Prescription of non-steroidal anti-inflammatory drugs for patients with inflammatory arthritis decreases with the initiation of tumour necrosis factor inhibitor therapy: results from the ICEBIO registry.

OBJECTIVE: To study the impact of tumour necrosis factor-α inhibitor (TNFi) therapy on the use of non-steroidal anti inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) in Iceland. METHOD: This registry cohort study used data from the nationwide database on biologics in Iceland (ICEBIO) and the Icelandic Prescription Medicines Register on disease activity, and filled prescriptions for NSAIDs, to study the period from 2 years before to 2 years after initiation of a first TNFi. Five randomly selected individuals from the general population matched on age, sex, and calendar time for each patient served as comparators. RESULTS: Data from 940 patients and 4700 comparators were included. Patients with arthritis were prescribed 6.7 times more defined daily doses of NSAIDs than comparators (149 vs 22 per year). After TNFi initiation, NSAID use decreased to a mean of 85 DDD per year, or by 42% in RA, 43% in PsA, and 48% in axSpA. At TNFi initiation, the quintile of axSpA patients who used most NSAIDs reported significantly worse pain (mean ± sd 66 ± 21 vs 60 ± 23 mm), global health (70 ± 20 vs 64 ± 23 mm), and Health Assessment Questionnaire score (1.21 ± 0.66 vs 1.02 ± 0.66) than the other patients, whereas no significant differences were observed in the groups with peripheral arthritis. CONCLUSION: Patients with inflammatory arthritides requiring TNFi therapy use more NSAIDs than matched comparators, and consumption decreased following TNF initiation. Patient-reported measures are not associated with high NSAID use in patients with peripheral arthritis.

Enthesitis in a European registry-based cohort of patients with psoriatic arthritis treated with tumour necrosis factor inhibitors: clinical burden, patient-reported outcomes, and treatment response.

OBJECTIVE: To explore the registration of enthesitis among biologic-naïve patients with psoriatic arthritis (PsA) initiating tumour necrosis factor inhibitor (TNFi) treatment across 12 European registries, compare the disease burden and patient-reported outcomes (PROs) between patients with and without enthesitis, and assess the enthesitis treatment response. METHOD: Demographics, clinical characteristics, and PROs at first TNFi (TNFi-1) initiation (baseline) were assessed in patients with PsA, diagnosed by a rheumatologist, with versus without assessment of entheses and between those with versus without enthesitis. Enthesitis scores and resolution frequency were identified at follow-up. RESULTS: Of 10 547 patients in the European Spondyloarthritis (EuroSpA) Research Collaboration Network initiating TNFi, 1357 underwent evaluation for enthesitis. Eight registries included a validated scoring system for enthesitis. At baseline, 874 patients underwent entheses assessment [Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) 485 patients, Spondyloarthritis Research Consortium of Canada (SPARCC) 389 patients]. Enthesitis was detected by MASES in 170/485 (35%, mean score ± sd 3.1 ± 2.4) and by SPARCC in 236/389 (61%, 4 ± 3.4). Achilles enthesitis was most frequent, by both MASES (unilateral/bilateral 28%/9%) and SPARCC (48%/18%). MASES/SPARCC baseline and follow-up scores for TNFi-1 were available for 100/105 patients. Of these, 63 patients (63%) (MASES) and 46 (43.8%) (SPARCC) achieved resolution of enthesitis. The site-specific enthesitis resolution was overall lower at SPARCC sites (peripheral; 63-80%) than at MASES sites (mainly axial; 82-100%) following TNFi-1. Disease activity and PROs were worse in patients with versus without enthesitis. CONCLUSION: Entheseal assessments are only registered in a minority of patients with PsA in routine care. When assessed, enthesitis was common, and a substantial proportion demonstrated resolution following treatment with TNFi-1.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010-2016: a collaboration between five biological registries.

OBJECTIVES: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS. METHOD: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010-2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010-2016 (n = 4392), baseline characteristics and disease activity measures were retrieved. RESULTS: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010-2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5-6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7-3.8) (both p < 0.0001). CONCLUSION: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Disease activity in and quality of life of patients with psoriatic arthritis mutilans: the Nordic PAM Study.

