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Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data

BackgroundEvidence reveals sex differences in physiology, disease presentation and response to treatment in axial spondyloarthritis (axSpA). Pooled data from four randomized controlled trials demonstrated reduced treatment efficacy of a tumor necrosis factor inhibitor (TNFi) in females compared to males with ankylosing spondylitis1. However, real-life evidence confirming these data in large cohorts is scarce. We sought to validate prior studies using data from a large multinational cohort based on real-life clinical practice.ObjectivesTo investigate sex differences in treatment response and drug retention rates in clinical practice among patients with axSpA, treated with their first TNFi.MethodsData from biologic-naïve axSpA patients initiating a TNFi in the EuroSpA registries were pooled. In the primary analysis, propensity-score weighting was applied to assess the causal effect of sex on clinically important improvement (CII) according to ASDAS-CRP at 6 months. A generalized linear regression model was used to estimate the causal risk difference (RD) and relative risk (RR) of sex on CII. Possible covariates influencing the outcome were determined a priori and selected based on availability in the database (ResultsIn total, 6,451 axSpA patients with available data on ASDAS-CRP at baseline and 6 months were assessed for treatment response. Baseline characteristics are shown in the Table 1. In the adjusted analysis, the probability for females to have CII was 15% (RR, 0.85; 95% confidence interval [CI], 0.82 to 0.89) lower compared to males and the difference in probability for having CII was 9.4 percentage points (RD, 0.094; 95% CI, 0.069 to 0.12). The survival analysis included 28,608 axSpA patients with available data on retention rates. The TNFi 6/12/24-month retention rates were significantly lower in females (81%/69%/58%) compared to males (89%/81%/72%), see Figure 1.Table 1.FemaleMaleMean (SD), Median [IQR] or percentagesMean (SD), Median [IQR] or percentagesAge (years)42.0 (12.1)41.4 (12.3)Fulfilment of mNYC66%80%Disease duration (years)2.0 [1.0, 7.0]3.0 [1.0, 9.0]TNFi start year Start 1999-20097.2%9.8% Start 2010-201326%27% Start 2014-201637%36% Start 2017-202030%27%BASDAI, mm59 (20)54 (21)BASFI, mm48 (25)46 (24)ASDAS, units3.5 (0.9)3.5 (1.0)CRP (mg/L)6.7 [2.5, 16.0]11.9 [4.0, 25.0]SJC (0-28)0 [0, 0]0 [0, 0]TJC (0-28)0 [0, 2]0 [0, 1]VAS pain, mm63 (22)59 (24)VAS fatigue, mm65 (25)59 (26)mNYC, modified New York criteria; TNFi, tumor necrosis factor inhibitor; BASDAI, Bath Ankylosing Spondylitis Disease Activity Indexf; BASFI, Bath Ankylosing Spondylitis Functional Index; ASDAS, Ankylosing Spondylitis Disease Activity Score; CRP, C-reactive protein; SJC, swollen joint count; TJC, tender joint count; VAS, visual analogue scale.ConclusionTreatment efficacy and retention rates are lower among female patients with axSpA initiating their first TNFi. Females presented with lower C-reactive protein levels and higher scores on patient reported outcomes at baseline, reflecting differences in disease expression. Recognizing these sex differences is of relevance for customized patient care and may improve patient education.References[1]van der Horst-Bruinsma et al. Ann Rheum Dis. 2013 Jul;72(7):1221-4.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsPasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: UCB, Consultant of: Abbvie, Eli Lily, Novartis and UCB, Grant/research support from: Novartis, Janssen, UCB and Eli Lilly, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis, Thomas Klausch: None declared, Michael Nurmohamed Speakers bureau: Abbvie, Janssen and Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS, Ronald van Vollenhoven Consultant of: AbbVie, AstraZeneca, Biogen, BMS, Galapagos, Janssen, Miltenyi, Pfizer, UCB and speaker fees from Abbvie, Galapagos, GSK, Janssen, Pfizer, R-Pharma and UCB, Grant/research support from: BMS, GSK and UCB, Dan Nordström Consultant of: Abbvie, BMS, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Anna-Mari Hokkanen Grant/research support from: MSD, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis and Pfizer, Elsa Vieira-Sousa Speakers bureau: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Consultant of: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Grant/research support from: MSD, Celgene, Novartis, Janssen, Abbvie and Pfizer, Anne Gitte Loft Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche and UCB, Grant/research support from: Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie and BMS, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene and Novartis, Ulf Lindström: None declared, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly and Novartis, Brigitte Michelsen Grant/research support from: Novartis, Adrian Ciurea Speakers bureau: AbbVie and Novartis, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis and Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis and Pfizer, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis and Pfizer, Corina Mogosan Speakers bureau: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Consultant of: AbbVie, Ewopharma, Lilly, Novartis and Pfizer, Gary Macfarlane Grant/research support from: GSK, Gareth T. Jones Grant/research support from: AbbVie, Pfizer, UCB, Amgen and GSK, Karin Laas Speakers bureau: Amgen, Janssen, Novartis and Abbvie, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek and Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi and Sandoz-Lek, Isabel Castrejon Speakers bureau: Eli Lilly, BMS, Janssen, MSD and Abbvie, Consultant of: Eli Lilly, BMS, Janssen, MSD and Abbvie, Manuel Pombo-Suarez Consultant of: Abbvie, MSD and Roche, Björn Gudbjornsson Speakers bureau: Amgen and Novartis, Consultant of: Amgen and Novartis, Arni Jon Geirsson: None declared, Eirik kristianslund: None declared, Jiří Vencovský Speakers bureau: Abbvie, Argenx, Boehringer-Ingelheim, Eli-Lilly, Gilead, MSD, Novartis, Octapharma, Pfizer, Roche, Sanofi and UCB, Consultant of: Abbvie, Argenx, Boehringer-Ingelheim, Eli-Lilly, Gilead, MSD, Novartis, Octapharma, Pfizer, Roche, Sanofi and UCB, Lucie Nekvindova: None declared, Semih Gulle: None declared, Berrin Zengin: None declared, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz and Novartis, Irene van der Horst-Bruinsma Speakers bureau: BMS, AbbVie, Pfizer and MSD, Consultant of: Abbvie, UCB, MSD, Novartis and Lilly, Grant/research support from: MSD, Pfizer, AbbVie and UCB.

