A study of the reliability and construct validity of the 1-minute sit-to-stand test for individuals with systemic sclerosis.

OBJECTIVE: This study seeks to assess the reliability and construct validity of the 1-minute sit-to-stand test as an efficient tool for evaluating the functional capacity of individuals with systemic sclerosis, considering its time and space effectiveness. METHODS: This cross-sectional study recruited forty-nine individuals with systemic sclerosis from a university hospital in Denmark. The 1-minute sit-to-stand test was conducted twice on the same day, with an interval of approximately 10 to 15 minutes between administrations, followed by a single administration of the 6-minute walk test. Reliability and validity were estimated using Bland-Altman statistics, intraclass correlation coefficient (ICC2,1), paired t-test, and Spearman's rank correlation coefficient (ρ). RESULTS: The 1-minute sit-to-stand test exhibited excellent test-retest reliability with an ICC2,1 (CI) of 0.97 (0.95-0.99). The minimal metrically detectable change between separate measures on a subject for the difference in the measures to be considered real at the 95% confidence level was 2.9 repetitions and 11%, respectively. A learning effect of one repetition was observed between repeated measures. High construct validity was observed between the 1-minute sit-to-stand and 6-minute walk test (ρ = 0.78, p < .001). CONCLUSIONS: This study demonstrates the 1-minute sit-to-stand test as highly reliable, with an 11% change indicating a true outcome change. It also demonstrates robust construct validity compared to the 6-minute walk test. The 1-minute sit-to-stand test appears feasible for assessing functional capacity in well-functioning individuals with systemic sclerosis, but prior familiarization with the task is recommended, as a small learning effect was observed with one repetition.

High-resolution peripheral quantitative computed tomography for the assessment of acro-osteolysis and calcinosis in patients with systemic sclerosis.

OBJECTIVE: To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc. METHODS: HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales. RESULTS: Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66-99%) and 80% (95% CI: 59-93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47-90%) and 95% (95% CI: 76-99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1-3) versus 0 (IQR: 0-1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability. CONCLUSION: HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.

Validity and reliability of measurement of peripheral oxygen saturation during the 6-Minute Walk Test in patients with systemic sclerosis.

Peripheral oxygen saturation (SpO2) using the fingers may have important limitations due to Raynaud's phenomenon and sclerodactyly in patients with systemic sclerosis (SSc). Sensors located at more central body positions may be more accurate as these as less prone to Raynaud attacks. To determine the validity and reliability of the SpO2 measured at the finger, forehead, and earlobe during the 6-Minute Walk Test (6MWT). Eighty two patients with SSc had an arterial line placed while performing the 6MWT. Peripheral oxygen saturation was simultaneously measured by finger, forehead, and earlobe sensors and compared to the arterial oxygen saturation (SaO2) measured before and after the 6MWT. 40 patients repeated the 6MWT one week later to determine re-test reliability. We used Bland-Altman plots to display the agreement between SpO2 and SaO2. The intraclass correlation coefficient for repeated measurement of minimum SpO2 was calculated. The mean difference between SpO2 and SaO2 after the 6MWT was - 3% (SD: ± 5), 0% (SD: ± 2), and 1% (SD: ± 2) for the finger, forehead, and earlobe, respectively. The minimum SpO2 measured at the finger demonstrated the poorest re-test reliability: The ICC (95% CI) showed good agreement using the ear and forehead probe (ICCear = 0.89 [95% CI 0.80; 0.94]; ICCforehead = 0.77 [95% CI 0.60; 0.87]), while a modest reliability was found using the finger probe (ICCfinger = 0.65 95% CI [0.43; 0.80]). SpO2 should be measured using either the earlobe or forehead during the 6MWT in patients with SSc. Clinical Trials.Gov (NCT04650659).

Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a vasospastic condition of the extremities in response to cold or stress, affecting approximately 3% to 5% of the population. While most patients have primary RP, the condition can also occur secondary to a variety of underlying medical conditions. RP may be the presenting symptom of connective tissue diseases, especially systemic sclerosis, and RS may therefore provide an opportunity for early diagnosis and treatment. This review addresses the causes, clinical features, diagnostic workup, and treatment possibilities of RS.

An overlook on the current registries for rare and complex connective tissue diseases and the future scenario of TogethERN ReCONNET.

Background: Patient registries play a crucial role in supporting clinical practice, healthcare planning and medical research, offering a real-world picture on rare and complex connective tissue diseases (rCTDs). ERN ReCONNET launched the first European Registry Infrastructure with the aim to plan, upgrade and link registries for rCTDs, with the final goal to promote a harmonized data collection approach all over Europe for rCTDs. Methods: An online survey addressed to healthcare professionals and patients' representatives active in the field of rCTDs was integrated by an extensive database search in order to build a mapping of existing registries for rCTDs. Findings: A total of 140 registries were found, 38 of which include multiple diseases. No disease-specific registry was identified for relapsing polychondritis, mixed connective tissue disease and undifferentiated connective tissue disease. Discussion: This overview on the existing registries for rCTDs provides a useful starting point to identify the gaps and the strengths of registries on the coverage of rCTDs, and to develop a common data set and data collection approach for the establishment of the TogethERN ReCONNET Infrastructure.

