Anti-apolipoprotein A-1 IgG, incident cardiovascular events, and lipid paradox in rheumatoid arthritis.

Objective: To validate the prognostic accuracy of anti-apolipoprotein A-1 (AAA1) IgG for incident major adverse cardiovascular (CV) events (MACE) in rheumatoid arthritis (RA) and study their associations with the lipid paradox at a multicentric scale. Method: Baseline AAA1 IgG, lipid profile, atherogenic indexes, and cardiac biomarkers were measured on the serum of 1,472 patients with RA included in the prospective Swiss Clinical Quality Management registry with a median follow-up duration of 4.4 years. MACE was the primary endpoint defined as CV death, incident fatal or non-fatal stroke, or myocardial infarction (MI), while elective coronary revascularization (ECR) was the secondary endpoint. Discriminant accuracy and incidence rate ratios (IRR) were respectively assessed using C-statistics and Poisson regression models. Results: During follow-up, 2.4% (35/1,472) of patients had a MACE, consisting of 6 CV deaths, 11 MIs, and 18 strokes; ECR occurred in 2.1% (31/1,472) of patients. C-statistics indicated that AAA1 had a significant discriminant accuracy for incident MACE [C-statistics: 0.60, 95% confidence interval (95% CI): 0.57-0.98, p = 0.03], mostly driven by CV deaths (C-statistics: 0.77; 95% CI: 0.57-0.98, p = 0.01). IRR indicated that each unit of AAA1 IgG increase was associated with a fivefold incident CV death rate, independent of models' adjustments. At the predefined and validated cut-off, AAA1 displayed negative predictive values above 97% for MACE. AAA1 inversely correlated with total and HDL cholesterol. Conclusions: AAA1 independently predicts CV deaths, and marginally MACE in RA. Further investigations are requested to ascertain whether AAA1 could enhance CV risk stratification by identifying patients with RA at low CV risk.

Development and validation of a self-updating gout register from electronic health records data.

OBJECTIVE: To develop an automatic gout register from electronic health records (EHRs) data. METHODS: We analysed the EHR of all patients >18 years old from a tertiary academic hospital (2013-2022) based on six criteria: International Classification of Diseases 10 gout diagnosis, urate-lowering therapy prescription, monosodium urate crystals in joint aspiration and gout-related terms in problem lists, clinical or imaging reports. We assessed the positive and negative predictive value (PPV and NPV) of the query by chart reviews. RESULTS: Of 2 110 902 outpatients and inpatients, 10 289 had at least one criterion for gout. The combination of joint aspiration OR diagnostic in the problem list OR≥2 other criteria created a register of 5138 patients, with a PPV of 92.4% (95% CI 88.5% to 95.0%) and an NPV of 94.3% (95% CI 91.9% to 96.0%). PPV and NPV were similar among outpatients and inpatients. Incidence was 2.9 per 1000 person-year and dropped by 30% from the COVID-19 pandemic onward. Patients with gout were on average 71.2 years old (SD 14.9), mainly male (76.5%), overweight (69.5%) and polymorbid (mean number of comorbidities of 3, IQR 1-5). More than half (57.4%) had received a urate-lowering treatment, 6.7% had a gout that led to a hospitalisation or ≥2 flares within a year and 32.9% received a rheumatology consultation. CONCLUSION: An automatic EHR-based gout register is feasible, valid and could be used to evaluate and improve gout management. Interestingly, the register uncovered a marked underdiagnosis or under-reporting of gout since the COVID-19 pandemic.

Comparative effectiveness of baricitinib and alternative biological DMARDs in a Swiss cohort study of patients with RA.