BackgroundIn axial spondyloarthritis (axSpA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a key patient-reported outcome. However, one or more of its components may be missing when recorded in clinical practice.ObjectivesTo determine whether an individual patient’s BASDAI at a given timepoint can be reliably calculated with different single imputation techniques and to explore the impact of the number of missing components and/or differences between missingness of individual components.MethodsReal-life data from axSpA patients receiving tumour necrosis factor inhibitors (TNFi) from 13 countries in the European Spondyloarthritis (EuroSpA) Research Collaboration Network were utilized [1]. We studied missingness in BASDAI components based on simulations in a complete dataset, where we applied and expanded the approach of Ramiro et al. [2]. After introducing one or more missing components completely at random, BASDAI was calculated from the available components and with three different single imputation techniques: possible middle value (i.e. 50) of the component and mean and median of the available components. Differences between the observed (original) and calculated scores were assessed and correct classification of patients as having BASDAIResultsA total of 19,894 axSpA patients with at least one complete BASDAI registration at any timepoint were included. 59,126 complete BASDAI registrations were utilized for the analyses with a mean BASDAI of 38.5 (standard deviation 25.9). Calculating BASDAI from the available components and imputing with mean or median showed similar levels of agreement (Table 1). When allowing one missing component, >90% had a difference of ≤6.9 mm between the original and calculated scores and >95% were correctly classified as BASDAI90% (Figure 1, upper panels). As expected, it was observed that regardless of the BASDAI component set to missing and the imputation technique used, correct classification of patients as BASDAITable 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAILevel of agreement with Dif≤6.9 mm* (%)Correct classification for BASDAI1 missing componentAvailable93.996.9Value 5073.996.3Mean94.296.8Median93.196.82 missing componentsAvailable83.794.8Value 5040.792.8Mean83.594.8Median82.894.73 missing componentsAvailable71.992.6Value 5028.187.3Mean72.292.6Median69.792.2* The levels of agreement with a difference (Dif) of ≤6.9 mm between the original and calculated scores were based on the half of the smallest detectable change. Agreement of >90% was considered as acceptable. ** Correct classification of >95% was considered as acceptable.Figure 1.Level of agreement between the original and calculated BASDAI and correct classification for BASDAIConclusionBASDAI calculation with available components gave similar results to single imputation of missing components with mean or median. Only when missing one of BASDAI components 5 or 6, single imputation techniques can reliably calculate individual BASDAI scores. However, missing any single component value results in misclassification of patients with original BASDAI scores close to 40.References[1]Ørnbjerg et al. (2019). Ann Rheum Dis, 78(11), 1536-1544.[2]Ramiro et al. (2014). Rheumatology, 53(2), 374-376.AcknowledgementsNovartis Pharma AG and IQVIA for supporting the EuroSpA collaboration.Disclosure of InterestsStylianos Georgiadis Grant/research support from: Novartis, Myriam Riek Grant/research support from: Novartis, Christos Polysopoulos Grant/research support from: Novartis, Almut Scherer Grant/research support from: Novartis, Daniela Di Giuseppe: None declared, Gareth T. Jones Speakers bureau: Janssen, Grant/research support from: AbbVie, Pfizer, UCB, Amgen, GSK, Merete Lund Hetland Grant/research support from: Abbvie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Fonden, MSD, Medac, Pfizer, Roche, Samsung Biopies, Sandoz, Novartis, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, UCB, Grant/research support from: Abbvie, BMS, Merck, Celgene, Novartis, Simon Horskjær Rasmussen Grant/research support from: Novartis, Johan K Wallman Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Novartis, Bente Glintborg Grant/research support from: Pfizer, Abbvie, BMS, Anne Gitte Loft Speakers bureau: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: AbbVie, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Karel Pavelka Speakers bureau: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Consultant of: Pfizer, MSD, BMS, UCB, Amgen, Egis, Roche, AbbVie, Jakub Zavada Speakers bureau: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Consultant of: Abbvie, Elli-Lilly, Sandoz, Novartis, Egis, UCB, Merih Birlik: None declared, Ayten Yazici Grant/research support from: Roche, Brigitte Michelsen Grant/research support from: Novartis, Eirik kristianslund: None declared, Adrian Ciurea Speakers bureau: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Michael J. Nissen Speakers bureau: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Janssens, Novartis, Pfizer, Ana Maria Rodrigues Speakers bureau: Abbvie, Amgen, Consultant of: Abbvie, Amgen, Grant/research support from: Novartis, Pfizer, Amgen, Maria Jose Santos Speakers bureau: Abbvie, AstraZeneca, Lilly, Novartis, Pfizer, Gary Macfarlane Grant/research support from: GSK, Anna-Mari Hokkanen Grant/research support from: MSD, Heikki Relas Speakers bureau: Abbvie, Celgene, Pfizer, UCB, Viatris, Consultant of: Abbvie, Celgene, Pfizer, UCB, Viatris, Catalin Codreanu Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Ewopharma, Lilly, Novartis, Pfizer, Corina Mogosan: None declared, Ziga Rotar Speakers bureau: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Consultant of: Abbvie, Novartis, MSD, Medis, Biogen, Eli Lilly, Pfizer, Sanofi, Lek, Janssen, Matija Tomsic Speakers bureau: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Consultant of: Abbvie, Amgen, Biogen, Eli Lilly, Janssen, Medis, MSD, Novartis, Pfizer, Sanofi, Sandoz-Lek, Björn Gudbjornsson Speakers bureau: Amgen, Novartis, Consultant of: Amgen, Novartis, Arni Jon Geirsson: None declared, Pasoon Hellamand Grant/research support from: Novartis, Marleen G.H. van de Sande Speakers bureau: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Consultant of: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Grant/research support from: Eli Lilly, Novartis, UCB, Janssen, Abbvie, Isabel Castrejon: None declared, Manuel Pombo-Suarez Consultant of: Abbvie, MSD, Roche, Bruno Frediani: None declared, Florenzo Iannone Speakers bureau: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Abbvie, Amgen, AstraZeneca, BMS, Galapagos, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, UCB, Lykke Midtbøll Ørnbjerg Grant/research support from: Novartis

