Difficult-to-treat axial spondyloarthritis is associated with psoriasis, peripheral involvement and comorbidities: results of an observational nationwide study.

OBJECTIVES: To determine the cumulative incidence and identify the factors associated with difficult-to-treat axial spondyloarthritis (D2T-axSpA) in French patients newly benefiting from the French 'long-term illness' (LTI) social security scheme for axial spondyloarthritis (axSpA). METHODS: This national cohort study was based on the French National Medico-Administrative Database, SNDS, which contains data on hospitalisation, LTI and outpatient care consumption. All French patients newly receiving LTI benefits for ankylosing spondylitis (AS) between 2010 and 2013 were included in the study. In France, LTI is required to access biological/targeted synthetic DMARDs (b/tsDMARDs). The follow-up period ended on 31 December 2018. So-called D2T-axSpA was defined as the failure of three b/tsDMARDs or of two b/tsDMARDs with different modes of action. Comorbidities and extra-musculoskeletal manifestations were identified using previously described algorithms. Characteristics were compared between patients with D2T-axSpA and patients with non-D2T-axSpA who had received at least one b/tsDMARD with bivariate and multivariate analysis using logistic regression. Incidence rates of major cardiovascular event (MACE) and death were compared using competitive risk analysis. RESULTS: 22 932 patients were included. 10 798 (47.08%) patients received at least one bDMARD. None received tsDMARD. During follow-up, 2115 patients were classified as having D2T-axSpA, representing 19.59% of patients who received at least one bDMARD. In multivariate analysis, D2T-axSpA was significantly associated with female gender, peripheral involvement, psoriasis, hypertension and depression (p<0.001 for each case). There was no difference in the incidence of MACE (p=0.92) or death (p=0.87). CONCLUSION: D2T-axSpA affects one in five patients exposed to bDMARDs in this national cohort. D2T-axSpA is more common in women and patients with peripheral involvement and/or comorbidities.

Acute heart failure in elderly patients admitted to the emergency department with acute dyspnea: a multimarker approach diagnostic study.

BACKGROUND AND IMPORTANCE: Diagnosing acute heart failure (AHF) is difficult in elderly patients presenting with acute dyspnea to the emergency department. OBJECTIVES: To assess the diagnostic accuracy of NT-proBNP, high-sensitivity cardiac troponin-I (Hs-cTnI), soluble ST2 (ST2), galectin-3 and CD146 alone and in combination for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency department. DESIGN, SETTINGS AND PARTICIPANTS: This was a prospective, multicenter study performed between September 2016 and January 2020, including elderly patients presenting with acute dyspnea to the emergency department of 6 French hospitals. INTERVENTION: Measurement of NT-proBNP, hs-cTnI, ST2, galectin-3 and CD146. OUTCOME MEASURE AND ANALYSIS: The reference standard, AHF, was adjudicated by two independent physicians based on ED and hospitalization clinical, biological (excluding biomarkers), radiological and echocardiography data (performed by a cardiologist in the cardiology department specifically for this study). Three exploratory methods (two using a cross-sectional approach with logistic regression and counting all biomarker combinations, and one using a sequential approach with gray zone optimizations) were applied to create comprehensive combinations of the 5 biomarkers for measuring diagnostic accuracy. MAIN RESULTS: Two hundred thirty-eight patients (median age of 85 years, IQR = 8) were analyzed, and 110 (46%) were diagnosed with AHF. The accuracies of NT-proBNP, CD146, hs-cTnI, galectin-3, and ST2 were 0.72 [95% confidence interval (CI) 0.66-0.77], 0.63 (95% CI 0.57-0.69), 0.59 (95% CI 0.53-0.65), 0.55 (95% CI 0.49-0.61) and 0.51 (95% CI 0.45-0.57), respectively. Regardless of the approach used or how the 5 biomarkers were combined, the best accuracy for diagnosing AHF (0.73, 95% CI 0.67-0.78) did not differ from that of NT-proBNP alone. CONCLUSION: In this study, NT-proBNP alone exhibited the best diagnostic accuracy for diagnosing AHF in elderly patients presenting with acute dyspnea to the emergency departments. None of the other biomarkers alone or combined improved the accuracy compared to NT-proBNP, which is the only biomarker to use in this setting.

Impact of NSAIDs on 8-year cumulative incidence of major cardiovascular events in patients with ankylosing spondylitis: a nationwide study.

