Mutation Rate of AmpC ß-Lactamase-Producing Enterobacterales and Treatment in Clinical Practice: A Word of Caution.

In a retrospective multicenter study of 575 patients with bloodstream infections or pneumonia due to wild-type AmpC ß-lactamase-producing Enterobacterales, species with low in vitro mutation rates for AmpC derepression were associated with fewer treatment failures due to AmpC overproduction (adjusted hazard ratio, 0.5 [95% CI, .2-.9]). However, compared to cefepime/carbapenems, using third-generation cephalosporins as definitive therapy remained associated with this adverse outcome (15% vs 1%).

Direct and indirect impact of the COVID-19 pandemic on the survival of kidney transplant recipients: A national observational study in France.

During the pandemic period, health care systems were substantially reorganized for managing COVID-19 cases. Corresponding consequences on persons with chronic diseases remain insufficiently documented. This observational cohort study investigated the direct and indirect impact of the pandemic period on the survival of kidney transplant recipients (KTR). Using the French National Health Data System, incident persons with end-stage kidney disease between 2015 and 2020, and who received a kidney transplant during this period were included and followed up from their transplantation date to December 31, 2021. The survival of KTR during the prepandemic and pandemic periods was investigated using Cox models with time-dependent covariates. There were 10 637 KTR included in the study, with 324 and 430 deaths observed during the prepandemic and pandemic periods, respectively. The adjusted risk of death during the pandemic period was similar to that observed during the prepandemic period (hazard ratio [HR] [95% confidence interval]: 0.92 [0.77-1.11]), COVID-19-related hospitalization was associated with an increased risk of death (HR: 10.62 [8.46-13.33]), and a third vaccine dose was associated with a lower risk of death (HR: 0.42 [0.30-0.57]). The pandemic period was not associated with an indirect higher risk of death in KTR with no COVID-19-related hospitalization.

Effectiveness and safety of cefazolin versus cloxacillin in endocarditis due to methicillin-susceptible Staphylococcus spp.: a multicenter propensity weighted cohort study.

PURPOSE: To compare the effectiveness and safety of cefazolin versus cloxacillin for the treatment of infective endocarditis (IE) due to methicillin-sensitive Staphylococci (MSS). METHODS: Data were retrospectively collected on patients treated for a definite MSS endocarditis who received cefazolin or cloxacillin for at least 10 consecutive days in six French hospitals between January-1 2014 and December-31 2020. The primary endpoint was treatment failure defined as a composite of death within 90 days of starting antibiotherapy, or embolic event during antibiotherapy, or relapse of IE within 90 days of stopping antibiotherapy. We used Cox regression adjusted for the inverse probability of treatment weighting of receiving cefazolin. RESULTS: 192 patients were included (median age 67.8 years). IE was caused by S.aureus in 175 (91.1%) and by coagulase-negative staphylococci in 17 (8.9%). Ninety-four patients (48.9%) received cefazolin, and 98 (51%) received cloxacillin. 34 patients (34.7%) with cefazolin and 26 (27.7%) with cloxacillin met the composite primary endpoint, with no significant differences between groups (adjusted HR = 1.13, 95% CI 0.63 to 2.03). There were no significant differences in secondary efficacy endpoints or biological safety events. CONCLUSION: The effectiveness of cefazolin did not significantly differ from cloxacillin for the treatment of MSS endocarditis.

Development and validation of the tic score for early detection of traumatic coagulopathy upon hospital admission: a cohort study.

