Person:

Lee, Grace

Background: Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system. Methods: We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1) expected vaccination benefit from averted influenza; 2) expected vaccination risk from vaccine-associated febrile seizures; 3) expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4) expected change in vaccine-seeking behavior in future influenza seasons. Results: Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3∶1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior. Conclusions: The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.

Whole genome sequencing of 616 asymptomatically carried pneumococci was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates revealed the role of transformation in facilitating capsule switching to non-vaccine serotypes and the emergence of drug resistance. However, such recombination was found to occur at significantly different rates across the species, and the evolution of the population was primarily driven by changes in the frequency of distinct genotypes extant pre-vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the fall in pneumococcal disease rates after the vaccine’s introduction.

Objectives: To determine the health and economic burdens of post-partum Staphylococcus aureus breast abscess. Study design We conducted a matched cohort study (N = 216) in a population of pregnant women (N = 32,770) who delivered at our center during the study period from 10/1/03–9/30/10. Data were extracted from hospital databases, or via chart review if unavailable electronically. We compared cases of S. aureus breast abscess to controls matched by delivery date to compare health services utilization and mean attributable medical costs in 2012 United States dollars using Medicare and hospital-based estimates. We also evaluated whether resource utilization and health care costs differed between cases with methicillin-resistant and -susceptible S. aureus isolates. Results: Fifty-four cases of culture-confirmed post-partum S. aureus breast abscess were identified. Breastfeeding cessation (41%), milk fistula (11.1%) and hospital readmission (50%) occurred frequently among case patients. Breast abscess case patients had high rates of health services utilization compared to controls, including high rates of imaging and drainage procedures. The mean attributable cost of post-partum S. aureus breast abscess ranged from $2,340–$4,012, depending on the methods and data sources used. Mean attributable costs were not significantly higher among methicillin-resistant vs. –susceptible S. aureus cases. Conclusions: Post-partum S. aureus breast abscess is associated with worse health and economic outcomes for women and their infants, including high rates of breastfeeding cessation. Future study is needed to determine the optimal treatment and prevention of these infections.

Background: Guillain-Barré Syndrome (GBS) can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1) pandemic in the United States, monovalent inactivated influenza vaccine (MIV) availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited. Methods: We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009–10 MIV, 2010–11 trivalent inactivated influenza vaccine (TIV), and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls. Results: Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009–10 MIV recipients and 2.80 million 2010–11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009–10 MIV/2010–11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI), 0.59–3.99; risk difference = 0.93 per million doses, 95% CI, −0.71–5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60–16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49–26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior vaccination shorter than 6 weeks. Conclusions: After adjusting for antecedent infections, we found no evidence for an elevated GBS risk following 2009–10 MIV/2010–11 TIV influenza vaccines. However, the association between GBS and antecedent infection was strongly elevated.

Background In October 2008, the Centers for Medicare and Medicaid Services (CMS) discontinued additional payments for certain hospital-acquired conditions that were deemed preventable. The effect of this policy on rates of health care–associated infections is unknown. Methods Using a quasi-experimental design with interrupted time series with comparison series, we examined changes in trends of two health care–associated infections that were targeted by the CMS policy (central catheter–associated bloodstream infections and catheter-associated urinary tract infections) as compared with an outcome that was not targeted by the policy (ventilator-associated pneumonia). Hospitals participating in the National Healthcare Safety Network and reporting data on at least one health care–associated infection before the onset of the policy were eligible to participate. Data from January 2006 through March 2011 were included. We used regression models to measure the effect of the policy on changes in infection rates, adjusting for baseline trends. Results A total of 398 hospitals or health systems contributed 14,817 to 28,339 hospital unit– months, depending on the type of infection. We observed decreasing secular trends for both targeted and nontargeted infections long before the policy was implemented. There were no significant changes in quarterly rates of central catheter– associated bloodstream infections (incidence-rate ratio in the postimplementation vs. preimplementation period, 1.00; P=0.97), catheter-associated urinary tract infections (incidence-rate ratio, 1.03; P=0.08), or ventilator-associated pneumonia (incidence-rate ratio, 0.99; P=0.52) after the policy implementation. Our findings did not differ for hospitals in states without mandatory reporting, nor did it differ according to the quartile of percentage of Medicare admissions or hospital size, type of ownership, or teaching status. Conclusions We found no evidence that the 2008 CMS policy to reduce payments for central catheter–associated bloodstream infections and catheter-associated urinary tract infections had any measurable effect on infection rates in U.S. hospitals.

