Rapid Rule-Out of Myocardial Infarction After 30 Minutes as an Alternative to 1 Hour: The RACING-MI Cohort Study.

STUDY OBJECTIVE: The aim of this study was to investigate whether myocardial infarction can be safely ruled in or out after 30 minutes as an alternative to 1 hour. METHODS: This was a prospective, single-center clinical study enrolling patients admitted to the emergency department. Patients with chest pain suggestive of myocardial infarction were eligible for inclusion. There was no walk-in to the emergency department, and patients with highly elevated out-of-hospital troponin were transferred directly to an invasive heart center. High-sensitivity troponin I was measured at admission (0 hour), 30 minutes, 1 hour, and 3 hours. Diagnostic performance was assessed using the sensitivity and negative predictive value (primary endpoints) as measures of ability to rule out myocardial infarction. Specificity and positive predictive value of myocardial infarction were used as measures for the ability to rule in myocardial infarction (secondary endpoints). RESULTS: In total, 1,003 patients qualified for analysis. Median age was 64 (interquartile range 52 to 74) years, and 42% were women. Myocardial infarction was confirmed in 9% of patients. In the validation cohort (n=503), the 0-h/30-min algorithm assigned 242 (48%) patients to rule out, 54 (11%) to rule in, and 207 (41%) to the observational zone. This resulted in a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (95% confidence interval 98.5% to 100%), specificity of 96.7% (94.7% to 98.2%), and positive predictive value of 72.2% (58.4% to 83.5%). In comparison, the 0-h/1-h algorithm performed with a sensitivity of 100% (92.0% to 100%), negative predictive value of 100% (98.5% to 100%), specificity of 97.2% (95.2% to 98.5%), and positive predictive value of 75.5% (61.7% to 86.2%). CONCLUSION: The accelerated 0-h/30-min algorithm allowed for safe rule-out of myocardial infarction 30 minutes after admission. The rule-in ability of the 0-h/30-min algorithm was comparable to that of the 0-h/1h algorithm.

Methotrexate pharmacokinetic is influenced by co-administration of cyclosporin in rheumatoid arthritis patients. Results from a randomized clinical trial.

The aim was to investigate if the pharmacokinetics of methotrexate (MTX) are affected by the addition of cyclosporin (CsA). Forty patients diagnosed with early rheumatoid arthritis (RA) were included in this open prospective study: 20 patients were treated with a dose of 7.5 mg MTX and a dose of 2.5 mg/kg CsA, 20 patients were treated with a dose of 7.5 mg MTX and placebo. Baseline measurements of plasma MTX and erythrocyte MTX were made. Area under the plasma concentration versus time curve (AUC) and other pharmacokinetic variables were estimated by means of a population based software model. Clinical improvement of 20-50-70% according to the American College of Rheumatology (ACR) and adverse events were evaluated ongoing for 52 weeks. We found that mean peak plasma MTX concentration was significantly higher in the MTX + CsA combination treatment group (p = .003). No differences in AUC, erythrocyte MTX or other pharmacokinetic parameters were found between the two treatment groups. Estimated Glomerular Filtration Rate (eGFR) decreased significantly in the MTX + CsA treatment group (p < .001), but no serious adverse events occurred in either of the two groups. In conclusion, CsA added to methotrexate treatment in early RA significantly increased peak-plasma MTX concentration, but other pharmacokinetic parameters and measurements of MTX were unchanged.

NT-proBNP to exclude heart failure in primary care - a pragmatic, cluster-randomized study.

Heart failure (HF) is difficult to recognize in primary care. N-terminal pro B-type natriuretic peptide (NT-proBNP) can be used as a rule-out test in HF due to its high negative predictive value. We aim to determine whether the number per 1000 patients of HF diagnoses increase among patients referred from primary care to an outpatient HF clinic, if general practitioners (GPs) were offered NT-proBNP in a real-life setting. All GP practices covered by Randers Regional Hospital were randomized to an intervention group (34 GP practices) and a control group (35 GP practices) in this pragmatic, cluster-randomized controlled trial. The main outcome was the number of patients referred to echocardiography and diagnosed with HF in each group. The number of patients per 1000 diagnosed with HF in the two groups was the same (0.09 (0.02-0.16) vs. 0.14 (0.07-0.21), p = .3541). A total of 700 NT-proBNP analyses, of which 611 were unique, were requested from 31 GP practices in 17.5 months. A total of 184 patients were referred to echocardiography on suspicion of HF. The number of patients per 1000 referred in the intervention group was significantly higher (p < .010). NT-proBNP was measured in 36.6% of referred patients in the intervention group. Significantly more women were diagnosed with HF in the intervention group (56.3% vs. 0%, p = .019). Hence, increased diagnostic effectiveness could not be shown in this real-life setting.

