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Summary: Higher incidences of fractures are seen in people with type 1 diabetes (T1D), but knowledge on different fracture sites is sparse. We found a higher incidence mainly for distal fracture sites in people with T1D compared to controls. It must be further studied which fractures attributed to the higher incidence rates (IRs) at specific sites. Introduction: People with T1D have a higher incidence of fractures compared to the general population. However, sparse knowledge exists on the incidence rates of individual fracture sites. Therefore, we examined the incidence of various fracture sites in people with newly treated T1D compared to matched controls. Methods: All people from the UK Clinical Practice Research Datalink GOLD (1987–2017), of all ages with a T1D diagnosis code (n = 6381), were included. People with T1D were matched by year of birth, sex, and practice to controls (n = 6381). Fracture IRs and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex. Results: The IR of all fractures was significantly higher in people with T1D compared to controls (IRR: 1.39 (CI95%: 1.24–1.55)). Compared to controls, the IRR for people with T1D was higher for several fracture sites including carpal (IRR: 1.41 (CI95%: 1.14–1.75)), clavicle (IRR: 2.10 (CI95%: 1.18–3.74)), foot (IRR: 1.70 (CI95%: 1.23–2.36)), humerus (IRR: 1.46 (CI95%: 1.04–2.05)), and tibia/fibula (IRR: 1.67 CI95%: 1.08–2.59)). In women with T1D, higher IRs were seen at the ankle (IRR: 2.25 (CI95%: 1.10–4.56)) and foot (IRR: 2.11 (CI95%: 1.27–3.50)), whereas in men with T1D, higher IRs were seen for carpal (IRR: 1.45 (CI95%: 1.14–1.86)), clavicle (IRR: 2.13 (CI95%: 1.13–4.02)), and humerus (IRR: 1.77 (CI95%: 1.10–2.83)) fractures. Conclusion: The incidence of carpal, clavicle, foot, humerus, and tibia/fibula fractures was higher in newly treated T1D, but there was no difference at other fracture sites compared to controls. Therefore, the higher incidence of fractures in newly treated people with T1D has been found mainly for distal fracture sites. [ABSTRACT FROM AUTHOR]

Summary: Circulating microvesicles (MVs) from patients with systemic lupus erythematosus (SLE) express the type 1 interferon (IFN)‐inducible protein galectin‐3 binding protein (G3BP), which may enhance their deposition in the glomerular basement membrane. The release of G3BP‐expressing MVs from normal peripheral blood mononuclear cells (PBMCs) is induced by Toll‐like receptor 9 (TLR‐9) ligands, and these vesicles contain autoantibody‐accessible double‐stranded DNA (dsDNA). This study compares the release of MVs expressing G3BP and dsDNA from PBMCs derived from SLE patients with or without active lupus nephritis (LN) and from healthy donors, and taps further into the potential dependency on IFN‐α for their generation and impacts of TLR‐7/TLR‐9 co‐stimulation. PBMCs from 10 healthy donors and 12 SLE patients, six of whom had active LN at study inclusion, were stimulated in‐vitro with recombinant human IFN‐α and the TLR‐9 agonists oligodeoxynucleotide (ODN)2216 or ODN2395 alone or in combination with the TLR‐7 agonist gardiquimod. MVs in the supernatants were subsequently isolated by differential centrifugation and their expression of G3BP and dsDNA was quantified by flow cytometry. Stimulation with ODN2395 significantly increased the release of MVs co‐expressing G3BP and dsDNA from PBMCs isolated from healthy donors and SLE patients. The expression of G3BP on individual MVs and the proportion of G3BP and dsDNA double‐positive MVs released were increased in active LN patients. Neither co‐stimulation with gardiquimod nor with the IFN‐α inhibitor IN‐1 had any effect on the MV release induced by ODN2395. In conclusion, the TLR‐9‐mediated inducibility of MVs co‐expressing G3BP and dsDNA is increased in SLE patients with active LN. [ABSTRACT FROM AUTHOR]

