Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Wild-Type AmpC Beta-Lactamase-Producing Enterobacterales Are a Risk Factor for Empirical Treatment Failure in Patients with Bloodstream Infection.

Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal was to assess the potential role of AE as a predictive factor for clinical failure in patients with BSIs. Materials and Methods: We retrospectively analyzed patients admitted to Cannes hospital between 2021 and 2022 for BSIs due to Enterobacterales. Patient demographics, comorbidities, and main clinical and laboratory parameters during hospitalization were collected. The risk factors for clinical instability after 48 h or death, as well as for ineffective initial empirical therapy, were assessed using univariate and multivariate analyses. Results: From January 2021 to December 2022, 101 subjects were included (mean age 79 years, 60% men, 97% with comorbidities, 17% with healthcare-associated infection, 13% with septic shock, 82% with qPitt severity score < 2, 58% with urinary tract infection, and 18% with AE). Septic shock [adjusted odds ratio (ORadj) = 5.30, 95% confidence interval (CI): 1.47-22.19, p = 0.014] and ineffective initial empirical therapy [ORadj 5.54, 95% CI: 1.95-17.01, p = 0.002] were independent predictive factors for clinical instability or death. Extended-spectrum beta-lactamases [ORadj 9.40, 95% CI: 1.70-62.14, p = 0.012], AE group [ORadj 5.89, 95% CI: 1.70-21.40, p = 0.006], and clinical instability or death [ORadj 4.71, 95% CI: 1.44-17.08, p = 0.012] were independently associated with ineffective empirical therapy. Conclusions: Infection with AE was associated with treatment failure. Empirical therapy may result in failure if restricted to 3GC.

COVID-19 patient experiences in prehospital pathways: a processual approach using life-events calendar method and state sequence analysis shows detrimental delays.

OBJECTIVES: To our best knowledge, no study in France has comprehensively investigated the prehospital history of patients admitted for severe cases of COVID-19. 'Patients' voice is an excellent means to capture data on primary care pathways.We aimed to identify clusters of COVID-19 hospitalised patients with similar prehospital symptom sequences, and to test whether these clusters were associated with a higher risk of poor clinical outcomes. DESIGN: Cross-sectional online survey using life-event calendars. SETTING: All patients hospitalised for COVID-19 between September 2020 and May 2021 in the Infectious Disease Departments in Nice and in Marseilles in France. PARTICIPANTS: 312 patients responded to the survey. MAIN OUTCOME MEASURES: From the day of symptom onset to the day of hospitalisation, we defined a symptom sequence as the time-ordered vector of the successive symptom grades (grade 1, grade 2, grade 3). State sequence analysis with optimal matching was used to identify clusters of patients with similar symptom sequences. Multivariate logistic regressions were performed to test whether these clusters were associated with admission to intensive care unit (ICU) and COVID-19 sequelae after hospitalisation. RESULTS: Three clusters of symptom sequences were identified among 312 complete prehospital pathways. A specific group of patients (29%) experienced extended symptoms of severe COVID-19, persisting for an average duration of 7.5 days before hospitalisation. This group had a significantly higher probability of being admitted to ICU (adjusted OR 2.01). They were less likely to know a loved one who was a healthcare worker, and more likely to have a lower level of education. Similarly, this group of patients, who were more likely to have previously visited the emergency room without exhibiting severe symptoms at that time, may have been inclined to postpone reassessment when their health worsened.Their relatives played a decisive role in their hospitalisation. CONCLUSION AND RELEVANCE: This study highlights the negative impact of delayed hospitalisation on the health outcomes of French patients with severe COVID-19 symptoms during the first wave and underscores the influence of socioeconomic factors, such as lower education levels and limited connections to the medical field, on patients' experiences.

Enhancing multi-sectoral collaboration in health: the open arena for public health as a model for bridging the knowledge-translation gap.

