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Purpose: The Danish National Patient Registry (DNPR) is recognized for providing high-quality data. However, only a few minor studies have validated inflammatory bowel disease (IBD) diagnoses in the DNPR, reporting various degrees of validity. To pave the way for large-scale studies of IBD in Denmark, we aimed to investigate the validity of IBD among >8000 patients registered in the DNPR between 2002 and 2020 in the North Denmark Region. Patients and Methods: To evaluate the reliability of the diagnoses in the DNPR, we initially compared all patients registered with one IBD diagnosis during 2002-2020 to a list of already verified patients in the regional IBD database GASTROBIO. Medical records on all DNPR registered patients not on the list were manually reviewed by a gastroenterologist to verify or dismiss the IBD diagnosis. Positive predictive values (PPV) were calculated. Results: Of 8040 patients with at least one IBD diagnosis in DNPR, 5263 were already confirmed cases, leaving 2777 for medical record evaluation, of whom 849 had IBD. In total, 6112 were correctly registered with IBD based on one diagnosis, and 1343 were incorrectly registered, resulting in a PPV of 0.82 (95% CI, 0.81-0.83). For patients registered with at least two diagnoses, the PPV was 0.95 (95% CI, 0.95-0.96), and with at least three diagnoses, the PPV was 0.98 (95% CI, 0.98-0.99). Results were similar for UC and CD separately. Of note, the completeness of valid cases went from 6112 to 4606 (75%; 95% CI, 74%-76%) when demanding at least two registered diagnoses and to 3320 (54%; 95% CI, 53%-56%) when demanding at least three registered diagnoses. Conclusion: Reassuringly, the validity of IBD diagnoses in DNPR is high, especially for patients registered more than once. However, the reduced completeness when applying a true case definition of at least two registered diagnoses should be considered. Keywords: inflammatory bowel disease, Danish National Patient Registry, validation, diagnosis codes, positive predictive value, completeness

Background: Proton pump inhibitors (PPIs) use has been linked to adverse outcomes in patients with inflammatory bowel disease (IBD). However, it remains unknown whether this is due to protopathic bias (i.e., when the outcome precedes exposure). Objectives: We aimed to conduct a propensity-weighted study of the association between PPI use and IBD-related hospitalizations and surgery in patients with IBD. Design: Historical propensity score (PS)-weighted cohort study. Methods: We identified all Danish residents diagnosed with IBD in 2000–2022 in the Danish National Patient Registry. We analyzed separate PPI treatment episodes allowing an individual to contribute with more than one PPI episode. We used PS-weighted Cox regression to estimate the hazard ratio (HR) for IBD-related hospitalization and surgery for current PPI-users compared with current nonusers. Results: We identified 50,460 patients with IBD (67% with ulcerative colitis, 33% with Crohn’s disease). Five years after their diagnosis, two-thirds of patients with IBD had used PPI at some point and 10% were in current treatment. The weighted HR for IBD-related hospitalizations was 1.45 (95% confidence interval (CI): 1.38–1.52) during the first year after PPI prescription, and 1.16 (95% CI: 1.05–1.28) thereafter. The weighted HR for IBD-related surgery was 1.21 (95% CI: 1.11–1.32) the first year and 1.35 (95% CI: 1.18–1.54) thereafter. Conclusion: We observed a 20%–40% higher rate of IBD-related hospitalization and surgery, the first year after PPI prescription in patients with IBD which most likely represents a protopathic bias, yet the rate of IBD-related surgery remained elevated more than 1 year after PPI prescription. Plain language summary Effect of common acid suppressive medications on the disease course of inflammatory bowel disease We studied how the commonly used drug class proton pump inhibitors, that suppresses stomach acid production, affects the clinical course of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis). We found that it is unlikely that proton pump inhibitors affects patients with Crohn’s disease, whereas they most likely increase the risk of having surgery performed in patients with ulcerative colitis. Graphical abstract

IntroductionInflammatory bowel diseases (IBDs) are chronic diseases of unknown cause characterised by a progressive and unpredictable disease course. In the last decade, biological treatment has become a cornerstone in the treatment of IBD. However, one-in-three-to-four patients do not respond to first-line biological agents and another third of patients see their response diminish over time. This highlights an unmet need for optimising the use of biologicals and the prediction of treatment response. Considering the multifaceted nature of IBD, we hypothesise that multiomics profiling of sequential samples from single patients could facilitate the discovery of predictive biomarkers of response to biological therapy and disease course.MethodsThis is a multicentre prospective cohort study which will enrol 840 biological-naïve patients with IBD who initiate biological therapy in a 3-year period. Primary outcomes are the occurrence of primary non-response (evaluated at weeks 14–16) and loss of response (evaluated during entire follow-up in patients who obtain partial or full response after induction period). Each patient will be followed up for their clinical data for at least 1 year or till the end of study period (up to 4 years). Blood and stool samples will be collected sequentially during the first year of biological treatment. Intestinal tissue will be sampled after 1 year of treatment and whenever an endoscopy is performed. Samples will undergo transcriptomic, proteomic and microbial DNA analyses. Omics data will be integrated with clinical data to identify a panel of predictive biomarkers of response to biological therapy and disease behaviour in patients with IBD.Ethics and disseminationEthical approval has been obtained from the Danish Ethics Committee (H-18064178). Inclusion is ongoing at three study centres and will be initiated in two additional centres. Both positive and negative study results will be disseminated through peer-reviewed journals according to Strengthening the Reporting of Observational Studies in Epidemiology guidelines, as well as presented at international conferences.

The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD) receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. The study population comprises all Danish patients with IBD (both children and adults) with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator, a standard has been defined based on the available evidence. National results will be published in an annual report and local results on a quarterly basis. The indicators will be reported as department-specific proportions with 95% confidence intervals, and the national average will be provided for comparison. An estimated 1,200-1,300 new biological therapies are initiated each year in Danish patients with IBD. The database will be available for research during 2016. Data will be made available by The Danish Clinical Registries (www.rkkp.dk).

IntroductionBiologic therapies, such as vedolizumab (VDZ) and ustekinumab (UST), offer effective treatment options for inflammatory bowel disease. In spite of limited evidence, it is common practice to escalate the dosing regimen if clinical symptoms or biomarkers give suspicion of loss of response. This study aims to determine whether model-informed precision dosing (MIPD) can provide equal efficacy and possibly superior cost-effectiveness compared with symptom-based management.Methods and analysisThis study is an unblinded, randomised controlled trial, conducted at six centres in Denmark. A total of 166 patients diagnosed with Crohn’s disease or ulcerative colitis who have been on stable VDZ or UST therapy for at least 3 months will be enrolled. Participants will be randomised to receive either continued symptom and biomarker-based dosing (control group) or dosing guided by therapeutic drug monitor using pharmacokinetic (PK) models together with PK-pharmacodynamic targets (=MIPD; intervention group). The primary endpoint is the fraction of patients in steroid-free remission at the end of the observation period. Secondary endpoints include mucosal healing, clinical remission, biochemical disease control, PK assessment and cost-effectiveness.Ethics and disseminationThe trial has been approved by the Danish Medicines Agency and The Medical Research Ethics Committee. No study-related procedures will take place before patients have signed written informed consent. Results will be published in peer-reviewed journals and presented at international conferences.Trial registration numbersEUCT, 2024-517123-39-00; NCT06788340.

Background Staphylococcus aureus gene expression has been sparsely studied in deep-sited infections in humans. Here, we characterized the staphylococcal transcriptome in vivo and the joint fluid metabolome in a prosthetic joint infection with an acute presentation using deep RNA sequencing and nuclear magnetic resonance spectroscopy, respectively. We compared our findings with the genome, transcriptome and metabolome of the S. aureus joint fluid isolate grown in vitro. Result From the transcriptome analysis we found increased expression of siderophore synthesis genes and multiple known virulence genes. The regulatory pattern of catabolic pathway genes indicated that the bacterial infection was sustained on amino acids, glycans and nucleosides. Upregulation of fermentation genes and the presence of ethanol in joint fluid indicated severe oxygen limitation in vivo. Conclusion This single case study highlights the capacity of combined transcriptome and metabolome analyses for elucidating the pathogenesis of prosthetic infections of major clinical importance.

Abstract Background Inflammatory bowel diseases (IBD) can affect body image, quality of life, and sexual health. This study examined sexual challenges and dysfunctions among Danish individuals with and without IBD. Methods In this population-based cross-sectional study, 62 675 participants from the Project SEXUS cohort were linked to the Danish National Patient Register, identifying 655 individuals diagnosed with IBD between 1996 and 2017 (437 with ulcerative colitis [UC] and 218 with Crohn’s disease [CD]). In addition to study-specific measures, the 5-item International Index of Erectile Function and the 6-item Female Sexual Function Index were utilized to assess sexual dysfunctions. Logistic regression was used to compare individuals with UC or CD to those without IBD. Results were reported as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results Compared with those without IBD, individuals with IBD reported similar overall sex life satisfaction and relationship quality. However, individuals with UC more often reported hypoactive sexual desire disorder (men: aOR, 2.18; 95% CI, 1.13-4.19; women: aOR, 1.66; 95% CI, 1.04-2.66), and women with UC more often reported genital pain dysfunction (aOR, 2.30; 95% CI, 1.26-4.19). Subgroup analyses revealed that patients with active disease, stoma, or perianal involvement had particularly elevated odds of sexual dysfunctions compared with non-IBD control subjects. Conclusions Although the 5-item International Index of Erectile Function and 6-item Female Sexual Function Index scores did not indicate an excess of sexual dysfunction in the overall UC and CD populations, individuals with UC as well as patients with IBD experiencing active disease, stoma, or perianal involvement faced more sexual challenges than those without IBD. This highlights the need for gastroenterologists to proactively address sexual health and provide tailored support for patients with IBD. Lay Summary People living with ulcerative colitis or complicated inflammatory bowel disease (IBD) are more likely to face sexual problems than those without IBD. These findings call for increased clinical attention to sexual health in IBD care.

Background: The aim of this prospective study was to assess the diagnostic value of nuclear imaging with 18F-FDG PET/CT (FDG PET/CT), combined 111In-WBC/99mTc-Nanocoll, and 99mTc-HDP SPECT/CT (dual-isotope WBC/bone marrow scan) for patients with chronic problems related to knee or hip prostheses (TKA or THA) scheduled by a structured multidisciplinary algorithm. Materials and Methods: Fifty-five patients underwent imaging with 99mTc–HDP SPECT/CT (bone scan), dual-isotope WBC/bone marrow scan, and FDG PET/CT. The final diagnosis of prosthetic joint infection (PJI) and/or loosening was based on the intraoperative findings and microbiological culture results and the clinical follow-up. Results: The diagnostic performance of dual-isotope WBC/bone marrow SPECT/CT for PJI showed a sensitivity of 100% (CI 0.74–1.00), a specificity of 97% (CI 0.82–1.00), and an accuracy of 98% (CI 0.88–1.00); for PET/CT, the sensitivity, specificity, and accuracy were 100% (CI 0.74–1.00), 71% (CI 0.56–0.90), and 79% (CI 0.68–0.93), respectively. Conclusions: In a standardized prospectively scheduled patient group, the results showed highly specific performance of combined dual-isotope WBC/bone marrow SPECT/CT in confirming chronic PJI. FDG PET/CT has an appropriate accuracy, but the utility of its use in the clinical diagnostic algorithm of suspected PJI needs further evidence.

While the incidence of inflammatory bowel disease (IBD) is rising globally, it has been suggested to stabilize in westernized countries, but this has not yet been shown in exhaustive and large cohorts. We generated an IBD cohort in North Denmark (NorDIBD) of 6,158 patients with IBD diagnosed from 1978 to 2020, based on all recorded and verified IBD diagnoses in the region. While describing the establishment of this cohort, we aimed to present the accurate incidence and prevalence of IBD over 4 decades. The NorDIBD cohort covered all pediatric and adult patients with an IBD diagnosis dated between January 1, 1978, and December 31, 2020, and living in North Denmark, hence forming an unselected population-based patient cohort. IBD incidence rates between 1978 and 2020 and IBD point prevalences between 2003 and 2020 were calculated. We observed a 4-fold increase in the incidence of IBD from 11.5 per 100,000 persons (95% confidence interval [CI] 8.4-14.6) in the year 1978 to 51.3/100,000 (95% CI 45.5-57.1) in the year 2014, whereas in 2020, this rate stabilized. The overall prevalence of IBD more than doubled from 2003 to 2020, from 424 (95% CI 407-443) in 2003 to 872 (95% CI 849-896) IBD cases per 100,000 persons in 2020. Our population-based NorDIBD cohort suggests stabilizing of the incidence of IBD in Denmark, whereas the prevalence continues to rise. Because the data represent a 10% sample of the entire Danish IBD population, we believe that data can be extrapolated to the IBD population in general and used for healthcare planning.

The predominant indications for revision surgery after total hip (THA) or knee arthroplasty (TKA) are an aseptic failure (AF) and prosthetic joint infection (PJI). Accurate diagnosis is crucial. Therefore, we evaluated prospectively a multidisciplinary diagnostic algorithm including multi-modal radionucleid imaging (RNI) and extended microbiological diagnostics. If the surgeon suspected PJI or AF, revision surgery was performed with multiple samples obtained in parallel for special culture procedures and later molecular analyses. Alternatively, if the underlying cause was not evident, RNI was scheduled comprising 99Tc—HDP SPECT/CT, 111In-labeled white blood cells combined with 99Tc-nanocoll bone marrow SPECT/CT, and 18F-FDG PET/CT. A multidisciplinary clinical team made a recommendation on the indication for a diagnostic procedure guided by RNI images or revision surgery. A total of 156 patients with 163 arthroplasties were included. Fifty-five patients underwent RNI. In all, 118 revision surgeries were performed in 112 patients: 71 on the indication of AF and 41 revision of PJI. Thirty-four patients were concluded with chronic pain, and revision surgery refrained. The effective median follow-up period was 13 months. A structured approach offered by the algorithm was useful for the clinician in the evaluation of patients with a failing TKA or THA. Surgical revision was possibly obviated in approximately 20% of patients where an explanation or cause of failure was not found. The algorithm served as an effective tool.