We investigated if signs of active Epstein–Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein–Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein–Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein–Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein–Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein–Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients. [ABSTRACT FROM AUTHOR]

Background Tracheal intubation may cause vocal fold damage. The trial was designed to assess laryngeal morbidity comparing the Endoflex® tube with a conventional endotracheal tube with stylet. We hypothesised that laryngeal morbidity within the first 24 h after extubation would be lower with the Endoflex tube than with the conventional endotracheal tube with stylet because of less rigidity. Methods This randomised trial included 130 elective surgical patients scheduled for general anaesthesia with endotracheal intubation. Pre- and post-operative assessment of hoarseness, vocal fold pathology, and voice analysis using the Multidimensional Voice Program was performed. Induction of anaesthesia was standardised. After complete neuromuscular paralysis, intubation was done with an Endoflex tube or a conventional endotracheal tube with stylet. Results Post-operative hoarseness was found in 45% with the Endoflex tube and 55% with the endotracheal tube with stylet at 24 h after extubation ( P = 0.44). Post-operative vocal fold injury was present in 23% in the Endoflex tube group and in 36% in the endotracheal tube with stylet group ( P = 0.13). The increase in shimmer, the voice analysis variable reflecting vocal fold oedema, was 0.5% in the Endoflex tube group and 2.5% in the endotracheal tube with stylet group ( P = 0.02). Conclusion No significant difference was found in the incidence of hoarseness or vocal fold injury using the Endoflex tube. However, the statistically significant lower increase in the shimmer values in that group implies that the Endoflex may be associated with less laryngeal morbidity. [ABSTRACT FROM AUTHOR]

Antineutrophil cytoplasm autoantibodies ( ANCA) directed against bactericidal/permeability-increasing protein ( BPI) are common in patients with cystic fibrosis ( CF), and serum levels are correlated with lung colonization by Pseudomonas aeruginosa and the severity of lung damage. The production of BPI- ANCA may be due to the costimulation of BPI when mounting an immune response against P. aeruginosa. The effect of surgery aiming to eradicate bacteria and infected tissue on BPI- ANCA levels is sparsely described. A cohort of patients with CF were included: 53 patients having extensive image-guided sinus surgery ( EIGSS) with topical postoperative antibiotic treatment, 131 non-operated controls and 36 who had double lung transplantation ( LTX). In all 219 patients, serum samples before and after surgery or at similar intervals were analysed for Ig G and Ig A BPI- ANCA. The EIGSS group showed a highly significant decrease in both Ig A and Ig G BPI- ANCA levels compared with their own preoperative values and control group values ( P < 0.001-0.02). The LTX patients also showed a highly significant decrease in both Ig A and Ig G BPI- ANCA levels ( P < 0.001). EIGSS and LTX decrease Ig A and Ig G BPI- ANCA levels in patients with CF, indicating that extensive removal of infected tissue influences the pathogenic process of autoantibody production. The results shown herein are in favour of applying EIGSS in selected patients with CF and for using BPI- ANCA as a surrogate marker for guiding further therapeutic interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Standard therapy for antineutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) with cyclophosphamide (CYC) and prednisolone is limited by toxicity. This unblinded, prospective, randomized, controlled trial was undertaken to determine whether methotrexate (MTX) could replace CYC in the early treatment of AASV. METHODS: Patients with newly diagnosed AASV, with serum creatinine levels <150 mumoles/liter, and without critical organ manifestations of disease were randomized to receive either standard oral CYC, 2 mg/kg/day or oral MTX, 20-25 mg/week; both groups received the same prednisolone regimen. All drug treatments were gradually tapered and withdrawn by 12 months. Followup continued to 18 months. The primary end point was the remission rate at 6 months (noninferiority testing). RESULTS: One hundred patients were recruited from 26 European centers; 51 patients were randomized to the MTX group and 49 to the CYC group. At 6 months, the remission rate in patients treated with MTX (89.8%) was not inferior to that in patients treated with CYC (93.5%) (P = 0.041). In the MTX group, remission was delayed among patients with more extensive disease (P = 0.04) or pulmonary involvement (P = 0.03). Relapse rates at 18 months were 69.5% in the MTX group and 46.5% in the CYC group; the median time from remission to relapse was 13 months and 15 months, respectively (P = 0.023, log rank test). Two patients from each group died. Adverse events (mean 0.87 episodes/patient) included leukopenia, which was less frequent in the MTX versus the CYC group (P = 0.012), and liver dysfunction, which was more frequent in the MTX group (P = 0.036). CONCLUSION: MTX can replace CYC for initial treatment of early AASV. The MTX regimen used in the present study was less effective for induction of remission in patients with extensive disease and pulmonary involvement and was associated with more relapses than the CYC regimen after termination of treatment. The high relapse rates in both treatment arms support the practice of continuation of immunosuppressive treatment beyond 12 months. [ABSTRACT FROM AUTHOR]

