Bio

Bio


Dr. Lee's work focuses on developing quality metrics for use in pediatrics, evaluating the impact of payment policies on health outcomes, preventing healthcare-associated infections, and conducting near real-time surveillance to monitor the safety of medical product use. She served as the Principal Investigator (PI) on the CDC-funded Vaccine Safety Datalink project, Associate Director of the FDA-funded Mini-Sentinel Project, and PI of an AHRQ-funded grant to develop a national surveillance definition for pediatric ventilator-associated events and to identify potential intervention bundles to improve quality of care. She is currently the PI of an AHRQ-funded grant to evaluate the health and economic impact of the CMS Hospital-Acquired Conditions and Value-Based Purchasing policies, which is called the Preventing Avoidable Infectious Complications by Adjusting Payment (PAICAP) study (www.paicap.org). Dr. Lee previously served as a member on the Institute of Medicine Committee (IOM) to Review Priorities in the National Vaccine Plan, the IOM Committee on the Ethical and Scientific Issues in Studying the Safety of Approved Drugs, and the AHRQ Healthcare Safety and Quality Improvement Research Study Section. Currently, she serves as a Board Member for the Society for Healthcare Epidemiology of America (SHEA), Pediatric Infectious Diseases Society (PIDS), and the National Academy of Medicine Board on Population Health and Public Practice, as well as a voting member the CDC's Advisory Committee on Immunization Practices.

Clinical Focus


  • Pediatric Infectious Diseases
  • Healthcare associated infections
  • Antimicrobial stewardship
  • Vaccines

Academic Appointments


Administrative Appointments


  • Associate Chief Medical Officer for Practice Innovation, Stanford Children's Health (2017 - Present)
  • Leadership Team, California Perinatal Quality Care Collaborative (2017 - Present)

Boards, Advisory Committees, Professional Organizations


  • Board of Directors, Pediatric Infectious Diseases Society (PIDS) (2015 - Present)
  • Member, Advisory Committee on Immunization Practices (2016 - Present)
  • Member, Board on Population Health and Public Practice, National Academies of Medicine (2016 - Present)
  • Ventilator-Associated Events Hospital-Acquired Conditions Workgroup, Leadership Team, Children’s Hospitals’ Solutions for Patient Safety National Children’s Network (2016 - Present)
  • Executive Committee, Board of Trustees, Society for Healthcare Epidemiology of America (2017 - Present)

Professional Education


  • Board Certification: Pediatric Infectious Diseases, American Board of Pediatrics (2003)
  • Fellowship:Boston Children's Hospital Training Verifications (2003) MA
  • Medical Education:Perelman School of Medicine University of Pennsylvania (1997) PA
  • Residency:Boston Children's Hospital (Combined Residency in Pediatrics) (2000)

Publications

All Publications


  • Comparison of hospital surgical site infection rates and rankings using claims versus National Healthcare Safety Network surveillance data. Infection control and hospital epidemiology Rhee, C., Wang, R., Jentzsch, M. S., Broadwell, C., Hsu, H., Jin, R., Horan, K., Lee, G. M. 2018: 1–3

    Abstract

    National policies target healthcare-associated infections using medical claims and National Healthcare Safety Network surveillance data. We found low concordance between the 2 data sources in rates and rankings for surgical site infection following colon surgery in 155 hospitals, underscoring the limitations in evaluating hospital quality by claims data.

    View details for DOI 10.1017/ice.2018.310

    View details for PubMedID 30509332

  • Variability in antimicrobial use in pediatric ventilator-associated events. Infection control and hospital epidemiology Karandikar, M. V., Coffin, S. E., Priebe, G. P., Sandora, T. J., Logan, L. K., Larsen, G. Y., Toltzis, P., Gray, J. E., Klompas, M., Sammons, J. S., Harper, M. B., Horan, K., Lakoma, M., Cocoros, N. M., Lee, G. M. 2018: 1–8

    Abstract

    OBJECTIVE: To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).DESIGN: Descriptive retrospective cohort with nested case-control study.SETTING: Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.PatientsChildren≤18 years ventilated for≥1 calendar day.METHODS: We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.RESULTS: Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20-67%; PICU, 0-70%; and NICU, 0-43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.CONCLUSIONS: Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.

