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Signe Vaeth,1 Uffe Birk Jensen,1 Rikke Christensen,1 Henning Andersen2 1Department of Clinical Genetics, Aarhus University Hospital, Aarhus N, 2Department of Neurology, Aarhus University Hospital, Aarhus C, Denmark Purpose: To validate the diagnostic codes for Charcot–Marie–Tooth disease (CMT) in the Danish National Patient Registry (DNPR) using positive predictive value (PPV) as a measure of validity. Patients and methods: We used the DNPR to identify all patients diagnosed with at least one primary CMT diagnosis at a specialized department in the Central Denmark Region during the period 1977–2012. From this population, we randomly selected 123 patients for the validation study. Medical files were reviewed and used as reference standard. We estimated the PPV of the CMT diagnoses and stratified the analysis according to age at diagnosis, gender, and calendar time. Results: In the DNPR, 275 patients were identified. We were able to retrieve 96 medical files from the random sample of 123 patients, and 85 CMT diagnoses were confirmed. The average age at diagnosis was 42.5 years, and 34% were female. The PPV was 88.5% (95% confidence interval: 80.4–94.1). Conclusion: The CMT diagnoses in the DNPR have high validity. The DNPR can be used as a data source for epidemiologic research on CMT. Keywords: registries, positive predictive value, International Classification of Disease codes, epidemiology

Lone Schaadt,1,2 Robin Christensen,2 Lars Erik Kristensen,2 Marius Henriksen1,21Department of Physio- and Occupational Therapy, 2The Parker Institute, Copenhagen University Hospital Bispebjerg-Frederiksberg, Copenhagen, DenmarkIntroduction: Intensity of exercise is believed to be a key determinant of response to chronic obstructive pulmonary disease (COPD) rehabilitation. We hypothesized that a higher intensity of exercise, in combination with physiotherapist-led instructions and education in management of breathlessness, would lead to better self-management, possibly delaying calls to the emergency service and preventing hospitalization.Objective: We aimed to test this hypothesis in a subsequent randomized trial, and in order to test study processes and estimate hospitalization rates, we did a small preliminary prospective cohort study on severe COPD patients referred to outpatient rehabilitation.Methods: In 2013, four rehabilitation courses were scheduled (spring, summer, autumn, and winter) each lasting 8 weeks and including eight to ten patients. This preliminary study was designed as a controlled cohort study. The bi-weekly exercise sessions in the spring and autumn courses included a high-intensity walking exercise at 95% of estimated VO2max for as long as possible. The other two rehabilitation courses included the usual walking exercise intensity (85% of estimated VO2max). Hospitalization rates were assessed from the participants’ medical records in an 18-month period.Results: We were able to enroll 31 patients in total (15 in the high-intensity exercise group and 16 in regular intensity). There were no group differences in the hospitalization rates. However, during review of the medical records, we observed a striking mortality rate among participants who had attended the high-intensity rehabilitation courses (five deaths) compared to the standard rehabilitation (zero deaths). Four of the five deaths were COPD exacerbations. Fisher’s exact test was statistically significant (P=0.046), as was a log-rank test (P=0.019) of the Kaplan–Meier estimated survival rates.Conclusion: These results from this small preliminary cohort study are alarming and raise concerns about the possible serious risks associated with high-intensity exercise rehabilitation of severe COPD patients.Keywords: Chronic obstructive pulmonary disease, exercise, rehabilitation, mortality

Background: An updated psoriatic arthritis (PsA) core outcome set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016. Objectives: To synthesize the evidence on measurement properties of patient reported outcome measures (PROMs) for PsA and thereby contribute to development of a PsA core outcome measurement set (COMS) as described by the OMERACT Filter 2.0. Methods: A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO on Jan 1, 2017 to identify full-text articles with an aim of assessing the measurement properties of PROMs in PsA. Two independent reviewers rated the quality of studies using the COnsensus based standards for the Selection of health Measurement INstruments (COSMIN) checklist, and performed a qualitative evidence synthesis. Results: Fifty-five studies were included in the systematic review. Forty-four instruments and a total of 89 scales were analyzed. PROMs measuring COS domains with at least fair quality evidence for good validity and reliability (and no evidence for poor properties) included the Stockerau Activity Score for PsA (German), Psoriasis Symptom Inventory, visual analogue scale for Patient Global, 36 Item Short Form Health Survey Physical Function subscale, Health Assessment Questionnaire Disability Index, Bath Ankylosing Spondylitis Functional Index, PsA Impact of Disease questionnaire, PsA Quality of Life questionnaire, VITACORA-19, Functional Assessment of Chronic Illness Therapy Fatigue scale and Social Role Participation Questionnaire. Conclusions: At least one PROM with some evidence for aspects of validity and reliability was available for six of the eight mandatory domains of the PsA COS.

