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.

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.

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.

Mouse Models of Osteoarthritis: A Summary of Models and Outcomes Assessment.

Osteoarthritis (OA) is a multidimensional health problem and a common chronic disease. It has a substantial impact on patient quality of life and is a common cause of pain and mobility issues in older adults. The functional limitations, lack of curative treatments, and cost to society all demonstrate the need for translational and clinical research. The use of OA models in mice is important for achieving a better understanding of the disease. Models with clinical relevance are needed to achieve 2 main goals: to assess the impact of the OA disease (pain and function) and to study the efficacy of potential treatments. However, few OA models include practical strategies for functional assessment of the mice. OA signs in mice incorporate complex interrelations between pain and dysfunction. The current review provides a comprehensive compilation of mouse models of OA and animal evaluations that include static and dynamic clinical assessment of the mice, merging evaluation of pain and function by using automatic and noninvasive techniques. These new techniques allow simultaneous recording of spontaneous activity from thousands of home cages and also monitor environment conditions. Technologies such as videography and computational approaches can also be used to improve pain assessment in rodents but these new tools must first be validated experimentally. An example of a new tool is the digital ventilated cage, which is an automated home-cage monitor that records spontaneous activity in the cages.

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.

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.

What have we learned from the first to the second wave of COVID-19 pandemic? An international survey from the ESCMID Study Group for Infection in the Elderly (ESGIE) group.

The purpose of this survey is to explore changes in the management of COVID-19 during the first versus the second wave, with particular emphasis on therapies, antibiotic prescriptions, and elderly care. An internet-based questionnaire survey was distributed to European Society of Clinical Microbiology and Infectious Diseases (ESCMID) members. Therapeutic approach to patients with mild-to-moderate (PiO2/FiO2 200-350) and severe (PiO2/FiO2 < 200) COVID-19, antibiotic use, and reasons for excluding patients from the intensive care unit (ICU) were investigated. A total of 463 from 21 countries participated in the study. Most representatives were infectious disease specialists (68.3%). During the second wave of pandemic, physicians abandoned the use of hydroxychloroquine, lopinavir/ritonavir, and azithromycin in favor of dexamethasone, low-molecular weight heparin (LMWH), and remdesivir in mild-to-moderate COVID-19. In critically ill patients, we detected an increased use of high-dose steroids (51%) and a decrease in tocilizumab use. The use of antibiotics at hospital admission decreased but remained high in the second wave. Age was reported to be a main consideration for exclusion of patients from ICU care by 25% of responders; a third reported that elderly were not candidates for ICU admission in their center. The decision to exclude patients from ICU care was based on the individual decision of an intensivist in 59.6% of cases. The approach of physicians to COVID-19 changed over time following evidence accumulation and guidelines. Antibiotic use at hospital admission and decision to exclude patients from ICU care remain critical aspects that should be better investigated and harmonized among clinicians.

Management of preoperative pain in elderly patients with moderate to severe cognitive deficits and hip fracture: a retrospective, monocentric study in an orthogeriatric unit.

BACKGROUND: Patients with cognitive deficits are 3 times more likely to suffer a hip fracture than geriatric patients of the same age group without cognitive deficits. The persistence of perioperative pain following hip fracture is a risk factor for the occurrence of delirium, poor functional prognosis, and the development of secondary chronic pain. Patients with cognitive deficits receive 20 to 60% less analgesics than those without cognitive deficits. Our retrospective descriptive monocentric study was performed in an orthogeriatric unit on a cohort of elderly patients hospitalized for hip fracture. The aim of the study was to compare the quantity of strong opioids delivered in a morphine sulfate equivalent daily during the preoperative period after a hip fracture between cognitively intact patients and those with cognitive deficits. RESULTS: Our total population of 69 patients had a median age of 90 years old, and 46% of these patients had moderate or severe cognitive deficits. During the preoperative period, the same quantity of strong opioids was administered to both groups of patients (13.1 mg/d versus 10.8 mg/d (p = 0.38)). Patients with moderate to severe cognitive deficits more often experienced delirium during their hospitalization (p < 0.01) and received more psychotropic drugs in the first 3 postoperative days (p = 0.025). CONCLUSIONS: We reported that with standardized pain management in an orthogeriatric unit, patients aged 75 years and older received the same daily average quantity of strong opioids during the preoperative period regardless of the presence of cognitive deficits.

Outbreaks of COVID-19 in Nursing Homes: A Cross-Sectional Survey of 74 Nursing Homes in a French Area.

In this multi-centric cross-sectional survey conducted in nursing homes of the French Alps, from 1 March to 31 May 2020, we analyze the relationship between the occurrence of an outbreak of COVID 19 among residents and staff members. Out of 225 eligible nursing homes, 74 (32.8%) completed the survey. Among 5891 residents, the incidence of confirmed or probable COVID-19 was 8.2% (95CI, 7.5% to 8.9%), and 22 (29.7%) facilities had an outbreak with at least 3 cases. Among the 4652 staff members, the incidence of confirmed or probable COVID-19 was 6.3% (95CI, 5.6% to 7.1%). A strong positive correlation existed between residents and staff members for both numbers of cases (r2 = 0.77, p < 0.001) and the incidence (r2 = 0.76, p < 0.001). In univariate analyses, cases among the staff were the only factor associated with the occurrence of an outbreak among residents (OR = 11.2 (95CI, 2.25 to 53.6)). In bivariate analysis, this relationship was not influenced by any nursing home characteristics, nor the action they implemented to mitigate the COVID-19 crisis. Staff members were, therefore, likely to be a source of contamination and spread of COVID-19 among nursing home residents during the first wave of the pandemic.