Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

Immunogenicity of high-dose trivalent inactivated influenza vaccine: a systematic review and meta-analysis

Introduction: High-dose trivalent, inactivated, split-virus influenza vaccine (IIV3-HD) has been available in the US since 2009 for adults aged ≥ 65 years. To better understand how IIV3-HD provides improved protection against influenza, we systematically reviewed clinical studies comparing immune responses to IIV3-HD and standard-dose trivalent vaccine (IIV3-SD). Areas covered: The primary objective was to determine the relative hemagglutination inhibition (HAI) antibody response of IIV3-HD vs. IIV3-SD in adults aged ≥ 65 years. Based on seven randomized studies including more than 18,500 adults aged ≥ 65 years, combined HAI geometric mean titer (GMT) ratios (95% confidence interval) approximately 1 month post-vaccination were 1.74 (1.65–1.83) for influenza A/H1N1, 1.84 (1.73–1.95) for influenza A/H3N2, and 1.47 (1.36–1.58) for influenza B. HAI GMT ratios in these studies were similar irrespective of sex, older age (≥ 75 years), frailty, and underlying conditions. Trends were similar for A/H3N2 neutralization and anti-neuraminidase antibody titers. In immunocompromised individuals, HAI GMT ratios were mostly > 1. Expert opinion: In agreement with its improved efficacy and effectiveness, IIV3-HD is consistently more immunogenic than IIV3-SD in adults aged ≥ 65 years. IIV3-HD also appears more immunogenic in immunocompromised individuals

Antibody-mediated NK cell activation as a correlate of immunity against influenza infection

Abstract Antibodies play a critical role in protection against influenza; yet titers and viral neutralization represent incomplete correlates of immunity. Instead, the ability of antibodies to leverage the antiviral power of the innate immune system has been implicated in protection from and clearance of influenza infection. Here, post-hoc analysis of the humoral immune response to influenza is comprehensively profiled in a cohort of vaccinated older adults (65 + ) monitored for influenza infection during the 2012/2013 season in the United States (NCT: 01427309). While robust humoral immune responses arose against the vaccine and circulating strains, influenza-specific antibody effector profiles differed in individuals that later became infected with influenza, who are deficient in NK cell activating antibodies to both hemagglutinin and neuraminidase, compared to individuals who remained uninfected. Furthermore, NK cell activation was strongly associated with the NK cell senescence marker CD57, arguing for the need for selective induction of influenza-specific afucosylated NK activating antibodies in older adults to achieve protection. High dose vaccination, currently used for older adults, was insufficient to generate this NK cell-activating humoral response. Next generation vaccines able to selectively bolster NK cell activating antibodies may be required to achieve protection in the setting of progressively senescent NK cells