The article presents information on the European therapeutic trials in antineutrophil cytoplasmic antibodies-associated systemic vasculitis. The systemic vasculitides are a significant health issue in the European Union (EU) with an annual incidence of approximately 40 per million and estimated direct health costs to the EU of 500 million ECU per year. The relative rarity and heterogeneous nature of systemic vasculitis have impeded controlled clinical trials and dictate a mulidisciplinary and multicentre approach to their clinical investigation, which has been assisted by recent advances in classification and diagnosis.

The article presents a case study of 46-year-old cystic fibrosis patient with pain and swelling of the knees and ankles. Topics discussed include presence of synovitis in the knees as reported from ultrasound, administration of prednisolone drug doses without proper inflammatory control and had developed osteoporosis, treatment of the patient with etanercept, tumor necrosis factor (TNF)-α inhibitor., which reduced the symptoms.

A response from the authors of the article "Laryngeal Morbidity After Tracheal Intubation: The Endoflex Tube Compared to Conventional Endotracheal Intubation With a Stylet" is presented.

Respiratory difficulties caused by exercise-induced laryngeal obstructions (EILOs) are reported with increasing frequency. The aim of this study was to assess the prevalence and symptoms of EILOs and their relation to airway hyperresponsiveness (AHR). In total, 556 randomly selected youths in Copenhagen aged 14-24 years were invited over a 2-year period. The study included a mailed questionnaire and two visits: day 1 (an interview-based questionnaire, methacholine bronchial provocation test and physical exertion test); and day 2 [an exercise test with continuous laryngoscopic recordings (CLE test)]. The diagnosis of EILOs was based on the CLE test. In total, 237 answered the mailed questionnaire and 150 participated on day 1 whereof 98 participated on day 2 also. AHR was verified in 23 (4.1% of invitees) and EILOs in 42 (7.5% of invitees). Co-morbidity was verified in 6 cases (26.1% of verified AHR cases). No symptoms were found specific for either AHR or EILOs. The minimum prevalence of EILOs in this cohort was 7.5%. EILOs were verified in 26.1% of participants with AHR. Questionnaires could not differentiate between AHR and EILOs. [ABSTRACT FROM AUTHOR]

Objective: This paper describes the outcome for the first 148 patients referred to a lithium clinic. Method: Two-year follow-up data from treatment charts are reported for all patients entering a lithium clinic in the study period. Results: Lithium was given as the only mood stabilizer in 132 (89.2%) of the cases. Thirty-two (21.6%) patients were readmitted with a new affective disorder episode. Twenty-nine (19.6%) patients discontinued treatment prematurely. Variables predicting the recurrence of new affective disorder episodes as well as premature discontinuation of treatment were identified. Conclusion: The majority of bipolar patients received lithium for prophylaxis against recurrent affective disorder episodes. The outcome was moderate but comparable to the 30-40% improvement usually reported in follow-up studies of bipolar patients given long-term prophylactic treatment with lithium. Better long-term treatment results for bipolar patients depend on both the development of more effective mood stabilizing drugs or drug combinations and the improvement of patients' adherence to treatment. [ABSTRACT FROM AUTHOR]