BACKGROUND: Critically injured patients need rapid and appropriate hemostatic treatment, which requires prompt identification of trauma-induced coagulopathy (TIC) upon hospital admission. We developed and validated the performance of a clinical score based on prehospital resuscitation parameters and vital signs at hospital admission for early diagnosis of TIC. METHODS: The score was derived from a level-1 trauma center registry (training set). It was then validated on data from two other level-1 trauma centers: first on a trauma registry (retrospective validation set), and then on a prospective cohort (prospective validation set). TIC was defined as a PTratio > 1.2 at hospital admission. Prehospital (vital signs and resuscitation care) and admission data (vital signs and laboratory parameters) were collected. We considered parameters independently associated with TIC in the score (binomial logistic regression). We estimated the score's performance for the prediction of TIC. RESULTS: A total of 3489 patients were included, and among these a TIC was observed in 22% (95% CI 21-24%) of cases. Five criteria were identified and included in the TIC Score: Glasgow coma scale < 9, Shock Index > 0.9, hemoglobin < 11 g.dL-1, prehospital fluid volume > 1000 ml, and prehospital use of norepinephrine (yes/no). The score, ranging from 0 and 9 points, had good performance for the identification of TIC (AUC: 0.82, 95% CI: 0.81-0.84) without differences between the three sets used. A score value < 2 had a negative predictive value of 93% and was selected to rule-out TIC. Conversely, a score value ≥ 6 had a positive predictive value of 92% and was selected to indicate TIC. CONCLUSION: The TIC Score is quick and easy to calculate and can accurately identify patients with TIC upon hospital admission.

Computerized decision support system (CDSS) use for surveillance of antimicrobial resistance in urinary tract infections in primary care.

BACKGROUND: Hospital-based surveillance of antimicrobial resistance may be irrelevant as a guide to antimicrobial use for urinary tract infections (UTIs) in primary care. OBJECTIVES: To highlight the value of online computerized decision support systems (CDSS) in providing information on the surveillance of antimicrobial resistance in community-acquired UTIs. METHODS: We collected the susceptibility profile for key antibiotics by type of UTI involving Escherichia coli from 2017 to 2020, using queries for UTI (Q-UTI) submitted to a French CDSS. We compared these results with those from the MedQual French surveillance system for community-acquired UTI and the European Antimicrobial Resistance Surveillance Network (EARS-NET) for invasive infections. RESULTS: We collected 43 591 Q-UTI, of which 10 192 (23%) involved E. coli: 40% cystitis, 32% male-UTI, and 27% pyelonephritis. Resistance was 41.3% (95% CI, 40.3%-42.2%) for amoxicillin, 16.6% (95% CI, 15.9%-17.3%) for fluoroquinolones, 6.6% (95% CI, 6.1%-7.0%) for third-generation cephalosporins (3GC), and 5.7% (95% CI, 5.2%-6.1%) for aminoglycosides. Resistance to amoxicillin was lower than that reported in MedQual (42.7%, P value = 0.004), and in EARS-NET (55.2%, P value < 0.001). For fluoroquinolones, resistance was higher than in MedQual (12.0%, P value < 0.001) and EARS-NET (15.8%, P value = 0.041). In complicated pyelonephritis and male UTI, fluoroquinolone resistance peaked at ∼20%. For 3GC, all UTI had higher resistance than in MedQual (3.5%, P value < 0.001), but lower than in EARS-NET (9.5%, P value < 0.001). Aminoglycoside resistance was not reported by MedQual, and was lower than in EARS-NET (7.1%, P value < 0.001). CONCLUSIONS: CDSS can inform prescribers in real-time about the ecology and surveillance of E. coli resistance in community-acquired UTI. In complicated upper UTIs, they can underline the risk of empirical use of fluoroquinolones and suggest preferential use of 3GC.

Family medicine practitioners' stress during the COVID-19 pandemic: a cross-sectional survey.

BACKGROUND: The COVID-19 pandemic has shaken the world in early 2020. In France, General Practitioners (GPs) were not involved in the care organization's decision-making process before and during the first wave of the COVID-19 pandemic. This omission could have generated stress for GPs. We aimed first to estimate the self-perception of stress as defined by the 10-item Perceived Stress Score (PSS-10), at the beginning of the pandemic in France, among GPs from the Auvergne-Rhône-Alpes, a french administrative area severely impacted by COVID-19. Second, we aimed to identify factors associated with a self-perceived stress (PSS-10 ≥ 27) among socio-demographic characteristics of GPs, their access to reliable information and to personal protective equipment during the pandemic, and their exposure to well established psychosocial risk at work. METHODS: We conducted an online cross-sectional survey between 8th April and 10th May 2020. The self-perception of stress was evaluated using the PSS-10, so to see the proportion of "not stressed" (≤20), "borderline" (21 ≤ PSS-10 ≤ 26), and "stressed" (≥27) GPs. The agreement to 31 positive assertions related to possible sources of stress identified by the scientific study committee was measured using a 10-point numeric scale. In complete cases, factors associated with stress (PSS-10 ≥ 27) were investigated using logistic regression, adjusted on gender, age and practice location. A supplementary analysis of the verbatims was made. RESULTS: Overall, 898 individual answers were collected, of which 879 were complete. A total of 437 GPs (49%) were stressed (PSS-10 ≥ 27), and 283 GPs (32%) had a very high level of stress (PSS-10 ≥ 30). Self-perceived stress was associated with multiple components, and involved classic psychosocial risk factors such as emotional requirements. However, in this context of health crisis, the primary source of stress was the diversity and quantity of information from diverse sources (614 GPs (69%, OR = 2.21, 95%CI [1.40-3.50], p < 0.001). Analysis of verbatims revealed that GPs felt isolated in a hospital-based model. CONCLUSION: The first wave of the pandemic was a source of stress for GPs. The diversity and quantity of information received from the health authorities were among the main sources of stress.

