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.

Validation of French versions of the 15-item picker patient experience questionnaire for adults, teenagers, and children inpatients.

Objectives: No French validated concise scales are available for measuring the experience of inpatients in pediatrics. This study aims to adapt the adult PPE-15 to a pediatric population, and translating it in French, as well as to establish reference values for adults, teenagers, and parents of young children. Methods: Cultural adaptation involved forward and backward translations, along with pretests in all three populations. Dimensional structure and internal consistency were assessed using principal component analysis, exploratory factor analysis, and Cronbach's alpha. Construct validity was assessed by examining established associations between patient satisfaction and inpatient variables, including length of stay, and preventable readmission. Results: A total of 25,626 adults, 293 teenagers and 1,640 parents of young children completed the French questionnaires. Factor analysis supported a single dimension (Cronbach's alpha: adults: 0.85, teenagers: 0.82, parents: 0.80). Construct validity showed the expected pattern of association, with dissatisfaction correlating with patient- and stay-related factors, notably length of stay, and readmission. Conclusion: The French versions of the PPE-15 for adults, teenagers and parents of pediatric patients stand as valid and reliable instruments for gauging patient satisfaction regarding their hospital stay after discharge.

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.

Development and validation of the physical effort scale (PES).

OBJECTIVES: Previous literature has primarily viewed physical effort as an aversive experience. However, recent research suggests that effort can also be valued positively. These differences in approach and avoidance tendencies toward physical effort may play a key role in the self-regulation of physical activity behaviors. The aim of this study was to develop a scale that measures these tendencies and contributes to a better understanding of physical effort and how it affects behavior. METHODS: The Physical Effort Scale (PES) was developed in Study 1 based on expert evaluations (n = 9) and cognitive interviews (n = 10). In Study 2 (n = 680, 69% female), content validity and dimensional structure were examined using principal component analysis and confirmatory factor analysis. Item reduction was conducted using item response theory. Preliminary construct validity was explored using regression. Study 3 (n = 297, 71% female) was used to validate dimensional structure, internal consistency, and construct validity, and to assess test-retest reliability. RESULTS: In Study 1, 44 items were rated for content validity, of which 18 were selected and refined based on cognitive interviews. Analyses from Study 2 allowed reducing the scale to 8 items with a two-dimension structure: tendency to approach (n = 4) and to avoid physical effort (n = 4). The two subscales showed high internal consistency (α = 0.897 for the approach dimension and 0.913 for the avoidance dimension) and explained usual levels of physical activity, providing preliminary evidence of construct validity. Study 3 confirmed the two-dimension structure with high internal consistency (α = 0.907 and 0.916 for the approach and avoidance dimension, respectively) and revealed acceptable test-retest reliability (intraclass correlation >0.66). Patterns of associations with other constructs showed expected relationships, confirming the concurrent, convergent, and discriminant validity of the scale. CONCLUSIONS: The PES is a valid and reliable measure of individual differences in the valuation of physical effort. This scale can assess the propensity to engage in physically demanding tasks in non-clinical populations. The PES and its manual are available in the Supplementary Material.

Comparison of patients with isolated cutaneous lupus erythematosus versus systemic lupus erythematosus with cutaneous lupus erythematosus as the sole clinical feature: A monocentric study of 149 patients.

BACKGROUND: Cutaneous lupus erythematosus (CLE) may present as an isolated entity or be classified as Systemic lupus erythematosus (SLE) by the presence of laboratory abnormalities, including cytopenia, low complement levels, and/or autoantibodies (CLE with laboratory SLE). OBJECTIVE: To compare isolated CLE and CLE with laboratory SLE and to validate an existing 3-item score with age < 25 years (1 point), phototypes V to VI (1 point), antinuclear antibodies ≥ 1:320 (5 points) to predict the risk of progression from CLE to severe SLE (sSLE). METHODS: Monocentric cohort study including consecutive patients with CLE. CLE with laboratory SLE was defined by 2019 American College of Rheumatology/European League Against Rheumatism classification criteria for SLE score of ≥10 points at baseline with CLE as the sole clinical feature. RESULTS: Of the 149 patients with CLE, 20 had CLE with laboratory SLE. The median follow-up duration was 11.3 years (IQR: 5.1-20.5). Ten patients (7%) had sSLE developed. In survival analysis, the risk of progression to sSLE was higher among CLE with laboratory SLE (hazard ratio = 6.69; 95% CI: 1.93-23.14, P < .001) compared to isolated CLE. In both groups, none of the patients with a risk score ≤ 2 had sSLE developed. LIMITATIONS: Monocentric study with a limited number of patients. CONCLUSIONS: CLE with laboratory patients with SLE have a higher risk of progression to sSLE than isolated CLE.