Neutron Spectroscopy employing extreme-conditions sample environments is nowadays a crucial tool for the understanding of fundamental scientific questions as well as for the investigation of materials and chemical-physical properties. For all these kinds of studies, an increased neutron flux over a small sample area is needed. The prototype of a focusing neutron guide component, developed and produced completely at the neutron source FRM II in Garching (Germany), has been installed at the time-of-flight (TOF) disc-chopper neutron spectrometer TOFTOF and came into routine-operation. The design is based on the compressed Archimedes' mirror concept for finite-size divergent sources. It represents a unique device combining the supermirror technology with Adaptive Optics, suitable for broadbandwidth thermal-cold TOF neutron spectroscopy (here optimized for 1.4-10Å). It is able to squeeze the beam cross section down to a square centimeter, with a more than doubled signal-to-background ratio, increased efficiency at high scattering angles, and improved symmetry of the elastic resolution function. We present a comparison between the simulated and measured beam cross sections, as well as the performance of the instrument within real experiments. This work intends to show the unprecedented opportunities achievable at already existing instruments, along with useful guidelines for the design and construction of next-generation neutron spectrometers. [ABSTRACT FROM AUTHOR]

Adequate information about physical activity habits is essential for surveillance, implementing, and evaluating public health initiatives in this area. Previous studies have shown that question order and differences in wording result in systematic differences in people's responses to questionnaires; however, this has never been shown for physical activity questions. The aim was to study the influence of different formulations and question order on self-report physical activity in a population-based health interview survey. Four samples of each 1000 adults were drawn at random from the National Person Register. A new question about physical activity was included with minor differences in formulations in samples 1-3. Furthermore, the question in sample 2 was included in sample 4 but was placed in the end of the questionnaire. The mean time spent on moderate physical activity varied between the four samples from 57 to 100 min/day. Question order was associated with the reported number of minutes spent on moderate-intensity physical activity and with prevalence of meeting the recommendation, whereas physical inactivity was associated with the differences in formulation of the question. Questionnaire context influences the way people respond to questions about physical activity significantly and should be tested systematically in validation studies of physical activity questionnaires. [ABSTRACT FROM AUTHOR]

There has been an ongoing confusion among pathologists in their attempt to accurately identify lesions of Reinke’s space. Nodules, polyps and Reinke’s edema fall in the same basket and differentiation between them relies largely on the clinical description of the pathologic specimen by the operating surgeon than on their distinct pathologic features. By revising the pertinent literature, the need for an establishment of the aforementioned term still remains and is further stressed out, as confusion among the various pathologic descriptions of these lesions still exists. This is further verified by a study conducted in the Department of Otorhinolaryngology–Head and Neck Surgery of the University Hospital of Louvain at Mont-Godinne, Belgium, involving 323 operative specimens obtained from 200 patients with macroscopic picture. Statistical analysis showed lack of agreement between surgical and histopathologic diagnosis in almost a third of the cases (Cohen’s kappa coefficient of 0.683 ± 0.037, P < 0.001). We, therefore, propose the term “exudative lesions of Reinke’s space” to include Reinke’s edema, polyps and nodules. These lesions share common histologic features, which are located in the Reinke’s space and whose macroscopic appearance is largely dependent upon the presence and duration of certain causative factors. [ABSTRACT FROM AUTHOR]