OBJECTIVES: This observational study compares the effectiveness of baricitinib (BARI), a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), with alternative biological DMARDs (bDMARDs) in patients with rheumatoid arthritis (RA), from a prospective, longitudinal cohort. METHODS: We compared patients initiating a treatment course (TC) of BARI, tumour necrosis factor inhibitors (TNFi) or bDMARDs with other modes of action (OMA), during a period when all these DMARDs were available in Switzerland. The primary outcome was drug maintenance; secondary outcomes included discontinuation rates related specifically to ineffectiveness and adverse events. We further analysed rates of low disease activity (LDA) and remission (REM) at 12 months and drug maintenance in bDMARD-naïve and tsDMARD-naïve population. RESULTS: A total of 1053 TCs were included: 273 on BARI, 473 on TNFi and 307 on OMA. BARI was prescribed to older patients with longer disease duration and more previous treatment failures than TNFi. Compared with BARI, the adjusted drug maintenance was significantly shorter for TNFi (HR for discontinuation: 1.76; 95% CI, 1.32 to 2.35) but not compared with OMA (HR 1.27; 95% CI, 0.93 to 1.72). These results were similar in the b/tsDMARD-naïve population. The higher discontinuation of TNFi was mostly due to increased discontinuation for ineffectiveness (HR 1.49; 95% CI, 1.03 to 2.15), with no significant differences in drug discontinuation for adverse events (HR 1.46; 95% CI, 0.83 to 2.57). The LDA and REM rates at 12 months did not differ significantly between the three groups. CONCLUSIONS: BARI demonstrated a significantly higher drug maintenance compared with TNFi, mainly due to lower drug discontinuations for ineffectiveness. We found no difference in drug maintenance between BARI and OMA. Clinical outcomes did not differ between the three groups. Our results suggest that BARI is an appropriate therapeutic alternative to bDMARDs in the management of RA.

Time trends and modifiable factors of COVID-19 contact tracing coverage, Geneva, Switzerland, June 2020 to February 2022.

BackgroundContact tracing was one of the central non-pharmaceutical interventions implemented worldwide to control the spread of SARS-CoV-2, but its effectiveness depends on its ability to detect contacts.AimEvaluate the proportion of secondary infections captured by the contact tracing system in Geneva.MethodsWe analysed 166,892 concomitant infections occurring at the same given address from June 2020 until February 2022 using an extensive operational database of SARS-CoV-2 tests in Geneva. We used permutation to compare the total number of secondary infections occurring at the same address with that reported through manual contact tracing.ResultsContact tracing captured on average 41% of secondary infections, varying from 23% during epidemic peaks to 60% during low epidemic activity. People living in wealthy neighbourhoods were less likely to report contacts (odds ratio (OR): 1.6). People living in apartment buildings were also less likely to report contacts than those living in a house (OR: 1.1-3.1) depending on the SARS-CoV-2 variant, the building size and the presence of shops. This under-reporting of contacts in apartment buildings decreased during periods of mandatory wearing of face masks and restrictions on private gatherings.ConclusionContact tracing alone did not detect sufficient secondary infections to reduce the spread of SARS-CoV-2. Campaigns targeting specific populations, such as those in wealthy areas or apartment buildings, could enhance coverage. Additionally, measures like wearing face masks, improving ventilation and implementing restrictions on gatherings should also be considered to reduce infections resulting from interactions that may not be perceived as high risk.

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the 'JAK-pot' study).

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the 'JAK-pot' collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Oral glucocorticoid use in patients with rheumatoid arthritis initiating TNF-inhibitors, tocilizumab or abatacept: Results from the international TOCERRA and PANABA observational collaborative studies.

OBJECTIVE: To evaluate and compare the use of oral glucocorticoids with three classes of bDMARDs in patients with rheumatoid arthritis (RA). METHODS: We included patients from 13 observational registries treated with a TNF-inhibitor, abatacept or tocilizumab and with available information on the use of oral glucocorticoids. The main outcome was oral glucocorticoid withdrawal. A McNemar test was used to analyse the change in the use of glucocorticoids after 1 year. Kaplan-Meier estimates and Cox regressions, adjusted for patient, treatment, and disease characteristics, were used to evaluate glucocorticoid discontinuation in patients with glucocorticoids at baseline. Because of heterogeneity, analyses were done by registers and pooled using random-effects meta-analysis. RESULTS: A total of 12,334 participants treated with TNF-inhibitors, 2100 with tocilizumab and 3229 with abatacept were included. At one-year, oral glucocorticoid use decreased in all treatment groups (odds ratio for stopping vs. starting of 2.19 [95% CI 1.58; 3.04] for TNF-inhibitors, 2.46 [1.39; 4.35] for tocilizumab; 1.73 [1.25; 2.21] for abatacept). Median time to glucocorticoid withdrawal was ≈2 years or more in most countries, with a gradual decrease over time. Compared to TNF-inhibitors, crude hazard ratios of glucocorticoid discontinuation were 0.65[0.48-0.87] for abatacept, and 1.04 [0.76-1.43] for tocilizumab, and adjusted hazard ratios were 1.1 [0.83-1.47] for abatacept, and 1.30 [0.96-1.78] for tocilizumab. CONCLUSION: After initiation of a bDMARD, glucocorticoid use decreased similarly in all treatment groups. However, glucocorticoid withdrawal was much slower than advocated by current international guidelines. More effort should be devoted to glucocorticoid tapering when low disease activity is achieved.

