[Clostridioides difficile infections: Update and therapeutic guidelines]. / Infections à Clostridioides difficile : mise au point et repères thérapeutiques.

Clostridioides difficile infection (CDI) represents a significant challenge due to its increasing incidence, severity, and treatment difficulty. Effective management requires a multifactorial approach that includes preventive strategies, prudent antibiotic use, and adapted therapeutic options. Ongoing research and innovation offer promising prospects for improving ICD management, making vigilance and informed practices essential among healthcare professionals. Two main complications of ICD are pseudomembranous colitis (PMC) and toxic megacolon. PMC involves severe colonic inflammation due to C. difficile toxins, leading to pseudomembrane formation. Diagnosis relies on clinical criteria, microbiological tests, and endoscopy. Toxic Megacolon is characterized by severe colonic dilation and systemic toxicity, requiring immediate medical intervention. ICD diagnosis combines clinical signs and microbiological tests. These tests include toxin tests, GDH antigen detection, PCR for toxin genes, and stool culture. Imaging techniques assess colonic inflammation and complications. Combined diagnostic criteria from the American Gastroenterological Association (AGA) and European guidelines emphasize integrating clinical and laboratory findings for accurate diagnosis. ICD treatment involves stopping the implicated antibiotics and starting specific antimicrobial therapy. Common treatments include mainly fidaxomicin and oral vancomycin. Fecal microbiota transplantation (TMF) is recommended for recurrent cases unresponsive to standard treatments. Bezlotoxumab, an antibody targeting C. difficile toxin B, is used to prevent recurrence in high-risk adults. ICD poses a major challenge due to its increasing incidence, severity, and difficulty in treatment. A multifactorial approach involving rigorous preventive strategies, prudent antibiotic management, and adapted therapeutic options is essential for controlling the infection. Ongoing research and innovations in treatment offer promising prospects for improving patient management. Healthcare professionals must remain vigilant and informed to ensure effective practices in combating this infection and utilizing available resources optimally.

Perioperative pain management intervention in older patients with hip fracture in an orthogeriatric unit. A controlled before/after study assessing an audit and feedback intervention (PAIN-AGE).

BACKGROUND: Postoperative pain delays ambulation, extends hospital stay, reduces the probability of recovery, and increases risk of long-term functional impairment. Pain management in hip fractured patients poses a challenge to the healthcare teams. Older adults are more vulnerable to opioid-associated side effect and it is primordial to minimize their exposure to opioids. Acetaminophen is associated with reduced opioid use so we need to focus on acetaminophen use in first-line analgesia. METHODS: We conducted a controlled before/after study to assess the ability of an audit and feedback (A&F) intervention built with nurses to improve the quality of perioperative pain management in older patients hospitalized for hip fracture in an orthogeriatric unit (experimental group) versus a conventional orthopedic unit (no A&F intervention). The primary endpoint was the percentage of patients who received 3 g/day of acetaminophen during the three postoperative days, before and after the A&F intervention. Secondary endpoints included nurses' adherence to medical prescriptions, clinical data associated with patients and finally factors associated with intervention. The significative level was set at 0.05 for statistical analysis. RESULTS: We studied data from 397 patients (mean age 89 years, 75% female). During the postoperative period, 16% of patients from the experimental group received 3 g/day of acetaminophen before the A&F intervention; the percentage reached 60% after the intervention. The likelihood of receiving 3 g/day of acetaminophen during the postoperative period and adhering to the medical prescription of acetaminophen were significantly increased in the experimental group as compared with the control group. The patient's functional status at discharge (assessed by Activities of Daily Living scores) was significantly better and the length of hospital stay significantly reduced after the A&F intervention. CONCLUSION: Our controlled before/after study showed that an A&F intervention significantly improved perioperative pain management in older adults hospitalized for hip fracture. Involving teams in continuous education programs appears crucial to improve the quality of pain management and ensure nurses' adherence to medical prescriptions.

The desire of autonomy: A lever for vaccination of the elderly? Results of a qualitative study.