Objective—To assess organ involvement according to a modified Medsger severity scale and its relation to outcome and prognosis in patients with systemic sclerosis. Methods—One hundred consecutive patients observed in Lund with systemic sclerosis were followed up for a period of 14 years. The mean follow up time was 7.7 years. Initial assessment and an annual evaluation was performed for each patient, with a mean visit frequency of 5.6 per patient. Results—Age at referral, high total skin score, truncal skin involvement, low vital capacity, low static lung compliance, low Cr-EDTA clearance, and ECG abnormalities at the initial assessment predict poor outcome. A severity scoring system for five organ systems indicates a slow progression of organ dysfunction after recruitment into the study. The female: male ratio was 2:1, the mean age at onset of symptoms was 42.3 (range 3‐82), and the mean age at recruitment was 47.2 years (range 17‐82). Thirty patients died during the follow up period at the mean age of 61.3 years (range 33‐85). The causes of death were directly related to systemic sclerosis in at least 10 patients, infections in six, cancers in nine, and other causes in four patients. The standardised mortality ratio was 3.5 and 3.7 for men and women, respectively. Conclusion—A high severity score for function of vital organs was shown to predict shortened survival. In this study a severity score based on simple clinical assessment variables was able to predict poor outcome from extensive skin changes, ECG changes, and compromised lung and renal function. Organ dysfunction mainly became manifest during the first five years of the disease, whereafter organ function remained largely stable. (Ann Rheum Dis 2001;60:1117‐1122)