Effect of SARS-CoV-2 prior infection and mRNA vaccination on contagiousness and susceptibility to infection.

The immunity conferred by SARS-CoV-2 vaccines and infections reduces the transmission of the virus. To answer how the effect of immunity is shared between a reduction of infectiousness and an increased protection against infection, we examined >50,000 positive cases and >110,000 contacts from Geneva, Switzerland (June 2020 to March 2022). We assessed the association between secondary attack rate (i.e. proportion of new cases among contacts) and immunity from natural infection and/or vaccination, stratifying per four SARS-CoV-2 variants and adjusting for index cases and contacts' socio-demographic characteristics and the propensity of the contacts to be tested. Here we show that immunity protected contacts from infection, rather than reducing infectiousness of index cases. Natural infection conferred the strongest immunity. Hybrid immunity did not surpass recent infection. Although of smaller amplitude, the reduction in infectiousness due to vaccination was less affected by time and by the emergence of new SARS-CoV-2 variants than the susceptibility to infection. These findings support the role of vaccine in reducing infectiousness and underscore the complementary role of interventions reducing SARS-CoV-2 propagation, such as mask use or indoor ventilation.

COVID-19 Vaccination Rate under Different Political Incentive: A Counterfactual Trend Approach Using Nationwide Data.

(1) Background: France implemented a COVID-19 certificate in July 2021 to incentivize the population to uptake COVID-19 vaccines. However, little is known about the variation in its impact across age groups and its dependence on socio-demographic, economic, logistic, or political factors. (2) Methods: Using France's weekly first dose vaccination rate, a counterfactual trend approach allowed for the estimation of the vaccination rate across age groups at a small geographical level before and after the implementation of the health pass. The effect of the health pass was operationalized as the vaccination rate among those who would not be vaccinated without it. (3) Results: Vaccination before the health pass varied greatly among age groups and was mainly influenced by territory (lower in rural and overseas territories when compared to urban and metropolitan ones), political beliefs, and socio-economic disparities. Vaccine logistics played a minor but significant role, while the impact of COVID-19 did not affect the vaccination rate. The health pass increased the vaccination overall but with varying efficiency across groups. It convinced mainly young people politically close to the governmental vaccination strategy and living in urban metropolitan areas with low socio-economical discrepancies. The selected variables explained most of the variability of the vaccination rate before the health pass; they explained, at most, a third of the variation in the health pass effect on vaccination. (4) Conclusions: From a public health perspective, the French health pass increased the overall vaccination, but failed to promote preventive behaviours in all segments of society, particularly in vulnerable communities.

Time to Publication and Time-Lag Publication Bias for Randomized Trials on Connective Tissue Diseases.

OBJECTIVE: To assess the time from completion to publication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs), investigate the factors associated with, and explore the influence of significance of study results on time to publication (time-lag publication bias). METHODS: We included interventional, phase 2/3, 3, or 4 RCTs on CTDs registered in Clinicaltrials.gov from 2000 to 2016, whose results had been published in a peer-review journal less than 5 years after their completion. Main trial features, including the significance of primary outcome results, were collected. Time to publication was the time from study completion to the earliest publication date. Multivariable linear regression was used to identify factors associated with time to publication. RESULTS: We included 62 studies, mostly phase 3 (61%) trials on pharmacologic treatments (94%); we recruited patients with systemic lupus (55%) or systemic sclerosis (23%) and planned to enroll a median of 131 (IQR [interquartile range]: 61-288) patients. Twenty-two (35%) reported at least a statistically significant primary outcome. Median time to publication was 28 months (IQR: 17-36). In a multivariable analysis, time to publication progressively improved over time (faster publication in recent years, with the average time to publication decreasing by 1.3 [95% CI: 0.3-2.3] months per year) and was not influenced by the significance of primary outcome results, funder, impact factor of the journal, number of recruiting countries, and comparator. CONCLUSION: A high proportion of CTDs-RCTs is published beyond 2 years from completion. We did not find evidence of time-lag publication bias, and time to publication improved over time.