Aim: The aim of this study was to determine predictive values of gynaecological alarm symptoms in the general population. Materials and Methods: A population-based prospective cohort study combining questionnaire data with register data of gynaecological cancer and premalignant conditions in a one-year follow-up period. Results: Among 25,866 women, some 2,957 (11.4%) reported at least one newly onset gynaecological cancer alarm symptom within a four-week time period. A total of 71 women were diagnosed with a gynaecological cancer or a premalignant condition. The positive predictive values (PPVs) ranged between 0.1% (95%-CI: 0.1-0.1) for cancer among women reporting at least one of the 18 unspecific and specific gynaecological cancer alarm symptoms and 0.3% (95%-CI: 0.2-0.4) for dysplasia among women reporting at least one of the specific alarm symptoms that lead to a GP contact. The positive likelihood ratios (LR+s) ranged between 0.9 (95%-CI: 0.7;1.2) for cancer among women reporting at least one unspecific symptom and 1.7 (95%-CI: 1.1-2.5) for dysplasia among women reporting at least one specific alarm symptom. Conclusion: The PPVs and LR+s of gynaecological alarm symptoms in the general population are very low, and only few of the patients diagnosed with gynaecological cancer reported specific alarm symptoms. Thus targeted diagnosis of gynaecological cancer cannot be based on cancer alarm symptoms only.

Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities. © 2018 Article author(s).

Objective. To assess the efficacy and safety of treatment modalities for major organ involvement of Behçet’s syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods. A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. Results. We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. Conclusion. The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Osteonecrosis of the jaws (ONJ) is a rare but severe complication of antiresorptive medications, such as bisphosphonates, used in the treatment of bone malignancy or osteoporosis. Tooth extraction and dental disease have been strongly associated with ONJ development. Here, we investigated molecular and cellular markers of socket healing after extraction of healthy or teeth with experimental periodontitis (EP) in Wistar-Han rats treated with zoledronic acid (ZA). We included 4 experimental groups: vehicle-treated animals with extraction of healthy teeth or teeth with ligature-induced EP and ZA-treated animals with extraction of healthy teeth or teeth with EP. Animals were pretreated with vehicle or ZA for a week, and EP was induced. Four weeks later, the second maxillary molars were extracted; sockets were allowed to heal for 4 wk; animals were euthanized; and maxillae were isolated. Radiographically, extraction sockets in groups 1, 2, and 3 demonstrated normal healing. Contrary incomplete socket healing was noted after extraction of teeth with EP in ZA-treated rats of group 4. Histologically, persistent inflammation and extensive osteonecrosis were seen in group 4. Disorganization of the collagen network, collagen type III predominance, and lack of collagen fiber insertion in the necrotic bone were associated with impaired socket healing. Cells positive for MMP-9, MMP-13, and α-SMA expression were present at the areas of epithelial invagination and adjacent to osteonecrotic bone. Importantly, human biopsies from patients with ONJ showed similar findings. Our data emphasize the importance of dental disease and tooth extraction in ONJ pathogenesis and help delineate an altered profile in wound-healing markers during ONJ development. © 2017, © International & American Associations for Dental Research 2017.

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Objective.To test the reliability of the consensus-based ultrasound (US) definitions of elementary gout lesions in patients.Methods.Eight patients with microscopically proven gout were evaluated by 16 sonographers for signs of double contour (DC), aggregates, erosions, and tophi in the first metatarsophalangeal joint and the knee bilaterally. The patients were examined twice using B-mode US to test agreement and inter- and intraobserver reliability of the elementary components.Results.The prevalence of the lesions were DC 52.8%, tophus 61.1%, aggregates 29.8%, and erosions 32.4%. The intraobserver reliability was good for all lesions except DC, where it was moderate. The best reliability per lesion was seen for tophus (κ 0.73, 95% CI 0.61–0.85) and lowest for DC (κ 0.53, 95% CI 0.38–0.67). The interobserver reliability was good for tophus and erosions, but fair to moderate for aggregates and DC, respectively. The best reliability was seen for erosions (κ 0.74, 95% CI 0.65–0.81) and lowest for aggregates (κ 0.21, 95% CI 0.04–0.37).Conclusion.This is the first step to test consensus-based US definitions on elementary lesions in patients with gout. High intraobserver reliability was found when applying the definition in patients on all elementary lesions while interobserver reliability was moderate to low. Further studies are needed to improve the interobserver reliability, particularly for DC and aggregates.