The COVID-19 pandemic has highlighted the challenges of vaccination and the infectious risks among the elderlies. However, immunization rates for recommended vaccines in this population are insufficient in France. We aimed in this study to identify the levers and obstacles to vaccination among seniors, and to establish the arguments that could lead to some new vaccination behaviors. A qualitative survey based on 14 semi-structured interviews was conducted with people aged 65 and over, living at home in the Auvergne Rhône-Alpes region (France) from March to May 2022. The interviews were recorded, entirely transcribed, then subjected to a thematic content analysis. The results show that participants are keen to preserve their health by maintaining their physical capacity, taking regular exercise and eating a balanced diet. However, vaccination was not mentioned as a mean of preventing infectious diseases. Infections were not perceived as a cause for concern. Furthermore, the physical and cognitive consequences of infectious diseases, which could result in a loss of autonomy, were not known. These elements could be a good lever to bring hesitant elderly people to reconsider their position toward vaccination. Vaccines were not seen as a strategy to prevent loss of autonomy among elderlies. Since vaccines against influenza, COVID-19, shingles, pneumococcus have proved to be effective in protecting against cardiovascular events, this argument might be the starting point for a prevention campaign for the elderly.

The relative effectiveness of a high-dose quadrivalent influenza vaccine versus standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021-2022 influenza season.

OBJECTIVES: High-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/2022 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccine (SD-QIV). The aim of this study is to estimate the relative vaccine effectiveness of HD-QIV vs. SD-QIV against influenza-related hospitalizations in France. METHODS: Community-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/2022 influenza season were included in the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the five previous years. Hospitalizations for influenza and other causes were recorded from 14 days after vaccination until the end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination, and region. Incidence rate ratios were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models. RESULTS: We matched 405 385 HD-QIV to 1 621 540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95% CI, 8.4-35.8) lower rate of influenza hospitalizations compared with SD-QIV (69.5/100 000 person years vs. 90.5/100 000 person years). Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and negative control outcomes, suggesting residual confounding by indication. DISCUSSION: HD-QIV was associated with lower influenza-related hospitalization rates vs. SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.

Cost-Effectiveness of Adjuvanted Quadrivalent Influenza Vaccine for Adults over 65 in France.

BACKGROUND: In France, influenza accounts for an average of over one million consultations with GPs, 20,000 hospitalizations, and 9000 deaths per year, particularly among the over-65s. This study evaluates the cost-effectiveness of the adjuvanted quadrivalent influenza vaccine (aQIV) compared to standard (SD-QIV) and high-dose (HD-QIV) quadrivalent influenza vaccines for individuals aged 65 and older in France. METHODS: The age-structured SEIR transmission model, calibrated to simulate a mean influenza season, incorporates a contact matrix to estimate intergroup contact rates. Epidemiological, economic, and utility outcomes are evaluated. Vaccine effectiveness and costs are derived from literature and national insurance data. Quality of life adjustments for influenza attack rates and hospitalizations are applied. Deterministic and probabilistic analyses are also conducted. RESULTS: Compared to SD-QIV, aQIV demonstrates substantial reductions in healthcare utilization and mortality, avoiding 89,485 GP consultations, 2144 hospitalizations, and preventing 1611 deaths. Despite an investment of EUR 110 million, aQIV yields a net saving of EUR 14 million in healthcare spending. Compared to HD-QIV, aQIV saves 62 million euros on vaccination costs. Cost-effectiveness analysis reveals an incremental cost-effectiveness ratio of EUR 7062 per QALY. CONCLUSIONS: This study highlights the cost-effectiveness of aQIV versus SD-QIV and HD-QIV, preventing influenza cases, hospitalizations, and deaths.

One Hundred Explicit Definitions of Potentially Inappropriate Prescriptions of Antibiotics in Hospitalized Older Patients: The Results of an Expert Consensus Study.

