment may, however, result in fatal complications. In this retrospective cohort study, we assessed temporal variation in the incidence of treatment-related death and associated risk factors among children diagnosed with cancer in Denmark during 2001-2021. METHOD: Among all children diagnosed with first incident cancer before age 15 years recorded in the Danish Childhood Cancer Register (n = 3,255), we estimated cumulative incidence of treatment-related death (death in the absence of progressive cancer) within 5 years from diagnosis using Aalen-Johansen estimators and assessed associated risk factors using Cox regression. RESULTS: Among all 3,255 children with cancer, 93 (20% of all 459 deaths) died from treatment. Of these treatment-related deaths, 39 (42%) occurred within 3 months of diagnosis. The 5-year cumulative incidences of treatment-related death were 3.3% during 2001-2010 and 2.5% during 2011-2021 (p = 0.20). During 2011-2021, treatment-related deaths accounted for more than half of all deaths among children with haematological cancers. Risk factors varied according to cancer group and included female sex, age below 1 year at diagnosis, disease relapse, stem cell transplantation, central nervous system involvement, and metastasis at diagnosis. INTERPRETATION: Despite increasing treatment intensities, the incidence of treatment-related death has remained stable during the past 20 years in Denmark. Still, clinical attention is warranted to prevent treatment-related deaths, particularly among children with haematological cancers. Patient characteristics associated with increased treatment-related death risk support patient-specific treatment approaches to avoid these fatalities.

Implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting.

BACKGROUND AND PURPOSE: Length of hospital stay after hip and knee arthroplasty is about 1 day in Denmark with few patients discharged on the day of surgery. Hence, a protocol for multicenter implementation of discharge on day of surgery has been instituted. We aimed to describe the implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting. METHODS: We performed a prospective multicenter study from 7 public hospitals across Denmark. Patients were screened using well-defined in- and exclusion criteria and were discharged on day of surgery when fulfilling functional discharge criteria. The study period was from September 2022 to February 2023 with variable start of implementation. Data from the same centers in a 6-month period before the COVID pandemic from July 2019 to December 2019 was used for baseline control. RESULTS: Of 2,756 primary hip and knee arthroplasties, 37% (95% confidence interval [CI] 35-39) were eligible (range 21-50% in centers) and 52% (range 24-62%) of these were discharged on day of surgery. 21% (CI 20-23) of all patients (eligible and non-eligible) were discharged on day of surgery with a range of 10-31% within centers. This was an additional 15% (CI 13-17, P < 0.001) compared with patients discharged in the control period (6% in 2019). CONCLUSION: We found it possible to perform outpatient hip and knee replacement in 21% of patients in a public healthcare setting, probably to be increased with further center experience.

Dividing time-An absolute chronological study of material culture from Early Iron Age urnfields in Denmark.

Chronological frameworks based on artefact typologies are essential for interpreting the archaeological record, but they inadvertently treat transitions between phases as abrupt events and disregard the temporality of transformation processes within and between individual phases. This study presents an absolute chronological investigation of a dynamic material culture from Early Iron Age urnfields in Denmark. The chronological framework of Early Iron Age in Southern Scandinavia is largely unconstrained by absolute dating, primarily due to it coinciding with the so-called 'Hallstatt calibration plateau' (c.750 to 400 cal BC), and it is difficult to correlate it with Central European chronologies due to a lack of imported artefacts. This study applies recent methodological advances in radiocarbon dating and Bayesian chronological modelling, specifically a statistical model for wood-age offsets in cremated bone and presents the first large-scale radiocarbon investigation of regional material culture from Early Iron Age in Southern Jutland, Denmark. Dated material is primarily cremated bone from 111 cremation burials from three urnfields. The study presents absolute date ranges for 16 types of pottery and 15 types of metalwork, which include most of the recognised metalwork types from the period. This provides new insights into gradual change in material culture, when certain artefact types were in production and primary use, how quickly types were taken up and later abandoned, and distinguishing periods of faster and slower change. The study also provides the first absolute chronology for the period, enabling correlation with chronologies from other regions. Urnfields were introduced at the Bronze-Iron Age transformation, which is often assumed to have occurred c.530-500 BC. We demonstrate that this transformation took place in the 7th century BC, however, which revives the discussion of whether the final Bronze Age period VI should be interpreted as a transitional phase to the Iron Age.