    View details for DOI 10.1017/ice.2018.264

    View details for PubMedID 30409233

  • Costs of Quality and Safety in Radiology. Radiographics : a review publication of the Radiological Society of North America, Inc Donnelly, L. F., Lee, G. M., Sharek, P. J. 2018; 38 (6): 1682–87

    Abstract

    With the movement toward at-risk population health management-related payment models, a core factor for the success and survival of health care organizations has become understanding and decreasing costs. In medical specialties such as radiology, understanding models for procedure-based costing will become increasingly important. Using bottom-up models for procedure-based costing, such as time-driven activity-based costing, is more advantageous than using the inaccurate ratio of costs to charges approach; however, these approaches are more resource intensive when compared to top-down approaches. Understanding the costs of quality is also important for creating an accounting and budgeting process that reflects the total cost of quality. The costs of quality are divided into two main categories: the cost of control (also referred to as the costs of conformance) and the costs of failure of control (also referred to as the costs of nonconformance). The costs of control are the expenditures that occur to ensure quality. The costs of noncontrol are the expenses that arise from the lack of quality and safety. The cost of control has two subcategories: prevention costs and appraisal costs. The cost of noncontrol also has two subcategories: internal failure costs and external failure costs. Adopting a mind-set that takes into account the costs of control, or the costs to ensure high-quality care, and the costs of noncontrol, or the hidden costs of poor-quality care, will be essential for successful health care organizations in the future. ©RSNA, 2018.

    View details for DOI 10.1148/rg.2018180020

    View details for PubMedID 30303806

  • Impact of the 2012 Medicaid Health Care-Acquired Conditions Policy on Catheter-Associated Urinary Tract Infection and Vascular Catheter-Associated Infection Billing Rates. Open forum infectious diseases Rhee, C., Wang, R., Jentzsch, M. S., Hsu, H., Kawai, A. T., Jin, R., Horan, K., Broadwell, C., Lee, G. M. 2018; 5 (9): ofy204

    Abstract

    In July 2012, the Centers for Medicare & Medicaid Services ceased hospital Medicaid reimbursements for certain health care-acquired conditions. Using billing data from 2008-2014, we found no impact of this policy on rates of 2 targeted conditions, vascular catheter-associated infections and catheter-associated urinary tract infections, among Medicaid or non-Medicaid patients.

    View details for DOI 10.1093/ofid/ofy204

    View details for PubMedID 30191157

  • The Impact of the Medicaid Healthcare-Associated Condition Program on Mediastinitis Following Coronary Artery Bypass Graft. Infection control and hospital epidemiology Hsu, H. E., Kawai, A. T., Wang, R., Jentzsch, M. S., Rhee, C., Horan, K., Jin, R., Goldmann, D., Lee, G. M. 2018; 39 (6): 694–700

    Abstract

    OBJECTIVEIn 2012, the Centers for Medicare and Medicaid Services expanded a 2008 program that eliminated additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) to include Medicaid. We aimed to evaluate the impact of this Medicaid program on mediastinitis rates reported by the National Healthcare Safety Network (NHSN) compared with the rates of a condition not targeted by the program, deep-space surgical site infection (SSI) after knee replacement.DESIGNInterrupted time series with comparison group.METHODSWe included surveillance data from nonfederal acute-care hospitals participating in the NHSN and reporting CABG or knee replacement outcomes from January 2009 through June 2017. We examined the Medicaid program's impact on NHSN-reported infection rates, adjusting for secular trends. The data analysis used generalized estimating equations with robust sandwich variance estimators.RESULTSDuring the study period, 196 study hospitals reported 273,984 CABGs to the NHSN, resulting in 970 mediastinitis cases (0.35%), and 294 hospitals reported 555,395 knee replacements, with 1,751 resultant deep-space SSIs (0.32%). There was no significant change in incidence of either condition during the study. Mediastinitis models showed no effect of the 2012 Medicaid program on either secular trend during the postprogram versus preprogram periods (P=.70) or an immediate program effect (P=.83). Results were similar in sensitivity analyses when adjusting for hospital characteristics, restricting to hospitals with consistent NHSN reporting or incorporating a program implementation roll-in period. Knee replacement models also showed no program effect.CONCLUSIONSThe 2012 Medicaid program to eliminate additional payments for mediastinitis following CABG had no impact on reported mediastinitis rates.Infect Control Hosp Epidemiol 2018;39:694-700.