BACKGROUND: In geriatrics, explicit criteria for potentially inappropriate prescriptions (PIPs) are useful for optimizing drug use. OBJECTIVE: To produce an expert consensus on explicit definitions of antibiotic-PIPs for hospitalized older patients. METHODS: We conducted a Delphi survey involving French experts on antibiotic stewardship in hospital settings. During the survey's rounds, the experts gave their opinion on each explicit definition, and could suggest new definitions. Definitions with a 1-to-9 Likert score of between 7 and 9 from at least 75% of the participants were adopted. The results were discussed during consensus meetings after each round. RESULTS: Of the 155 invited experts, 128 (82.6%) participated in the whole survey: 59 (46%) infectious diseases specialists, 45 (35%) geriatricians, and 24 (19%) other specialists. In Round 1, 65 explicit definitions were adopted and 21 new definitions were suggested. In Round 2, 35 other explicit definitions were adopted. The results were validated during consensus meetings (with 44 participants after Round 1, and 54 after Round 2). CONCLUSIONS: The present study is the first to have provided a list of explicit definitions of potentially inappropriate antibiotic prescriptions for hospitalized older patients. It might help to disseminate key messages to prescribers and reduce inappropriate prescriptions of antibiotics.

Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study.

PURPOSE: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival. METHODS: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression. RESULTS: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality. CONCLUSION: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality.

Individual and contextual risk factors for mortality in nursing home residents during the first wave of COVID-19 in France: a multilevel analysis of a nationwide cohort study.

BACKGROUND: Mortality amongst nursing home (NH) residents increased by 43% during the first wave of coronavirus disease 2019 (COVID-19). We estimated the 'contextual effect' on mortality, tried to explain it by NH characteristics and identified resident- and NH-level risk factors for mortality. METHODS: The contextual effect was measured for two cohorts of NH residents managed by the general scheme in metropolitan France (RESIDESMS data from 03/01/2020 to 05/31/2020 and 03/01/2019 to 05/31/2019) by the intraclass correlation coefficient (ICC) estimated from mixed-effects logistic regression. RESULTS: Amongst 385,300 residents (5,339 NHs) included in 2020 (median age 89 years, 25% men), 9.1% died, versus 6.7% of 379,926 residents (5,270 NHs) in 2019. In the empty model, the ICC was 9.3% in 2020 and 1.5% in 2019. Only the geographic location partially explained the heterogeneity observed in 2020 (ICC: 6.5% after adjustment). Associations with mortality were stronger in 2020 than in 2019 for male sex and diabetes and weaker for heart disease, chronic respiratory disease and residence <6 months. Mortality was higher in 2020 (15.1%) than 2019 (6.3%) in NHs with at least one death with a mention of COVID-19 and more heterogeneous (ICC: 8.0%) than in the others (mortality: 6.7% in both years; ICC: 1.1%). CONCLUSION: Our results suggest that the COVID-19 crisis had a heterogeneous impact on mortality in NH residents and that geographic location explain a part of the contextual effect, which appears to have had little influence on mortality in NHs not being affected by the virus.

Impact of influenza, herpes zoster, and pneumococcal vaccinations on the incidence of cardiovascular events in subjects aged over 65 years: a systematic review.

This systematic review aims to summarize the impact of vaccination against influenza, shingles, and pneumococcus on the incidence on the risk of cardiovascular events in the elderly. This protocol was developed in accordance with PRISMA guidelines. We conducted a literature search and identified all relevant articles published regarding the matter up to September 2022. We retrieved 38 studies (influenza vaccine = 33, pneumococcal vaccine = 5, and zoster vaccine = 2). A total of 28 and 2 studies have shown that influenza and pneumococcal vaccines significantly lower the risk of cardiovascular disease in the elderly. Also, repeated influenza vaccination shows a consistent and dose-dependent protective effect against acute coronary syndromes and stroke. Moreover, dual influenza and pneumococcal vaccination was associated with lower risks of some cardiovascular events (stroke, congestive heart failure, ischemic heart disease, and myocardial infarction). However, the impact of PCV13 on cardiovascular events has not been studied, nor has the currently recommended vaccination schedule (PCV13 + PPV23). As for herpes zoster vaccination, only the protective effect against stroke has been studied with the live attenuated herpes zoster vaccine, but no studies have been conducted with the recombinant subunit herpes zoster vaccine. This review outlines the benefits of the vaccines mentioned above beyond their preventive action on infectious diseases. It is intended for health professionals who wish to inform and advise their elderly patients.