Effective public health interventions at local level must involve communities and stakeholders beyond the health services spectrum. A dedicated venue for structured discussion will ensure ongoing multi-sectoral collaboration more effectively than convening ad hoc meetings. Such a venue can be created using existing resources, at minimal extra cost. The University Hospital in Nice (France) has established an Open Arena for Public Health which can serve as a model for promoting collaborative partnerships at local level. The Arena has been successful in implementing sustainable interventions thanks to a set of principles, including: non-hierarchical governance and operating, fair representation of stakeholders, consensus as to best available evidence internationally and locally, policy dialogues: open, free-flowing discussions without preconceived solutions, and an experimental approach to interventions.

Both Humoral and Cellular Immune Responses to SARS-CoV-2 Are Essential to Prevent Infection: a Prospective Study in a Working Vaccinated Population from Southern France.

COVID-19 vaccines have significantly decreased the number of severe cases of the disease, but the virus circulation remains important, and questions about the need of new vaccination campaigns remain unanswered. The individual's protection against SARS-CoV-2 infection is most commonly measured by the level and the neutralizing capacity of antibodies produced against SARS-CoV-2. T cell response is a major contributor in viral infection, and several studies have shown that cellular T cell response is crucial in fighting off SARS-CoV-2 infection. Actually, no threshold of protective immune response against SARS-CoV2 infection has been identified. To better understand SARS-CoV-2-mediated immunity, we assessed both B cell (measuring anti-Spike IgG titer and neutralization capacity) and T cell (measuring IFNγ release assay after specific SARS-CoV2 stimulation) responses to SARS-CoV-2 vaccination with or without virus encounter in a cohort of 367 working volunteers. Vaccinated individuals who had previously been infected had a stronger and more lasting immunity in comparison to vaccinated individuals naive to infection whose immunity started to decline 3 months after vaccination. IFNγ release ≥ 0.285 IU/mL and anti-Spike IgG antibodies ≥ 244 BAU/mL were associated with a sufficient immune response following vaccination preventing future infections. Individuals with comorbidities had a lower chance of reaching the protective thresholds of T cell and B cell responses as identified in multivariate analysis. A combined B cell and T cell analysis of immune responses to determine protective thresholds after SARS-CoV-2 vaccination will allow us to identify individuals in need of a booster vaccine dose, particularly in comorbid subjects.

Trends in Cancer Incidence in Different Antiretroviral Treatment-Eras amongst People with HIV.

Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006-2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006-2007, 7.54 [6.59, 8.59] in 2020-2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63-3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

Impact of social and demographic factors on the spread of the SARS-CoV-2 epidemic in the town of Nice.

INTRODUCTION: Socio-demographic factors are known to influence epidemic dynamics. The town of Nice, France, displays major socio-economic inequalities, according to the National Institute of Statistics and Economic Studies (INSEE), 10% of the population is considered to live below the poverty threshold, i.e. 60% of the median standard of living. OBJECTIVE: To identify socio-economic factors related to the incidence of SARS-CoV-2 in Nice, France. METHODS: The study included residents of Nice with a first positive SARS-CoV-2 test (January 4-February 14, 2021). Laboratory data were provided by the National information system for Coronavirus Disease (COVID-19) screening (SIDEP) and socio-economic data were obtained from INSEE. Each case's address was allocated to a census block to which we assigned a social deprivation index (French Deprivation index, FDep) divided into 5 categories. For each category, we computed the incidence rate per age and per week and its mean weekly variation. A standardized incidence ratio (SIR) was calculated to investigate a potential excess of cases in the most deprived population category (FDep5), compared to the other categories. Pearson's correlation coefficient was computed and a Generalized Linear Model (GLM) applied to analyse the number of cases and socio-economic variables per census blocks. RESULTS: We included 10,078 cases. The highest incidence rate was observed in the most socially deprived category (4001/100,000 inhabitants vs 2782/100,000 inhabitants for the other categories of FDep). The number of observed cases in the most social deprivated category (FDep5: N = 2019) was significantly higher than in the others (N = 1384); SIR = 1.46 [95% CI:1.40-1.52; p < 0.001]. Socio-economic variables related to poor housing, harsh working conditions and low income were correlated with the new cases of SARS-CoV-2. CONCLUSION: Social deprivation was correlated with a higher incidence of SARS-CoV-2 during the 2021 epidemic in Nice. Local surveillance of epidemics provides complementary data to national and regional surveillance. Mapping socio-economic vulnerability indicators at the census block level and correlating these with incidence could prove highly useful to guide political decisions in public health.