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.

Gut microbiome and intestinal inflammation in preclinical stages of rheumatoid arthritis.

BACKGROUND: Faecal Prevotellaceae, and other microbes, have been associated with rheumatoid arthritis (RA) and preclinical RA. We have performed a quantitative microbiome profiling study in preclinical stages of RA. METHODS: First-degree relatives of patients with RA (RA-FDRs) from the SCREEN-RA cohort were categorised into four groups: controls, healthy asymptomatic RA-FDRs; high genetic risk, asymptomatic RA-FDRs with two copies of the shared epitope; autoimmunity, asymptomatic RA-FDRs with RA-associated autoimmunity; and symptomatic, clinically suspect arthralgias or untreated new-onset RA.Faecal samples were collected and frozen. 16S sequencing was performed, processed with DADA2 pipeline and Silva database. Cell counts (cytometry) and faecal calprotectin (enzyme-linked immunosorbent assay, ELISA) were also obtained. Microbial community analyses were conducted using non-parametric tests, such as permutational multivariate analysis of variance (PERMANOVA), Wilcoxon and Kruskal-Wallis, or Aldex2. RESULTS: A total of 371 individuals were included and categorised according to their preclinical stage of the disease. Groups had similar age, gender and body mass index. We found no significant differences in the quantitative microbiome profiles by preclinical stages (PERMANOVA, R2=0.00798, p=0.56) and, in particular, no group differences in Prevotellaceae abundance. Results were similar when using relative microbiome profiling data (PERMANOVA, R2=0.0073, p=0.83) or Aldex2 on 16S sequence counts. Regarding faecal calprotectin, we found no differences between groups (p=0.3). CONCLUSIONS: We could not identify microbiome profiles associated with preclinical stages of RA. Only in a subgroup of individuals with the most pronounced phenotypes did we modestly retrieve the previously reported associations.

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.

A potential role for chlamydial infection in rheumatoid arthritis development.

OBJECTIVES: To assess the relationship between self-reported and serologic evidence of prior chlamydial infection, rheumatoid arthritis (RA)-related autoantibodies and risk of RA-development. METHODS: This is a nested study within a prospective Swiss-based cohort including all first-degree relatives of RA patients (RA-FDR) who answered a question on past chlamydial infections. Primary outcome was systemic autoimmunity associated with RA (RA-autoimmunity) defined as positivity for anti-citrullinated peptide antibodies (ACPA) and/or rheumatoid factor (RF). Secondary outcomes were high levels of RA-autoimmunity, RA-associated symptoms and RA-autoimmunity, and subsequent seropositive RA diagnosis. We conducted a nested case-control analysis by measuring the serological status against Chlamydia trachomatis' major outer membrane protein. We replicated our analysis in an independent United States-based RA-FDR cohort. RESULTS: Among 1231 RA-FDRs, 168 (13.6%) developed RA-autoimmunity. Prevalence of self-reported chlamydial infection was significantly higher in individuals with RA-autoimmunity compared with controls (17.9% vs 9.8%, OR = 2.00, 95%CI: 1.27-3.09, p < 0.01). This association remained significant after adjustments (OR = 1.91, 95%CI: 1.20-2.95). Stronger effect sizes were observed in later stages of RA development. There was a similar trend between a positive C. trachomatis serology and high levels of RA-autoimmunity (OR = 3.05, 95% CI: 1.10-8.46, p= 0.032). In the replication cohort, there were significant associations between chlamydial infection and RF positivity and incident RA, but not anti-CCP positivity. CONCLUSIONS: Self-reported chlamydial infections are associated with elevated RA-autoimmunity in at risk individuals. The differing association of chlamydial infections and ACPA/RF between cohorts will need to be explored in future studies but is consistent with a role of mucosal origin of RA-related autoimmunity.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/ targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15­30mg of prednisolone or equivalent for >2­4 weeks. These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

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.

When Illegitimate Tasks Threaten Patient Safety Culture: A Cross-Sectional Survey in a Tertiary Hospital.