Background: Current therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis are limited by toxicity.Objective: To compare pulse cyclophosphamide with daily oral cyclophosphamide for induction of remission.Design: Randomized, controlled trial. Random assignments were computer-generated; allocation was concealed by faxing centralized treatment assignment to providers at the time of enrollment. Patients, investigators, and assessors of outcomes were not blinded to assignment.Setting: 42 centers in 12 European countries.Patients: 149 patients who had newly diagnosed generalized ANCA-associated vasculitis with renal involvement but not immediately life-threatening disease.Intervention: Pulse cyclophosphamide, 15 mg/kg every 2 to 3 weeks (76 patients), or daily oral cyclophosphamide, 2 mg/kg per day (73 patients), plus prednisolone.Measurement: Time to remission (primary outcome); change in renal function, adverse events, and cumulative dose of cyclophosphamide (secondary outcomes).Results: Groups did not differ in time to remission (hazard ratio, 1.098 [95% CI, 0.78 to 1.55]; P = 0.59) or proportion of patients who achieved remission at 9 months (88.1% vs. 87.7%). Thirteen patients in the pulse group and 6 in the daily oral group achieved remission by 9 months and subsequently had relapse. Absolute cumulative cyclophosphamide dose in the daily oral group was greater than that in the pulse group (15.9 g [interquartile range, 11 to 22.5 g] vs. 8.2 g [interquartile range, 5.95 to 10.55 g]; P < 0.001). The pulse group had a lower rate of leukopenia (hazard ratio, 0.41 [CI, 0.23 to 0.71]).Limitations: The study was not powered to detect a difference in relapse rates between the 2 groups. Duration of follow-up was limited.Conclusion: The pulse cyclophosphamide regimen induced remission of ANCA-associated vasculitis as well as the daily oral regimen at a reduced cumulative cyclophosphamide dose and caused fewer cases of leukopenia.Primary Funding Source: The European Union. [ABSTRACT FROM AUTHOR]

The systemic vaculitides are multisystem disorder with considerable mortality and morbidity and frequent relapses. In the absence of reliable serological markers, accurate clinical tools are required to assess disease activity and damage for treatment decisions, and for the performance of clinical trials. This article reviews and summarises the development and the use of disease assessment tools for determining activity and damage in systemic vasculitis and reports ongoing initiatives for further development of disease assessment tools. A literature search was conducted using PubMed and reference lists for vasculitis, assessment, clinical trials, outcome and prognosis. The findings indicate that comprehensive disease assessment in vasculitis requires documentation of disease activity, chronic irreversible damage and impairment of function. [ABSTRACT FROM AUTHOR]

To assess whether the use of six main therapeutic groups was congruent with the occurrence of related diseases across educational groups.Two data sources were analysed: (i) Interview data from The Danish Health and Morbidity Survey 2000 on a representative sample of the Danish population ages 16 years and above (n = 16 690); (ii) Prescription records linked to a health survey on a representative sample of the population of Funen County 2000–2001 (n = 3 422).The use of six therapeutic main groups (ATC groups A, B, C, M, N and R) and related diseases in educational groups was analysed by indirect standardization. Age and gender standardized prevalence ratios (SPRs) and 95% confidence intervals were calculated on the basis of the total study population.In general, respondents in the two least educated groups used medicines more frequently and a higher proportion of them reported the related disease than could be expected from indirect standardization. The opposite picture appeared for respondents in the two highest educational groups (SPR < 100). The overall patterns were similar for the six medicine groups, although some of the SPRs were not significant.The results show the uneven distribution of disease in the general population. The distribution of medicine use generally followed this pattern, which means that those in the greatest medical need used the most medicine. Hence, individual co-payment for medicine did not seem to be a barrier to access to medicine in any of the educational groups. [ABSTRACT FROM AUTHOR]

Objective: To examine whether trends in smoking behaviour in Western Europe between 1985 and 2000 differed by education group. Design: Data of smoking behaviour and education level were obtained from national cross sectional surveys conducted between 1985 and 2000 (a period characterised by intense tobacco control policies) and analysed for countries combined and each country separately. Annual trends in smoking prevalence and the quantity of cigarettes consumed by smokers were summarised for each education level. Education inequalities in smoking were examined at four time points. Setting: Data were obtained from nine European countries: Norway, Sweden, Denmark, Finland, the United Kingdom, the Netherlands, Germany, Italy, and Spain. Participants: 451 386 non-institutionalised men and women 25-79 years old. Main outcome measures: Smoking status, daily quantity of cigarettes consumed by smokers. Results: Combined country analyses showed greater declines in smoking and tobacco consumption among tertiary educated men and women compared with their less educated counterparts. in country specific analyses, elementary educated British men and women, and elementary educated Italian men showed greater declines in smoking than their more educated counterparts. Among Swedish, Finnish, Danish, German, Italian, and Spanish women, greater declines were seen among more educated groups. Conclusions: Widening education inequalities in smoking related diseases may be seen in several European countries in the future. More insight into effective strategies specifically targeting the smoking behaviour of low educated groups may be gained from examining the tobacco control policies of the UK and Italy over this period. [ABSTRACT FROM AUTHOR]