The Centers for Medicare and Medicaid Services (CMS) implemented a policy in October 2008 to eliminate additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) surgery. To evaluate the impact of this policy on mediastinitis rates, using Medicare claims and National Healthcare Safety Network (NHSN) prospective surveillance data. We used an interrupted time series design to compare mediastinitis rates before and after the policy, adjusted for secular trends. Billing rates came from Medicare inpatient claims following 638,761 CABG procedures in 1,234 US hospitals (January 2006-September 2010). Prospective surveillance rates came from 151 NHSN hospitals in 29 states performing 94,739 CABG procedures (January 2007-September 2010). Logistic regression mixed-effects models estimated trends for mediastinitis rates. We found a sudden drop in coding for index admission mediastinitis at the time of policy implementation (odds ratio, 0.36 [95% confidence interval (CI), 0.23-0.57]) and a decreasing trend in coding for index admission mediastinitis in the postintervention period compared with the preintervention period (ratio of slopes, 0.83 [95% CI, 0.74-0.95]). However, we saw no impact of the policy on infection rates as measured using NHSN data. Our results were not affected by changes in patient risk over time, heterogeneity in hospital demographics, or timing of hospital participation in NHSN. The CMS policy of withholding additional Medicare payment for mediastinitis on the basis of claims-based evidence of infection was associated with changes in coding for infections but not with changes in actual infection rates during the first 2 years after policy implementation.

Abstract Purpose To develop the infrastructure to conduct timely active surveillance for safety of influenza vaccines and other medical countermeasures in the Sentinel System (formerly the Mini‐Sentinel Pilot), a Food and Drug Administration‐sponsored national surveillance system that typically relies on data that are mature, settled, and updated quarterly. Methods: Three Data Partners provided their earliest available (“fresh”) cumulative claims data on influenza vaccination and health outcomes 3–4 times on a staggered basis during the 2013–2014 influenza season, collectively producing 10 data updates. We monitored anaphylaxis in the entire population using a cohort design and seizures in children ≤4 years of age using both a self‐controlled risk interval design (primary) and a cohort design (secondary). After each data update, we conducted sequential analysis for inactivated (IIV) and live (LAIV) influenza vaccines using the Maximized Sequential Probability Ratio Test, adjusting for data‐lag. Results: Most of the 10 sequential analyses were conducted within 6 weeks of the last care‐date in the cumulative dataset. A total of 6 682 336 doses of IIV and 782 125 doses of LAIV were captured. The primary analyses did not identify any statistical signals following IIV or LAIV. In secondary analysis, the risk of seizures was higher following concomitant IIV and PCV13 than historically after IIV in 6‐ to 23‐month‐olds (relative risk = 2.7), which requires further investigation. Conclusions: The Sentinel System can implement a sequential analysis system that uses fresh data for medical product safety surveillance. Active surveillance using sequential analysis of fresh data holds promise for detecting clinically significant health risks early. Limitations of employing fresh data for surveillance include cost and the need for careful scrutiny of signals. © 2015 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Policymakers may wish to align healthcare payment and quality of care while minimizing unintended consequences, particularly for safety net hospitals. To determine whether the 2008 Centers for Medicare and Medicaid Services Hospital-Acquired Conditions policy had a differential impact on targeted healthcare-associated infection rates in safety net compared with non–safety net hospitals. Interrupted time-series design. Nonfederal acute care hospitals that reported central line–associated bloodstream infection and ventilator-associated pneumonia rates to the Centers for Disease Control and Prevention’s National Health Safety Network from July 1, 2007, through December 31, 2013. We did not observe changes in the slope of targeted infection rates in the postpolicy period compared with the prepolicy period for either safety net (postpolicy vs prepolicy ratio, 0.96 [95% CI, 0.84–1.09]) or non–safety net (0.99 [0.90–1.10]) hospitals. Controlling for prepolicy secular trends, we did not detect differences in an immediate change at the time of the policy between safety net and non–safety net hospitals (P for 2-way interaction, .87). The Centers for Medicare and Medicaid Services Hospital-Acquired Conditions policy did not have an impact, either positive or negative, on already declining rates of central line–associated bloodstream infection in safety net or non–safety net hospitals. Continued evaluations of the broad impact of payment policies on safety net hospitals will remain important as the use of financial incentives and penalties continues to expand in the United States.

