Attributable Perioperative Cost of Frailty after Major, Elective Noncardiac Surgery: A Population-based Cohort Study.

BACKGROUND: Patients with frailty consistently experience higher rates of perioperative morbidity and mortality; however, costs attributable to frailty remain poorly defined. This study sought to identify older patients with and without frailty using a validated, multidimensional frailty index and estimated the attributable costs in the year after major, elective noncardiac surgery. METHODS: The authors conducted a retrospective population-based cohort study of all patients 66 yr or older having major, elective noncardiac surgery between April 1, 2012, and March 31, 2018, using linked health data obtained from an independent research institute (ICES) in Ontario, Canada. All data were collected using standard methods from the date of surgery to the end of 1-yr follow-up. The presence or absence of preoperative frailty was determined using a multidimensional frailty index. The primary outcome was total health system costs in the year after surgery using a validated patient-level costing method capturing direct and indirect costs. Secondary outcomes included costs to postoperative days 30 and 90 along with sensitivity analyses and evaluation of effect modifiers. RESULTS: Of 171,576 patients, 23,219 (13.5%) were identified with preoperative frailty. Unadjusted costs were higher among patients with frailty (ratio of means 1.79, 95% CI 1.76 to 1.83). After adjusting for confounders, an absolute cost increase of $11,828 Canadian dollar (ratio of means 1.53; 95% CI, 1.51 to 1.56) was attributable to frailty. This association was attenuated with additional control for comorbidities (ratio of means 1.24, 95% CI, 1.22 to 1.26). Among contributors to total costs, frailty was most strongly associated with increased postacute care costs. CONCLUSIONS: For patients with preoperative frailty having elective surgery, the authors estimate that attributable costs are increased 1.5-fold in the year after major, elective noncardiac surgery. These data inform resource allocation for patients with frailty.

Hemagglutinin stalk-binding antibodies enhance effectiveness of neuraminidase inhibitors against influenza via Fc-dependent effector functions.

The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next-generation universal influenza vaccines. Protection provided by hemagglutinin stalk-binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.