Biomarkers for risk stratification and antibiotic stewardship in elderly patients.

PURPOSE: Optimal treatment of infections in the elderly patients population is challenging because clinical symptoms and signs may be less specific potentially resulting in both, over- and undertreatment. Elderly patients also have a less pronounced immune response to infection, which may influence kinetics of biomarkers of infection. METHODS: Within a group of experts, we critically reviewed the current literature regarding biomarkers for risk stratification and antibiotic stewardship in elderly patients with emphasis on procalcitonin (PCT). RESULTS: The expert group agreed that there is strong evidence that the elderly patient population is particularly vulnerable for infections and due to ambiguity of clinical signs and parameters in the elderly, there is considerable risk for undertreatment. At the same time, however, this group of patients is particularly vulnerable for off-target effects from antibiotic treatment and limiting the use of antibiotics is therefore important. The use of infection markers including PCT to guide individual treatment decisions has thus particular appeal in geriatric patients. For the elderly, there is evidence that PCT is a valuable biomarker for assessing the risk of septic complications and adverse outcomes, and helpful for guiding individual decisions for or against antibiotic treatment. There is need for additional educational efforts regarding the concept of "biomarker-guided antibiotic stewardship" for health care providers caring for elderly patients. CONCLUSION: Use of biomarkers, most notably PCT, has high potential to improve the antibiotic management of elderly patients with possible infection for improving both, undertreatment and overtreatment. Within this narrative review, we aim to provide evidence-based concepts for the safe and efficient use of PCT in elderly patients.

Intrinsic values of procalcitonin in bacterial bloodstream infections in people aged 75 years and over: a retrospective study.

OBJECTIVE: To evaluate PCT measurement in the diagnosis of bloodstream infection (BSI) in hospitalized patients aged 75+. METHOD: Descriptive, retrospective, monocentric study conducted in France, in patients with at least one blood culture and PCT and CRP measurements within the 24 hours before or after blood culture. RESULTS: The mean PCT and CRP values for the 118 (15.2%) positive blood cultures were 18.90 ng/ml [95%CI: 0.007-334.7] and 153.93 mg/l [1-557], respectively. With a threshold of 0.3 ng/ml, PCT measurement had a sensitivity of 84%, a specificity of 53%, a PPV of 24%, and an NPV of 95%, making it possible to rule out BSI in 350 (45.1%) patients (α-risk=5%). CONCLUSION: PCT measurement may eliminate BSI diagnosis more quickly than does blood culture reducing the inadequate and detrimental use of antibiotic therapy. A prospective study is required to validate its usefulness and confirm the cut-off value in geriatric populations.

Procalcitonin to reduce exposure to antibiotics and individualise treatment in hospitalised old patients with pneumonia: a randomised study.

BACKGROUND: Treating pneumonia in old patients remains challenging for clinicians. Moreover, bacterial antimicrobial resistance is a major public health threat. OBJECTIVE: The PROPAGE study evaluated the interest of a strategy using serial measurements of procalcitonin (PCT) to reduce the duration of antibiotic therapy in old patients with pneumonia. METHODS: PROPAGE took place from Dec.-2013 to Jun.-2016 in eight French geriatric units. It was a prospective, comparative, randomised, open-label study involving old patients (≥ 80 years) who had initiated antibiotic treatment for pneumonia in the previous 48 h. PCT was monitored in all patients and two decision-making PCT-based algorithms guided antibiotic therapy in patients from the PCT group. RESULTS: 107 patients were randomised (PCT, n = 50; Control, n = 57). Antibiotic therapy exposure was reduced in the PCT group as compared to the Control group (median duration of antibiotic therapy, 8 vs. 10 days [rank-test, p = 0.001]; antibiotic persistence rates on Days 6 and 8, 54% and 44% vs. 91% and 72%) and no significant difference was found in recovery rate (84% vs. 89.5%; Pearson Chi² test, p = 0.402). CONCLUSION: Although, the superiority of the strategy was not tested using a composite criterion combining antibiotic therapy duration and recovery rate was not tested due to the small sample size, the present study showed that monitoring associated with PCT-guided algorithm could help shorten antibiotic treatment duration in the very old patients without detrimental effects. Measuring PCT levels between Day 4 and Day 6 could be helpful when making the decision regarding antibiotic discontinuation. TRIAL REGISTRATION: NCT02173613. This study was first registered on 25/06/2014.