A computerized decision support system (CDSS) for antibiotic prescription in primary care-Antibioclic: implementation, adoption and sustainable use in the era of extended antimicrobial resistance.

OBJECTIVES: To describe the implementation and use of a computerized decision support system (CDSS) for antibiotic prescription in primary care in France (Antibioclic). The CDSS targets 37 infectious diseases and has been freely available on a website since 2011. METHODS: Description and implementation of the architecture of a CDSS for antibiotic prescription in general practice. Analysis of the queries made between 2012 and 2018 on the CDSS by GPs. Analysis of two cross-sectional studies of users in 2014 and 2019. RESULTS: The number of queries increased from a median of 796/day [IQR, 578-989] in 2012 to 11 125/day [5592-12 505] in 2018. Unique users increased from 414/day [245-494] in 2012 to 5365/day [2891-5769] in 2018. Time taken to make a query was 2 min [1.9-2.1]. Among 3 542 347 queries in 2018, 78% were for adults. Six situations accounted for ≥50% of queries: cystitis; acute otitis media; acute sinusitis; community-acquired pneumonia; sore throat; and pyelonephritis. Queries concerned pathologies for which antibiotic prescription was necessary (64%), was conditional on additional clinical steps (34%) or was not recommended (2%). Most users (81%) were GPs, with median age of 38 years [31-52] and 58% were female. Among the 4016 GPs who responded to the surveys, the vast majority (96%) reported using the CDSS during the consultation, with 24% systematically using Antibioclic to initiate an antibiotic course and 93% having followed the CDSS recommendation for the latest prescription. Most GPs were comfortable using the CDSS in front of a patient. CONCLUSIONS: Antibioclic has been adopted and is widely used in primary care in France. Its interoperability could allow its adaptation and implementation in other countries.

Paving the Way for the Implementation of a Decision Support System for Antibiotic Prescribing in Primary Care in West Africa: Preimplementation and Co-Design Workshop With Physicians.

BACKGROUND: Suboptimal use of antibiotics is a driver of antimicrobial resistance (AMR). Clinical decision support systems (CDSS) can assist prescribers with rapid access to up-to-date information. In low- and middle-income countries (LMIC), the introduction of CDSS for antibiotic prescribing could have a measurable impact. However, interventions to implement them are challenging because of cultural and structural constraints, and their adoption and sustainability in routine clinical care are often limited. Preimplementation research is needed to ensure relevant adaptation and fit within the context of primary care in West Africa. OBJECTIVE: This study examined the requirements for a CDSS adapted to the context of primary care in West Africa, to analyze the barriers and facilitators of its implementation and adaptation, and to ensure co-designed solutions for its adaptation and sustainable use. METHODS: We organized a workshop in Burkina Faso in June 2019 with 47 health care professionals representing 9 West African countries and 6 medical specialties. The workshop began with a presentation of Antibioclic, a publicly funded CDSS for antibiotic prescribing in primary care that provides personalized antibiotic recommendations for 37 infectious diseases. Antibioclic is freely available on the web and as a smartphone app (iOS, Android). The presentation was followed by a roundtable discussion and completion of a questionnaire with open-ended questions by participants. Qualitative data were analyzed using thematic analysis. RESULTS: Most of the participants had access to a smartphone during their clinical consultations (35/47, 74%), but only 49% (23/47) had access to a computer and none used CDSS for antibiotic prescribing. The participants considered that CDSS could have a number of benefits including updating the knowledge of practitioners on antibiotic prescribing, improving clinical care and reducing AMR, encouraging the establishment of national guidelines, and developing surveillance capabilities in primary care. The most frequently mentioned contextual barrier to implementing a CDSS was the potential risk of increasing self-medication in West Africa, where antibiotics can be bought without a prescription. The need for the CDSS to be tailored to the local epidemiology of infectious diseases and AMR was highlighted along with the availability of diagnostic tests and antibiotics using national guidelines where available. Participants endorsed co-design involving all stakeholders, including nurses, midwives, and pharmacists, as central to any introduction of CDSS. A phased approach was suggested by initiating and evaluating CDSS at a pilot site, followed by dissemination using professional networks and social media. The lack of widespread internet access and computers could be circumvented by a mobile app with an offline mode. CONCLUSIONS: Our study provides valuable information for the development and implementation of a CDSS for antibiotic prescribing among primary care prescribers in LMICs and may, in turn, contribute to improving antibiotic use, clinical outcomes and decreasing AMR.