The value of using the faecal immunochemical test in general practice on patients presenting with non-alarm symptoms of colorectal cancer.

BACKGROUND: Around 50% of individuals with colorectal cancer (CRC) initially present with non-alarm symptoms. METHODS: We investigated the value of using the faecal immunochemical test (FIT) in the diagnostic process of CRC and other serious bowel disease in individuals presenting with non-alarm symptoms in general practice. The study was conducted in the Central Denmark Region from 1 September 2015 to 30 August 2016. The FIT was used as a rule-in test on patients aged ≥30 years with non-alarm symptoms of CRC. The cut-off value was set to 10 µg Hb/g faeces. RESULTS: A total of 3462 valid FITs were performed. Of these, 540 (15.6%) were positive. Three months after FIT performance, 51 (PPV: 9.4% (95% CI: 7.0;11.9)) individuals with a positive FIT were diagnosed with CRC and 73 (PPV: 13.5% (95%CI: 10.6;16.4)) with other serious bowel disease. Of CRCs, 66.7% were diagnosed in UICC stage I & II and 19.6% in stage IV. The false negative rate for CRC was <0.1% for the initial 3 months after FIT performance. CONCLUSION: The FIT may be used as a supplementary diagnostic test in the diagnostic process of CRC and other serious bowel disease in individuals with non-alarm symptoms of CRC in general practice.

Effects of hyperoxia on myocardial injury following cardioversion-A randomized clinical trial.

Oxygen has long been assumed beneficial for all ill and injured patients. However, hyperoxia may be harmful and aggravate myocardial injury such as that caused by myocardial infarction. We aimed to investigate if hyperoxia increases myocardial injury following direct current cardioversion compared with room air. METHODS: Patients undergoing elective biphasic cardioversion for atrial fibrillation or atrial flutter were randomized to receive room air or oxygen (10-15 L/min) during the procedure. The primary endpoint was the difference in high-sensitive Troponin I (hs-cTnI) and -T (hs-cTnT) measured 2 hours before and 4 hours after cardioversion. Secondary endpoints were differences in Copeptin and NT-pro-BNP. RESULTS: A total of 65 patients were randomized to high-flow oxygen (male: 71%, mean age 66.9 years) and 59 patients to room air (male: 80%, mean age 65.5 years). There was no difference in hs-cTnI between patients treated with oxygen compared to patients treated with room air (P=.09) and no significant difference for hs-cTnT, ratio 1.08 (95% CI: 0.99-1.18) (P=.09). Median hs-cTnI difference before and after cardioversion was 0.1 (interquartile range (IQR): -0.5 to 0.5) ng/L for the high-flow oxygen group and -0.3 (IQR: -1.1 to 0.4) ng/L for the room air group. There was no difference in Copeptin between patients treated with oxygen compared to room air (ratio 1.06 (95% CI: 0.89-1.27) (P=.51) or NT-pro-BNP (difference-6.0 ng/L (95% CI: -78.5 to 66.6) P=.87). CONCLUSION: Direct current cardioversion of atrial fibrillation/flutter with and without high-flow oxygen supplement was not associated with myocardial injury evaluated by high sensitive myocardial biomarkers.

Calprotectin in patients with chronic rheumatoid arthritis correlates with disease activity and responsiveness to methotrexate.