Coadministration of seasonal influenza and COVID-19 vaccines: A systematic review of clinical studies.

The lifting of non-pharmaceutical measures preventing transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources and fears of an increased number of cases of influenza and COVID-19. For the 2021-2022 influenza season, the WHO and >20 European countries promoted coadministration of influenza and COVID-19 vaccines. Recently, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022-2023 influenza vaccination campaign for healthcare professionals and people at risk of severe COVID-19. The present systematic review examines published data on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. The results should reassure vaccinees and vaccinators in case of coadministration and increase vaccine coverage. Healthcare systems promoting coupled campaigns must provide the necessary means for successful coadministration.

The lifting of non-pharmaceutical measures recommended to prevent transmission of SARS-CoV-2 (and other viruses, including influenza viruses) raises concerns about healthcare resources, already under pressure. It also raises fears of an increase in the number of cases of influenza or COVID-19 infection during the winter season. For the 2021­2022 influenza season, the World Health Organization and several European countries promoted concomitant administration in distinct anatomic sites (i.e., coadministration) of influenza and COVID-19 vaccines to avoid additional stress on healthcare systems. In May 2022, the French Health Authority recommended coupling the COVID-19 vaccination with the 2022­2023 influenza vaccination campaign (i.e., starting COVID-19 vaccination at the date of influenza vaccination) for healthcare professionals and people at risk of severe COVID-19, in case of epidemic wave. Coadministration of influenza and COVID-19 vaccines is one of the factors of success for a coupled campaign. The present systematic review examines all published data (articles or reports, clinical trials, or surveys) on the safety, immunogenicity, efficacy/effectiveness, and acceptability/acceptance of coadministration of influenza and COVID-19 vaccines. The PRISMA method was used to collect information. No safety concerns or immune interferences were found whatever the vaccines or the age of vaccinated subjects (65- or 65+). No efficacy/effectiveness data were available. Acceptability and acceptance were good but could be improved. By reassuring vaccinees and vaccinators, these results are expected to favor coadministration and ultimately increase vaccine coverage, thus offering better protection. Healthcare systems promoting coupled campaigns with coadministration must provide the necessary means for their successful implementation.

Tolerance of Fentanyl Pectin Nasal Spray for Procedural Pain in Geriatric Patients.

OBJECTIVES: We aimed to assess the tolerance of fentanyl pectin nasal spray (FPNS) when used to treat procedural pain caused by wound dressing or physiotherapy in patients older than 75 years with or without opioid background treatment. DESIGN: This is a prospective monocentric, noncontrolled, nonrandomized study conducted from December 2014 to October 2017 in 2 geriatric wards (rehabilitation and acute medicine). SETTING AND PARTICIPANTS: Fifty-seven patients were included and 314 procedures were monitored. METHODS: For each patient, 6 procedures were monitored: the first 2 without specific treatment, then fentanyl was started at 100 µg with a titration over a few procedures up to 800 µg in non-opioid-naïve patients and 400 µg in opioid-naïve. Sedation and respiratory scale were monitored during the procedures. All adverse drug events occurring from inclusion to 5 days after the intervention were collected and their imputability was assessed separately by 2 pharmacovigilance experts. RESULTS: Overall, 14.4% of the sessions with FPNS administration resulted in adverse drug events. Main adverse drug events were nausea and vomiting, somnolence, and confusion. Most of them were of mild to moderate severity. Four severe adverse events were due to accidental overdoses. No unexpected adverse event occurred. Tolerance was similar for opioid-naïve and non-opioid-naïve patients (P value = .93). CONCLUSION AND IMPLICATIONS: FPNS was overall well tolerated in geriatric patients. Given its interesting pharmacokinetics, fentanyl is a promising lead for procedural pain treatment in geriatric patients, even those who are opioid naïve.

