Epidemiology of systemic sclerosis: a multi-database population-based study in Tuscany (Italy)

Abstract Background Systemic Sclerosis (SSc) is a chronic autoimmune disease with a complex pathogenesis that includes vascular injury, abnormal immune activation, and tissue fibrosis. We provided a complete epidemiological characterization of SSc in the Tuscany region (Italy), considering prevalence and incidence, survival, comorbidities and drug prescriptions, by using a multi-database population-based approach. Cases of SSc diagnosed between 1st January 2003 and 31st December 2017 among residents in Tuscany were collected from the population-based Rare Diseases Registry of Tuscany. All cases were linked to regional health and demographic databases to obtain information about vital statistics, principal causes of hospitalization, complications and comorbidities, and drug prescriptions. Results The prevalence of SSc in Tuscany population resulted to be 22.2 per 100,000, with the highest prevalence observed for the cases aged ≥ 65 years (33.2 per 100,000, CI 95% 29.6–37.3). In females, SSc was predominant (86.7% on the total) with an overall sex ratio F/M of 6.5. Nevertheless, males presented a more severe disease, with a lower survival and significant differences in respiratory complications and metabolic comorbidities. Complications and comorbidities such as pulmonary involvement (HR = 1.66, CI 95% 1.17–2.35), congestive heart failure (HR = 2.76, CI 95% 1.80–4.25), subarachnoid and intracerebral haemorrhage (HR = 2.33, CI 95% 1.21–4.48) and malignant neoplasms (HR = 1.63, CI 95% 1.06–2.52), were significantly associated to a lower survival, also after adjustment for age, sex and other SSc-related complications. Disease-modifying antirheumatic drugs, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors were the drugs with the more increasing prevalence of use in the 2008–2017 period. Conclusions The multi-database approach is important in the investigation of rare diseases where it is often difficult to provide accurate epidemiological indicators. A population-based registry can be exploited in synergy with health databases, to provide evidence related to disease outcomes and therapies and to assess the burden of disease, relying on a large cohort of cases. Building an integrated archive of data from multiple databases linking a cohort of patients to their comorbidities, clinical outcomes and survival, is important both in terms of treatment and prevention.

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THU0351 MUSCLE INVOLVEMENT IN PATIENTS WITH SYSTEMIC SCLEROSIS AND ANTI-PM/SCL+ ANTIBODIES IS ASSOCIATED WITH CARDIAC AND PULMONARY INVOLVEMENT. ANALYSIS OF THE MULTICENTRE EUSTAR COHORT.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3525 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 407.1-407

Author(s):

M. G. Lazzaroni ◽

S. Zingarelli ◽

P. Airò ◽

Y. Allanore ◽

O. Distler

Keyword(s):