OBJECTIVE: To describe the social status and health-related quality of life of patients with psoriatic arthritis mutilans (PAM) in the Nordic countries. METHOD: Patients with at least one mutilated joint confirmed by radiology were studied. Disease activity involving joints and skin, physician-assessed disease activity, and patient's education and work status were recorded. Data from the 36-item Short Form Health Survey, Health Assessment Questionnaire and Dermatology Life Quality Index questionnaire were gathered and correlated with disease duration, pain, and general well-being (visual analogue scale). The controls were 58 Swedish patients with long-standing psoriatic arthritis sine PAM. RESULTS: Sixty-seven patients were included. Patients with PAM had a protracted disease history (33 ± 14 years) and disease onset at a relatively early age (30 ± 12 years). Overall inflammatory activity at inclusion was mild to moderate. The mean number of mutilated joints was 8.2 and gross deformity was found in 16% of patients. Forty per cent were treated with biological and 32% with conventional synthetic disease-modifying anti-rheumatic drugs. Forty-two per cent had retired early or were on sick leave. Impaired functional capacity with little or no ability to perform self-care or everyday tasks was reported by 21% of the patients. Patients between 45 and 60 years of age reported the most impaired quality of life in comparison to the control group. CONCLUSION: PAM seriously affects social functioning. Whether early recognition of PAM and new forms of therapy can improve disease outcome and quality of life remains to be studied.

Activation of Complement Following Total Hip Replacement.

The aim of this study was to investigate whether complement activation, via the classical and alternative pathways, occurs following a cemented total hip replacement (THR) surgery due to osteoarthritis. Blood samples were collected systematically from 12 patients - six male and six women, with a median age of 75 (range: 59-90 years) - preoperatively, 6 h post-operatively and on the first, second and third post-operative day. Total function of classical (CH50) and alternative pathways (AH50) was evaluated, along with the determination of serum concentrations of the complement proteins C3, C4, C3d, the soluble terminal complement complex (sTCC) sC5b-9, as well as C-reactive protein (CRP) and albumin. Measurements of CRP and albumin levels elucidated a marked inflammatory response following the operation. The CH50, AH50 and C3 and C4 levels were significantly lower 6 h after the surgery compared with the preoperative levels, but elevated above the preoperative levels during the following 3 days. The complement activation product C3d levels increased continually during the whole observation period, from 13.5 AU/ml (range: 8-19 AU/ml) preoperative to 20 AU/ml (range: 12-34 AU/ml) on the third post-operative day. Furthermore, we observed an increase in the sC5b-9 levels between the preoperative and the third post-operative day. These results demonstrate a significant activation of the complement system following cemented THR. Further studies are needed to elucidate the time frame and the pathogenic role of this observed complement activation.

Psoriatic arthritis mutilans (PAM) in the Nordic countries: demographics and disease status. The Nordic PAM study.

OBJECTIVE: To determine the prevalence and clinical characteristics of psoriatic arthritis mutilans (PAM) in the Nordic countries. METHOD: Patients with putative PAM aged ≥ 18 years were recruited. Fifty-nine patients were included after clinical examination. RESULTS: The prevalence of PAM in the adult Nordic population was estimated to be 3.69 per million inhabitants [95% confidence interval (CI) 2.75-4.63]. The female to male ratio was close to 1:1. The mean age of skin disease onset was 25 years and the mean age of onset of joint disease was 30 years. The onset of skin disease was 2 years earlier among female patients. At inclusion, the mean duration of arthritis was 27 ± 11 years for male patients and 33 ± 11 years for female patients. PAM was most frequently seen in the distal interphalangeal (DIP) joints of the toes, followed by the IP joint of the thumb and the DIP joint of the little finger on the left hand. Female and male patients had similar numbers of painful and swollen joints. Enthesitis was found in 19 patients (32%), while 38 patients (64%) had a history of dactylitis. Twenty-three of these 38 patients (61%) had a history of dactylitis in the same finger/toe as they had PAM. At the time of inclusion, 45% of the patients were found to have clear or almost clear skin. CONCLUSIONS: PAM in the Nordic countries has a low prevalence, with only three to five cases per million inhabitants. The majority of the patients present with mild skin disease.

Small joint involvement in psoriatic arthritis is associated with onycholysis: the Reykjavik Psoriatic Arthritis Study.