OBJECTIVE: Calprotectin (myeloid-related protein 8/14) is elevated in inflammatory diseases and a correlation of serum calprotectin and disease activity in rheumatoid arthritis (RA) has been shown. In this study, we investigated plasma calprotectin as a disease marker in patients with chronic RA treated with methotrexate (MTX) monotherapy and compared plasma calprotectin with C-reactive protein (CRP) in this matter. METHODS: Seventy-six patients with chronic RA were included in this open prospective study and of these 40 were included prior to initiation of MTX therapy. The patients were followed with laboratory and clinical parameters for 52-56 weeks. Plasma calprotectin was analyzed at the start of study and at various intervals. Radiographic evaluation was performed at baseline and after 17.2 months and progression in joint destruction was measured with Larsen score. The response to MTX was evaluated according to the American College of Rheumatology criteria. RESULTS: Patients starting MTX treatment had significantly higher levels of plasma calprotectin compared to patients well established on MTX therapy (p = .008). Among the 40 patients naive to MTX, 25 responded to MTX therapy and serum calprotectin decreased significantly in these patients (p = .0007). The radiographic damage showed no relation to calprotectin. CONCLUSIONS: Plasma calprotectin is associated with disease activity in patients with chronic RA and is more strongly correlated to MTX response compared to CRP. The role of calprotectin as a disease marker is promising and the advantages compared to CRP needs to be further investigated.

Elevated calprotectin in patients with atrial fibrillation with and without heart failure.

Calprotectin is an inflammatory marker, which has been found elevated in patients suffering from cardiac conditions, e.g. myocardial infarction, unstable angina and chronic heart failure. Inflammation has further been linked to atrial fibrillation (AF). However, the association between calprotectin and AF is unknown. We aimed to compare calprotectin levels in patients suffering from AF with healthy adults. In addition, AF patients with and without heart failure were compared. Calprotectin was measured in patients undergoing elective direct current cardioversion for AF. Calprotectin was determined before, 4 hours and 3 months after cardioversion. Healthy blood donors were used to verify the reference interval for calprotectin. In total, 104 prospectively enrolled patients were included. The median serum calprotectin level for AF patients was 1.6 µg/mL before cardioversion. Calprotectin levels increased significantly 4 h (1.9 µg/mL) and 3 months (2.2 µg/mL) after cardioversion. Blood donors' median serum calprotectin (1.3 µg/mL) was significantly lower than AF patients. AF patients with heart failure had significantly higher calprotectin at baseline compared with AF patients without a history of heart failure (2.0 µg/mL vs. 1.5 µg/mL). The difference was not significant at 4 h (2.0 µg/mL vs. 1.7 µg/mL) or 3 months (2.5 µg/mL vs. 2.2 µg/mL). In conclusion, the calprotectin levels in patients with AF were significantly higher than healthy blood donors and were further increased after cardioversion. AF patients with heart failure had significantly higher levels of calprotectin than AF patients without heart failure.

Delayed sample arrival at the laboratory does not lead to more false negatives in the Danish population screening for colorectal cancer.

In Denmark, biennial population screening for colorectal cancer was introduced in 2014 for all aged 50-74 years. Five laboratories representative for the regional division of Denmark perform the immunochemical testing of faecal occult blood in the screening samples (iFOBT, OC-Sensor (Eiken Chemical, cut-off 100 µg/L)). In July 2016, a new agreement on the public post-delivery entailed an increased lag time (five days) from the screening participant drops the screening sample into a mail-box until sample arrival at the laboratories. Previous work had reported that a lag time above five days led to more false negative iFOBT tests. We investigated if this was true also under Danish conditions. We performed two stability tests; one with sample storage at 30 °C for 14 days (N = 60), and another with sample storage at room temperature for 13 days (N = 10). We extracted data from our laboratory information system (LABKA) on all iFOBT tests performed in the entire Central Denmark Region (N = 104,328 patients) during the last six months for each calendar year 2014-16. For each year, we computed the distribution of iFOBT tests below and above cut-off. Our stability tests showed no positive samples switching to false negative after storage; however, some negative samples turned false positive, especially at 30 °C. The data showed no change in the distribution of iFOBT tests below and above cut-off after July 2016. We found no evidence that an enhanced lag time increased the number of false negative iFOBT tests in the Danish screening program for colorectal cancer.

Implementation of immunochemical faecal occult blood test in general practice: a study protocol using a cluster-randomised stepped-wedge design.