Systemic Sclerosis ◽

Cardiac Involvement ◽

Severe Disease ◽

Disease Onset ◽

Pulmonary Involvement ◽

Left Ventricular ◽

Research Support ◽

Muscle Involvement ◽

Group A ◽

Tendon Friction Rubs

Background:Anti-PM/Scl antibodies positivity has been associated with frequent skeletal muscle involvement in patients with Systemic Sclerosis (SSc) in different studies, including the EUSTAR cohort (1). Moreover, although myositis has been previously associated with heart involvement in SSc patients (2), this issue has never been explored among anti-PM/Scl+ patients.Objectives:To evaluate the cardiac involvement in anti-PM/Scl patients with SSc in the large multicentre EUSTAR database, with focus on the subgroup of patients with muscle involvement.Methods:Patients from the EUSTAR database were included when the item anti-PM/Scl was fulfilled in at least one visit.Results:Anti-PM/Scl status was available in 7,353 SSc patients from EUSTAR database: 295 were anti-PM/Scl+. After exclusion of 151 patients with multiple autoantibody positivity, 144 anti-PM/Scl + patients were compared with 7,058 anti-PM/Scl- patients. Among them, 3,120 (44.2%) were positive for ACA, 2,361 (33.5%) for anti-Topo I and 274 (3.88%) for anti-RNAP3.Regarding the specific cardiac outcomes, in the anti-PM/Scl+ as compared to the anti-PM/Scl- group, a decreased rate of elevated sPAP at ECHO was recorded (12.8% vs 25.0%, p:0.001), while no differences were observed in the frequency of conduction blocks (26.2% vs 23.7%, p:0.526), abnormal diastolic function (33.9% vs 36.4%, p:0.582), pericardial effusion (10.2% vs 10.9%, p:1.000) and LVEF ≤50% (4.76% vs 6.11%, p:0.818). In multivariate analysis, adjusted for age at disease onset, sex, and disease duration, the negative association of anti-PM/Scl with elevated sPAP was not confirmed (p:0.061).When comparing anti-PM/Scl+ patients with (n=47) and without (n=87) CK elevation, the former group had a higher frequency of conduction blocks (43.2% vs 17.5%, p:0.005; OR 95% CI 3.47, 1.51-7.97) and left ventricular dysfunction, both diastolic (45.6% vs 27.2%, p:0.050; OR 95% CI 2.25, 1.05-4.81) and systolic (LVEF ≤50% 13.3% vs 0%, p:0.018; OR 95% CI 16.8, 0.87-324). Moreover, anti-PM/Scl+ patients with CK elevation had significantly increased rate of lung fibrosis on HRCT (p:0.045), intestinal symptoms (p:0.017), joint contractures (p:0.045) and tendon friction rubs (p:0.034).Conclusion:In the largest series of anti-PM/Scl positive SSc patients so far reported, muscle involvement in anti-PM/Scl+ patients (defined as increased serum CK) seems to represent a marker of a more severe disease phenotype, including a higher frequency of cardio-pulmonary involvement.References:[1]Lazzaroni MG, et al. Ann Rheum Dis 2018. 77 (2), 421-2.[2]Follansbee WP, et al. Am Heart J 1993. 125: 194-203.Acknowledgments:Authors would like to thank the patients’ association GILS (Gruppo Italiano Lotta Sclerodermia) for the grant that supported the project.Disclosure of Interests:Maria Grazia Lazzaroni: None declared, Stefania Zingarelli: None declared, Paolo Airò: None declared, Yannick Allanore Grant/research support from: BMS, Inventiva, Roche, Sanofi, Consultant of: Actelion, Bayer AG, BMS, BI, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche

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SARS-CoV-2-Laden Respiratory Aerosol Deposition in the Lung Alveolar-Interstitial Region Is a Potential Risk Factor for Severe Disease: A Modeling Study

Journal of Personalized Medicine ◽

10.3390/jpm11050431 ◽

2021 ◽

Vol 11 (5) ◽

pp. 431

Author(s):

Sabine Hofer ◽

Norbert Hofstätter ◽

Albert Duschl ◽

Martin Himly

Keyword(s):

Risk Factor ◽

Particle Deposition ◽

Early Stage ◽

Severe Disease ◽

Ambient Air ◽

Aerosol Deposition ◽

Pulmonary Involvement ◽

Mild Disease ◽

Disease Initiation

COVID-19, predominantly a mild disease, is associated with more severe clinical manifestation upon pulmonary involvement. Virion-laden aerosols and droplets target different anatomical sites for deposition. Compared to droplets, aerosols more readily advance into the peripheral lung. We performed in silico modeling to confirm the secondary pulmonary lobules as the primary site of disease initiation. By taking different anatomical aerosol origins into consideration and reflecting aerosols from exhalation maneuvers breathing and vocalization, the physicochemical properties of generated respiratory aerosol particles were defined upon conversion to droplet nuclei by evaporation at ambient air. To provide detailed, spatially-resolved information on particle deposition in the thoracic region of the lung, a top-down refinement approach was employed. Our study presents evidence for hot spots of aerosol deposition in lung generations beyond the terminal bronchiole, with a maximum in the secondary pulmonary lobules and a high preference to the lower lobes of both lungs. In vivo, initial chest CT anomalies, the ground glass opacities, resulting from partial alveolar filling and interstitial thickening in the secondary pulmonary lobules, are likewise localized in these lung generations, with the highest frequency in both lower lobes and in the early stage of disease. Hence, our results suggest a disease initiation right there upon inhalation of virion-laden respiratory aerosols, linking the aerosol transmission route to pathogenesis associated with higher disease burden and identifying aerosol transmission as a new independent risk factor for developing a pulmonary phase with a severe outcome.