OBJECTIVES: Psoriasis and psoriatic arthritis (PsA) are associated with nail changes. Recent reports suggest that nail changes may be a part of the enthesitis of PsA and that they predict the onset of arthritis among patients with psoriasis, but they have not reported on subclasses of nail changes. However, earlier reports suggested that onycholysis is the nail change most strongly associated with PsA. If nail changes in PsA are a sign of enthesitis, they might be associated with small joint disease in general and the objective of this study was to test this hypothesis. METHODS: A total of 154 patients recruited through the Reykjavik Psoriatic Arthritis Study had a joint, skin, and nail evaluation. Associations with small joint disease were tested using univariate analysis, and confirmed in a multivariate model. RESULTS: Onycholysis had a strong association with small joint involvement [odds ratio (OR) 3.42, 95% confidence interval (CI) 1.41-8.92], while other types of nail changes did not. The number of swollen joints and shorter disease duration were also associated with small joint disease. CONCLUSIONS: Onycholysis is associated with small joint disease in PsA. Future studies of PsA should report the subtypes of nail changes. Longitudinal studies are needed to determine whether onycholysis predicts PsA.

Inflammatory cytokines in relation to adrenal response following total hip replacement.

Our objective was to investigate the initiation and course of pro- and anti-inflammatory cytokines in early inflammatory response and to elucidate the cytokine system in relation to the adrenal response caused by stress. Seven blood samples were collected, pre- and postoperatively (0-72 h) after total hip replacement (THR) due to osteoarthritis. The following cytokines were measured using Cytometric Bead Array: interleukin-1beta (IL-1beta), IL-6, tumour necrosis factor-alpha, IL-8, IL-12 and IL-10 (B&D). Thirteen patients took part in the study (67 +/- 9 years). C-reactive protein increased from <6 to over 200 mg/l on the second post-op day. The concentration of IL-6 increased 10-fold just 3 h post-op (4-47 pg/ml) and reached its maximum value 6 h post-op (77 pg/ml; Wilcoxon test P < 0.01) Repeated measurements were also significant (Friedman P < 0.05). The concentration of IL-8 doubled the day of surgery but did not reach a significant level (Friedman test =0.069). None of the other cytokines showed any significant changes. The diurnal cortisol rhythm was interrupted after the surgery and there was a significant correlation between the cortisol secretion and IL-6 response. This study demonstrates an isolated elevation in IL-6 levels with only a minor elevation in IL-8 following THR. This pro-inflammatory response seemed to decline without activation of anti-inflammatory cytokines (IL-10), but cortisol seemed to play a complicated role in halting the acute inflammatory response.

Synovial concentrations of the angiogenic peptides bFGF and VEGF do not discriminate rheumatoid arthritis from other forms of inflammatory arthritis.

OBJECTIVES: To investigate whether concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in aspirated synovial fluid can be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis. METHODS: bFGF and VEGF concentrations were measured in aspirated synovial fluid and serum samples from 66 patients with active arthritis (clinical diagnoses: rheumatoid arthritis (35 patients), psoriatic arthritis (9), reactive arthritis (11) and arthritis UNS (11)) utilizing commercial ELISA kits. RESULTS: In comparison with controls, elevated concentrations of VEGF were found in synovial fluid compared with in serum in all forms of arthritis. There were no significant differences in synovial fluid bFGF or VEGF concentrations between rheumatoid arthritis and the other forms of inflammatory arthritis. CONCLUSION: Both serum bFGF and VEGF concentrations were increased in patients with rheumatoid arthritis. Patients treated with steroids had lower synovial fluid bFGF concentrations. Synovial fluid levels of bFGF and VEGF were elevated but could not be used to distinguish rheumatoid arthritis from other forms of inflammatory arthritis.

Prevalence of long term steroid treatment and the frequency of decision making to prevent steroid induced osteoporosis in daily clinical practice.