BACKGROUND: Colorectal cancer is a common malignancy and a leading cause of cancer-related death. Half of patients with colorectal cancer initially present with non-specific or vague symptoms. In the need for a safe low-cost test, the immunochemical faecal occult blood test (iFOBT) may be part of the evaluation of such patients in primary care. Currently, Danish general practitioners have limited access to this test. The aim of this article is to describe a study that will assess the uptake and clinical use of iFOBT in general practice. Furthermore, it will investigate the diagnostic value and the clinical implications of using iFOBT in general practice on patients presenting with non-alarm symptoms of colorectal cancer. METHODS/DESIGN: The study uses a cluster-randomised stepped-wedge design and is conducted in the Central Denmark Region among 836 GPs in 381 general practices. The municipalities of the Region and their appertaining general practitioners will be included sequentially in the study during the first 7 months of the 1-year study period. The following intervention has been developed for the study: a mandatory intervention providing all general practitioners with a starting package of 10 iFOBTs, a clinical instruction on iFOBT use in general practice and online information material from the date of inclusion, and an optional intervention consisting of a continuous medical education on colorectal cancer diagnostics and use of iFOBT. DISCUSSION: This study is among the first and largest trials to investigate the diagnostic use and the clinical value of iFOBT on patients presenting with non-alarm symptoms of colorectal cancer. The findings will be of national and international importance for the future planning of colorectal cancer diagnostics, particularly for 'low-risk-but-not-no-risk' patients with non-alarm symptoms of colorectal cancer. TRIAL REGISTRATION: A Trial of the Implementation of iFOBT in General Practice NCT02308384 . Date of registration: 26 November 2014.

Fecal calprotectin in healthy children.

Calprotectin is a protein found in the cytosol of inflammatory cells and is a marker of the presence and the degree of inflammation in the bowel system. Calprotectin in feces has great diagnostic value in the matter of inflammatory bowel disease (IBD). In feces, the protein is stable up to seven days, and since the protein can easily be measured with an ELISA, the use of fecal calprotectin (FC) means no invasive measures. For adults and children over 4 years, a cut-off level of 50 mg/kg has been well established for diagnostic purposes. Because previous studies have proven that children under the age of four in general have higher FC values than older children and adults, there is a need for a cut-off level for this age group. In order to establish that, the normal values for FC in children from 0-4 years were investigated. Some 75 stool samples from healthy children were collected and the levels of FC were analyzed. The results were compared to 157 pediatric cases where FC analysis had been performed for diagnostic purposes. As a result, three cut-off levels were established based on the 97.5% percentiles of FC in different age groups: 538 mg/kg (1 < 6 months), 214 mg/kg (6 months < 3 years) and 75 mg/kg (3 < 4 years).

A substantial number of scientific publications originate from non-university hospitals.

INTRODUCTION: As we found no recent published reports on the amount and kind of research published from Danish hospitals without university affiliation, we have found it relevant to conduct a bibliometric survey disclosing these research activities. MATERIAL AND METHODS: We retrieved all scientific papers published in the period 2000-2009 emanating from all seven Danish non-university hospitals in two regions, comprising 1.8 million inhabitants, and which were registered in a minimum of one of the three databases: PubMed MEDLINE, Thomson Reuters Web of Science and Elsevier's Scopus. RESULTS: In 878 of 1,252 papers, the first and/or last author was affiliated to a non-university hospital. Original papers made up 69% of these publications versus 86% of publications with university affiliation on first or last place. Case reports and reviews most frequently had authors from regional hospitals as first and/or last authors. The total number of publications from regional hospitals increased by 48% over the 10-year period. Publications were cited more often if the first or last author was from a university hospital and even more so if they were affiliated to foreign institutions. Cardiology, gynaecology and obstetrics, and environmental medicine were the three specialities with the largest number of regional hospital publications. CONCLUSION: A substantial number of scientific publications originate from non-university hospitals. Almost two thirds of the publications were original research published in international journals. Variations between specialities may reflect local conditions. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

[Haemoglobin A1c measurements when to use and when not].

Haemoglobin A1c (HbA1c) reflects the glycaemic status of the latest 2-3 month and is used in both diagnosing and monitoring diabetes. Different circumstances may lead to spurious HbA1c results as summarised in this review. HbA1c is susceptible to changes in erythrocyte turnover (e.g. anaemia) regardless of measurement method, and to analytical interference (e.g. haemoglobin variants) depending on the method. The laboratory may detect and warn of suspected analytical interference. However, if the clinical presentation and glycaemic measures are incoherent, spurious HbA1c should be suspected and fasting glucose should be measured.

External validation of a high-sensitive troponin I algorithm for rapid evaluation of acute myocardial infarction in a Danish cohort.