Impact of SARS-CoV2 infection on anti-apolipoprotein A-1 IgG response in inflammatory rheumatic diseases.

Objectives: To investigate the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on anti-apolipoprotein A-1 IgG (AAA1) humoral response in immunosuppressed inflammatory rheumatic diseases (IRD) patients. Methods: This is a nested cohort study from the prospective Swiss Clinical Quality Management registry. A total of 368 IRD patients for which serum samples were available before and after the SARS-CoV2 pandemic were included. Autoantibodies against ApoA-1 (AAA1) and its c-terminal region (AF3L1) were measured in both samples. The exposure of interest was anti-SARS-CoV2 spike subunit 1 (S1) seropositivity measured in the second sample. The effect of SARS-CoV2 infection (anti-S1 seropositivity) on becoming AAA1 or AF3L1 positive and on the change of AAA1 or AF3L1 optical density (OD) between the two samples was tested with multivariable regressions. Results: There were 12 out of 368 IRD patients who were seroconverted against S1. The proportion of patients becoming AF3L1 seropositive was significantly higher in anti-S1-positive patients, compared with anti-S1-negative patients (66.7% versus 21.6%, p = 0.001). Adjusted logistic regression analyses indicated that anti-S1 seroconversion was associated with a sevenfold increased risk of AFL1 seropositivity (odds ratio: 7.4, 95% confidence interval (95% CI): 2.1-25.9) and predicted median increase in AF3L1 OD values (+0.17, 95% CI: 0.08-0.26). Conclusions: SARS-CoV2 infection is associated with a marked humoral response against the immunodominant c-terminal region of ApoA-1 in IRD patients. The possible clinical impact of AAA1 and AF3L1 antibodies on disease progression, cardiovascular complications, or long COVID syndrome deserves future investigations.

Extent of and Reasons for Discontinuation and Nonpublication of Interventional Trials on Connective Tissue Diseases: An Observational Study.

OBJECTIVE: To assess the proportion, the reasons, and the factors associated with the discontinuation or nonpublication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs). METHODS: We searched all interventional RCTs on CTDs registered in ClinicalTrials.gov since 2000. Two reviewers selected studies according to prespecified eligibility criteria. Completion status, publication status, and reported reasons for discontinuation or nonpublication were retrieved on ClinicalTrials.gov, through literature search, and by contacting investigators. Multivariable logistic regression was used to identify factors associated with study noncompletion and nonpublication. RESULTS: We included 175 studies, mostly phase III, placebo-controlled trials on pharmacologic treatments recruiting patients with systemic lupus erythematosus (51%), systemic sclerosis (20%), Sjögren's syndrome (12%), or other CTDs. Fifty-eight (33%) had been discontinued, mainly for insufficient patient accrual, with no differences in discontinuation rates across the CTDs (P > 0.5). Forty-six (35%) of 130 studies having included at least 1 patient were unpublished, and 86 (65%) were published in a peer-reviewed journal after a median of 24 months (interquartile range 15-41) from completion, with a significantly higher publication rate in completed versus discontinued studies (81% versus 22%; P < 0.001). We were able to obtain reasons for nonpublication in one-third of cases. Small sample size (<100 participants) was the only factor associated with study noncompletion and nonpublication. CONCLUSION: One of 3 registered RCTs on CTDs fails to be completed or published. This represents a waste of resources and raises ethical concerns regarding hidden clinical data and unfruitful participation by patients.

Incidence of healthcare-associated coronavirus disease 2019 (COVID-19) in the state of Geneva.