Dalbavancin in clinical practice: a particular place for the elderly?

We investigate dalbavancin efficiency and tolerance among elderly in Grenoble-Alpes 32 university hospital. Among the 65 patients who received dalbavancin, 51% (33) were considered as old. Patients presented mainly bones and joint infections (52%), surgical site infection 34 (31%), and infective endocarditis (IE) (8%). Clinical cure was confirmed for 79% of old 35 patients at 1, 3, and 6 months. Six adverse events (9%) were reported after 36 dalbavancin's administration, but each time in combination with other antibiotics. 37 Dalbavancin had a significant effectiveness and safety profile and represents a real 38 therapeutic option in the management of deep and complex infections of elderly patients.

Zoledronic Acid Contraindications Prevalence among Hip-Fractured Patients Aged 75 Years or Over Hospitalized in an Orthogeriatric Unit.

OBJECTIVE: Zoledronic acid (ZA) is an antiosteoporotic drug that has been proven to reduce mortality after a hip fracture (HF). ZA is however underused with older HF patients. One possible cause may be the high prevalence of severe renal failure and hypocalcemia which contraindicate ZA administration. The aim of this study was to assess the prevalence of these 2 contraindications in patients aged 75 years or older admitted into an orthogeriatric (OG) unit after a low-energy HF. The secondary objective was to assess the prevalence of situations in which ZA must be used with caution. METHODS: Our retrospective descriptive monocentric study was performed in an OG unit on a cohort of elderly patients hospitalized for HF from August 2015 to August 2017. Prevalence of hypocalcemia lower than 2 mmol/L and Cockcroft creatinine clearance lower than 35 mL/min was recorded. RESULTS: Among the 194 patients admitted for HF, 136 patients (mean age 86 ± 5.6 years; 101 women) were included. The mean length of hospital stay was 15 ± 9 days. 111 (81.5%) had no contraindications to ZA administration. More than 80% presented situations in which ZA had to be used with caution, including 25(OH)D deficiency (20%). CONCLUSION: The majority of subjects aged 75 years or older admitted to hospital after an HF seem to have no contraindication for ZA administration during their immediate postoperative hospital stay. The hospitalization period after HF repair gives the opportunity to give most of them this treatment to improve their prognosis, taking into account situations in which ZA must be used with caution.

Estimating the burden of influenza-related and associated hospitalizations and deaths in France: An eight-season data study, 2010-2018.

BACKGROUND: In France, each year, influenza viruses are responsible for seasonal epidemics leading to 2-6 million cases. Influenza can cause severe disease that may lead to hospitalization or death. As severe disease may be due to the virus itself or to disease complications, estimating the burden of severe influenza is complex. The present study aimed at estimating the epidemiological and economic burden of severe influenza in France during eight consecutive influenza seasons (2010-2018). METHODS: Influenza-related hospitalization and mortality data and patient characteristics were taken from the French hospital information database, PMSI. An ecological approach using cyclic regression models integrating the incidence of influenza syndrome from the Sentinelles network supplemented the PMSI data analysis in estimating excess hospitalization and mortality (CépiDc-2010-2015) and medical costs. RESULTS: Each season, the average number of influenza-related hospitalizations was 18,979 (range: 8627-44,024), with an average length of stay of 8 days. The average number of respiratory hospitalizations indirectly related with influenza (i.e., influenza associated) was 31,490 (95% confidence interval [CI]: 24,542-39,012), with an average cost of €141 million (range: 54-217); 70% of these hospitalizations and 77% of their costs concerned individuals ≥65 years of age (65+). More than 90% of excess mortality was in 65+ subjects. CONCLUSIONS: The combination of two complementary approaches allowed estimation of both influenza-related and associated hospitalizations and deaths and their burden in France, showing the substantial impact of complications. The present study highlighted the major public health burden of influenza and its severe complications, especially in 65+ subjects.