The diagnostic value of measuring rheumatoid factor (RF) by agglutination or isotype-specific enzyme-linked immunosorbent assay (ELISA) was compared. The study included 70 patients with rheumatoid arthritis (RA) and 205 patients with various other rheumatic conditions. Of the RA patients, 74% were RF-positive by agglutination and 90% had one or more RF isotypes elevated by ELISA compared to 14% and 22%, respectively, of the other patients. Strikingly, 70% of the RF-positive RA patients had an elevation of two or more RF isotypes compared to only 16% of the other RF-positive patients (P

OBJECTIVES--To investigate the incidence, prevalence and clinical features of systemic sclerosis (SS) in Iceland. METHODS--All patients diagnosed with SS from 1975-90 were included. Retrieval for the study began in 1980 and was carried out by computerised search from registers of all hospitals and health care clinics and death registration files, and with personal communication with doctors in Iceland. RESULTS--Over a 16 year period from 1975-90, 15 new cases were found with an incidence of 0.7 and 0.05/100,000, for females and males at risk respectively, and 0.38 for both sexes. At the end of 1990 there were 18 patients alive with SS, 13 with limited and five with diffuse cutaneous involvement. The age standardised prevalence was 11.9 and 1.5/100,000 for females and males at risk respectively. The crude prevalence rate for both sexes was 7.1/100,000. There were five deaths, two patients died of SS related causes, one had SS renal disease. The relative risk of death was similar to that in the general population. The calculated five year survival rate was 100% and the 10 year survival rate 81%. No HLA antigen association was found. CONCLUSION--Compared with previous surveys this study shows a low incidence of systemic sclerosis and a high proportion of patients with limited cutaneous involvement.

High dropout rate in first year programming courses is a problem in many universities but the reasons for dropout can be different for different students. Students in first year programming courses may have different backgrounds that can influence what teaching methods are most relevant and the level and rate of the teaching. This paper describes students' attitude towards teaching and learning material in a first year programming course at Reykjavik University in Iceland. In the survey described in this paper, novice students considered the task to divide activity into functions and classes and to find errors in one's own programs to be the most difficult tasks. The most useful tasks were to work on assignments, recordings of teachers lecture and teacher's lectures.

To determine the prevalence of fibromyalgia and chronic widespread musculoskeletal pain (CWP) in Iceland in two demographic different areas.Population based prevalence study on 1200 females and 1200 males 18-79 years old in South-West- and South-Iceland. Established musculoskeletal pain questionnaire and telephone screening of nonresponders was used. Tender point examination was done on the subjects with CWP and the diagnosis of fibromyalgia was made in accordance with the American College of Rheumatology (ACR) 1990 criteria.The prevalence of fibromyalgia in females based on 60.4% of the sample is 9.8%. The comparable prevalence in males based on 46.4% of the sample is 1.3%. The prevalence of CWP is 26.9% in females and 12.9% in males. A sharp increase in the prevalence of fibromyalgia and CWP in females is seen in the age group 31-40 compared with the age group 18-30. For female responders a statistical higher prevalence of CWP but not fibromyalgia is seen in South-West-Iceland, compared with South-Iceland. No regional differences were seen for males.The prevalence of fibromyalgia and CWP is very high in Iceland. A matter of special concern is the high prevalence in young females. Possible causes are long working hours and stressful living conditions.

Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis. Although there is a large body of evidence suggesting that RA is immune mediated, the etiology remains unresolved. Twin studies have shown disease concordance rates of approximately 15% in monozygotic twins and 4% in dizygotic twins, while the estimated risk ratio for siblings of RA patients ranges from 5 to 8. Our goal was to use genealogic data from Iceland to further investigate the genetic component of RA.Data were obtained from a population-based, computerized genealogy database that was developed to examine multigenerational relationships among individuals in the relatively homogeneous population of Iceland. Using an algorithm, the minimum founder test, we calculated the least number of founders required to account for a list of RA patients, and compared it with 1,000 sets of same-sized matched control groups. In addition, we estimated the kinship coefficient and risk ratios for relatives of the RA patients.Several familial clustering tests demonstrated that the RA patients were more related to each other than were the average control set of Icelanders. A significantly fewer number of founders was necessary to account for our patient list than for the random sets of matched controls (P0.001), and the average pairwise identity-by-descent sharing was greater among the patients than among the control sets (P0.001). In addition, there was an increased risk of RA in first- and second-degree relatives of the patients; e.g., for siblings, the risk ratio was 4.38 (95% confidence interval 3.26-5.67), and for uncles/aunts, the risk ratio was 1.95 (95% confidence interval 1.52-2.43).The familial component of RA is shown to extend beyond the nuclear family, thus providing stronger evidence for a significant genetic component to RA.

To examine left ventricular (LV) myocardial perfusion and function, in systemic sclerosis. Myocardial perfusion was assessed at rest, during cold exposure, and at peak exercise in 10 patients with systemic sclerosis. Seven of the 10 patients were examined with Doppler echocardiography; before and after long-term diltiazem treatment. Compared with average resting values, isotope uptake was increased by 48% after exercise, compared with cold exposure the exercise value was increased by 35%. After 11 months of diltiazem treatment there was no change in myocardial uptake, compared with respective values before treatment. Doppler echocardiography showed an increase in LV end-diastolic diameter, fractional shortening, and left ventricular outflow tract velocity, after treatment. This indicates that long-term diltiazem treatment does not increase myocardial perfusion at rest, post-exercise, or during cold exposure. On the other hand diltiazem treatment may improve left ventricular performance.

To measure the effect of cooling on digital blood pressure we used a strain-gauge and photoplethysmograph, with an automatic cooling device. Eighteen patients were compared with 18 matched controls. Laser-doppler technique was used to measure the perfusion changes after heating a small area of the skin in 5 locations on the body, readings were given in perfusion units. Eighteen patients with systemic sclerosis were compared with 25 individuals with primary Raynaud's phenomenon and 30 healthy controls. Cooling to 10 degrees C caused a significant digital blood pressure drop of 58 mmHg in patients with systemic sclerosis and 61 mmHg in Raynaud's phenomenon, as compared with controls. The microcirculation in patients with systemic sclerosis responded in the same way to local heating as in the normal population, increasing the perfusion to the same extent. In conclusion, an unselected group of patients with systemic sclerosis have normal dermal microcirculatory response to heating in spite of severe cold intolerance.

Sixteen patients with classic rheumatoid arthritis (RA) complicated by severe vasculitis were studied and compared with a matched control group of 16 RA patients without vasculitis. Seven of the patients with vasculitis died within 4 to 120 months (median 32 months) after developing vasculitic symptoms. Gangrene of digits and extremities, bowel ulcers or bowel perforation, or both, and cardiac involvement were more common among the patients who died than among those with a more favourable course. The present data suggest that large vessel vasculitis in RA is associated with high frequency of arteriosclerotic vascular disease. The serum concentrations of complement components C3 and C4 were lower, and concentrations of IgM rheumatoid factor, complement activating rheumatoid factor, and C1q binding immune complexes (C1q solid and C1q fluid phase assay) were significantly higher among vasculitic patients than in the control group. Laboratory data provided little prognostic information with regard to rheumatoid vasculitis, with the exception that IgM and IgG rheumatoid factors were significantly higher among patients with fatal course of disease than in those who achieved remission.

Cineradiography of the esophagus showed signs of esophageal candidiasis in 11 out of 71 patients with progressive systemic sclerosis (PSS) - both in diffuse scleroderma and the CREST syndrome. Culture of esophageal brushings confirmed the presence of Candida albicans in eight of these 11 patients. Antimycotic treatment decreased the cineradiographic signs of candidiasis and the degree of dysphagia. Since impaired esophageal motility and treatment with immunosuppressive drugs may predispose to candida esophagitis, and since dysphagia will decrease after antimycotic treatment esophageal mycosis should always be sought in patients with PSS.

Etude realisee chez 40 malades. Evaluation de la frequence et de l'importance des lesions cardiaques (troubles du rythme, troubles de la conduction, ischemie). Comparaison des patients ayant un syndrome CREST avec ceux atteints d'une forme disseminee de la maladie. Resultats obtenus sur un ECG de repos, un ECG a l'effort et un halter sur 24 heures