Serum Albumin as a Prognostic Marker for Serious Non-AIDS Endpoints in the Strategic Timing of Antiretroviral Treatment (START) Study.

Background: Serum albumin may be used to stratify human immunodeficiency virus (HIV)-infected persons with high CD4 count according to their risk of serious non-AIDS endpoints. Methods: Cox proportional hazards models were used to analyze the risk of serious non-AIDS events in the Strategic Timing of Antiretroviral Treatment (START) study (NCT00867048) with serum albumin as a fixed and time-updated predictor. Models with exclusion of events during initial follow-up years were built to assess the ability of serum albumin to predict beyond shorter periods of time. Secondarily, we considered hospitalizations and AIDS events. Results: Among 4576 participants, 71 developed a serious non-AIDS event, 788 were hospitalized, and 63 experienced an AIDS event. After adjusting for a range of variables associated with hypoalbuminemia, higher baseline serum albumin (per 1 g/dL) was associated with a decreased risk of serious non-AIDS events (hazard ratio, 0.37 [95% confidence interval, .20-.71]; P = .002). Similar results were obtained in a time-updated model, after controlling for interleukin 6, and after excluding initial follow-up years. Serum albumin was independently associated with hospitalization but not with risk of AIDS. Conclusions: A low serum albumin level is a predictor for short- and long-term serious non-AIDS events, and may be a useful marker of risk of noncommunicable diseases, particularly in resource-limited settings.

Foscarnet, zidovudine and dolutegravir combination efficacy and tolerability for late stage HIV salvage therapy: A case-series experience.

Salvage therapy including foscarnet (PFA), zidovudine (ZDV) and an optimized background ART (OBT) has been shown to be effective in patients with advanced HIV infection, and no therapeutic options. Dolutegravir (DTG) may offer a more active combination. Objective was to describe efficacy and tolerability of PFA-ZDV-DTG containing regimen. In our cohort, we identified patients who: (i) had plasma HIV-1 RNA load (pVL) >50 c/ml (>100 for HIV-2) on combination ART (cART); (ii) had at least 1 PI/r, 1 NRTI, 1 NNRTI (for HIV-1), and at least 1 raltegravir resistance mutations; (iii) were naive to DTG; and (iv) initiated on a PFA-ZDV-DTG containing-regimen with 48 weeks (W48) of follow-up. Out of 5 patients, 2 were infected with HIV-2. At PFA-ZDV-DTG initiation, CD4 cell count was (/mm(3) ) of 64, 40, 10, in HIV-1, and 37, 199, in HIV-2 infected patients; and pVL (log10 c/ml) of 4.8, 5.1, 4.4, in HIV-1, and 3.6, 4.2, in HIV-2 infected patients, respectively. Median OBT genotypic sensitivity score was 1.5 [1-2]. PFA was discontinued in one patient, due to an acute renal failure. At W48, one HIV-1 infected patient had a pVL <50 c/ml and two <200 c/ml; the two HIV-2 infected patients had pVL >100 c/ml. No lack of treatment adherence was observed. In treatment experienced HIV-infected patients, failing cART and without other therapeutic options, a PFA-ZDV-DTG combination therapy could be effective. Renal adverse events should be monitored.