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AB0597 PULMONARY FUNCTION IN PATIENTS DIAGNOSED OF EARLY SYSTEMIC SCLEROSIS: A NEW TOOL FOR SYSTEMIC SCLEROSIS CLASIFFICATION?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4423 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1595.1-1595

Author(s):

F. M. Ortiz Sanjuan ◽

C. Pávez Perales ◽

E. Vicens Bernabeu ◽

C. Alcañiz Escandell ◽

I. Cánovas Olmos ◽

...

Keyword(s):

Systemic Sclerosis ◽

Pulmonary Function ◽

Airway Obstruction ◽

Pulmonary Involvement ◽

Classification Criteria ◽

Small Airway ◽

University Hospital ◽

Ventilatory Pattern ◽

Small Airway Obstruction

Background:Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc) and is often progressive and has a poor prognosis. A restrictive ventilatory defect could suggest ILD either alone or in combination with pulmonary arterial hypertension.Nowadays, Early-SSc is well defined as preliminary stage of SSc. Patients who meet criteria for Early-SSc could benefit from an early diagnosis of pulmonary involvement.Objectives:Our aim was to assess the pulmonary function in patients diagnosed of Early SSc.Methods:Retrospective observational study of a wide and unselected series of patients diagnosed as Early-SSc from a single university hospital from 2012 to 2019. Patients were classified as Early-SSc following Le Roy criteria. Despite this, patients already did not meet 2013 ACR/EULAR classification criteria for SSc. We reviewed pulmonary function through conventional spirometry and diffusing capacity of lung for carbon monoxide (DLCO).Results:We included 56 patients with a mean age of 52.3±12.1 years (96.4% women; 3.6% men).At the diagnosis of Early-SSc, no one of our patients evidenced a restrictive ventilatory pattern. DLCO was below normal limits in 18 patients (32.1%). Small airway obstruction expressed according decreased maximal (mid-) expiratory flow (MMEF) 25-75 was present in 24 patients (42.8%).After a mean follow-up period of 38.3±2.4 months, 29 (51.8%) patients fulfilled 2013 ACR/EULAR criteria. The average time between diagnosis of Early-SSc and achieve SSc classification was 24.4±1.8 months. The remaining 27 patients continued classified as Early-SSc.An analysis of the subgroup of patients which progressed to SSc showed that DLCO was decreased in 15 of those 29 patients (51.7%) and 18 of 29 patients (62.1%) presented decreased MMEF 25-75. Comparing with the subgroup of patients which not progressed to SSc were significant differences (Decreased DLCO: 51.7% vs 11.1%; p=0.02 and decreased MMEF 25-75: 42.8% vs 22.2%; p=0.05).The analysis of pulmonary function of the subgroup of patients continued classified as Early-SSc after follow-up period did not show significative changes after follow-up.Conclusion:In our study, a third of the patients classified as Early-SSc presented at diagnosis abnormal values of DLCO and/or signs of small airway obstruction without the presence of a restrictive ventilatory pattern. Moreover, this pulmonary disfunction was significantly more frequent in patients who progressed to definitive SSc. Patients which remains classified as Early-SSc did not experience significative changes.Our results support the concept that pulmonary function was impaired in Early-SSc and that I should probably be considered for future Early-SSc classification criteria.Disclosure of Interests:None declared

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Systemic sclerosis portends increased risk of conduction and rhythm abnormalities at diagnosis and during disease course: A US population-based cohort

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211034074 ◽

2021 ◽

pp. 239719832110340

Author(s):

Yasser A Radwan ◽

Reto D Kurmann ◽

Avneek S Sandhu ◽

Edward A El-Am ◽

Cynthia S Crowson ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Confidence Interval ◽

Cumulative Incidence ◽

Disease Onset ◽

Population Based ◽

Hazard Ratio ◽

Conduction Disorders ◽

Increased Risk

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.