BACKGROUND: The use of oral corticosteroids (CS) is one of the most common causes of iatrogenic osteoporosis. Recently, therapeutic guidelines dealing with the skeletal complication of CS have been published. OBJECTIVE: To evaluate how CS are used in the community and the frequency of active intervention against corticosteroid induced osteoporosis in daily clinical practice. MATERIAL AND METHODS: After approval by the Committee on Medical Ethics and the Data Protection Commission all prescriptions for CS which were filled by pharmacies in the northeast area of Iceland (population 26,664) during a two year period were collected. Thereafter, clinical information was obtained from medical records at the healthcare centres and from the local hospital. Patients who were taking CS for at least three months a year or for repeated periods (for a total of three months annually) were included in the study. These patients also received a questionnaire about hormone replacement therapy, bisphosphonates, and dietary consumption of calcium and vitamin D. RESULTS: A total of 191 patients were included in the study or 0.7% of the population. Their mean age was 66 years (17-93) and 106/191 (55%) were women. Only 63 (33%) patients had no registered complication due to the treatment, according their medical records. Thirty nine (20%) patients had had an osteoporosis related fracture and 50 (26%) of the patients had presumed CS induced osteoporosis. A total of 52% patients were receiving supplementary vitamin D (fish liver oil) and 37% were taking calcium tablets regularly, while 91% of the patient group were consuming milk products regularly. Only 17 (9%) patients were taking bisphosphonates and 18/81 (22%) of the postmenopausal women were receiving hormone replacement therapy. CONCLUSIONS: Relatively few patients receiving long term treatment with CS are also receiving primary prevention against CS induced osteoporosis, although several patients are taking vitamin D and calcium tablets. Specific treatment against osteoporosis was in most cases instituted secondary to osteoporotic complications. Thus although there are available treatment alternatives against CS induced osteoporosis, the doctors who prescribed CS did not make use of this form of treatment for their patients.

Inflammation and structural changes in the airways of patients with primary Sjögren's syndrome.

The present study aimed to compare the cellular pattern and structural changes in the airways of patients with primary Sjögren's syndrome (pSS) with healthy controls. Bronchial biopsy specimens were obtained from seven subjects with pSS and seven healthy controls. All the patients with pSS had increased bronchial responsiveness to methacholine. In the biopsies inflammatory cells, cytokine-producing cells, tenascin and laminin were visual zed by immunostaining. Patients with pSS had a higher number of neutrophils and mast cells than healthy controls, while the number of eosinophils was similar in the two groups. The number of IL-8-positive cells was higher in pSS butthe numbers of IL-4-and IL-5-positive cells were not significantly different between pSS and healthy controls. The numbers of T cells in patients with pSS were higher than in healthy controls, while the numbers of CD25-positive cells were similar to the healthy controls. The degree of epithelial integrity in patients with pSS was significantly lower than in the control group and the tenascin and laminin layers were significantly thicker in the pSS group. There was a correlation between the number of mast cells and the thickness of the tenascin and laminin layers in pSS. In conclusion, we found that the cellular pattern in the bronchial mucosa of patients with pSS displayed large numbers of neutrophils, mast cells and T-lymphocytes. These changes in inflammatory cell numbers seemed to relate to the observed increased epithelial damage and structural changes of the subepithelium. The structural findings, but not the pattern of inflammatory cells, are shared with atopic asthma and may relate to the increased bronchial hyper-responsiveness seen in both diseases.

Sleep disturbances in patients with systemic lupus erythematosus: a questionnaire-based study.

OBJECTIVE: To assess the prevalence of subjective sleeping complaints by patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between various sleeping complaints and disease activity. METHODS: A standardised sleep questionnaire, The Uppsala Sleep Inventory, was used to investigate the sleeping habits of 30 outpatients with systemic lupus erythematosus (SLE) in comparison to population-based age- and sex-matched controls. RESULTS: Sleep deficit (difference between need of sleep and actual sleeping time) was similar in patients with SLE (0.8 +/- 0.9 hour) and age-matched female controls (0.4 +/- 0.8 hour). However, patients with SLE reported more frequent disturbances due to pain, both when trying to fall asleep (p < 0.01) and during the night (p < 0.01). They also reported frequent awakenings due to headache (p < 0.01) and disturbances due to other vegetative symptoms. Furthermore, the SLE patients were awake for significantly longer periods during the night and they estimated their degree of fatigue as significantly higher than the female controls (p < 0.0001). CONCLUSION: Patients with SLE seem to get a fairly normal amount of sleep, but are frequently disturbed by pain and by various vegetative symptoms, e.g. breathlessness, sweating, and palpitation, which indicate not only pain but also possible involvement of the nervous system. The nervous system may therefore play a role in sleep disturbances reported by patients with SLE.