Impact of the COVID-19 Pandemic on COPD Patient Mortality: A Nationwide Study in France.

Objectives: We investigated the mortality patterns of chronic obstructive pulmonary disease (COPD) patients in France relative to a control population, comparing year 2020 to pre-pandemic years 2017-2019. Methods: COPD patient and sex, age and residence matched control cohorts were created from the French National Health Data System. Survival was analyzed using Cox regressions and standardized rates. Results: All-cause mortality increased in 2020 compared to 2019 in the COPD population (+4%), but to a lesser extent than in the control population (+10%). Non-COVID-19 mortality decreased to a greater extent in COPD patients (-5%) than in the controls (-2%). Death rate from COVID-19 was twice as high in the COPD population relative to the control population (547 vs. 279 per 100,000 person-years). Conclusion: The direct impact of the pandemic in terms of deaths from COVID-19 was much greater in the COPD population than in the control population. However, the larger decline in non-COVID-19 mortality in COPD patients could reflect a specific protective effect of the containment measures on this population, counterbalancing the direct impact they had been experiencing.

Appropriateness of intended antibiotic prescribing using clinical case vignettes in primary care, and related factors.

BACKGROUND: Factors associated with the appropriateness of antibiotic prescribing in primary care have been poorly explored. In particular, the impact of computerised decision-support systems (CDSS) remains unknown. OBJECTIVES: We aim at investigating the uptake of CDSS and its association with physician characteristics and professional activity. METHODS: Since May 2022, users of a CDSS for antibiotic prescribing in primary care in France have been invited, when registering, to complete three case vignettes assessing clinical situations frequently encountered in general practice and identified as at risk of antibiotic misuse. Appropriateness of antibiotic prescribing was defined as the rate of answers in line with the current guidelines, computed by individuals and by specific questions. Physician's characteristics associated with individual appropriate antibiotic prescribing (< 50%, 50-75% and > 75% appropriateness) were identified by multivariate ordinal logistic regression. RESULTS: In June 2023, 60,067 physicians had registered on the CDSS. Among the 13,851 physicians who answered all case vignettes, the median individual appropriateness level of antibiotic prescribing was 77.8% [Interquartile range, 66.7%-88.9%], and was < 50% for 1,353 physicians (10%). In the multivariate analysis, physicians' characteristics associated with appropriateness were prior use of the CDSS (OR = 1.71, 95% CI 1.56-1.87), being a general practitioner vs. other specialist (OR = 1.34, 95% CI 1.20-1.49), working in primary care (OR = 1.14, 95% CI 1.02-1.27), mentoring students (OR = 1.12, 95% CI 1.04-1.21) age (OR = 0.69 per 10 years increase, 95% CI 0.67-0.71). CONCLUSION: Individual appropriateness for antibiotic prescribing was high among CDSS users, with a higher rate in young general practitioners, previously using the system. CDSS could improve antibiotic prescribing in primary care.

Individual appropriateness for antibiotic prescribing is high among CDSS users.CDSS use could passively improve antibiotic prescribing in primary care.Factors associated with appropriateness for antibiotic prescribing for primary care diseases are: prior use of CDSS, general practice speciality vs. other specialities, younger age and mentoring of students.

SARS-CoV-2 in Nursing Homes: Analysis of Routine Surveillance Data in Four European Countries.