An examination of all coronavirus disease 2019 (COVID-19) cases and patient movements in Geneva indicated important disease activity within the healthcare system since the beginning of the pandemic. We estimate that 4.3% of all COVID-19 cases were likely acquired within the healthcare system, contributing to 62% of the COVID-19-related deaths.

Heart rate recovery to assess fitness: comparison of different calculation methods in a large cross-sectional study.

We propose a cross-sectional study based on 980 maximal effort tests to quantify the effect of the calculation method of heart rate recovery (HRR) on its association with cardiorespiratory fitness (CRF). For five different time t0 after exercise cessation, HRR has been calculated as: the difference and the ratio between maximal measured heart rate and heart rate (HR) at t0HR at t0the decay time of an exponential decay encompassing the first t0 minutes of the HR recovery.The associations between HRR indices and CRF were estimated from generalized estimating equations stratified by gender and adjusted for age and body mass index. For HRR indices based on exponential regression, no significant association with CRF was found, whereas the other HRR indices are associated with CRF when t0 is at least 1 minute and is maximum for t0 = 2 minutes for females and t0 = 3 minutes for males.

Glucocorticoids prescribing practices in systemic sclerosis: an analysis of the EUSTAR database.

OBJECTIVES: To estimate the prevalence of long-term exposure to glucocorticoids (GCs) and to identify factors associated with, and variations in prescribing practices over time and across recruiting countries. METHODS: We included patients with SSc having a visit recorded in the EUSTAR database from January 2013 onward. We analysed the prevalence and the main features of GCs users, their exposure to GCs over time, and their GCs dosages. Multivariable linear regression was used to analyse the factors identified as associated with GCs intake duration. Time trends, and variations in GCs utilization across recruiting countries were explored. Missing data were imputed using multiple imputation with chained equations. RESULTS: The 9819 patients included were mostly females (85%), the majority had lcSSc (73%), and the median age was 58 years. At baseline, 34% of patients (n = 2769/8109) (48% dcSSc vs 29% lcSSc) were on GCs, and the median dose was 7.5 mg/day. GCs users were more frequently males and anti-Scl70 positive, and more commonly had dcSSc and more severe disease. On average, GCs users spent 25% of their follow-up time (median 33.2 months) on GCs, with no significant between-subsets difference. Notably, 33% (n = 971/2959) and 22% (n = 647/2959) of patients followed up for >1 year had received GCs for >6 and >12 months, respectively. Multivariable analysis showed that patient and disease characteristics poorly explained the variability in GCs exposure (adjusted-R2 = 0.06, P < 0.001). GCs utilization varied within and across countries, and gradually decreased over time (36% in 2013 vs 23% in 2018). CONCLUSIONS: GCs are widely and long-term prescribed in SSc, with significant between-countries and within-country differences. A gradual decrease in their utilization has been observed.

After JAK inhibitor failure: to cycle or to switch, that is the question - data from the JAK-pot collaboration of registries.

OBJECTIVES: The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi. METHODS: This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders. RESULTS: 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies. CONCLUSIONS: After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

Reporting and Representativeness of Race, Ethnicity, and Socioeconomic Status in Systemic Sclerosis Randomized Trials: An Observational Study.

OBJECTIVE: To assess how and to what extent socioeconomic status and ethnicity/race of participants are reported in randomized controlled trials (RCTs) on systemic sclerosis (SSc), and to estimate the representativeness of different ethnic/racial groups in SSc RCTs. METHODS: We searched all published RCTs on SSc indexed in PubMed. We retrieved information on main features of RCTs published from 2000 onward and recorded for each study whether race/ethnicity was reported; how ethnicity/race was defined and assigned; and the number of patients included for each racial/ethnic group. Multivariable logistic regression was used to identify factors associated with race/ethnicity reporting. Proportion of races/ethnicities included in US-based RCTs on SSc was examined and compared with US demographic data. RESULTS: We included 106 studies, mostly conducted in Europe (42%) or North America (25%), published after 2010 (74%), and enrolling a total of 6,693 patients. About one-third of studies provided information about race/ethnicity, with no improved reporting over time. Only 2 papers reported patient's socioeconomic status. Study location (US or intercontinental) was the only significant factor associated with a better reporting of race/ethnicity in multivariable analysis. In studies where race/ethnicity was reported, White patients were mostly represented (79%), followed by Asian (7%), and African American (6%). In the sensitivity analysis limited to studies from the US, underrepresentation of African American patients was observed in the 2000-2010 time period, but not later. CONCLUSION: Documentation of race/ethnicity and socioeconomic status is poor in RCTs on SSc. More effort should be made to document race/ethnicity and socioeconomic status and to promote diversity in SSc RCTs.

