Cost-effectiveness and public health impact of using high dose quadrivalent influenza vaccine in the French older adults population.

BACKGROUND: Seasonal influenza outbreaks in France cause a surge in patients, exacerbating the overburdened healthcare system each winter. Older adults are particularly vulnerable to serious events related to influenza. Quadrivalent influenza high dose (QIV HD) vaccines have been developed to offer better clinical protection in older adults, who often exhibit suboptimal immune response to quadrivalent influenza standard dose vaccines (QIV SD). This study aims to evaluate the public health impact and cost-effectiveness of administering HD versus SD vaccines to individuals aged 65+ in France. METHODOLOGY: Using a static model and decision-tree approach, the study analyzed health outcomes such as influenza cases, GP (general practitioner) visits, hospitalizations, and mortality; relative vaccine efficacy (rVE) estimates were derived from a pivotal randomized-controlled trial and a meta-analysis comparing HD to SD vaccines. Two approaches were implemented to model hospitalizations (conditional on influenza or not), and analyses on bed occupancy were performed. RESULTS: Results showed that using QIV HD instead of QIV SD during an average influenza season in France led to the prevention of 57,209 additional cases of influenza, 13,704 GP visits, and 764 influenza-related deaths. Moreover, switching to QIV HD resulted in an additional 1,728-15,970 hospitalizations avoided and 15,124-138,367 reduced days of hospitalization depending on the hospitalization approach used. The cost-utility analysis showed a cost per quality-adjusted life year (QALY) gained ranging from 24,020 €/QALY to 5,036 €/QALY. CONCLUSIONS: Switching to QIV HD in older adults was shown to be cost-effective, with even greater public health benefits at a higher coverage rate, regardless of the season severity.

Excess hospitalizations and mortality associated with seasonal influenza in Spain, 2008-2018.

BACKGROUND: Influenza may trigger complications, particularly in at-risk groups, potentially leading to hospitalization or death. However, due to lack of routine testing, influenza cases are infrequently coded with influenza-specific diagnosis. Statistical models using influenza activity as an explanatory variable can be used to estimate annual hospitalizations and deaths associated with influenza. Our study aimed to estimate the clinical and economic burden of severe influenza in Spain, considering such models. METHODS: The study comprised ten epidemic seasons (2008/2009-2017/2018) and used two approaches: (i) a direct method of estimating the seasonal influenza hospitalization, based on the number of National Health Service hospitalizations with influenza-specific International Classification of Diseases (ICD) codes (ICD-9: 487-488; ICD-10: J09-J11), as primary or secondary diagnosis; (ii) an indirect method of estimating excess hospitalizations and deaths using broader groups of ICD codes in time-series models, computed for six age groups and four groups of diagnoses: pneumonia or influenza (ICD-9: 480-488, 517.1; ICD-10: J09-J18), respiratory (ICD-9: 460-519; ICD-10: J00-J99), respiratory or cardiovascular (C&R, ICD-9: 390-459, 460-519; ICD-10: I00-I99, J00-J99), and all-cause. Means, excluding the H1N1pdm09 pandemic (2009/2010), are reported in this study. RESULTS: The mean number of hospitalizations with a diagnosis of influenza per season was 13,063, corresponding to 28.1 cases per 100,000 people. The mean direct annual cost of these hospitalizations was €45.7 million, of which 65.7% was generated by patients with comorbidities. Mean annual influenza-associated C&R hospitalizations were estimated at 34,894 (min: 16,546; max: 52,861), corresponding to 75.0 cases per 100,000 (95% confidence interval [CI]: 63.3-86.3) for all ages and 335.3 (95% CI: 293.2-377.5) in patients aged ≥ 65 years. We estimate 3.8 influenza-associated excess C&R hospitalizations for each hospitalization coded with an influenza-specific diagnosis in patients aged ≥ 65 years. The mean direct annual cost of the estimated excess C&R hospitalizations was €142.9 million for all ages and €115.9 million for patients aged ≥ 65 years. Mean annual influenza-associated all-cause mortality per 100,000 people was estimated at 27.7 for all ages. CONCLUSIONS: Results suggest a relevant under-detected burden of influenza mostly in the elderly population, but not neglectable in younger people.