Background: Sepsis is the focus of national quality improvement programs and a recent public reporting measure from the Centers for Medicare and Medicaid Services. However, diagnosing sepsis requires interpreting nonspecific signs and can therefore be subjective. We sought to quantify interobserver variability in diagnosing sepsis. Methods: We distributed five case vignettes of patients with suspected or confirmed infection and organ dysfunction to a sample of practicing intensivists. Respondents classified cases as systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, or none of the above. Interobserver variability was calculated using Fleiss’ κ for the five-level classification, and for answers dichotomized as severe sepsis/septic shock versus not-severe sepsis/septic shock and any sepsis category (sepsis, severe sepsis, or septic shock) versus not-sepsis. Results: Ninety-four physicians completed the survey. Most respondents (88 %) identified as critical care specialists; other specialties included pulmonology (39 %), anesthesia (19 %), surgery (9 %), and emergency medicine (9 %). Respondents had been in practice for a median of 8 years, and 90 % practiced at academic hospitals. Almost all respondents (83 %) felt strongly or somewhat confident in their ability to apply the traditional consensus sepsis definitions. However, overall interrater agreement in sepsis diagnoses was poor (Fleiss’ κ 0.29). When responses were dichotomized into severe sepsis/septic shock versus not-severe sepsis/septic shock or any sepsis category versus not-sepsis, agreement was still poor (Fleiss’ κ 0.23 and 0.18, respectively). Seventeen percent of respondents classified one of the five cases as severe sepsis/septic shock, 27.7 % rated two cases, 33.0 % respondents rated three cases, 19.2 % rated four cases, and 3.2 % rated all five cases as severe sepsis/septic shock. Among respondents who felt strongly confident in their ability to use sepsis definitions (n = 45), agreement was no better (Fleiss’ κ 0.28 for the five-category classification, and Fleiss’ κ 0.21 for the dichotomized severe sepsis/septic shock classification). Cases were felt to be extremely or very realistic in 74 % of responses; only 3 % were deemed unrealistic. Conclusions: Diagnosing sepsis is extremely subjective and variable. Objective criteria and standardized methodology are needed to enhance consistency and comparability in sepsis research, surveillance, benchmarking, and reporting. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1266-9) contains supplementary material, which is available to authorized users.

Background: The success of 7-valent pneumococcal conjugate vaccination (PCV-7) introduced to the US childhood immunization schedule in 2000 was partially offset by increases in invasive pneumococcal disease (IPD) and pneumococcal carriage due to non-vaccine serotypes, in particular 19A, in the years that followed. A 13-valent conjugate vaccine (PCV-13) was introduced in 2010. As part of an ongoing study of the response of the Massachusetts pneumococcal population to conjugate vaccination, we report the findings from the samples collected in 2011, as PCV-13 was introduced. Methods: We used multilocus sequence typing (MLST) to analyze 367 pneumococcal isolates carried by Massachusetts children (aged 3 months-7 years) collected during the winter of 2010–11 and used eBURST software to compare the pneumococcal population structure with that found in previous years. Results: One hundred and four distinct sequence types (STs) were found, including 24 that had not been previously recorded. Comparison with a similar sample collected in 2009 revealed no significant overall difference in the ST composition (p = 0.39, classification index). However, we describe clonal dynamics within the important replacement serotypes 19A, 15B/C, and 6C, and clonal expansion of ST 433 and ST 432, which are respectively serotype 22F and 21 clones. Conclusions: While little overall change in serotypes or STs was evident, multiple changes in the frequency of individual STs and or serotypes may plausibly be ascribed to the introduction of PCV-13. This 2011 sample documents the initial impact of PCV-13 and will be important for comparison with future studies of the evolution of the pneumococcal population in Massachusetts. Electronic supplementary material The online version of this article (doi:10.1186/s12879-015-0797-z) contains supplementary material, which is available to authorized users.