Objectives: The current study investigates the prevalence of illegitimate tasks in a hospital setting and their association with patient safety culture outcomes, which has not been previously investigated. Methods: We conducted a cross-sectional survey in a tertiary referral hospital. Patient safety culture outcomes were measured using the Hospital Survey on Patient Safety Culture questionnaire; the primary outcome measures were a low safety rating for the respondent's unit and whether the respondent had completed one or more safety event reports in the last 12 months. Analyses were adjusted for hospital department and staff member characteristics relating to work and health. Results: A total of 2,276 respondents answered the survey (participation rate: 35.0%). Overall, 26.2% of respondents perceived illegitimate tasks to occur frequently, 8.1% reported a low level of safety in their unit, and 60.3% reported having completed one or more safety event reports. In multivariable analyses, perception of a higher frequency of illegitimate tasks was associated with a higher risk of reporting a low safety rating and with a higher chance of having completed event reports. Conclusion: The prevalence of perceived illegitimate tasks was rather high. A programme aiming to reduce illegitimate tasks could provide support for a causal effect of these tasks on safety culture outcomes.

Validation of the regret coping scale for healthcare professionals (RCS-HCP) in portuguese for Brazil

Introduction: assessing the ability to cope with regret can contribute to support strategies for health professionals. However, in Brazil only few instruments evaluate this ability in general. Objective: this study aimed was to adapt and validate the Regret Coping Scale for Healthcare Professionals (RCS-HCP) to Brazilian Portuguese . Methods: the instruments were translated, and the psychometric properties evaluated for validity and reliability. Three hundred and forty-one professionals participated, with an average age of 38.6 ± 9.2, and 87 participated in a retest survey 30 days later. Results: exploratory factor analysis showed adequacy of the structure (KMO = 0.786) composed of three factors. In the confirmation, the performance was close to acceptable. Reliability was good for the maladaptive strategies (α = 0.834) and adequate for the problem-focused initiatives (α = 0.717), but slightly too low for adaptive strategies (α = 0.595). Test- retest showed lower than expected values, with a Spearman- Brown coefficient of 0.703. Conclusion: the RCS-HCP scale showed satisfactory performance in relation to the properties evaluated.

Introdução: a avaliação da capacidade de lidar com o arrependimento pode contribuir para estratégias de apoio aos profissionais de saúde. No entanto, no Brasil existem poucos instrumentos que avaliam essa habilidade no contexto geral. Objetivo: o objetivo do estudo foi adaptar e validar a Regret Coping Scale for Healthcare Professionals (RCS-HCP) para profissionais de saúde brasileiros. Método: na validação, os instrumentos foram traduzidos e as propriedades psicométricas avaliadas quanto à validade e confiabilidade. Participaram 341 profissionais, com média de idade de 38,6 ± 9,2, e 87 participaram de uma pesquisa de reteste 30 dias depois. Resultados: a análise fatorial exploratória mostrou adequação da estrutura (KMO = 0,786) composta por três fatores. Na confirmação, o desempenho ficou próximo do aceitável. A confiabilidade foi boa para as estratégias mal adaptativas (α = 0,834) e adequada para as estratégias focadas no problema (α = 0,717), mas um pouco baixa demais para as estratégias adaptativas (α = 0,595). Teste-reteste apresentou valores abaixo do esperado, com coeficiente de Spearman-Brown de 0,703. Conclusão: a escala RCS-HCP apresentou desempenho satisfatório em relação às propriedades avaliadas.

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.

Deep learning diagnostic and severity-stratification for interstitial lung diseases and chronic obstructive pulmonary disease in digital lung auscultations and ultrasonography: clinical protocol for an observational case-control study.

BACKGROUND: Interstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP), and chronic obstructive pulmonary disease (COPD) are severe, progressive pulmonary disorders with a poor prognosis. Prompt and accurate diagnosis is important to enable patients to receive appropriate care at the earliest possible stage to delay disease progression and prolong survival. Artificial intelligence-assisted lung auscultation and ultrasound (LUS) could constitute an alternative to conventional, subjective, operator-related methods for the accurate and earlier diagnosis of these diseases. This protocol describes the standardised collection of digitally-acquired lung sounds and LUS images of adult outpatients with IPF, NSIP or COPD and a deep learning diagnostic and severity-stratification approach. METHODS: A total of 120 consecutive patients (≥ 18 years) meeting international criteria for IPF, NSIP or COPD and 40 age-matched controls will be recruited in a Swiss pulmonology outpatient clinic, starting from August 2022. At inclusion, demographic and clinical data will be collected. Lung auscultation will be recorded with a digital stethoscope at 10 thoracic sites in each patient and LUS images using a standard point-of-care device will be acquired at the same sites. A deep learning algorithm (DeepBreath) using convolutional neural networks, long short-term memory models, and transformer architectures will be trained on these audio recordings and LUS images to derive an automated diagnostic tool. The primary outcome is the diagnosis of ILD versus control subjects or COPD. Secondary outcomes are the clinical, functional and radiological characteristics of IPF, NSIP and COPD diagnosis. Quality of life will be measured with dedicated questionnaires. Based on previous work to distinguish normal and pathological lung sounds, we estimate to achieve convergence with an area under the receiver operating characteristic curve of > 80% using 40 patients in each category, yielding a sample size calculation of 80 ILD (40 IPF, 40 NSIP), 40 COPD, and 40 controls. DISCUSSION: This approach has a broad potential to better guide care management by exploring the synergistic value of several point-of-care-tests for the automated detection and differential diagnosis of ILD and COPD and to estimate severity. Trial registration Registration: August 8, 2022. CLINICALTRIALS: gov Identifier: NCT05318599.

Effectiveness of a Mobile App (PIMPmyHospital) in Reducing Therapeutic Turnaround Times in an Emergency Department: Protocol for a Pre- and Posttest Study.

BACKGROUND: Delays in reviewing issued laboratory results in emergency departments (EDs) can adversely affect efficiency and quality of care. One opportunity to improve therapeutic turnaround time could be to provide real-time access to laboratory results on mobile devices available to every caregiver. We developed a mobile app named "Patients In My Pocket in my Hospital" (PIMPmyHospital) to help ED caregivers automatically obtain and share relevant information about the patients they care for including laboratory results. OBJECTIVE: This pre- and posttest study aims to explore whether the implementation of the PIMPmyHospital app impacts the timeliness with which ED physicians and nurses remotely access laboratory results while actively working in their real-world environment, including ED length of stay, technology acceptance and usability among users, and how specific in-app alerts impact on its effectiveness. METHODS: This single-center study of nonequivalent pre- and posttest comparison group design will be conducted before and after the implementation of the app in a tertiary pediatric ED in Switzerland. The retrospective period will cover the previous 12 months, and the prospective period will cover the following 6 months. Participants will be postgraduate residents pursuing a ≤6-year residency in pediatrics, pediatric emergency medicine fellows, and registered nurses from the pediatric ED. The primary outcome will be the mean elapsed time in minutes from delivery of laboratory results to caregivers' consideration by accessing them either through the hospital's electronic medical records or through the app before and after the implementation of the app, respectively. As secondary outcomes, participants will be queried about the acceptance and usability of the app using the Unified Theory of Acceptance and Use of Technology model and the System Usability Scale. ED length of stay will be compared before and after the implementation of the app for patients with laboratory results. The impact of specific alerts on the app, such as a flashing icon or sound for reported pathological values, will be reported. RESULTS: Retrospective data collection gathered from the institutional data set will span a 12-month period from October 2021 to October 2022, while the 6-month prospective collection will begin with the implementation of the app in November 2022 and is expected to cease at the end of April 2023. We expect the results of the study to be published in a peer-reviewed journal in late 2023. CONCLUSIONS: This study will show the potential reach, effectiveness, acceptance, and use of the PIMPmyHospital app among ED caregivers. The findings of this study will serve as the basis for future research on the app and any further development to improve its effectiveness. Trial Registration: ClinicalTrials.gov NCT05557331; https://clinicaltrials.gov/ct2/show/NCT05557331. TRIAL REGISTRATION: ClinicalTrials.gov NCT05557331; https://clinicaltrials.gov/ct2/show/NCT05557331. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/43695.

Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection.

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of widely available commercial high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. Here we show that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals previously infected by SARS-CoV-2. Leveraging repeated serological measurements between April 2020 and December 2021 on 1083 participants of a population-based cohort in Geneva, Switzerland, and using antibody kinetic modeling, we found up to a three-fold reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. These results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.