Nationwide Study in France To Predict One Year Major Bleeding and Validate the OAC3-PAD Score in Patients Undergoing Revascularisation for Lower Extremity Arterial Disease.

OBJECTIVE: Antithrombotic strategies are currently recommended for the treatment of lower extremity artery disease (LEAD) but specific scores to assess the risk of bleeding in these patients are scarce. To fill the gap, the OAC3-PAD bleeding score was recently developed and validated in German cohorts. The aim of this study was to determine whether this score performs appropriately in another real world nationwide cohort. METHODS: This 10 year retrospective, multicentre study based on French national electronic health data included patients who underwent revascularisation for LEAD between January 2013 and June 2022. The OAC3-PAD score was calculated and from this, the population was classified into four groups: low, low to moderate, moderate to high and high risk. A binary logistic regression model was applied, with major bleeding occurring at one year (defined using the International Classification of Diseases ICD-10) as the dependent variable. The performance of the OAC3-PAD bleeding score was investigated using a receiver operating characteristic curve. RESULTS: Among 161 205 patients hospitalised for LEAD treatment in French institutions, the one year incidence of major bleeding was 13 672 patients (8.5%). The distribution of the population according to the OAC3-PAD bleeding score was: 88 835 patients (55.1%), 34 369 (21.3%), 27 914 (17.3%), and 10 087 (6.3%) in the low, low to moderate, moderate to high, and high risk groups, respectively; with an incidence of one year major bleeding of 5.0%, 9.8%, 13.2%, and 21.3%. The OAC3-PAD model achieved an AUC of 0.650 to predict one year major bleeding following LEAD repair (95% CI 0.645 - 0.655), with a sensitivity of 0.67 and a specificity of 0.57. CONCLUSION: This nationwide analysis confirmed the accuracy of the OAC3-PAD model to predict one year major bleeding and served as external validation. Although further studies are required, it adds evidence and perspectives to further generalise its use to guide the management of patients with LEAD.

Immune response to BNT162b2 SARS-CoV-2 vaccine in patients living with HIV: The COVIH-DAPT study.

Introduction: Data on immune response to SARS-CoV-2 vaccine in patients living with HIV (PLWH) over a period longer than 3 months are currently limited. We measured the immune response after BNT162b2 vaccination against SARS-CoV-2 in this population. Methods: We prospectively enrolled PLWH on successful antiretroviral therapy, initiating vaccination with two doses of the BNT162b2 SARS-CoV-2 vaccine administered at six-week interval. SARS-CoV-2 humoral and cellular responses and lymphocyte cell subsets were recorded at inclusion and 6 weeks (W6), 3 months (M3) and 6 months (M6) later. Humoral, humoral strong and cellular responders were defined by IgG titers >10, ≥264BAU/mL and IFN-γ T cell release, respectively. Results: Nineteen subjects without SARS-CoV-2 infection were included (74% men, mean age 51 years, CD4 nadir 399/mm3). All subjects were humoral responders, their antibody titer peak reached at M3. Strong responders' rates were 63% and 21% at M3 and M6, respectively. CD19+CD10+ B cells had increased significantly at W6 then decreased at M3, while CD19+CD27+ B cells remained unchanged. Rates of patients with a cellular response increased from 39% at W6 to 69% at M6. Cellular responders had significantly higher CD3+, CD4+ and CD8+ Effector Memory cells at inclusion (p=0.048, p=0.024, p=0.012, respectively) and CD4+ Terminally Differentiated Effector Memory cells at M3 (p=0.044). Discussion: PLWH have a robust immune response after SARS-CoV-2 vaccination, but a rapid decline in humoral response from 3 months onwards, due to a blunted memory B cell response. Analysis of lymphocyte subsets may help identify optimal times for vaccine boosters.

Factors influencing participation in breast cancer screening in an urban setting. A study of organized and individual opportunistic screening among potentially active and retired women in the city of Nice.

Participation in breast cancer screening in urban settings is poor. Identifying factors accounting for participation and non-participation is essential to target priority areas, tackle health inequalities and suggest innovative approaches. We studied organized and individual opportunistic participation in breast cancer screening within the 144 aggregated units for statistical information (Ilôts regroupés pour l'information statistique: IRIS) of the city of Nice from 2019 to 2021. In each IRIS was assessed a local human development index, among potentially active women aged 50 to 59 years and retired women aged 60 to 74 years. Modelling participation and non-participation in screening according to the IRIS units' socio-economical characteristics was performed using the SURE method (Seemingly Unrelated Regression Equations). Over a 2-year period, 24,396 breast screening tests were conducted (11,173 as organised screening, 13,223 as individual opportunistic screening). The local human development index was positively correlated with the two types of screening, respectively. Access to public transport facilitated participation. Managerial status was negatively correlated with organised screening. Single working women had a higher risk of non-participation. With regard to their socio-economic characteristics, screening rates were lower than expected in 16 IRIS units in the city of Nice. Local human development index, access to public transport, family and professional context appear to be associated with breast cancer screening in an urban setting. An innovative approach targeting these factors is called for to reduce health inequalities.

Recent abacavir use and incident cardiovascular disease in contemporary-treated people with HIV.

OBJECTIVE: Assessing whether the previously reported association between abacavir (ABC) and cardiovascular disease (CVD) remained amongst contemporarily treated people with HIV. DESIGN: Multinational cohort collaboration. METHODS: RESPOND participants were followed from the latest of 1 January 2012 or cohort enrolment until the first of a CVD event (myocardial infarction, stroke, invasive cardiovascular procedure), last follow-up or 31 December 2019. Logistic regression examined the odds of starting ABC by 5-year CVD or chronic kidney disease (CKD) D:A:D risk score. We assessed associations between recent ABC use (use within the past 6 months) and risk of CVD with negative binomial regression models, adjusted for potential confounders. RESULTS: Of 29 340 individuals, 34% recently used ABC. Compared with those at low estimated CVD and CKD risks, the odds of starting ABC were significantly higher among individuals at high CKD risk [odds ratio 1.12 (95% confidence interval = 1.04-1.21)] and significantly lower for individuals at moderate, high or very high CVD risk [0.80 (0.72-0.88), 0.75 (0.64-0.87), 0.71 (0.56-0.90), respectively]. During 6.2 years of median follow-up (interquartile range; 3.87-7.52), there were 748 CVD events (incidence rate 4.7 of 1000 persons-years of follow up (4.3-5.0)]. The adjusted CVD incidence rate ratio was higher for individuals with recent ABC use [1.40 (1.20-1.64)] compared with individuals without, consistent across sensitivity analyses. The association did not differ according to estimated CVD (interaction P  = 0.56) or CKD ( P  = 0.98) risk strata. CONCLUSION: Within RESPOND's contemporarily treated population, a significant association between CVD incidence and recent ABC use was confirmed and not explained by preferential ABC use in individuals at increased CVD or CKD risk.

Air pollution exposure induces a decrease in type II interferon response: A paired cohort study.

BACKGROUND: While air pollution is a major issue due to its harmful effects on human health, few studies focus on its impact on the immune system and vulnerability to viral infections. The lockdown declared following the COVID-19 pandemic represents a unique opportunity to study the large-scale impact of variations in air pollutants in real life. We hypothesized that variations in air pollutants modify Th1 response represented by interferon (IFN) γ production. METHODS: We conducted a single center paired pilot cohort study of 58 participants, and a confirmation cohort of 320 participants in Nice (France), with for each cohort two samplings at six months intervals. We correlated the variations in the production of IFNγ after non-specific stimulation of participants' immune cells with variations in key regulated pollutants: NO2, O3, PM2.5, and PM10 and climate variables. Using linear regression, we studied the effects of variations of each pollutant on the immune response. FINDINGS: In the pilot cohort, IFNγ production significantly decreased by 25.7% post-lockdown compared to during lockdown, while NO2 increased significantly by 46.0%. After the adjustment for climate variations during the study period (sunshine and temperature), we observed a significant effect of NO2 variation on IFNγ production (P=0.03). In the confirmation cohort IFNγ decreased significantly by 47.8% and after adjustment for environmental factors and intrinsic characteristics we observed a significant effect of environmental factors: NO2, PM10, O3, climatic conditions (sunshine exposure, relative humidity) on variation in IFNγ production (P=0.005, P<0.001, P=0.001, P=0.002 and P<0.001 respectively) but not independently from the BMI at inclusion and the workplace P=0.007 and P<0.001 respectively). INTERPRETATION: We show a weakening of the antiviral cellular response in correlation with an increase of pollutants exposition. FUNDING: Agence Nationale de la Recherche, Conseil Départemental des Alpes-Maritimes and Region Sud.