Decrease of heart rate variability during exercise: An index of cardiorespiratory fitness.

The present study proposes to measure and quantify the heart rate variability (HRV) changes during effort as a function of the heart rate and to test the capacity of the produced indices to predict cardiorespiratory fitness measures. Therefore, the beat-to-beat cardiac time interval series of 18 adolescent athletes (15.2 ± 2.0 years) measured during maximal graded effort test were detrended using a dynamical first-order differential equation model. HRV was then calculated as the standard deviation of the detrended RR intervals (SDRR) within successive windows of one minute. The variation of this measure of HRV during exercise is properly fitted by an exponential decrease of the heart rate: the SDRR is divided by 2 every increase of heart rate of 20 beats/min. The HR increase necessary to divide by 2 the HRV is linearly inversely correlated with the maximum oxygen consumption (r = -0.60, p = 0.006), the maximal aerobic power (r = -0.62, p = 0.006), and, to a lesser extent, to the power at the ventilatory thresholds (r = -0.53, p = 0.02 and r = -0.47, p = 0.05 for the first and second threshold). It indicates that the decrease of the HRV when the heart rate increases is faster among athletes with better fitness. This analysis, based only on cardiac measurements, provides a promising tool for the study of cardiac measurements generated by portable devices.

A tutorial on ordinary differential equations in behavioral science: What does physics teach us?

The present tutorial proposes to use concepts of physics and mathematics to help behavioral scientists to use differential equations in their studies. It focuses on the first-order and the second-order (damped oscillator) differential equation. Simple examples allow to detail the meaning of the coefficients, the conditions of applicability of these differential equations, the underlying hypothesis, and their consequences for the researcher willing to use them. More complex psychological examples demonstrate the importance of parameters' interpretation. Particular attention is paid to how potential external perturbations should be considered. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the 'JAK-pot' collaboration.

BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

Neighbourhood socio-economic vulnerability and access to COVID-19 healthcare during the first two waves of the pandemic in Geneva, Switzerland: A gender perspective.

Background: Neighbourhood socio-economic inequities have been shown to affect COVID-19 incidence and mortality, as well as access to tests. This article aimed to study how associations of inequities and COVID-19 outcomes varied between the first two pandemic waves from a gender perspective. Methods: We performed an ecological study based on the COVID-19 database of Geneva between Feb 26, 2020, and June 1, 2021. Outcomes were the number of tests per person, the incidence of COVID-19 cases, the incidence of COVID-19 deaths, the positivity rate, and the delay between symptoms and test. Outcomes were described by neighbourhood socio-economic levels and stratified by gender and epidemic waves (first wave, second wave), adjusting for the proportion of inhabitants older than 65 years. Findings: Low neighbourhood socio-economic levels were associated with a lower number of tests per person (incidence rate ratio [IRR] of 0.88, 0.85 and 0.83 for low, moderate, and highly vulnerable neighbourhood respectively), a higher incidence of COVID-19 cases and of COVID-19 deaths (IRR 2.3 for slightly vulnerable, 1.9 for highly vulnerable). The association between socio-economic inequities and incidence of COVID-19 deaths was mainly present during the first wave of the pandemic, and was stronger amongst women. The increase in COVID-19 cases amongst vulnerable populations appeared mainly during the second wave, and originated from a lower access to tests for men, and a higher number of COVID-19 cases for women. Interpretation: The COVID-19 pandemic affected people differently depending on their socio-economic level. Because of their employment and higher prevalence of COVID-19 risk factors, people living in neighbourhoods of lower socio-economic levels, especially women, were more exposed to COVID-19 consequences. Funding: This research was supported by the research project SELFISH, financed by the Swiss National Science Foundation, grant number 51NF40-160590 (LIVES centre international research project call).