Analysis of traumatic event emergency department visits among care home residents aged 65 + years in Southern Jutland, Denmark: implications for comprehensive care and subsequent hospital admissions - a register-based cohort study.

BACKGROUND: Care home residents aged 65 + years frequently experience acute health issues, leading to emergency department visits. Falls and associated injuries are a common cause of these visits and falls in a geriatric population can be a symptom of an incipient acute illness such as infection. Conversely, the traumatic event can cause illnesses to arise due to consequences of the fall, e.g. delirium or constipation due to opioid use. We hypothesised that a traumatic event treat-and-release emergency department visit serves as an indicator for an upcoming acute hospital admission due to non-trauma-related conditions. METHODS: We studied emergency department visits for traumatic events among all care home residents aged 65+ (n = 2601) living in Southern Jutland, Denmark, from 2018 to 2019. Data from highly valid national registers were used to evaluate diagnoses, mortality, and admissions. Cox Regression was used to analyse the hazard of acute hospital admission following an emergency department treat-and-release visit. RESULTS: Most visits occurred on weekdays and during day shifts, and 72.0% were treated and released within 6 h. Contusions, open wounds, and femur fractures were the most common discharge diagnoses, accounting for 53.3% of all cases (n = 703). In-hospital mortality was 2.3%, and 30-day mortality was 10.4%. Among treat-and-release visits (n = 506), 25% resulted in a new hospital referral within 30 days, hereof 13% treat-and-release revisits (duration ≤ 6 h), and 12% hospital admissions (duration > 6 h). Over half (56%) of new hospital referrals were initiated within the first seven days of discharge. Almost three-fourths of subsequent admissions were caused by various diseases. The hazard ratio of acute hospital admissions was 2.20 (95% CI: 1.52-3.17) among residents with a recent traumatic event treat-and-release visit compared to residents with no recent traumatic event treat-and-release visit. CONCLUSION: Traumatic event treat-and-release visits among care home residents serve as an indicator for subsequent hospitalisations, highlighting the need for a more comprehensive evaluation, even for minor injuries. These findings have implications for improving care, continuity, and resource utilisation. TRIAL REGISTRATION: Not relevant.

Rethinking organizational culture in intersectoral coordination: the perspective of boundary work.

PURPOSE: The purpose of this paper is to rethink the concept of organizational culture as something that emerges bottom-up by using the sociological concepts of boundary object and boundary work as an analytical lens and to show how this approach can help understand and facilitate intersectoral coordination. DESIGN/METHODOLOGY/APPROACH: We used observations and qualitative interviews to develop "deep" knowledge about processes of intersectoral coordination. The study draws on a conceptual framework of "boundary work" and "boundary objects" to show how a bottom-up perspective on organizational culture can produce better understanding of and pave the way for intersectoral coordination. We use a case of health professionals engaged in two Danish intersectoral programs developing and providing health promotion services for women with gestational diabetes mellitus (GDM). FINDINGS: The study showed how boundary work revolves around negotiations on how to define, understand and act on the diagnosis of GDM. This diagnosis has the characteristics of a "boundary object", being more loosely structured in general terms, but strongly structured in local settings. Boundary objects help connect different professionals and facilitate coordination. The analysis showed how the introduction of time and the concept of "lifelong health promotion" helped to transgress existing organizational and professional boundaries. RESEARCH LIMITATIONS/IMPLICATIONS: The findings contribute to the literature on organizational culture and intersectoral coordination. We highlight the benefits of a practice-oriented, bottom-up perspective for a better understanding of how shared meaning is produced in cross professional coordination and collaboration. While the theoretical implications will be general applicable when studying organizational culture, the implications for practice are sensitive to context and the processes we have described as the outcomes of boundary work are generated from cases that were most likely to provide deep insight into our research topic. PRACTICAL IMPLICATIONS: For practice this can build bridges between organizational and professional boundaries. ORIGINALITY/VALUE: The findings contribute to the literature on organizational culture and intersectoral coordination. We highlight the benefits of a practice-oriented, bottom-up perspective for a better understanding of how shared meaning is produced in cross professional coordination. This may build bridges between organizational and professional boundaries in practice settings.

Pre-exposure prophylaxis against HIV infection.

