High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15.

IntroductionIt is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors.AimThis study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. MethodsWe linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard-dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. ResultsAmong 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24-59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23-32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10-62) and 25% (95% CI: 12-38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations.DiscussionThe HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

Comparing the impact of high-dose versus standard dose influenza vaccines on hospitalization cost for cardiovascular and respiratory diseases: Economic assessment in the US Veteran population during 5 respiratory seasons using an instrumental variable method.

OBJECTIVES: Cost savings associated with high-dose (HD) as compared to standard-dose (SD) influenza vaccination in the United States (US) Veteran's Health Administration (VHA) population have been attributed to better protection against hospitalization for cardiac and respiratory diseases. The relative contribution of each of these disease categories to the reported savings remains to be explored. METHODS: During a recently completed study of HD versus SD vaccine effectiveness (conducted in the VHA over five respiratory seasons from 2010/11 through 2014/15), we collected cost data for all healthcare services provided at both VHA and Medicare-funded facilities. In that analysis, we compared the costs of vaccination and hospital care for patients admitted with either cardiovascular or respiratory disease. Treatment selection bias and other confounding factors were adjusted using an instrumental variable (IV) method. In this brief report we use the same study cohort and methods to stratify the results by patients admitted for cardiovascular disease (CVD) and those admitted for respiratory disease. RESULTS: We analyzed 3.5 million SD and 0.16 million HD person-seasons. The IV-adjusted rVEs were 14% (7-20%) against hospitalizations for CVD and 15% (5-25%) against respiratory hospitalizations. Net cost savings per HD recipient were $138 ($66-$200) for CVD related hospitalizations and $62 ($10-$107) for respiratory disease related hospitalizations. CONCLUSIONS: In the US VHA population, the reduction in hospitalizations for CVD over five respiratory seasons contributed twice the cost savings (per HD recipient) of the reduction in hospitalizations for respiratory disease.

Identification of patients at risk of Clostridioides difficile infection for enrollment in vaccine clinical trials.

BACKGROUND: Clostridioides difficile infection (CDI) is an important cause of diarrheal disease associated with increasing morbidity and mortality. Efforts to develop a preventive vaccine are ongoing. The goal of this study was to develop an algorithm to identify patients at high risk of CDI for enrollment in a vaccine efficacy trial. METHODS: We conducted a 2-stage retrospective study of patients aged ≥ 50 within the US Department of Veterans Affairs Health system between January 1, 2009 and December 31, 2013. Included patients had at least 1 visit in each of the 2 years prior to the study, with no CDI in the past year. We used multivariable logistic regression with elastic net regularization to identify predictors of CDI in months 2-12 (i.e., days 31 - 365) to allow time for antibodies to develop. Performance was measured using the positive predictive value (PPV) and the area under the curve (AUC). RESULTS: Elements of the predictive algorithm included age, baseline comorbidity score, acute renal failure, recent infections or high-risk antibiotic use, hemodialysis in the last month, race, and measures of recent healthcare utilization. The final algorithm resulted in an AUC of 0.69 and a PPV of 3.4%. CONCLUSIONS: We developed a predictive algorithm to identify a patient population with increased risk of CDI over the next 2-12 months. Our algorithm can be used prospectively with clinical and administrative data to facilitate the feasibility of conducting efficacy studies in a timely manner in an appropriate population.

Incidence of Clostridioides difficile infections among young and middle-aged adults: Veterans Health Administration.

OBJECTIVE: Clostridioides difficile infection (CDI) remains a significant public health concern, resulting in excess morbidity, mortality, and costs. Additional insight into the burden of CDI in adults aged <65 years is needed. DESIGN/SETTING: A 6-year retrospective cohort study was conducted using data extracted from United States Veterans Health Administration electronic medical records. PATIENTS/METHODS: Patients aged 18-64 years on January 1, 2011, were followed until incident CDI, death, loss-to-follow-up, or December 31, 2016. CDI was identified by a diagnosis code accompanied by metronidazole, vancomycin, or fidaxomicin therapy, or positive laboratory test. The clinical setting of CDI onset was defined according to 2017 SHEA-IDSA guidelines. RESULTS: Of 1,073,900 patients, 10,534 had a CDI during follow-up. The overall incidence rate was 177 CDIs per 100,000 person years, rising steadily from 164 per 100,000 person years in 2011 to 189 per 100,000 person years in 2016. Those with a CDI were slightly older (55 vs 51 years) and sicker, with a higher baseline Charlson comorbidity index score (1.4 vs 0.5) than those without an infection. Nearly half (48%) of all incident CDIs were community associated, and this proportion rose from 41% in 2011 to 56% in 2016. CONCLUSIONS: The findings from this large retrospective study indicate that CDI incidence, driven primarily by increasing community-associated infection, is rising among young and middle-aged adult Veterans with high service-related disability. The increasing burden of community associated CDI in this vulnerable population warrants attention. Future studies quantifying the economic and societal burden of CDI will inform decisions surrounding prevention strategies.

Economic assessment of a high-dose versus a standard-dose influenza vaccine in the US Veteran population: Estimating the impact on hospitalization cost for cardio-respiratory disease.

OBJECTIVE: To compare the economic impact of high-dose trivalent (HD) versus standard-dose trivalent (SD) influenza vaccination on direct medical costs for cardio-respiratory hospitalizations in adults aged 65 years or older enrolled in the United States (US) Veteran's Health Administration (VHA). METHODS: Leveraging a relative vaccine effectiveness study of HD versus SD over five respiratory seasons (2010/11 through 2014/15), we collected cost data for healthcare provided to the same study population both at VHA and through Medicare services. Our economic assessment compared the costs of vaccination and hospital care for patients experiencing acute cardio-vascular or respiratory illness. RESULTS: We analyzed 3.5 million SD and 158,636 HD person-seasons. The average cost of HD and SD vaccination was $23.48 (95% CI: $21.29 - $25.85) and $12.21 (95% CI: $11.49 - $13.00) per recipient, respectively, while the hospitalization rates for cardio-respiratory disease in HD and SD recipients were 0.114 (95% CI: 0.108-0.121) and 0.132 (95% CI: 0.132-0.133) per person-season, respectively. Attributing the average cost per hospitalization of $11,796 (95% CI: $11,685 - $11,907) to the difference in hospitalization rates, we estimated savings attributable to HD to be $202 (95% CI: $115 - $280) per vaccinated recipient. CONCLUSIONS: For the five-season period of 2010/11 through 2014/15, HD influenza vaccination was associated with net cost savings due to fewer hospitalizations, and therefore lower direct medical costs, for cardio-respiratory disease as compared to SD influenza vaccination in the senior US VHA population.