Effects of gamma- and hydroxypropyl-gamma-cyclodextrins on the transport of doxorubicin across an in vitro model of blood-brain barrier.

Association between doxorubicin (DOX) and gamma-cyclodextrin (gamma-CD) or hydroxypropyl-gamma-CD (HP-gamma-CD) has been examined to increase the delivery of this antitumoral agent to the brain. The stoichiometry and the stability constant of gamma-CD or HP-gamma-CD and DOX complexes were determined in physiological medium by UV-visible spectroscopy. By using an in vitro model of the blood-brain barrier (BBB), endothelial permeability and toxicity toward the brain capillary endothelial cells of DOX, gamma-CD, and HP-gamma-CD were performed. For each CD, endothelial permeability was relatively low and a disruption of the BBB occurred at 20 microM, 20 mM, and 50 mM DOX, gamma-CD, and HP-gamma-CD, respectively. Increasing amounts of CDs were added to a fixed DOX concentration. Addition of gamma-CD or HP-gamma-CD, up to 15 and 35 mM, respectively, decreased the DOX delivery, probably due to the low complex penetration across the BBB and the decrease in free DOX concentration. Higher CD concentrations increased the DOX delivery to the brain, but this effect is due to a loss of BBB integrity. In contrast to what was observed on Caco-2 cell model with various drugs, CDs are not able to increase the delivery of DOX across our in vitro model of BBB.

Behavior of alpha-, beta-, and gamma-cyclodextrins and their derivatives on an in vitro model of blood-brain barrier.

Cyclodextrins (CDs) can be envisaged to cure some diseases related to the brain, but the behavior of these compounds toward the blood-brain barrier (BBB) remains largely unexplored to envisage such clinical applications. To fulfill this gap, the toxicity and endothelial permeability for native, methylated, and hydroxypropylated alpha-, beta-, and gamma-CDs have been studied on an in vitro model of BBB. As shown by the endothelial permeability for sucrose and immunofluorescence stainings, the native CDs are the most toxic CDs (alpha- > beta- > gamma-CD). Whereas the chemical modification of beta-CD did not affect the toxicity of this CD, differences are observed for the alpha- and gamma-CD. To determine the origin of toxicity, lipid effluxes on the brain capillary endothelial cells were performed in the presence of native CDs. It was found that alpha-CD removed phospholipids and that beta-CD extracted phospholipids and cholesterol. gamma-CD was less lipid-selective than the other CDs. Finally, the endothelial permeability of each CD has been determined. Surprisingly, no structure/permeability relationship has been observed according to the nature and chemical modifications of CDs.

[Thalamic hematoma: review of semiology and computed x-ray tomography in 14 cases]. / Les hématomes thalamiques: revue séméiologique et tomodensitométrique de quatorze observations.

Thalamic hematomas occur chiefly in hypertensive patients aged 50 to 70; characteristic presentation is a triad associating a sensory syndrome, oculomotor disorders, and alterations in consciousness; computed tomography not only establishes diagnosis but provides additional information, particularly on the size and volume effect of the hematoma which may, according to some authors, indicate surgical removal.

[Spontaneous primary hematomas of the cerebellum]. / Les hématomes spontanés primitifs du cervelet.

Spontaneous cerebellar hematoma is a well-defined radio-clinical entity. It may occur, not only in patients with risk factors (hypertension for instance), but also in those who have no specific etiologic factors. Onset is usually sudden. The characteristic clinical triad consists of alterations in consciousness, peripheral facial palsy and various oculomotor disorders. Poor prognosis factors related to the size and localization of the hematoma can be determined by computed tomography. We believe that surgery is indispensable in hydrocephalus as well as in increasing or secondary onset of alterations in consciousness.