Pre-exposure prophylaxis (PrEP) decreases the risk for HIV transmission in high-risk populations. PrEP has been available in Denmark since 2019 and consists of antiretroviral drugs in a combination tablet taken daily or on demand. The effect of this prophylaxis in Denmark is summarized in the review. PrEP is indicated in men and transgender persons with unprotected anal intercourse with multiple male partners in the latest 12 weeks or recent diagnoses of syphilis, chlamydia, or gonorrhoea. PrEP is provided by infectious disease specialists. Continued implementation could significantly reduce HIV transmission and potentially end the epidemic in Denmark.

Self-reported systemic symptoms among women with breast implants.

Around 2,500 women receive a breast augmentation with silicone-based implants yearly in Denmark. A number of these women report various uncharacteristic systemic symptoms, which they attribute to the breast implants, including impaired cognition, joint pain, etc. This condition has been termed "breast implant illness" and is currently not a recognised diagnosis. The correlation between the patient's self-reported symptoms and breast implants has not been established and there is limited evidence that surgery has any effect. In this review, the current literature on the topic has been reviewed.

Mortality after paediatric emergency calls for patients with or without pre-existing comorbidity: a nationwide population based cohort study.

BACKGROUND: Life-threatening conditions are infrequent in children. Current literature in paediatric prehospital research is centred around trauma and paediatric out-of-hospital cardiac arrests (POHCA). The aims of this study were to (1) outline the distribution of trauma, POHCA or other medical symptoms among survivors and non-survivors after paediatric emergency calls, and (2) to investigate these clinical presentations' association with mortality in children with and without pre-existing comorbidity, respectively. METHODS: Nationwide population-based cohort study including ground and helicopter emergency medical services in Denmark for six consecutive years (2016-2021). The study included all calls to the emergency number 1-1-2 regarding children ≤ 15 years (N = 121,230). Interhospital transfers were excluded, and 1,143 patients were lost to follow-up. Cox regressions were performed with trauma or medical symptoms as exposure and 7-day mortality as the outcome, stratified by 'Comorbidity', 'Severe chronic comorbidity' and 'None' based on previous healthcare visits. RESULTS: Mortality analysis included 76,956 unique patients (median age 5 (1-12) years). Annual all-cause mortality rate was 7 per 100,000 children ≤ 15 years. For non-survivors without any pre-existing comorbidity (n = 121), reasons for emergency calls were trauma 18.2%, POHCA 46.3% or other medical symptoms 28.9%, whereas the distribution among the 134 non-survivors with any comorbidity was 7.5%, 27.6% and 55.2%, respectively. Compared to trauma patients, age- and sex-adjusted hazard ratio for patients with calls regarding medical symptoms besides POHCA was 0.8 [0.4;1.3] for patients without comorbidity, 1.1 [0.5;2.2] for patients with comorbidity and 6.1 [0.8;44.7] for patients with severe chronic comorbidity. CONCLUSION: In both non-survivors with and without comorbidity, a considerable proportion of emergency calls had been made because of various medical symptoms, not because of trauma or POHCA. This outline of diagnoses and mortality following paediatric emergency calls can be used for directing paediatric in-service training in emergency medical services.

A Reanalysis of Mental Disorders Risk Following First-Trimester Abortions in Denmark.

Background: A previous Danish study of monthly and tri-monthly rates of first-time psychiatric contact following first induced abortions reported higher rates compared to first live births but similar rates compared to nine months pre-abortion. Therefore, the researchers concluded abortion has no independent effect on mental health; any differences between psychiatric contacts after abortion and delivery are entirely attributable to pre-existing mental health differences. However, these conclusions are inconsistent with similar studies that used longer time frames. Reanalysis of the published Danish data over slightly longer time frames may reconcile this discordance. Method: Monthly and tri-monthly data was extracted for reanalysis of cumulative effects over nine- and twelvemonths post-abortion. Results: Across all psychiatric diagnoses, cumulative average monthly rate of first-time psychiatric contact increased from an odds ratio of 1.12 (95% CI: 1.02 to 1.22) at 9-months to 1.49 (95% CI: 1.37 to 1.63) at 12 months post-abortion as compared to the 9 months pre-abortion rate. At 12 months post-abortion, first-time psychiatric contact was higher across all four diagnostic groupings and highest for personality or behavioral disorders (OR=1.87; 95% CI:1.48 to 2.36) and neurotic, stress related, or somatoform disorders (OR=1.60; 95% CI: 1.41 to 1.81). Conclusions: Our reanalysis revealed that the Danish data is consistent with the larger body of both record-based and survey- based studies when viewed over periods of observation of at least nine months. Longer periods of observation are necessary to capture both anniversary reactions and the exhaustion of coping mechanisms which may delay observation of post-abortion effects.