Transmission of SARS-CoV-2 in nursing homes is poorly documented. Using surveillance data of 228 European private nursing homes, we estimated weekly SARS-CoV-2 incidences among 21,467 residents and 14,371 staff members, compared to that in the general population, between August 3, 2020, and February 20, 2021. We studied the outcomes of "episodes of introduction" where one case was first detected and computed attack rates, reproduction ratio (R), and dispersion parameter (k). Out of 502 episodes of SARS-CoV-2 introduction, 77.1% (95%CI, 73.2%-80.6%) led to additional cases. Attack rates were highly variable, ranging from 0.4% to 86.5%. The R was 1.16 (95%CI, 1.11-1.22) with k at 2.5 (95%CI, 0.5-4.5). The timing of viral circulation in nursing homes did not mirror that in the general population (p-values<0.001). We estimated the impact of vaccination in preventing SARS-CoV-2 transmission. Before vaccination's roll-out, a cumulated 5,579 SARS-CoV-2 infections were documented among residents and 2,321 among staff. Higher staffing ratio and previous natural immunization reduced the probability of an outbreak following introduction. Despite strong preventive measures, transmission likely occurred, regardless of building characteristics. Vaccination started on January 15, 2021, and coverage reached 65.0% among residents, and 42.0% among staff by February 20, 2021. Vaccination yielded a 92% reduction (95%CI, 71%-98%) of outbreak probability, and lowered R to 0.87 (95%CI, 0.69-1.10). In the post-pandemic era, much attention will have to be paid to multi-lateral collaboration, policy making, and prevention plans.

Comments by Microbiologists for Interpreting Antimicrobial Susceptibility Testing and Improving the Appropriateness of Antibiotic Therapy in Community-Acquired Urinary Tract Infections: A Randomized Double-Blind Digital Case-Vignette Controlled Superiority Trial.

In primary care, urinary tract infections (UTIs) account for the majority of antibiotic prescriptions. Comments from microbiologists on interpreting the antimicrobial susceptibility testing (AST) profile for urinalysis were made to improve the prescription of antibiotics. We aimed to explore the added value of these comments on the quality of antibiotic prescribing by a superior double-blind digital randomized case-vignette trial among French general practitioners (GPs). One case vignette with (intervention) or without (control) a 'comment' after AST was randomly assigned to GPs. Among 815 participating GPs, 64.7% were women, at an average age of 37 years. Most (90.1%) used a computerized decision support system for prescribing antibiotics. Empirical antibiotic therapy was appropriate in 71.9% (95% CI, 68.8-75.0) of the cases, without differences between arms. The overall appropriateness of targeted antibiotic therapy (primary outcome) was not significantly increased when providing 'comments': 83.4% vs. 79.9% (OR = 1.26, 95% CI, 0.86-1.85). With the multivariate analysis, the appropriateness was improved by 2-folds (OR = 2.38, 95% CI, 1.02-6.16) among physicians working in healthcare facilities. Among digital-affine young general practitioners, the adjunction of a 'comment' by a microbiologist to interpret urinalysis in community-acquired UTIs did not improve the overall level of appropriateness of the targeted antibiotic.

Effectiveness of third-generation cephalosporins or piperacillin compared with cefepime or carbapenems for severe infections caused by wild-type AmpC ß-lactamase-producing Enterobacterales: A multi-centre retrospective propensity-weighted study.

BACKGROUND: The optimal treatment regimen for infections caused by wild-type AmpC ß-lactamase-producing Enterobacterales remains controversial. This study compared the outcomes of bloodstream infections (BSI) and pneumonia according to the type of definitive antibiotic therapy: third-generation cephalosporin (3GC), piperacillin ± tazobactam, cefepime or carbapenem. METHODS: All cases of BSI and pneumonia caused by wild-type AmpC ß-lactamase-producing Enterobacterales over 2 years in eight university hospitals were reviewed. Patients who received definitive therapy consisting of either a 3GC (3GC group), piperacillin ± tazobactam (piperacillin group), or cefepime or a carbapenem (reference group) were included in this study. The primary endpoint was 30-day all-cause mortality. The secondary endpoint was treatment failure due to infection by emerging AmpC-overproducing strains. Propensity-score-based models were used to balance confounding factors between groups. RESULTS: In total, 575 patients were included in this study: 302 (52%) with pneumonia and 273 (48%) with BSI. Half (n=271, 47%) received cefepime or a carbapenem as definitive therapy, 120 (21%) received a 3GC, and 184 (32%) received piperacillin ± tazobactam. Compared with the reference group, 30-day mortality was similar in the 3GC [adjusted hazard ratio (aHR) 0.86, 95% confidence interval (CI) 0.57-1.31)] and piperacillin (aHR 1.20, 95% CI 0.86-1.66) groups. The likelihood of treatment failure was higher in the 3GC (aHR 6.81, 95% CI 3.76-12.4) and piperacillin (aHR 3.13, 95% CI 1.69-5.80) groups. The results were similar when stratifying the analysis on pneumonia or BSI. CONCLUSION: Treatment of included BSI or pneumonia caused by wild-type AmpC ß-lactamase-producing Enterobacterales with 3GC or piperacillin ± tazobactam was not associated with higher mortality, but was associated with increased risk of AmpC overproduction leading to treatment failure compared with cefepime or a carbapenem.