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Outpatient healthcare utilization among incident cases of systemic sclerosis: results from a population-based US cohort (1988–2016)

Scandinavian Journal of Rheumatology ◽

10.1080/03009742.2021.1932581 ◽

2021 ◽

pp. 1-6

Author(s):

CM Coffey ◽

AS Sandhu ◽

CS Crowson ◽

D Asante ◽

EL Matteson ◽

...

Keyword(s):

Systemic Sclerosis ◽

Healthcare Utilization ◽

Population Based ◽

Incident Cases

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POS1232 COVID-19 IN PATIENTS WITH SYSTEMIC SCLEROSIS: ONE RHEUMATOLOGY CENTER EXPERIENCE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3086 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 899.2-899

Author(s):

M. Starovoytova ◽

O. Desinova ◽

L. P. Ananyeva ◽

O. Koneva ◽

L. Garzanova ◽

...

Keyword(s):

Systemic Sclerosis ◽

Severe Disease ◽

High Risk Group ◽

Nasopharyngeal Swab ◽

Frequent Use ◽

Diffuse Form ◽

Novel Coronavirus ◽

Almost All ◽

Dose Prednisone ◽

Frequent Presence

Background:Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) virus infection or COVID-19 is a serious problem for patients with systemic autoimmune diseases Given the serious complications, including acute lung injury, patients with systemic sclerosis (SSc), especially SSs associated with interstitial lung disease (ILD), may represent a high risk group for infection and the development of severe COVID-19.Objectives:We present an analysis of the COVID-19 course and outcomes in 110 SSc pts.Methods:The study included 147 patients with SSc. The information was clarified by means of telephone survey after 10 months of the pandemic (December 2020). Covid-19 was diagnosed when confirmed by positive oral /nasopharyngeal swab, in the presence of positive antibodies and/or characteristic symptoms, and data from chest computed tomography (CT). 110 pts (77%) out of 147 patients in the SSc registry, gave the necessary information. COVID-19 was diagnosed in 59 pts (53 %). 42 pts (71%) had SSc-ILD. Pts mean age was 54.96 (s.d.11, min 31, max 79), 83% women (49 women and 10 men). 38 pts (65%) had a limited form of SSc, 15 (26%) pts had diffuse form SSc, 6% had overlap (SSc-polymyositis (PM) and SSc had rheumatoid arthritis (RA) and 3% had visceral form of SSc). All patients received low-dose prednisone, and more than half of the pts received immunosuppressive therapy. Rituximab therapy was performed in 24 pts (41%).Results:Almost all patients had positive swab from the oral cavity/nasopharynx. And only in 4 (7%) pts nasopharyngeal swabs were negative, in these patients specific antibodies and characteristic CT changes were detected. Chest CT was performed in 51 (86%) pts. Novel coronavirus pneumonia developed in the vast majority of pts - in 46 (78 %) pts. CT1 (up to 25% of lung lesions) had 10 (17%) pts, CT2 (25-50%) – 21(36%) pts, CT 3 (50-75%) – 15(25%) pts. In 5 (8.5%) pts no changes were detected on CT. The course of COVID-19 was mild and moderate (20 (34%) pts and 18 (31%) pts respectively), severe course was observed in 21 (35%) pts, including fatal in 12 (20%) pts. Among the deceased pts, only 1 patient with SSc-PM had not had ILD, but 7 patients had been treated with rituximab.Conclusion:SSc SARS-CoV-2-infected patients may be at risk of severe disease and mortality due to the frequent presence of ILD and the frequent use of immunosuppressive, including biological, therapy.Disclosure of Interests:None declared

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Factors associated with non-medical use of prescription drugs among individuals with a legitimate prescription for medical purposes: A population-based study

Nordic Studies on Alcohol and Drugs ◽

10.1177/14550725211003417 ◽

2021 ◽

pp. 145507252110034

Author(s):

Minna Pylväs-Korolainen ◽

Karoliina Karjalainen ◽

Tomi Lintonen

Keyword(s):