Association of Antithrombotic Drug Use With Incident Intracerebral Hemorrhage Location.

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.

Identification of patients' smoking status using an explainable AI approach: a Danish electronic health records case study.

BACKGROUND: Smoking is a critical risk factor responsible for over eight million annual deaths worldwide. It is essential to obtain information on smoking habits to advance research and implement preventive measures such as screening of high-risk individuals. In most countries, including Denmark, smoking habits are not systematically recorded and at best documented within unstructured free-text segments of electronic health records (EHRs). This would require researchers and clinicians to manually navigate through extensive amounts of unstructured data, which is one of the main reasons that smoking habits are rarely integrated into larger studies. Our aim is to develop machine learning models to classify patients' smoking status from their EHRs. METHODS: This study proposes an efficient natural language processing (NLP) pipeline capable of classifying patients' smoking status and providing explanations for the decisions. The proposed NLP pipeline comprises four distinct components, which are; (1) considering preprocessing techniques to address abbreviations, punctuation, and other textual irregularities, (2) four cutting-edge feature extraction techniques, i.e. Embedding, BERT, Word2Vec, and Count Vectorizer, employed to extract the optimal features, (3) utilization of a Stacking-based Ensemble (SE) model and a Convolutional Long Short-Term Memory Neural Network (CNN-LSTM) for the identification of smoking status, and (4) application of a local interpretable model-agnostic explanation to explain the decisions rendered by the detection models. The EHRs of 23,132 patients with suspected lung cancer were collected from the Region of Southern Denmark during the period 1/1/2009-31/12/2018. A medical professional annotated the data into 'Smoker' and 'Non-Smoker' with further classifications as 'Active-Smoker', 'Former-Smoker', and 'Never-Smoker'. Subsequently, the annotated dataset was used for the development of binary and multiclass classification models. An extensive comparison was conducted of the detection performance across various model architectures. RESULTS: The results of experimental validation confirm the consistency among the models. However, for binary classification, BERT method with CNN-LSTM architecture outperformed other models by achieving precision, recall, and F1-scores between 97% and 99% for both Never-Smokers and Active-Smokers. In multiclass classification, the Embedding technique with CNN-LSTM architecture yielded the most favorable results in class-specific evaluations, with equal performance measures of 97% for Never-Smoker and measures in the range of 86 to 89% for Active-Smoker and 91-92% for Never-Smoker. CONCLUSION: Our proposed NLP pipeline achieved a high level of classification performance. In addition, we presented the explanation of the decision made by the best performing detection model. Future work will expand the model's capabilities to analyze longer notes and a broader range of categories to maximize its utility in further research and screening applications.

Cancer-related pain experienced in daily life is difficult to communicate and to manage - for patients and for professionals.

OBJECTIVES: The aim of this study was to gain qualitative insight into cancer patients' experiences, explanations, and management strategies regarding their cancer-related pain (CP). METHODS: Seventeen patients with CP were interviewed using a semi-structured interview approach. Braun and Clarke's thematic analysis method was used to analyze the transcribed interviews. The patients all participated in cancer rehabilitation courses arranged by the research clinic at The Danish Knowledge Centre for Rehabilitation and Palliative Care. RESULTS: Three themes were identified: (1) Explaining CP: Patients found it difficult to explain how they experienced their pain. They lacked words, and they frequently used invasive metaphors such as "Pain feels like a heart attack" (2). Strategies and barriers to the management of CP: Initiatives provided by healthcare professionals (HCPs) were perceived as insufficient, and the patients missed guidance in both pharmacological and non-pharmacological approaches to pain management. Several saw medicine as unnatural for their body, and they focused on side effects and the medicine affecting their quality of life. (3) Responsibility for managing CP: A lack of responsiveness from the HCPs and taking on responsibility for pain management were experienced by several of the patients. The patients expressed uncertainty about whom to contact for help with the management of their CP. CONCLUSION: The patients' difficulties in explaining, understanding, and communicating their pain and pain management contributed to insufficient pain management. They were also uncertain about who had the responsibility to help them to achieve pain relief. These results share the evidence drawn from studies on patients with chronic non-cancer pain. This qualitative study highlights the need for having more focus on a common language and shared understanding between patients and HCPs. It also underpins the importance of HCPs to assume their responsibility to help patients manage their pain conditions.