AIMS: An accelerated diagnostic algorithm for ruling-in or ruling-out myocardial infarction (MI) after 1 hour (1 h) has recently been derived and internally validated for the Siemens ADVIA Centaur TNIH assay. We aimed to validate the diagnostic performance of the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in a Danish cohort. METHODS AND RESULTS: Patients with chest pain suggestive of MI were prospectively enrolled. High-sensitive troponin I (TNIH) was measured at admission (0 h) and after 30 minutes (30 m), 1 h, and 3 hours (3 h). We externally validated the TNIH 0 h/1 h algorithm ad modum Boeddinghaus in Danish patients. Moreover, we applied the algorithm using the second TNIH measurement at 30 m instead of 1 h. We enrolled 1003 patients: median (Q1-Q3) age 64 (52-74) years, 42% female, and 23% with previous MI. Myocardial infarction was the final diagnosis in 9% of patients. Median (Q1-Q3) times from admission to 30 m and 1 h blood draw were 35 min (30-37 min) and 67 min (62-75 min), respectively. Using the 0 h and 1 h results, 468 (47%) patients were assigned to rule-out, 104 (10%) to rule-in, and 431 (43%) to the observational zone. This resulted in a negative predictive value of 100% (95% confidence interval: 99.2-100%), sensitivity of 100% (95.9-100%), positive predictive value of 79.8 (70.8-87.0%), and specificity of 97.7% (96.5-98.6%). The diagnostic performance after 30 m was similar. CONCLUSIONS: The TNIH 0 h/1 h algorithm ad modum Boeddinghaus performed excellently for rule-out of MI in a Danish cohort. The Boeddinghaus algorithm also performed excellently after only 30 m. TRIAL REGISTRATION NUMBER: NCT03634384. TRIAL REGISTRY NAME AND URL: Rapid Use of High-Sensitive Cardiac Troponin I for Ruling-in and Ruling-out Acute Myocardial Infarction (RACING-MI), https://clinicaltrials.gov/ct2/show/NCT03634384.

Single troponin measurement to rule-out acute myocardial infarction in early presenters.

BACKGROUND: A single high-sensitive cardiac troponin (hs-cTn) can be used to rule-out acute myocardial infarction (MI) in patients presenting >3 hours (3 h) after chest pain onset to the emergency department. This study aimed to investigate the safety of ruling-out MI in early presenters with chest pain ≤3 h using a single hs-cTnI at admission. METHODS: We prospectively enrolled patients presenting with chest pain suggestive of MI. Hs-cTnI (Siemens ADVIA Centaur TNIH, Limit of detection: 2.2 ng/L) was measured at admission. Two physicians adjudicated final diagnosis. A diagnostic cut-off value <3 ng/L was used to rule-out MI. Patients were classified as early (chest pain ≤3 h) or late presenters (>3 h). RESULTS: We included 1370 patients with available admission hs-cTnI results: median (Q1-Q3) age 65 (52-74), female sex: 43%, previous MI: 22%. We confirmed MI in 118 (8.6%) patients. Overall, 470 (34%) patients were classified as early, 770 (56%) as late presenters, and 130 (9%) patients had unknown onset. When applying the diagnostic cut-off value, MI was correctly ruled-out at admission in 370 (27%) patients: 134 (29%) early presenters, 206 (27%) late presenters and 30 (23%) patients with unknown onset. This resulted in an overall negative predictive value of 100% (95% CI: 99.0-100%), with both 100% (97.3-100%) for early and 100% (98.2-100%) for late presenters, respectively. Sensitivity was similarly high in the two groups. CONCLUSION: MI could be safely ruled-out in all patients presenting with chest pain ≤3 h when using a single hs-cTnI value <3 ng/L as diagnostic cut-off. TRIAL REGISTRATION NUMBER: NCT03634384.

Rapid use of high-sensitive cardiac troponin I for ruling-in and ruling-out of acute myocardial infarction (RACING-MI): study protocol.