Hospital admissions and mortality for acute exacerbations of COPD during the COVID-19 pandemic: A nationwide study in France.

Background: A global reduction in hospital admissions for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) was observed during the first months of the COVID-19 pandemic. Large-scale studies covering the entire pandemic period are lacking. We investigated hospitalizations for AECOPD and the associated in-hospital mortality at the national level in France during the first 2 years of the pandemic. Methods: We used the French National Hospital Database to analyse the time trends in (1) monthly incidences of hospitalizations for AECOPD, considering intensive care unit (ICU) admission and COVID-19 diagnoses, and (2) the related in-hospital mortality, from January 2016 to November 2021. Pandemic years were compared with the pre-pandemic years using Poisson regressions. Results: The database included 565,890 hospitalizations for AECOPD during the study period. The median age at admission was 74 years (interquartile range 65-83), and 37% of the stays concerned women. We found: (1) a dramatic and sustainable decline in hospitalizations for AECOPD over the pandemic period (from 8,899 to 6,032 monthly admissions, relative risk (RR) 0.65, 95% confidence interval (CI) 0.65-0.66), and (2) a concomitant increase in in-hospital mortality for AECOPD stays (from 6.2 to 7.6% per month, RR 1.24, 95% CI 1.21-1.27). The proportion of stays yielding ICU admission was similar in the pre-pandemic and pandemic years, 21.5 and 21.3%, respectively. In-hospital mortality increased to a greater extent for stays without ICU admission (RR 1.39, 95% CI 1.35-1.43) than for those with ICU admission (RR 1.09, 95% CI 1.05-1.13). Since January 2020, only 1.5% of stays were associated with a diagnosis of COVID-19, and their mortality rate was nearly three-times higher than those without COVID-19 (RR 2.66, 95% CI 2.41-2.93). Conclusion: The decline in admissions for AECOPD during the pandemic could be attributed to a decrease in the incidence of exacerbations for COPD patients and/or to a possible shift from hospital to community care. The rise in in-hospital mortality is partially explained by COVID-19, and could be related to restricted access to ICUs for some patients and/or to greater proportions of severe cases among the patients hospitalized during the pandemic.

Cervical Human Papillomavirus Infection (HPV) and High Oncogenic Risk Genotypes among Women Living with HIV in Asia: A Meta-Analysis.

Women living with HIV (WLHIV) are prone to harbor several high-risk human papillomavirus (HR-HPV) genotypes and to develop cervical cancerous lesions. Data on HPV prevalence in these women are needed to inform immunization programs, especially in Asia where few data are available. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV and HR-HPV cervical infection in WLHIV in Asia and identify possible sources of heterogeneity for HR-HPV carriage. Pooled prevalence and its 95% confidence interval (95CI) were estimated using the inverse-variance weighting method. Linear regression weighted on study size was used to identify sources of heterogeneity. Among 7834 WLHIV (40 studies), the prevalence of HPV infection was 42.6% (95CI, 38.2% to 47.1%), and 34.6% (95CI, 30.3% to 39.1%) harbored HR-HPV genotypes, with significant heterogeneity across countries. In India, Thailand, and China, HPV-16 was the most frequent genotype (10.3%), followed by HPV-52 (5.4%), HPV-58 (5.0%), HPV-18 (4.1%), and HPV-33 (3.3%). In these women, most of whom were receiving antiretroviral therapy, we did not identify determinants of heterogeneity for HR-HPV infection. Our results underline the need for immunization programs based on nonavalent or new generation vaccines to prevent cervical cancer in WLHIV in Asia.

Hesitancy towards COVID-19 Vaccination among Healthcare Workers: A Multi-Centric Survey in France.