Follow-Up Study of Effectiveness of 23-Valent Pneumococcal Polysaccharide Vaccine Against All-Type and Serotype-Specific Invasive Pneumococcal Disease, Denmark.

As a follow-up to a previous study, we investigated vaccine effectiveness (VE) of 23-valent pneumococcal polysaccharide vaccine (PPSV23) against invasive pneumococcal disease (IPD) among 1,254,498 persons >65 years of age as part of a vaccination program in Denmark during April 2020-January 2023. We assessed VE by using a Cox regression model and adjusted for age, sex, and underlying conditions. Using nationwide data, we estimated a VE of PPSV23 against all-type IPD of 32% and against PPSV23-serotype IPD of 41%. Because this follow-up study had more statistical power than the original study, we also estimated VE against IPD caused by PPSV23-serotypes excluding serotype 3; serotype 3; serotype 8; serotype 22F; PPSV23 non-PCV15 serotypes; PPSV23 non-PCV20 serotypes; and IPD over time. Our findings suggest PPSV23 vaccination can protect persons >65 years of age against IPD caused by all serotypes or serotype groupings, except serotype 3.

Correlation of drug dose estimated from national prescription registers with mean blood level of antiseizure medication in pregnancy.

PURPOSE: The purpose was to examine the correlation of antiseizure medication drug dose estimated from prescription fill records from prescription registers with blood levels during pregnancy. METHODS: We conducted a Nation-wide study of mothers who gave birth in Denmark between 1 January 2014 and 31 December 2018 using data from Danish Prescription and Laboratory Registers. We identified mothers with blood level measurements of antiseizure medication. The main exposure was estimated antiseizure medication dosage estimated from pregnancy-filled prescriptions in the Danish Prescription Register. The main outcome was the correlation of estimated dose with mean blood level of antiseizure medication in pregnancy. For privacy reasons, the number of blood level measurement and prescription fills were rounded to nearest 10, but proportions reported as exact values. RESULTS: Among 298 560 pregnancies, we identified pregnancies with recorded prescription fill from the prescription register for valproate (N = 90), lamotrigine (N = 1360), levetiracetam (N = 340), topiramate (N = 100), and carbamazepine (N = 60). In these pregnancies, blood level measurements were available in 50 (53%) pregnancies for valproate, 850 (62%) pregnancies for lamotrigine, 320 (93%) pregnancies for levetiracetam, 50 (68%) pregnancies for carbamazepine, and 40 (35%) pregnancies for topiramate. Pearsons's correlation coefficients for the correlation of estimated antiseizure medication dose with mean blood levels were 0.67 (p < 0.0001) for valproate, 0.63 (p < 0.0001) for lamotrigine, 0.63 (p < 0.0001) for levetiracetam, 0.76 (<0.0001) for carbamazepine and 0.89 (<0.0001) for topiramate. CONCLUSIONS: Dose of antiseizure medication estimated from prescription fills was a good proxy for blood levels and thus for biological exposure in pregnancy, suggesting that administrative prescription fill records may be a valuable resource for estimating exposure to antiseizure medication in pregnancy.

Compassionate Communication and Advance Care Planning to improve End-of-life Care in Treatment of Haematological Disease 'ACT': Study Protocol for a Cluster-randomized trial.

INTRODUCTION: To support the implementation of advance care planning and serious illness conversations in haematology, a previously developed conversation intervention titled 'Advance Consultations Concerning your Life and Treatment' (ACT) was found feasible. This study aims to investigate the effect of ACT on the quality of end-of-life care in patients with haematological malignancy and their informal caregivers. METHODS AND ANALYSIS: The study is a nationwide 2-arm cluster randomised trial randomising 40 physician-nurse clusters across seven haematological departments in Denmark to provide standard care or ACT intervention. A total of 400 patients with haematological malignancies and their informal caregivers will be included. The ACT intervention includes an ACT conversation that centres on discussing the patient's prognosis, worries, hopes and preferences for future treatment. The intervention is supported by clinician training and supervision, preparatory materials for patients and informal caregivers, and system changes including dedicated ACT-conversation timeslots and templates for documentation in medical records.This study includes two primary outcomes: (1) the proportion of patients receiving chemotherapy within the last 30 days of death and (2) patients' and informal caregivers' symptoms of anxiety (General Anxiety Disorder-7) at 3 6, 9, 12 and 18 months follow-up. Mixed effects models accounting for clusters will be used. ETHICS AND DISSEMINATION: The Declaration of Helsinki and the European GDPR regulations as practised in Denmark are followed through all aspects of the study. Findings will be made available to the participants, patient organisations, funding bodies, healthcare professionals and researchers at national and international conferences and through publication in peer-reviewed international journals. REGISTRATION DETAILS: The study is registered at ClinicalTrials.gov (NCT05444348). The Regional Ethics Committee of the Capital Region of Denmark (record no: 21067634) has decided that approval is not necessary as per Danish legislation. Study approval has been obtained from The Capital Region of Denmark Data Protection Agency (record no: P-2022-93). TRIAL REGISTRATION NUMBER: NCT05444348.