Evaluation of an Antibiotic Susceptibility Testing Method on Enterobacterales-Positive Blood Cultures in Less Than 8 h Using the Rapid Mueller-Hinton Diffusion Method in Conjunction with the SIRscan 2000 Automatic Reading Device.

Enterobacterales bloodstream infections are life-threatening and require rapid, targeted antibiotherapy based on antibiotic susceptibility testing (AST). A new method using Muller-Hinton Rapid-SIR (MHR-SIR) agar (i2a, Montpellier, France) allows complete direct AST (dAST) to be read from positive blood culture bottles (BCBs) for all Enterobacterales species after 6-8 h of incubation. We evaluated (i) the performance of dAST from positive BCBs on MHR-SIR agar using two different inoculum protocols; (ii) the categorical agreement between dAST results obtained with MHR-SIR agar vs. those obtained with Muller-Hinton (MH) agar; and (iii) the ability of the MHR-SIR medium to detect ß-lactam resistant Enterobacterales. Finally, we estimated the saved turnaround time (TAT) with MHR-SIR compared with MH agar in our 24/7 laboratory. Our results showed that the most suitable inoculation protocol for dAST on MHR-SIR agar was 1 drop of BCB/5 mL H2O. For monomicrobial Enterobacterales BCBs, dAST performed on MHR-SIR medium showed 99.3% categorical agreement with AST on MH agar. Furthermore, MHR-SIR agar allows early detection of ß-lactam resistance mechanisms, including AmpC hyperproduction, extended-spectrum ß-lactamase, and carbapenemase. Finally, TAT reduction in our 24/7 laboratory was 16 h, enabling a significantly faster provision of antibiotic advice.

Hospitalisation avec ou pour COVID-19 : quel indicateur de surveillance choisir ?

INTRODUCTION: In the SARS-CoV-2 epidemic, the monitoring of epidemiological surveillance indicators is a central issue. OBJECTIVE: We were able to describe the monitoring of the epidemic of hospitalized patients in the department of Alpes-Maritimes from three data sources: 1) Santé Publique France (SPF) via the SI-VIC software, 2) the Regional Health Agency (ARS Paca) with conventional hospitalization or department critical care data taken from SI-VIC, adjusting them to those of the Health Establishments (ES), 3) The ES of Alpes-Maritimes associated with the ARS of Alpes-Maritimes and the Department of Public Health (DSP) of the CHU, with the collection of patients hospitalized in the conventional sector or in critical/intensive care in the dedicated COVID-19 beds. The aim of this study was to verify the consistency of these three information systems. RESULTS: We observed disparities between the number of cases of hospitalization of SPF and the data from ES/ARS/DSP. We did not observe any differences in patients hospitized in intensive care/critical care units. The Scientific Council uses SPF data on the number of hospitalizations or intensive/critical beds to justify its recommendations.However, SPF data from SI-VIC have associated patients hospitalized for COVID and patients who tested positive for PCR, but whose reason for hospitalization is not related to SARS-CoV2 infection (formerly infected or asymptomatic patients). CONCLUSIONS: We believe that hospital surveillance indicators should only take into account the number of patients in conventional hospitalization or resuscitation for a COVID-19 infection.

Associations between integrase strand-transfer inhibitors and cardiovascular disease in people living with HIV: a multicentre prospective study from the RESPOND cohort consortium.