    View details for DOI 10.1017/ice.2018.69

    View details for PubMedID 29669607

  • Enhanced central venous catheter bundle for pediatric parenteral-dependent intestinal failure. American journal of infection control Ormsby, J. A., Bukoye, B., Lajoie, D., Shermont, H., Martin, L., Leger, K., Mahoney, J., Potter-Bynoe, G., Carpenter, J., Ozonoff, A., Lee, G. M. 2018

    Abstract

    BACKGROUND: Central line-associated bloodstream infections (CLABSIs) cause substantial morbidity and increase antimicrobial use and length of stay among hospitalized children in the United States. CLABSI occurs more frequently among high-risk pediatric patients, such as those with intestinal failure (IF) who are parenteral nutrition (PN) dependent. Following an increase in CLABSI rates, a quality improvement (QI) initiative was implemented.METHODS: Using QI methodology, an enhanced central venous catheter (CVC) maintenance bundle was developed and implemented on 2 units for pediatric PN-dependent patients with IF. CLABSI rates were prospectively monitored pre- and postimplementation, and bundle element adherence was monitored. Enhanced bundle elements included chlorhexidine-impregnated patch, daily bathing, ethanol locks, 2 nurses for CVC care in a distraction-free zone, peripheral laboratory draws, bundling routine laboratory tests, and PN administration set changes every 24 hours.RESULTS: Adherence to enhanced bundle elements increased to >90% over 3 months. CLABSI rates averaged 1.41 per 1,000 central line days preimplementation compared with 0.40 per 1,000 device days postimplementation (P=.003), an 85% absolute reduction in CLABSI rates over 12 months.CONCLUSIONS: Patients with IF are at an increased risk for CLABSI. Enhanced CVC maintenance bundles that specifically target prevention practices in this population may be beneficial.

    View details for DOI 10.1016/j.ajic.2018.04.209

    View details for PubMedID 29778436

  • The safety of live attenuated influenza vaccine in children and adolescents 2 through 17 years of age: A Vaccine Safety Datalink study. Pharmacoepidemiology and drug safety Daley, M. F., Clarke, C. L., Glanz, J. M., Xu, S., Hambidge, S. J., Donahue, J. G., Nordin, J. D., Klein, N. P., Jacobsen, S. J., Naleway, A. L., Jackson, M. L., Lee, G., Duffy, J., Weintraub, E. 2018; 27 (1): 59–68

    Abstract

    To evaluate the safety of live attenuated influenza vaccine (LAIV) in children 2 through 17 years of age.The study was conducted in 6 large integrated health care organizations participating in the Vaccine Safety Datalink (VSD). Trivalent LAIV safety was assessed in children who received LAIV between September 1, 2003 and March 31, 2013. Eighteen pre-specified adverse event groups were studied, including allergic, autoimmune, neurologic, respiratory, and infectious conditions. Incident rate ratios (IRRs) were calculated for each adverse event, using self-controlled case series analyses. For adverse events with a statistically significant increase in risk, or an IRR > 2.0 regardless of statistical significance, manual medical record review was performed to confirm case status.During the study period, 396 173 children received 590 018 doses of LAIV. For 13 adverse event groups, there was no significant increased risk of adverse events following LAIV. Five adverse event groups (anaphylaxis, syncope, Stevens-Johnson syndrome, adverse effect of drug, and respiratory failure) met criteria for manual medical record review. After review to confirm cases, 2 adverse event groups remained significantly associated with LAIV: anaphylaxis and syncope. One confirmed case of anaphylaxis was observed following LAIV, a rate of 1.7 per million LAIV doses. Five confirmed cases of syncope were observed, a rate of 8.5 per million doses.In a study of trivalent LAIV safety in a large cohort of children, few serious adverse events were detected. Anaphylaxis and syncope occurred following LAIV, although rarely. These data provide reassurance regarding continued LAIV use.

    View details for DOI 10.1002/pds.4349

    View details for PubMedID 29148124

  • Updated Framework for Development of Evidence-Based Recommendations by the Advisory Committee on Immunization Practices. MMWR. Morbidity and mortality weekly report Lee, G., Carr, W. 2018; 67 (45): 1271–72

    Abstract

    The Advisory Committee on Immunization Practices (ACIP)* is a federal advisory committee that provides expert advice to the Director of CDC and the Secretary of the U.S. Department of Health and Human Services in the form of recommendations on the use of vaccines and related agents for control of vaccine-preventable diseases in the U.S. civilian population (1,2). Work groups that gather, analyze, and prepare scientific information assist in the recommendation formulation process and present options for recommendations based on the scientific evidence they have assessed. Recommendations that are approved by a majority of ACIP's voting members are then reviewed by the Director of CDC and published in MMWR if approved by the director. This report briefly summarizes an update to the ACIP process for developing evidence-based recommendations that ACIP adopted at its February 2018 meeting.