Introduction: The European Society of Cardiology has suggested an accelerated algorithm for ruling-in and ruling-out myocardial infarction (MI) with high-sensitive cardiac troponin (hs-cTn) measured at admission (0 hour) and after 1 hour (1 hour) as an alternative to standard measurements at 0 hour and 3 hours. However, the 0 hour/1 hour algorithm has only been tested in a limited amount of patient cohorts and not for all hs-cTn assays. Moreover, it is unknown if MI can be ruled-out faster than 1 hour. In this single-centre, clinical trial, we will investigate whether MI safely can be ruled-in or ruled-out after 30 min and 1 hour. Methods and analysis: Patients with chest pain suggestive of MI admitted to the emergency department will be subjected to hs-cTn measurements at the following time points: 0 hour, 30 min, 1 hour and 3 hours. Chest pain characteristics will be recorded. In total, 1000 patients with all four blood samples will be included. The diagnostic algorithms will be derived based on the first 500 patients and validated in the subsequent 500 patients. The primary endpoint is the negative predictive value of the 0 hour/30 min and the 0 hour/1 hour algorithms. Secondary endpoints include positive predictive value, sensitivity and specificity. Results will be compared with the standard 0 hour/3 hour algorithm. Ethics and dissemination: Oral and written informed consent will be obtained from all patients. The trial is approved by The Regional Committee on Health Research Ethics and the Danish Data Protection Agency. Data will be disseminated and submitted to peer-reviewed scientific journals and meetings irrespective of study outcome. Trial registration number: NCT03634384.

Cardioversion Efficacy Using Pulsed Biphasic or Biphasic Truncated Exponential Waveforms: A Randomized Clinical Trial.

BACKGROUND: Several different defibrillators are currently used for cardioversion and defibrillation of cardiac arrhythmias. The efficacy of a novel pulsed biphasic (PB) waveform has not been compared to other biphasic waveforms. Accordingly, this study aims to compare the efficacy and safety of PB shocks with biphasic truncated exponential (BTE) shocks in patients undergoing cardioversion of atrial fibrillation or -flutter. METHODS AND RESULTS: This prospective, randomized study included patients admitted for elective direct current cardioversion. Patients were randomized to receive cardioversion using either PB or BTE shocks. We used escalating shocks until sinus rhythm was obtained or to a maximum of 4 shocks. Patients randomized to PB shocks received 90, 120, 150, and 200 J and patients randomized to BTE shocks received 100, 150, 200, and 250 J, as recommended by the manufacturers. In total, 69 patients (51%) received PB shocks and 65 patients (49%) BTE shocks. Successful cardioversion, defined as sinus rhythm 4 hours after cardioversion, was achieved in 43 patients (62%) using PB shocks and in 56 patients (86%) using BTE shocks; ratio 1.4 (95% CI 1.1-1.7) (P=0.002). There was no difference in safety (ie, myocardial injury judged by changes in high-sensitive troponin I levels; ratio 1.1) (95% CI 1.0-1.3), P=0.15. The study was terminated prematurely because of an adverse event. CONCLUSIONS: Cardioversion using a BTE waveform was more effective when compared with a PB waveform. There was no difference in safety between the 2 waveforms, as judged by changes in troponin I levels. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02317029.

Protocol Outlines for Parts 1 and 2 of the Prospective Endoscopy III Study for the Early Detection of Colorectal Cancer: Validation of a Concept Based on Blood Biomarkers.

BACKGROUND: Programs for population screening of colorectal cancer (CRC) have been implemented in several countries with fecal immunochemical testing (FIT) as the preferred platform. However, the major obstacle for a feces-based testing method is the limited compliance that reduces the clinical sensitivity for detection of participants with non-symptomatic CRC. Therefore, research approaches have been initiated to develop screening concepts based on biomarkers in blood. Preliminary results show that protein, genetic, epigenetic, and metabolomic components may be valuable in blood-based screening concepts, particularly when combinations of the various components appear to lead to significant improvements. OBJECTIVES: The protocol described in this paper focuses on the validation of concepts based on biomarkers in blood in a major population screened by FIT. METHODS: In Part 1, participants will be identified and included through the Danish CRC Screening Program comprising initial FIT and subsequent colonoscopy to those with a positive result. Blood samples will be collected from 8000 FIT-positive participants, who are offered subsequent colonoscopy. Findings and interventions at colonoscopy together with personal data including co-morbidity will be recorded. Blood samples and data will also be collected from 6000 arbitrarily chosen participants with negative FIT. In Part 2, blood samples and data will be collected from 30,000 FIT-negative participants three times within 4 years. The blood samples will be analyzed using various in-house and commercially available manual and automated analysis platforms. RESULTS: We anticipate Part 1 to terminate late August 2016 and Part 2 to terminate late September 2022. The results from Parts 1 and 2 will be presented within 12 to 18 months from termination. CONCLUSIONS: The purpose of this study is to improve the efficacy of identifying participants with neoplastic bowel lesions, to identify false negative participants, to identify participants at risk of interval neoplastic lesions, to improve the compliance in screening sessions, and to establish guidelines for out-patient follow-up of at-risk participants based on combinations of blood-based biomarkers.