[Community use of oral glucocorticosteroids in Iceland and prophylactic treatment for steroid-induced osteoporosis in daily clinical pratice.].

OBJECTIVE: The use of oral corticosteroids is one of the most common causes of iatrogenic osteoporosis. Recently, therapeutic guidelines dealing with the skeletal complication of corticosteroids have been published. Therefore, it is of interest to evaluate indication for long-term therapy with corticosteroids and the frequency of active intervention against steroid induced osteoporosis in daily clinical practise. MATERIAL AND METHODS: After approval by the Committee on Medical Ethics and the Comission of Data Protection all recipes on corticosteroids in drugstores during two years period in the area of North-east Iceland (population 26,664) were gathered. Thereafter, information was collected from medical records at the Health Care Centres and the local Hospital. Patients who were taking corticosteroids for at least three months per year or in a repeated periods (totally three months annually) were included in the study. These patients also received a questionnaire concerning hormone relpacement therapy and dieatary consumption of calcium and D-vitamin. RESULTS: One hundred and ninety-one patients were included in the study or 0.7% of the population. The mean age was 66 years (17-93) and 55% were females. Rheumatic and pulmonary disorders were the most frequent indication of the corticosteroid treatment. Twenty percents of the patients had expired an osteoporosis related fractures and 26% of the patients had supposed corticosteroids induced osteoporosis. Fifty-two percents of the patients were on sublimentary D-vitamin (fish liver oil) and 37% were taking calcium-tablets, while 91% of the patients were consuming milk products regularly. Nine percents of the patients were taking bisphosphonates and 21% of postmenopausal women were on hormone replacement therapy. CONCLUSIONS: Relatively few patients on long term corticosteroids are on primary prevention against corticosteroids induced osteoporosis, although several patients are on D-vitamin and calcium sublimentation. Specific treatment against osteoporosis was in most cases instituted secondary to osteoporotic complications. Thus, corticosteroids prescribing doctors are urged to applicate the new therapy alternatives against corticosteroid-induced osteoporosis to their patients.

Sleep disturbances in outpatients with ankylosing spondylitisa questionnaire study with gender implications.

OBJECTIVE: To study the sleep pattern in ankylosing spondylitis, and to investigate gender differences in sleep, pain, and fatigue. METHODS: Forty-three male and 27 female patients with ankylosing spondylitis completed a sleep questionnaire and the results were compared with earlier findings in 3,558 persons randomly selected from the general population. RESULTS: Too little sleep was reported by 80.8% of the female and 50.0% of the male patients, compared to 28.8% and 21.8% respectively in the reference group (p<0.0001). The main reason was pain in the pre-sleep and sleep-periods (p<0.0001). Daytime fatigue was a major problem (p<0.0001). Higher correlation was found between pain and daytime fatigue than between sleep disturbance and daytime fatigue. CONCLUSION: Sleep disturbance is a significant problem in ankylosing spondylitis. The disturbance is closely related to pain at bedtime and during the night. Gender differences exist in the subjective sleep disturbance, fatigue, and pain.

Psychological well-being in patients with primary Sjögren's syndrome.

OBJECTIVES: To evaluate quality of life and psychological symptoms in patients with primary Sjögren's syndrome and to compare this with patients with rheumatoid arthritis. METHODS: A standardised questionnaire, the Psychological General Well-Being Index (PGWB), was used to examine the quality of life and psychological symptoms in patients with primary Sjögren's syndrome (pSS; n = 34). Patients with rheumatoid arthritis (RA; n = 32) were used as patient controls. RESULTS: The total mean score +/- SD for PGWB was 84.9 +/- 16.2 in pSS patients and significantly lower (p = 0.001) than in RA patients (97.7 +/- 17.5). Patients with pSS had an increased propensity for depressed mood (p = 0.0009), and suffered from reduced well-being (p = 0.002) and impaired vitality (p = 0.003). CONCLUSION: The results suggest that patients with pSS have a reduced quality of life, a higher degree of distress and a lower sense of well-being than patients with RA.

Anxiety and depression in patients with primary Sjögren's syndrome.