Binge Drinking ◽

Prescription Drugs ◽

Multinomial Logistic Regression ◽

Labour Force ◽

Large City ◽

Population Based ◽

Drug Prescriptions ◽

Living Alone ◽

Preventive Actions ◽

Illicit Use

Background: Psychoactive prescription drugs are known to have abuse potential. This study was aimed at studying the non-medical use of prescription drugs (NMUPD) among individuals with prescriptions for anxiolytics, sedatives, or strong analgesics. We examined the association of socio-demographics, binge drinking, the number of drug prescriptions, and drug types prescribed for medical purposes with NMUPD among the general Finnish population. Methods: Data were derived from population-based (ages 15–69 years) Drug Surveys conducted in Finland in 2006, 2010, and 2014. The response rates varied between 48% and 55%. Individuals with prescriptions for one or more prescription drugs in the last 12 months were included ( n = 1,602) and divided into three groups: medical use only, NMUPD, and NMUPD with illicit drug use (ILLICIT USE). Multinomial logistic regression was used. Results: Among individuals with a prescription for at least one prescription drug, 5.7% reported NMUPD. Living alone and being outside the labour force were associated with NMUPD. Younger age, living in a large city, living alone, and unemployment were associated with ILLICIT USE. Frequent binge drinking and a high number of drug prescriptions were associated with both NMUPD and ILLICIT USE. Those reporting ILLICIT USE were more likely to have a prescription for sedatives. Conclusions: Although NMUPD is on a rather low level among those who have a prescription for legitimate purposes, having multiple prescriptions increased the likelihood of NMUPD. Low socio-economic position and binge drinking are associated with NMUPD and this should be taken into account when planning interventions and preventive actions.

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Validity of an algorithm to identify cardiovascular deaths from administrative health records: a multi-database population-based cohort study

BMC Health Services Research ◽

10.1186/s12913-021-06762-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lisa M. Lix ◽

Shamsia Sobhan ◽

Audray St-Jean ◽

Jean-Marc Daigle ◽

Anat Fisher ◽

...

Keyword(s):

Cohort Study ◽

Cardiovascular Mortality ◽

Population Based ◽

Vital Statistics ◽

Practice Research ◽

Clinical Practice Research Datalink ◽

Health Records ◽

Predictive Values ◽

Site Specific ◽

Hospital Deaths

Abstract Background Cardiovascular death is a common outcome in population-based studies about new healthcare interventions or treatments, such as new prescription medications. Vital statistics registration systems are often the preferred source of information about cause-specific mortality because they capture verified information about the deceased, but they may not always be accessible for linkage with other sources of population-based data. We assessed the validity of an algorithm applied to administrative health records for identifying cardiovascular deaths in population-based data. Methods Administrative health records were from an existing multi-database cohort study about sodium-glucose cotransporter-2 (SGLT2) inhibitors, a new class of antidiabetic medications. Data were from 2013 to 2018 for five Canadian provinces (Alberta, British Columbia, Manitoba, Ontario, Quebec) and the United Kingdom (UK) Clinical Practice Research Datalink (CPRD). The cardiovascular mortality algorithm was based on in-hospital cardiovascular deaths identified from diagnosis codes and select out-of-hospital deaths. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for the cardiovascular mortality algorithm using vital statistics registrations as the reference standard. Overall and stratified estimates and 95% confidence intervals (CIs) were computed; the latter were produced by site, location of death, sex, and age. Results The cohort included 20,607 individuals (58.3% male; 77.2% ≥70 years). When compared to vital statistics registrations, the cardiovascular mortality algorithm had overall sensitivity of 64.8% (95% CI 63.6, 66.0); site-specific estimates ranged from 54.8 to 87.3%. Overall specificity was 74.9% (95% CI 74.1, 75.6) and overall PPV was 54.5% (95% CI 53.7, 55.3), while site-specific PPV ranged from 33.9 to 72.8%. The cardiovascular mortality algorithm had sensitivity of 57.1% (95% CI 55.4, 58.8) for in-hospital deaths and 72.3% (95% CI 70.8, 73.9) for out-of-hospital deaths; specificity was 88.8% (95% CI 88.1, 89.5) for in-hospital deaths and 58.5% (95% CI 57.3, 59.7) for out-of-hospital deaths. Conclusions A cardiovascular mortality algorithm applied to administrative health records had moderate validity when compared to vital statistics data. Substantial variation existed across study sites representing different geographic locations and two healthcare systems. These variations may reflect different diagnostic coding practices and healthcare utilization patterns.

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