Background: The main objective of this study was to investigate the construct validity of the WHOQOL-BREF by use of Rasch and Item Response Theory models and to examine the stability of the model across high/low scoring individuals, gender, education, and depressive illness. Furthermore, the objective of the study was to estimate the reference data for the quality of life questionnaire WHOQOL-BREF in the general Danish population and in subgroups defined by age, gender, and education.Methods: Mail-out-mail-back questionnaires were sent to a randomly selected sample of the Danish general population. The response rate was 68.5%, and the sample reported here contained 1101 respondents: 578 women and 519 men (four respondents did not indicate their genders).Results: Each of the four domains of the WHOQOL-BREF scale fitted a two-parameter IRT model, but did not fit the Rasch model. Due to multidimensionality, the total score of 26 items fitted neither model. Regression analysis was carried out, showing a level of explained variance of between 10 and 14%. The mean scores of the WHOQOL-BREF are reported as normative data for the general Danish population.Conclusion: The profile of the four WHOQOL-BREF domains is a more adequate expression of quality of life than the total score of all 26 items. Although none of the subscales are statistically sufficient measures of their domains, the profile scores seem to be adequate approximations to the optimal score. [ABSTRACT FROM AUTHOR]

Objective: To clarify the relationship between cognitive functions and regional cerebral blood flow (rCBF) in a large group of depressed patients compared with healthy controls. Method: A set of principal components was extracted from scores of a battery of neuropsychological tests of 40 patients suffering from major depression and 49 healthy controls. The components were correlated by multiple linear regression analyses to selected regions of interest in the brain obtained from positron emission tomography images. Results: In contrast to findings in the healthy controls, cognitive functions in the depressed patients correlated significantly with rCBF in specified regions of interest in only a few instances. Conclusion: Our study indicates that disturbed cognitive functions in depression do not relate to specific areas of the brain in the same way as normal cognitive functioning, suggesting that the abnormalities of brain function in major depression may be qualitative, rather than quantitative, in nature. [ABSTRACT FROM AUTHOR]

Objective: We wanted to explore associations between clinical symptoms of depression and the blood flow to specific regions of the brain. Furthermore, we wanted to compare the regions-of-interest (ROI) method with the functions-of-interest (FOI) approach. Method: The resting blood flow to 42 ROI in the brain was obtained with positron emission tomography (PET) imaging in 42 representative in-patients with major depression and 47 matched healthy controls. Results: The patients had increased blood flow to hippocampus, cerebellum, anterior cingulate gyrus, and the basal ganglia. A strong negative correlation was found between the degree of psychomotor retardation of the patients and the blood flow to the dorsolateral and supraorbital prefrontal cortices. The total Hamilton score was correlated with the blood flow to the hippocampus. Conclusion: Our findings support the notion that depressed patients have disturbances in the loops connecting the frontal lobes, limbic system, basal ganglia, and cerebellum. [ABSTRACT FROM AUTHOR]

Nanometer-sized clusters of copper have been produced in a hollow cathode sputtering source and deposited on SiO. Halo-like structures consisting of micrometer sized protrusions in the silicon oxide surface surrounded by thin rings of smaller particles are observed. The area in between seems to be depleted of particles. We propose that the halo-like structures are a result of electrostatic forces acting between the incoming charged clusters and charged regions on the surface. A simple computer simulation supports this suggestion. [ABSTRACT FROM AUTHOR]