OBJECTIVE: To examine the degree of anxiety and depression and to assess well being and general symptoms in patients with primary Sjögren's syndrome (SS). METHODS: A standardized questionnaire, the Hospital Anxiety and Depression Scale, was used to examine the degree of anxiety and depression in patients with primary SS (n = 62) and in age matched healthy female controls. The Gothenburg quality of life instrument (GQOL) was used to assess well being and general symptoms. Patients with rheumatoid arthritis (RA; n = 38) were used as patient controls. RESULTS: The patients with primary SS had significantly higher scoring rate for "possible" clinical anxiety (48%) and for "possible" clinical depression (32%) compared with reference groups (p<0.05). The physical and mental well being of the patients with primary SS were significantly reduced compared with controls. Furthermore, patients with primary SS complained more commonly of low mood, irritability, headache, gastrointestinal symptoms, and impaired concentration and memory than the patients with RA. CONCLUSION: The results indicate that patients with primary SS often have psychiatric symptoms and worse well being, which may affect their quality of life.

Different airway responsiveness profiles in atopic asthma, nonatopic asthma, and Sjögren's syndrome. BHR Study Group. Bronchial hyperresponsiveness.

BACKGROUND: Different mechanisms may underlie bronchial hyperresponsiveness (BHR) in different diseases. The aim of this study was to investigate the bronchial responsiveness profile produced by three different challenge tests, methacholine, a direct stimulus, and two indirect stimuli, adenosine 5'-monophosphate (AMP) and cold air, in subjects with asthma and patients with Sjögren's syndrome. METHODS: The study population comprised 40 adult patients with asthma, 18 subjects with Sjögren's syndrome, and 20 controls. Blood samples were collected before each challenge for measurements of serum eosinophil peroxidase (S-EPO) and eosinophil cationic protein (S-ECP). The investigated subjects recorded peak expiratory flow and kept a symptom diary. RESULTS: Atopic subjects with asthma were significantly more hyperresponsive to AMP than nonatopic subjects with asthma (P=0.01) and subjects with Sjögren's syndrome (P=0.02). No difference was seen between atopic and nonatopic subjects with asthma in the case of challenges with methacholine or cold air. In atopic subjects with asthma, a significant correlation was found between challenges with methacholine and AMP (r=0.91, P=0.0001) and methacholine and cold air (r=0.83, P=0.004), but, in nonatopic subjects with asthma, no significant correlation was seen between methacholine and AMP or cold air challenges. In atopic subjects with asthma, the dose-response slope for AMP was correlated to S-EPO (r= -0.56; P = 0.01) and S-ECP (r= -0.51, P = 0.02), while no correlation between BHR and inflammation markers was found in the two other patient groups. CONCLUSIONS: The results of this study suggest that patients with asthma and subjects with Sjögren's syndrome display different bronchial responsiveness profiles for different challenge agents. Atopic subjects with asthma are more hyperresponsive to AMP than nonatopic subjects and patients with Sjögren's syndrome. More than one challenge may be required to detect different aspects of bronchial responsiveness.

[Deep vein thrombosis incidence at Akureyri Hospital, Iceland 1975-1990. Long term prognosis.].

OBJECTIVE: To evaluate the incidence of deep vein thrombosis (DVT) in a rural area of Iceland and the prevalence of post thrombotic syndrome (PTS) in patients with history of DVT. MATERIAL AND METHODS: A retrospective study where all phlebographies (n=177) performed at the department of radiology, Akureyri Hospital, during the period 1975-1990 were re-evaluated. Information on patients with DVT (n=32) were taken both from the Hospital and the Health Center records. All patients alive in December 1997 (n=17), 10.5 years after the diagnosis of DVT were interviewed concerning PTS. RESULTS: The incidence of DVT during the period 1975-1990 was 1/10,000 inhabitants/year, but was 2.3/10,000/ year for the period 1986-1996. The mean age was 60 years and 62% of the patients were males. In 37.5% cases DVT was localized below the popliteal vein, in another 34.4% below the inguinal ligament and 28.1% of the thrombosis extended to the pelvic vein system. Of the patients 23.3% had a history of malignancy and 20% had undergone a major operation or had trauma. Of the patients 46.7% were smokers. At 10.5 years follow-up, 71% of the patients had some problems due to PTS, and these symptoms influenced significantly their quality of daily life. CONCLUSIONS: The prevalence of DVT in Iceland seems to be only half of what foreign studies suggest and patients with history of DVT suffer frequently from PTS 10 years after the DVT. These data indicate that it is necessary to improve the long term treatment of patients with history of DVT.