Occupational exposure to respirable crystalline silica and risk of autoimmune rheumatic diseases: a nationwide cohort study.

BACKGROUND: Exposure to respirable crystalline silica is suggested to increase the risk of autoimmune rheumatic diseases. We examined the association between respirable crystalline silica exposure and systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and small vessel vasculitis. METHODS: In a cohort study of the total Danish working population, we included 1 541 505 male and 1 470 769 female workers followed since entering the labour market 1979-2015. Each worker was annually assigned a level of respirable crystalline silica exposure estimated with a quantitative job exposure matrix. We identified cases of autoimmune rheumatic diseases in a national patient register and examined sex-specific exposure-response relations by cumulative exposure and other exposure metrics. RESULTS: We identified 4673 male and 12 268 female cases. Adjusted for age and calendar year, men exposed to high levels of respirable crystalline silica compared with non-exposed showed increased incidence rate ratio (IRR) for the four diseases combined of 1.53 [95% confidence interval (CI): 1.39-1.69], for systemic sclerosis of 1.62 (1.08-2.44) and rheumatoid arthritis of 1.57 (1.41-1.75). The overall risk increased with increasing cumulative exposure attained since entering the workforce [IRR: 1.07 (1.05-1.09) per 50 µg/m3-years]. Female workers were less exposed to respirable crystalline silica, but showed comparable risk patterns with overall increased risk with increasing cumulative exposure [IRR: 1.04 (0.99-1.10) per 50 µg/m3-years]. CONCLUSIONS: This study shows an exposure-dependent association between occupational exposure to respirable crystalline silica and autoimmune rheumatic diseases and thus suggests causal effects, most evident for systemic sclerosis and rheumatoid arthritis.

A follow-up study of occupational styrene exposure and risk of autoimmune rheumatic diseases.

OBJECTIVES: Increased risk has been suggested for autoimmune rheumatic diseases following solvent exposure. The evidence for specific solvents is limited, and little is known about exposure-response relations. Styrene is an aromatic, organic solvent and the objective of this study was to analyse the association between occupational styrene exposure and autoimmune rheumatic diseases in men and women. METHODS: We followed 72 212 styrene-exposed workers of the Danish reinforced plastics industry from 1979 to 2012. We modelled full work history of styrene exposure from employment history, survey data and historical styrene exposure measurements. We identified cases in the national patient registry and investigated gender-specific exposure-response relations by cumulative styrene exposure for different exposure time windows adjusting for age, calendar year and educational level. RESULTS: During 1 515 126 person-years of follow-up, we identified 718 cases of an autoimmune rheumatic disease, of which 73% were rheumatoid arthritis. When adjusting for potential confounders and comparing the highest with the lowest styrene exposure tertile, we observed a statistically non-significantly increased risk of systemic sclerosis among women (incidence rate ratio (IRR)=2.50; 95% CI 0.50 to 12.50) and men (IRR=1.86; 95 % CI 0.50 to 7.00), based on 9 and 22 cases, respectively. Results were inconsistent for the other autoimmune rheumatic diseases examined. CONCLUSION: This study suggests an association between occupational styrene exposure and systemic sclerosis in men as well as in women but based on few cases. This is a new finding and has to be replicated before conclusions can be drawn.

A systematic review of occupational exposure to coal dust and the risk of interstitial lung diseases.

Objective: Exposure to coal dust can cause interstitial lung disease (ILD), but whether this is due to pure coal or to the contents of quartz in coal is less clear. Here, we systematically reviewed the relation between 'pure coal' and ILD. Methods: In a systematic review based on PRISMA criteria 2945 articles were identified. Strict eligibility criteria, which evaluated the 'pure coal effect', led to the inclusion of only nine studies. Results: Among these nine studies six studies indicated an independent effect of the non-quartz part of coal on the development and progression of ILD, two did not demonstrate an effect and one was inconclusive. Conclusions: Although an independent effect of non-quartz coal dust on the development of ILD is supported, due to methodological limitations the evidence is limited and further evidence is needed.

Traditional cardiovascular risk factors and coronary artery calcification in adults with polymyositis and dermatomyositis: a Danish multicenter study.

OBJECTIVE: To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM, and CAC score. METHODS: Traditional CV risk factors were assessed in a cross-sectional, observational study of 76 patients with PM/DM and in 48 sex- and age-matched healthy controls. CAC was quantified by means of cardiac computed tomography scan and expressed in Agatston units. The associations between CV risk factors, PM/DM, and CAC were studied by multivariate analyses. RESULTS: Thirty-three percent of the patients were obese compared to 11% of the controls (P = 0.005). Hypertension and diabetes mellitus were more frequent in patients (71% versus 42%; P = 0.002, and 13% versus 0%; P = 0.007), and patients had higher levels of triglycerides (P = 0.0009). High CAC score occurred more frequently in patients (20% versus 4%; P = 0.04). In multivariate analysis of patient factors associated with CAC were age (P = 0.02) and smoking (P = 0.02). CONCLUSION: In this study, traditional CV risk factors and severe CAC were commonly found in patients with PM/DM. However, severe CAC was not associated with PM/DM per se, but rather with age and smoking in these patients.

[Silica exposure and the risk of systemic sclerosis]. / Kvartseksponering øger risikoen for systemisk sklerodermi.

The aetiology of systemic sclerosis (Ssc) is unknown, but there is evidence of environmental factors playing a part in disease development in a number of cases. By examining a group of male patients with Ssc we found significant exposure to silica in 26% (6/23) of the patients compared to 2,1% in the general working population in Denmark. In the article we review the association between silica and Ssc and suggest how to question and refer patients with SSc who are suspected to have been exposed to silica.

Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon: a multicentre study in the prospective EULAR Scleroderma Trials and Research (EUSTAR) database.

OBJECTIVE: To assess patients with SSc who present without circulating ANAs or RP. METHODS: Five thousand three hundred and ninety patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials and Research (EUSTAR) database were screened for the absence of both RP and circulating ANA. To differentiate SSc from its mimics, additional information was gathered using a standardized questionnaire. RESULTS: Five thousand three hundred and seventy-eight (99.8%) of the 5390 SSc patients in the EUSTAR database had either detectable ANA or a history of RP. Twelve (0.2%) patients lacked both circulating ANA and RP. Details of the medical history could be obtained for seven patients. Three cases were compatible with ANA-negative and RP-negative SSc and were not typical of any known SSc mimic. Four patients had a malignancy: two had breast cancer, one had multiple myeloma with possible scleromyxoedema and one had bladder carcinoma. There was no temporal relationship between the onset of skin fibrosis and that of the tumour. Although no patient with confirmed nephrogenic systemic fibrosis was identified among the cases of ANA-negative and RP-negative SSc, the presentation of one patient could be compatible with that of nephrogenic systemic fibrosis other than for the absence of chronic kidney disease or of known prior gadolinium exposure. CONCLUSION: We have identified a very small subgroup of SSc patients who lack both circulating ANA and RP, none of whom fulfils the diagnostic criteria for any known SSc mimic. Prospective studies are needed to elucidate the clinical presentation, evolution and outcome of such patients.

Interstitial fluid contains higher in vitro IGF bioactivity than serum: a study utilizing the suction blister technique.

CONTEXT: Circulating insulin-like growth factors (IGFs) are bound in complexes which affect their tissue-accessibility. Interstitial fluid is in close proximity to target cells, but the IGF-system is not well-described herein. OBJECTIVE: To perform a thorough comparison of the IGF-system in suction blister fluid (SBF) vs. in serum, with emphasis on bioactive IGF levels. DESIGN: Eight hour study including samples collected in the fasting state (20 h) and after a meal. SETTING: Clinical research facility. PARTICIPANTS: Six healthy males (age 37.0±8.8 years, BMI 22.5±1.4 kg/m(2)) (mean±SD). MAIN OUTCOME MEASURE: Serum and SBF concentrations of bioactive IGF (determined in vitro by specific IGF-I receptor (IGF-IR) phosphorylation assay), immunoreactive IGF and IGF binding protein (IGFBP) levels, Western ligand blotting (WLB) of IGFBPs and IGFBP-3 Western immunoblotting (WiB). RESULTS: The ability of SBF to phosphorylate the IGF-IR in vitro was 41±27% higher than that of serum (P=0.007 by repeated measures ANOVA). By contrast, immunoreactive IGF and IGFBP-concentrations were approximately 50% lower in SBF than in serum (all P≤0.002). A marked difference in the composition of IGFBPs between serum and SBF was observed, including 3-fold elevated amounts of IGFBP-3 fragments in SBF (P<0.001). For both IGF-I, IGF-II and IGFBP-2, the effect of food intake differed between serum and SBF (all P≤0.03). CONCLUSION: Despite lower concentrations, the in vitro IGF bioactivity was higher in SBF than in serum. This may relate to an increased enzymatic IGFBP-degradation and an altered IGFBP-composition in SBF, making more IGF-I and -II accessible to the IGF-IR. The impact of food intake on the IGF system differs between serum and interstitial fluid.