Lower rates of hospitalization for respiratory illness vs standard doses
by Molly Walker, Staff Writer, MedPage Today July 20, 2017
Action Points
• Nursing homes whose residents received the high-dose influenza vaccine had fewer hospital admissions for respiratory illnesses compared to those who received standard-dose vaccine.
• Note that no significant difference was observed in all-cause mortality rates or the proportion of residents with a significant cognitive decline between the two groups.
Nursing homes whose residents received the high-dose influenza vaccine had fewer hospital admissions for respiratory illnesses compared to those who received standard-dose vaccine, a large randomized trial found.
Patients who were at least 65 years of age were randomized to receive high-dose vaccine had a significantly reduced risk of pulmonary and influenza-related hospital admissions (adjusted RR 0.87, 95% CI 0.78-0.98, P=0.02) compared to patients who only received the standard dose of the vaccine, reported Stefan Gravenstein, MD, of Brown University, and colleagues.
Significant differences were observed in all-cause hospital admissions (adjusted RR 0.92, 95% CI 0.87-0.97, P=0.003) and pneumonia-related hospital admissions (adjusted RR 0.79, 95% CI 0.27-0.95, P=0.01) among the high-dose vaccination group versus the standard dose group, the authors wrote in The Lancet Respiratory Medicine.
“If given to all approximately 1.5 million nursing home residents, a one percent drop in hospitalizations would translate to thousands fewer being hospitalized,” Gravenstein said in a statement.
The authors noted that lower respiratory tract infection, such as pneumonia and bronchitis, is the leading cause of admission to the hospital from infectious diseases and mortality among older adults, with influenza as the most important viral infection clinically.
While a high-dose influenza vaccine (Fluzone High-Dose from Sanofi-Pasteur), with four times more antigen than the standard dose vaccine, was approved in 2009, they said that only a single study examined immunogenicity of high-dose influenza vaccine in nursing homes.
Researchers conducted a randomized trial in Medicare-certified nursing homes in the U.S. within 50 miles of a CDC influenza reporting city, which had more than 50 long-stay residents, less than 20% of the population under 65 years of age and that were not already planning on administering the high-dose influenza vaccine to their patients.
In total, 823 facilities were randomized — 409 whose residents received the high-dose influenza vaccine and 414 whose residents received the standard dose vaccine. Eligible participants were at least 65 years of age and had been in the facility for 90 days or more prior to vaccination. Their Medicare hospital claims were then tracked.
There were 38,256 Medicare fee-for-service beneficiaries — 19,127 in the high-dose group and 19,129 in the standard-dose group. Patients in both groups were a mean age of 84 years old and about three-quarters were women and white race. Vaccination rates for each group ranged from 76% to 77%.
Overall, there was a 12.7% relative reduction in the incidence of hospital admission for respiratory illness among fee-for-service Medicare beneficiaries in high-dose vaccination facilities, the authors said. Incidence of all-cause hospital admissions was 8% lower in the high-dose vaccination group.
“The fact that we observed a lower rate of hospitalization from all causes, too, suggests that vaccine offers protection beyond flu-related outcomes, perhaps including heart and other conditions,” Gravenstein said.
However, no significant difference was observed in all-cause mortality rates or the proportion of residents with a significant functional decline (defined as a change in Activities of Daily Living score of at least four points) between the two groups.
An accompanying editorial by Marc-Alian Widdowson, MD, and Joseph S. Bresee, MD, both of the CDC, sounded a couple of notes of caution about the findings. While they pointed out that the authors estimated that vaccinating about 69 residents with the high-dose vaccine would prevent one hospital admission of any cause, they characterized the scale of reduction in this study as “unexpectedly large.”
“Since the respiratory-coded hospitalizations represented only one in five all-cause hospitalizations in the study, the 8·5% reduction in seasonal all-cause hospitalizations would [have mainly been] averted non-respiratory hospitalizations,” they reasoned.
And, they observed, “no more than 10% of all-cause seasonal mortality in elderly people has been attributed to influenza.”
Other limitations noted by Gravenstein and colleagues are that laboratory data were not available to confirm influenza activity, and that the predominant influenza strain during the study period — influenza A(H1N1)pdm09 — affects hospital admissions and functional decline to a lesser degree among older adults.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
• Primary Source
The Lancet Respiratory Medicine
Source Reference: Gravenstein S, et al “Comparative effectiveness of high-dose versus standard-dose influenza vaccination on numbers of US nursing home residents admitted to hospital: A cluster-randomised trial” Lancet Respir Med 2017; DOI: 10.1016/S2213-2600(17)30235-7.
• Secondary Source
The Lancet Respiratory Medicine
Source Reference: Widdowson MA, Bresee JS “High-dose influenza vaccine in nursing home residents: not to be sneezed at” Lancet Repir Med 2017; DOI: 10.1016/S2213-2600(17)30290-4.