Vaccination programs against COVID-19 are being scaled up. We aimed to assess the effects of vaccine characteristics on vaccine hesitancy among healthcare workers in a multi-center survey conducted within French healthcare facilities from 1 December 2020 to 26 March 2021. We invited any healthcare workers naïve of COVID-19 vaccination to complete an online self-questionnaire. They reported on their socio-demographic characteristics, as well as their perception and beliefs towards vaccination. We measured their willingness to get vaccinated in eight scenarios for candidates' vaccines presented sequentially (1 to 4-point scale). Candidates' vaccines varied for efficacy (25%, 50%, 100%), length of immunization (1 year or lifetime), frequency (<1/100, <1/10,000), and severity (none, moderate, severe) of adverse events. We analyzed 4349 healthcare workers' responses with interpretable questionnaires. The crude willingness to get vaccinated was 53.2% and increased over time. We clustered the trajectories of responses using an unsupervised classification algorithm (k-means) and identified four groups of healthcare workers: those willing to get vaccinated in any scenario (18%), those not willing to get vaccinated at all (22%), and those hesitating but more likely to accept (32%) or reject (28%) the vaccination depending on the scenario. In these last two subgroups, vaccine acceptance was growing with age, educational background and was higher among men with condition. Compared to an ideal vaccine candidate, a 50% reduced efficacy resulted in an average drop in acceptance by 0.8 (SD ± 0.8, -23.5%), while it was ranging from 1.4 (SD ± 1.0, -38.4%) to 2.1 (SD ± 1.0, -58.4%) in case of severe but rare adverse event. The acceptance of a mandatory immunization program was 29.6% overall and was positively correlated to the willingness to get vaccinated, ranging from 2.4% to 60.0%. Even if healthcare workers represent a heterogeneous population, most (80%) could accept the vaccination against COVID-19. Their willingness to get the vaccine increased over time and as immunization programs became available. Among hesitant professionals, the fear of adverse events was the main concern. Targeted information campaigns reassuring about adverse events may increase vaccine coverage, in a population with a strong opinion about mandatory immunization programs.

Effect of Professional and Extra-Professional Exposure on Seroprevalence of SARS-CoV-2 Infection among Healthcare Workers of the French Alps: A Multicentric Cross-Sectional Study.

We aimed to report SARS-CoV-2 seroprevalence after the first wave of the pandemic among healthcare workers, and to explore factors associated with an increased infection rate. We conducted a multicentric cross-sectional survey from 27 June to 31 September 2020. For this survey, we enrolled 3454 voluntary healthcare workers across four participating hospitals, of which 83.4% were female, with a median age of 40.6 years old (31.8-50.3). We serologically screened the employees for SARS-CoV-2, estimated the prevalence of infection, and conducted binomial logistic regression with random effect on participating hospitals to investigate associations. We estimated the prevalence of SARS-CoV-2 infection at 5.0% (95 CI, 4.3%-5.8%). We found the lowest prevalence in health professional management support (4.3%) staff. Infections were more frequent in young professionals below 30 years old (aOR = 1.59, (95 CI, 1.06-2.37)), including paramedical students and residents (aOR = 3.38, (95 CI, 1.62-7.05)). In this group, SARS-CoV-2 prevalence was up 16.9%. The location of work and patient-facing role were not associated with increased infections. Employees reporting contacts with COVID-19 patients without adequate protective equipment had a higher rate of infection (aOR = 1.66, (95 CI, 1.12-2.44)). Aerosol-generating tasks were associated with a ~1.7-fold rate of infection, regardless of the uptake of FFP2. Those exposed to clusters of infected colleagues (aOR = 1.77, (95 CI, 1.24-2.53)) or intra-familial COVID-19 relatives (aOR = 2.09, (95 CI, 1.15-3.80)) also had a higher likelihood of infection. This report highlights that a sustained availability of personal protective equipment limits the SARS-CoV-2 infection rate to what is measured in the general population. It also pinpoints the need for dedicated hygiene training among young professionals, justifies the systematic eviction of infected personnel, and stresses the need for interventions to increase vaccination coverage among any healthcare workers.

Fosfomycin-trometamol (FT) or fluoroquinolone (FQ) as single-dose prophylaxis for transrectal ultrasound-guided prostate biopsy (TRUS-PB): A prospective cohort study.

OBJECTIVES: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB. METHODS: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression. RESULTS: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602). CONCLUSIONS: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted.