Positive Predictive Value of Diagnostic Codes for Inflammatory Bowel Disease in the Danish National Patient Registry Among Individuals 50+ Years, Using Patient Records as Reference Standard.

PURPOSE: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic diseases. The aim was to validate diagnoses of IBD among patients aged 50+ years in the Danish National Patient Registry (NPR) by comparison with patient medical records. PATIENTS AND METHODS: Men and women in the Diet, Cancer and Health (DCH) cohort were linked to NPR, and cases with a diagnosis of IBD and their respective hospital records were identified. Validation was performed by comparing patient medical records with information on discharge diagnoses of IBD from the NPR. RESULTS: Of 57,053 individuals in the DCH-cohort, 339 were registered with an IBD diagnosis in NPR, with 277 (82%) records available for review. Among 277 patients, the positive predictive values (PPVs) of one CD or UC registration in NPR were 78% for IBD overall, 51% for CD and 54% for UC. One hundred fifty-seven patients had at least two CD and/or UC registrations with PPVs of 90% for IBD overall, 65% for CD and 73% for UC. One hundred and two patients had at least three registrations with PPVs of 97% for IBD overall, 75% for CD and 88% for UC. 96% were diagnosed at a specialized department. Other diagnoses coded as IBD mostly included microscopic colitis, irritable bowel syndrome and cancer. CONCLUSION: Validity of IBD diagnoses in the registry of individuals aged 50+ years increased with the number of registrations. It is recommended that these results are taken into consideration in future studies, especially in epidemiology research using NPR as a data source for patients diagnosed with IBD.

A Cost-Effective High-Throughput Plasma and Serum Proteomics Workflow Enables Mapping of the Molecular Impact of Total Pancreatectomy with Islet Autotransplantation.

Blood is an ideal body fluid for the discovery or monitoring of diagnostic and prognostic protein biomarkers. However, discovering robust biomarkers requires the analysis of large numbers of samples to appropriately represent interindividual variability. To address this analytical challenge, we established a high-throughput and cost-effective proteomics workflow for accurate and comprehensive proteomics at an analytical depth applicable for clinical studies. For validation, we processed 1 µL each from 62 plasma samples in 96-well plates and analyzed the product by quantitative data-independent acquisition liquid chromatography/mass spectrometry; the data were queried using feature quantification with Spectronaut. To show the applicability of our workflow to serum, we analyzed a unique set of samples from 48 chronic pancreatitis patients, pre and post total pancreatectomy with islet autotransplantation (TPIAT) surgery. We identified 16 serum proteins with statistically significant abundance alterations, which represent a molecular signature distinct from that of chronic pancreatitis. In summary, we established a cost-efficient high-throughput workflow for comprehensive proteomics using PVDF-membrane-based digestion that is robust, automatable, and applicable to small plasma and serum volumes, e.g., finger stick. Application of this plasma/serum proteomics workflow resulted in the first mapping of the molecular implications of TPIAT on the serum proteome.

Danish cohort of monozygotic inflammatory bowel disease twins: Clinical characteristics and inflammatory activity.

AIM: To describe the establishment of a Danish inflammatory bowel diseases (IBD) twin cohort with focus on concordance of treatment and inflammatory markers. METHODS: We identified MZ twins, likely to be discordant or concordant for IBD, by merging information from the Danish Twin Register and the National Patient Register. The twins were asked to provide biological samples, questionnaires, and data access to patient files and public registries. Biological samples were collected via a mobile laboratory, which allowed for immediate centrifugation, fractionation, and storage of samples. The mean time from collection of samples to storage in the -80 °C mobile freezer was less than one hour. The diagnoses where validated using the Copenhagen diagnostic criteria. RESULTS: We identified 159 MZ IBD twin pairs, in a total of 62 (39%) pairs both twins agreed to participate. Of the supposed 62 IBD pairs, the IBD diagnosis could be confirmed in 54 pairs. The cohort included 10 concordant pairs, whereof some were discordant for either treatment or surgery. The 10 concordant pairs, where both pairs suffered from IBD, included eight CD/CD pairs, one UC/UC pair and one UC/IBDU pair. The discordant pairs comprised 31 UC, 5 IBDU (IBD unclassified), and 8 CD discordant pairs. In the co-twins not affected by IBD, calprotectin was above 100 µg/g in 2 participants, and above 50 µg/g in a further 5 participants. CONCLUSION: The presented IBD twin cohorts are an excellent resource for bioinformatics studies with proper adjustment for disease-associated exposures including medication and inflammatory activity in the co-twins.

Familial risk of inflammatory bowel disease: a population-based cohort study 1977-2011.

OBJECTIVES: Estimates of familial risk of inflammatory bowel diseases (IBDs), Crohn's disease (CD), and ulcerative colitis (UC) are needed for counseling of patients and could be used to target future prevention. We aimed to provide comprehensive population-based estimates of familial risk of IBD. METHODS: The study encompassed the entire Danish population during 1977-2011 (N=8,295,773; 200 million person-years). From national registries, we obtained information on diagnosis date of IBD (N=45,780) and family ties. Using Poisson regression, we estimated incidence rate ratios (IRRs) of IBD in relatives of IBD cases compared with individuals with relatives of the same type without IBD. RESULTS: The risk of CD was significantly increased in first-degree (IRR, 7.77; 95% confidence interval (CI), 7.05-8.56), second-degree (IRR, 2.44; 95% CI, 2.01-2.96), and third-degree relatives (IRR, 1.88; 95% CI, 1.30-2.71) to patients with CD, and was less pronounced in relatives to UC cases. Likewise, the risk of UC was increased in first-degree (IRR, 4.08; 95% CI, 3.81-4.38), second-degree (IRR, 1.85; 95% CI, 1.60-2.13), and third-degree relatives (IRR, 1.51; 95% CI, 1.07-2.12) of UC cases, and less pronounced in relatives of CD cases. IRRs increased with two or more IBD-affected relatives and were modified by age, with the highest family-related IRR observed in early life. CONCLUSIONS: The risk of IBD is significantly increased in first -, second-, and third-degree relatives of IBD-affected cases, with up to 12% of all IBD cases being family cases. The risk is particularly pronounced in young individuals.

[Benzodiazepines and cyclopyrrolones prior to, during and after hospital admission]. / Benzodiazepiner og cyclopyrroloner før, under og efter hospitalsindlaeggelse.

INTRODUCTION: The aim was to describe the prescription patterns of benzodiazepines (BZD) and cyclopyrrolones (Z-drugs) in a population of medical and surgical patients prior to, during and after hospital admission. MATERIAL AND METHODS: Data were collected from medical records, the physicians' order entry system and the national electronic pharmacy registry. RESULTS: Overall, 38% of the 135 included patients did not receive BZD/Z-drugs at any time. A total of 30% were pre-admission users. While in hospital, 50% were users and 17% were users at discharge and 30% during the six months follow-up period (p < 0.0001). Changes in the usage pattern were mainly due to a significant increase in Z-drug use during hospital admission combined with a decrease in BZD and Z-drug use at discharge. During hospitalisation, 40% of the 94 pre-admission non-users of BZD/Z-drugs received BZD/Z-drugs. At the time of discharge, 61% of pre-admission users had become non-users, and 8.5% of the non-users had become users. Over the 6-month post-discharge period, 29 patients (21%) received >or= 3 prescriptions for BZD/Z-drugs (chronic users) compared with 21 (16%) before admission. CONCLUSION: Medical and surgical hospitalized patients are frequently treated with Z-drugs and BZDs prior to, during and after hospital admission. The usage pattern changes significantly during hospital admission, with more prescriptions for Z-drugs being issued.