BACKGROUND: Although associations between older antiretroviral drug classes and cardiovascular disease in people living with HIV are well described, there is a paucity of data regarding a possible association with integrase strand-transfer inhibitors (INSTIs). We investigated whether exposure to INSTIs was associated with an increased incidence of cardiovascular disease. METHODS: RESPOND is a prospective, multicentre, collaboration study between 17 pre-existing European and Australian cohorts and includes more than 32 000 adults living with HIV in clinical care after Jan 1, 2012. Individuals were eligible for inclusion in these analyses if they were older than 18 years, had CD4 cell counts and HIV viral load measurements in the 12 months before or within 3 months after baseline (latest of cohort enrolment or Jan 1, 2012), and had no exposure to INSTIs before baseline. These individuals were subsequently followed up to the earliest of the first cardiovascular disease event (ie, myocardial infarction, stroke, or invasive cardiovascular procedure), last follow-up, or Dec 31, 2019. We used multivariable negative binomial regression to assess associations between cardiovascular disease and INSTI exposure (0 months [no exposure] vs >0 to 6 months, >6 to 12 months, >12 to 24 months, >24 to 36 months, and >36 months), adjusted for cardiovascular risk factors. RESPOND is registered with ClinicalTrials.gov, NCT04090151, and is ongoing. FINDINGS: 29 340 people living with HIV were included in these analyses, of whom 7478 (25·5%) were female, 21 818 (74·4%) were male, and 44 (<1%) were transgender, with a median age of 44·3 years (IQR 36·2-51·3) at baseline. As of Dec 31, 2019, 14 000 (47·7%) of 29 340 participants had been exposed to an INSTI. During a median follow-up of 6·16 years (IQR 3·87-7·52; 160 252 person-years), 748 (2·5%) individuals had a cardiovascular disease event (incidence rate of 4·67 events [95% CI 4·34-5·01] per 1000 person-years of follow-up). The crude cardiovascular disease incidence rate was 4·19 events (3·83-4·57) per 1000 person-years in those with no INSTI exposure, which increased to 8·46 events (6·58-10·71) per 1000 person-years in those with more than 0 months to 6 months of exposure, and gradually decreased with increasing length of exposure, until it decreased to similar levels of no exposure at more than 24 months of exposure (4·25 events [2·89-6·04] per 1000 person-years among those with >24 to 36 months of exposure). Compared with those with no INSTI exposure, the risk of cardiovascular disease was increased in the first 24 months of INSTI exposure and thereafter decreased to levels similar to those never exposed (>0 to 6 months of exposure: adjusted incidence rate ratio of 1·85 [1·44-2·39]; >6 to 12 months of exposure: 1·19 [0·84-1·68]; >12 to 24 months of exposure: 1·46 [1·13-1·88]; >24 to 36 months of exposure: 0·89 [0·62-1·29]; and >36 months of exposure: 0·96 [0·69-1·33]; p<0·0001). INTERPRETATION: Although the potential for unmeasured confounding and channelling bias cannot fully be excluded, INSTIs initiation was associated with an early onset, excess incidence of cardiovascular disease in the first 2 years of exposure, after accounting for known cardiovascular disease risk factors. These early findings call for analyses in other large studies, and the potential underlying mechanisms explored further. FUNDING: The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands National Observational HIV cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The ICONA Foundation, The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort and The University of Cologne HIV Cohorts, ViiV Healthcare, and Gilead Sciences.

Inflammatory Markers after Switching to a Dual Drug Regimen in HIV-Infected Subjects: A Two-Year Follow-Up.

