High-dose influenza vaccine to reduce clinical outcomes in high-risk cardiovascular patients: Rationale and design of the INVESTED trial.

BACKGROUND: Influenza leads to significant cardiopulmonary morbidity and mortality-particularly in patients with cardiovascular disease-that may be prevented with a standard influenza vaccine. However, patients with cardiovascular conditions have a reduced immune response to influenza vaccine, potentially resulting in reduced effectiveness for preventing clinical events. High-dose vaccine augments immune response in cardiac patients, suggesting that a high-dose influenza vaccination strategy may further reduce morbidity and mortality. Alternatively, broader coverage with an influenza vaccine containing an increased number of viral strains is an alternative strategy without direct evaluation. RESEARCH DESIGN AND METHODS: INfluenza Vaccine to Effectively Stop Cardio Thoracic Events and Decompensated heart failure (INVESTED) is a pragmatic, randomized, double-blind, parallel-group, active-controlled trial comparing the effectiveness of an annual vaccination strategy of high-dose trivalent versus standard-dose quadrivalent influenza vaccine in patients with a history of recent heart failure or myocardial infarction hospitalization. The trial will enroll approximately 9,300 patients over 4 influenza seasons. The primary hypothesis is that high-dose influenza vaccine will reduce the composite outcome of all-cause mortality and hospitalization from a cardiovascular or pulmonary cause compared with standard-dose influenza vaccine within each enrolling season. Approximately 1,300 primary outcome events will provide >90% power to detect an 18% relative risk reduction at a 2-sided α level of .05. CONCLUSION: INVESTED is the largest and longest study to assess whether high-dose influenza vaccine is superior to standard-dose influenza vaccine in reducing cardiopulmonary events in a high-risk cardiovascular population (ClinicalTrials.gov Identifier: NCT02787044).

Community-associated methicillin-resistant Staphylococcus aureus in horses and humans who work with horses.

OBJECTIVE: To evaluate the prevalence of nasal colonization with methicillin-resistant Staphylococcus aureus (MRSA) in horses and horse personnel. DESIGN: Prospective prevalence study. SAMPLE POPULATION: 972 horses and 107 personnel from equine farms in Ontario, Canada and New York state. PROCEDURE: Nasal swab specimens were collected from horses and humans on farms with (targeted surveillance) and without (nontargeted surveillance) a history of MRSA colonization or infection in horses during the preceding year. Selective culture for MRSA was performed. Isolates were typed via pulsed-field gel electrophoresis, and antibiograms were determined. RESULTS: MRSA was isolated from 46 of 972 (4.7%) horses (0/581 via nontargeted surveillance and 46/391 [12%] via targeted surveillance). Similarly, MRSA was isolated from 14 of 107 (13%) humans (2/41 [5%] from nontargeted surveillance and 12/66 [18%] from targeted surveillance). All isolates were subtypes of Canadian epidemic MRSA-5, an uncommon strain in humans. All isolates were resistant to at least 1 antimicrobial class in addition to beta-lactams. On all farms with colonized horses, at least 1 human was colonized with an indistinguishable subtype. For horses, residing on a farm that housed > 20 horses was the only factor significantly associated with MRSA colonization. For humans, regular contact with > 20 horses was the only identified risk factor. CONCLUSIONS AND CLINICAL RELEVANCE: Results confirm a reservoir of colonized horses on a variety of farms in Ontario and New York and provide evidence that 1 MRSA strain is predominantly involved in MRSA colonization in horses and humans that work with horses.