[Research in regional hospitals in two Danish regions]. / Forskning på regionshospitaler i Region Midtjylland og Region Nordjylland.

The quantity of interest, experience, and barriers to research in non-university hospitals in Denmark is undocumented. Therefore, a questionnaire was distributed to all employees at non-university hospitals in two Danish regions. The results showed that a substantial number of medical doctors were engaged in ongoing research. 24% of the respondents were supervisors in research projects, and 19% conducted contract research. Thus, Danish non-university hospitals have employees with both interest and experience in medical research. The four most commonly stated barriers for research were lack of time, funding, supervision, and training courses.

[A survey of research funding at Danish regional hospitals]. / Forskning ved regionale hospitalsenheder i Vestdanmark.

INTRODUCTION: According to recently passed Danish legislation, all Danish hospitals are obliged to take part in scientific research. As data on financial support for research activities are lacking, we assessed the resources allocated to research from the budget of the central hospital management as a percentage of the total budget at Danish regional hospitals in 2007. MATERIAL AND METHODS: A postal survey was conducted at 13 hospitals in the Western part of Denmark. The questionnaire comprised items in the following major categories: 1) budget allocated specifically for research and travel grants; 2) employment of scientific and technical support staff; 3) facilities and equipment for research; and 4) research dissemination. RESULTS: Questionnaires were returned from 11 hospitals. Six hospitals reported to have dedicated fixed amounts on the budget for research, exact figures were reported in four cases only equivalent to 0.1%, 0.3%, 0.3% and 0.6% of the total budget. Most hospitals had associate professors, but only five had full professors. Seven hospitals supplied laboratories and technical facilities, eight hospitals held staff-meetings on a regular basis and four published an annual report on research activities. CONCLUSION: In the majority of regional hospitals in Western Denmark, less than 0.3% of the total budget administered by the central hospital management was allocated specifically for research. These figures, however, may not be accurate as individual departments may allocate additional resources from local budgets. We recommend that regional hospitals define research strategies and allocate the necessary funding in their budgets.

Plasma adiponectin in patients with active, early, and chronic rheumatoid arthritis who are steroid- and disease-modifying antirheumatic drug-naive compared with patients with osteoarthritis and controls.

OBJECTIVE: Rheumatoid arthritis (RA) is a systemic chronic inflammatory joint disease, whereas osteoarthritis (OA) is a local joint disease with low-level inflammatory activity. The pathogenic role of the adipocytokine adiponectin is largely unknown in these diseases. We hypothesized (1) that plasma adiponectin concentrations differ in healthy controls and patients with early disease-modifying antirheumatic drug (DMARD)-naive RA, chronic RA, and OA; (2) that changes in adiponectin are observed during methotrexate (MTX) treatment of chronic RA; and (3) that adiponectin correlates to disease activity measures in RA. METHODS: Plasma adiponectin was analyzed with a validated in-house immunoassay. We measured adiponectin in healthy controls (n = 45) and patients with early DMARD-naive RA (n = 40), chronic RA (n = 74), and OA (n = 35). In a subgroup of patients with chronic RA (n = 31), the longitudinal effect of MTX treatment on adiponectin (Week 0 vs Week 28) was investigated. RESULTS: Adiponectin differed significantly between healthy controls (mean 4.8 +/- SD 2.7 mg/l) and the 3 groups, with 8.9 +/- 4.8 mg/l in early RA, 11.6 +/- 5.6 mg/l in chronic RA, and 14.1 +/- 6.4 mg/l in OA. Longitudinally, MTX treatment increased adiponectin significantly from 9.7 +/- 4.5 mg/l at Week 0 to 11.0 +/- 4.5 mg/l at Week 28 in chronic RA. No correlations to disease activity measures were found. CONCLUSION: Both early DMARD-naive and chronic RA were associated with higher plasma adiponectin compared to healthy controls, but lower plasma adiponectin than OA. Adiponectin increased 13% during MTX treatment. In patients with RA and OA body mass index, age, sex, and disease activity measures failed to explain the findings.