OBJECTIVES: The objectives of this study were to describe the incidence of major adverse cardiovascular events (MACEs) in French patients newly benefiting from the French Long-term Illness scheme (LTI) for AS and to evaluate the effect of various treatments on the risk of MACE occurrence. METHODS: This national cohort study was based on the French national medico-administrative database SNDS containing data on hospitalization, the LTI, and outpatient care consumption. All French patients newly receiving LTI benefits for AS from 2010 to 2013 were included. The final follow-up date was 31 December 2018. The occurrences of MACEs [stroke and myocardial infarction (MI)] and comorbidities were identified from algorithms previously described in the literature. Competitive risk analysis using propensity score and inverse weighting was performed to calculate cumulative incidence functions and to determine subhazard ratios (SHRs) for the various treatments of interest. RESULTS: Between 2010 and 2013, 22 929 patients were included [mean age 43.0 (s.d. 13.9) years, 44.9% mal]. The 8-year cumulative incidences of MACE, stroke, and MI were 1.81% (1.61-2.05), 0.97% (0.83-1.14), and 0.85% (0.71-1.04), respectively. NSAIDs [SHR: 0.39 (0.32-0.50), P < 0.001] and anti-TNF [SHR 0.61 (0.46-0.80), P < 0.001], but not anti-IL17 [2.10 (0.79-5.57)] were associated with a lower risk of MACE occurrence. CONCLUSION: MACE incidence rates at 8 years are low in patients newly benefiting from LTI for AS. Our results support the hypothesis of a protective role of NSAIDs and anti-TNF in cardiovascular risk in these patients.

Short term association between air pollution (PM10, NO2 and O3) and secondary spontaneous pneumothorax.

Secondary spontaneous pneumothorax (SSP) occurs in the context of underlying pulmonary disease. Our objectives were to estimate the relationship between SSP and short term air pollution exposure with nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 µm (PM10). Patients with SSP were included between June 1, 2009 and May 31, 2013, in 14 Emergency Departments in France. In this case-crossover design study, PM10, NO2, and O3 data were collected hourly from monitoring stations. Quantitative values, fast increase in air pollutant concentration, and air quality threshold exceedance were retained. These assessments were calculated for each of the 4 days prior to the event (Lag 1-Lag 4) for all case and control period, and for the entire exposure period. A total of 135 patients with SSP were included, with a mean age of 55.56 (SD 18.54) years. For short term exposure of PM10, NO2 and O3, no differences were observed between case and control periods in terms of quantitative values of air pollutant exposure (P > 0.68), fast increase in concentration (P > 0.12) or air quality threshold exceedance (P > 0.68). An association between O3 exposures cannot be ruled out, especially when considering the Lag 2 prior to the event and in warm seasons.

Does air pollution really impact the onset of spontaneous pneumothorax? A French case-crossover study.

RATIONALE: A link is established between air pollution and respiratory diseases. Very few studies evaluated this link with primary spontaneous pneumothorax (PSP). Contrasted results, low statistical power and methodological limits of these studies brought us to evaluate in a more thorough way this link. OBJECTIVES: (1) to estimate the relation between PSP and air pollutants namely nitrogen dioxide (NO2), ozone (O3) and particulate matter with a diameter ≤ 10 µm (PM10); (2) to investigate a time lag effect between these pollutants and occurrence of PSP. METHODS: This study has a case-crossover design. Subjects aged ≥18 years admitted from 1st June 2009 to 31st May 2013, in 14 Emergency Departments centers on the French territory. Were excluded: patients with traumatic, secondary, recurrent or history of previous pneumothorax. NO2, O3 and PM10 data were collected hourly in monitoring stations. Three exposure assessments were retained: quantitative values, fast increase concentration of air pollutants and peak of pollution. These assessments were calculated for the entire exposure period and for each of the four days of all case and control periods. RESULTS: 948 subjects included. Whatever the pollutant considered, no differences were observed between case and control periods, regardless of whether the quantitative values of air pollutants exposure (p > 0.09), fast increase concentration (p > 0.46) and peak of pollution (p > 0.20). CONCLUSIONS: We failed to show a relation between PSP and short-term air pollution exposure to low levels of NO2 and PM10. An association between O3 exposure and PSP cannot be ruled out. An impact at higher exposure level, and/or a potentiating effect of different meteorological factors remain to be demonstrated.

How to set up a database?-a five-step process.

Database set-up directly impacts the quality and viability of research data, and therefore is a crucial part of the quality of clinical research. Setting up a quality database implies following a strict data-management process. Too much collected information threatens the quality of the information required to achieve the objectives of the study. Therefore, the data that will be collected and managed have to be cautiously discussed and selected. Case report forms (CRF) are the tools the most frequently used to collect the data specified by the protocol. An informative and well-structured document simplifies database design and data validation. Key elements are about choice of sequential or thematic structuring, information and type of information that should be entered and the importance of data standards and coding guide. Final database must be structured with unique ID patient, with one record per subject or per measure. Specific information must be provided for each variable according to the database specifications. The quality of the results is directly related to the quality of the collected data. The CRF should then be completed as fully and accurately as possible. Data validation relies on three key points: the CRF completion guidelines, the Edit Checks process and the Data clarification process. Various open source or business software applications provide all functionalities to set up a clinical data base and CRF. The General Data Protection Regulation (GDPR) standardizes and strengthens the protection of personal data across the EU and for other country's data being "processed" within the EU. The General principles include lawfulness, fairness and transparency, restricted use of data, data minimization, accuracy, limited storage, confidentiality and probity, and accountability.