Objective: Immunadapt is a study evaluating the impact of combination antiretroviral treatment (cART) simplification on immune activation. We previously showed that switching to dual therapies could be associated six months later with macrophage activation. Followup continued up to 24 months after treatment simplification. Materials and Methods: Immunadapt is a prospective single arm study of successfully treated subjects simplifying cART from triple to dual regimens. Before cART change, at 6 months, and between 18 and 24 months following the switch, we measured IP-10, MCP-1, soluble CD14 (sCD14), soluble CD163 (sCD163), and lipopolysaccharide binding protein. Patients were stratified according to lower or greater likelihood of immune activation (CD4 nadir < 200, previous AIDS-defining event or very-low-level viremia during follow-up). Variables were compared using matched Wilcoxon tests. Results: From April 2019 to September 2021, 14 subjects were included (mean age 60 years, 12 men, 26 years since HIV infection, CD4 nadir 302 cells/mm3, 18 years on cART, 53 months on last cART). Twenty-one months following the switch, all but one subject maintained their viral load < 50 cp/mL. One subject had two viral blips. For the entire population, the sCD163 values increased significantly from baseline (+36%, p = 0.003) and from 6 months after the switch. The other markers did not change. After 6 months, the sCD163 increase was more pronounced in subjects with greater likelihood of immune activation (+53% vs. +19%, p = 0.026) Conclusions: cART simplification to dual therapy was associated with macrophage activation despite successful virological control after almost two years' follow-up. This was more pronounced in those at risk of immune activation.

Validation of the Computerized Pediatric Triage Tool, pediaTRI, in the Pediatric Emergency Department of Lenval Children's Hospital in Nice: A Cross-Sectional Observational Study.

Introduction: A reliable pediatric triage tool is essential for nurses working in pediatric emergency departments to quickly identify children requiring priority care (high-level emergencies) and those who can wait (low-level emergencies). In the absence of a gold standard in France, the objective of our study was to validate our 5-level pediatric triage tool -pediaTRI- against the reference tool: the Pediatric Early Warning Score (PEWS) System. Materials and Methods: We prospectively included 100,506 children who visited the Pediatric Emergency Department at Lenval Children's Hospital (Nice, France) in 2016 and 2017. The performance of pediaTRI to identify high-level emergencies (severity levels 1 and 2) was evaluated in comparison with a PEWS ≥ 4/9. Data from 2018-19 was used as an independent validation cohort. Results: pediaTRI agreed with the PEWS score for 84,896 of the patients (84.5%): 15.0% (14.8-15.2) of the patients were over-triaged and 0.5% (0.5-0.6) under-triaged compared with the PEWS score. pediaTRI had a sensitivity of 76.4% (74.6-78.2), a specificity of 84.7% (84.4-84.9), and positive and negative likelihood ratios of 5.0 (4.8-5.1) and 0.3 (0.3-0.3), respectively, for the identification of high-level emergencies. However, the positive likelihood ratios were lower for patients presenting with a medical complaint [4.1 (4.0-4.2) v 10.4 (7.9-13.7 for trauma), and for younger children [1.2 (1.1-1.2) from 0 to 28 days, and 1.9 (1.8-2.0) from 28 days to 3 months]. Conclusion: pediaTRI has a moderate to good validity to triage children in a Pediatric Emergency Department with a tendency to over-triage compared with the PEWS system. Its validity is lower for younger children and for children consulting for a medical complaint.

Impact of Female Sex on Outcomes of Patients Undergoing Thoracic Endovascular Aortic Aneurysm Repair: A Ten-Year Retrospective Nationwide Study in France.

The impact of sex on the outcomes of patients with cardiovascular disease is still incompletely understood. The aim of this nationwide multicenter observational study was to investigate the impact of sex on post-operative outcomes in patients undergoing thoracic endovascular aortic repair (TEVAR) for intact thoracic aortic aneurysm (iTAA). The French National Health Insurance Information System was searched to identify these patients over a ten-year retrospective period. Post-operative outcomes, 30-day and overall mortality were recorded. Among the 7383 patients included (5521 men and 1862 women), females were significantly older than males (66.8 vs. 64.8 years, p < 0.001). They were less frequently diagnosed with cardiovascular comorbidities. Post-operatively, women had less frequently respiratory (10.9 vs. 13.7%, p = 0.002) as well as cardiac complications (34.3 vs. 37.3%, p = 0.023), but they had more frequently arterial complications (52.8 vs. 49.8%, p = 0.024). There was no significant difference on overall mortality for a mean follow-up of 2.2 years (26.9 vs. 27.6%, p = 0.58). In the multivariable regression model, female sex was not associated with 30-day or overall mortality. Although women had a favorable comorbidity profile, the short-term and long-term survival was similar. The significantly higher rate of arterial complications suggests that women may be at higher risk of access-vessel-related complications.