Utility of data from the Danish National School Test Program for health research purposes: Content and associations with sociodemographic factors and higher education.

The Danish National School Test Program is a set of nationwide tests performed annually since 2010 in all public schools in Denmark. To assess the utility of this data resource for health research purposes, we examined the association of school test performance with demographic and socioeconomic characteristics as well as correlations with ninth-grade exams and higher educational attainment. This nationwide descriptive register-based study includes children born between 1994 and 2010 who lived in Denmark at the age of six years. Norm-based test scores (range 1-100, higher scores indicate better performance) in reading (Danish) and mathematics from the Danish National School Test Program were obtained for children aged 6-16 attending public schools in Denmark from 2010 to 2019. Population registers were used to identify relevant demographic and socioeconomic variables. Mean test scores by demographic and socioeconomic variables were estimated using linear regression models. Among the full Danish population of 1,137,290 children (51.3% male), 960,450 (84.5%) children attended public schools. There were 885,360 children who completed one or more tests in reading or mathematics (test participation was 77.8% for the entire population, and 92.1% for children in public schools). Mean test scores varied by demographic and socioeconomic characteristics, most notably with education and labour market affiliation of parents. For every 1-point decrease in the test scores, there was a 0.95% (95% CI: 0.93%; 0.97%) lower probability of scoring B or higher in the ninth-grade exam and a 1.03% (95% CI: 1.00%; 1.05%) lower probability of completing high school within five years after graduating from lower secondary school. In this study of schoolchildren in Denmark, demographic and socioeconomic characteristics were associated with test scores from the Danish National School Test Program. Performance in school tests correlated closely with later educational attainment, suggesting that these early measures of school performance are good markers of subsequent academic potential.

Employment Status Following Heart Transplantation: Data From the Danish Nationwide Social Service Payment Register During 20 years.

Most studies on vocational rehabilitation after heart transplantation (HTX) are based on self-reported data. Danish registries include weekly longitudinal information on all public transfer payments. We intended to describe 20-year trends in employment status for the Danish heart-transplant recipients, and examine the influence of multimorbidity and socioeconomic position (SEP). Linking registry and Scandiatransplant data (1994-2018), we conducted a study in recipients of working age (19-63 years). The cohort contained 492 recipients (79% males) and the median (IQR) age was 52 years (43-57 years). Five years after HTX, 30% of the survived recipients participated on the labor market; 9% were in a flexible job with reduced health-related working capacity. Moreover, 60% were retired and 10% eligible for labor market participation were unemployed. Recipients with multimorbidity had a higher age and a lower prevalence of employment. Five years after HTX, characteristics of recipients with labor market participation were: living alone (27%) versus cohabitation (73%); low (36%) versus medium-high (64%) educational level; low (13%) or medium-high (87%) income group. Heart-transplant recipients with multimorbidity have a higher age and a lower prevalence of employment. Socioeconomically disadvantaged recipients had a lower prevalence of labor market participation, despite being younger compared with the socioeconomically advantaged.

Medicalization of Old Age: Experiencing Healthism and Overdiagnosis in a Nordic Welfare State.

In Denmark, people are expected to take responsibility for their health, not least as their bodies age and they experience signs of physical or mental decline. Drawing on fieldwork among older Danes, I illustrate that an excessive focus on health gives rise to social and structural controversies and disparities, linking ideas of healthy behavior at the individual level with the societal framing of disease and aging. I argue that this emphasis contributes to the unwarranted diagnosis of bodily variations that naturally occur in the aging process, a phenomenon referred to as overdiagnosis, adding to a broader medicalization of old age.