    View details for DOI 10.15585/mmwr.mm6745a4

    View details for PubMedID 30439877

  • Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMWR. Morbidity and mortality weekly report Dooling, K. L., Guo, A., Patel, M., Lee, G. M., Moore, K., Belongia, E. A., Harpaz, R. 2018; 67 (3): 103–8

    Abstract

    On October 20, 2017, Zoster Vaccine Recombinant, Adjuvanted (Shingrix, GlaxoSmithKline, [GSK] Research Triangle Park, North Carolina), a 2-dose, subunit vaccine containing recombinant glycoprotein E in combination with a novel adjuvant (AS01B), was approved by the Food and Drug Administration for the prevention of herpes zoster in adults aged ≥50 years. The vaccine consists of 2 doses (0.5 mL each), administered intramuscularly, 2-6 months apart (1). On October 25, 2017, the Advisory Committee on Immunization Practices (ACIP) recommended the recombinant zoster vaccine (RZV) for use in immunocompetent adults aged ≥50 years.

    View details for DOI 10.15585/mmwr.mm6703a5

    View details for PubMedID 29370152

    View details for PubMedCentralID PMC5812314

  • Recommendations of the Advisory Committee on Immunization Practices for use of herpes zoster vaccines. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Dooling, K. L., Guo, A., Patel, M., Lee, G. M., Moore, K., Belongia, E. A., Harpaz, R. 2018; 18 (3): 756–62

    View details for DOI 10.1111/ajt.14683

    View details for PubMedID 29462512

  • Maternal Tdap vaccination and risk of infant morbidity. Vaccine DeSilva, M., Vazquez-Benitez, G., Nordin, J. D., Lipkind, H. S., Klein, N. P., Cheetham, T. C., Naleway, A. L., Hambidge, S. J., Lee, G. M., Jackson, M. L., McCarthy, N. L., Kharbanda, E. O. 2017; 35 (29): 3655-3660

    Abstract

    An increased risk of diagnosed chorioamnionitis in women vaccinated with Tdap during pregnancy was previously detected at two Vaccine Safety Datalink (VSD) sites. The clinical significance of this finding related to infant outcomes remains uncertain.Retrospective cohort study of singleton live births born to women who were continuously insured from 6months prior to their last menstrual period through 6weeks postpartum, with ≥1 outpatient visit during pregnancy from January 1, 2010 to November 15, 2013 at seven integrated United States health care systems part of the VSD. We re-evaluated the association between maternal Tdap and chorioamnionitis and evaluated whether specific infant morbidities differ among infants born to mothers who did and did not receive Tdap during pregnancy. We focused on 2 Tdap exposure windows: the recommended 27-36weeks gestation or anytime during pregnancy. We identified inpatient diagnostic codes for transient tachypnea of the newborn (TTN), neonatal sepsis, neonatal pneumonia, respiratory distress syndrome (RDS), and newborn convulsions associated with an infant's first hospitalization. A generalized linear model with Poisson distribution and log-link was used to estimate propensity score adjusted rate ratios (ARR) with 95% confidence intervals (CI).The analyses included 197,564 pregnancies. Chorioamnionitis was recorded in 6.4% of women who received Tdap vaccination any time during pregnancy and 5.2% of women who did not (ARR [95% CI]: 1.23 [1.17, 1.28]). Compared with unvaccinated women, there were no significant increased risks (ARR [95% CI]) for TTN (1.04 [0.98, 1.11]), neonatal sepsis (1.06 [0.91, 1.23]), neonatal pneumonia (0.94 [0.72, 1.22]), RDS (0.91 [0.66, 1.26]), or newborn convulsions (1.16 [0.87, 1.53]) in infants born to Tdap-vaccinated women.Despite an observed association between maternal Tdap vaccination and maternal chorioamnionitis, we did not find increased risk for clinically significant infant outcomes associated with maternal chorioamnionitis.

    View details for DOI 10.1016/j.vaccine.2017.05.041

    View details for PubMedID 28552511

  • First Trimester Influenza Vaccination and Risks for Major Structural Birth Defects in Offspring. journal of pediatrics Kharbanda, E. O., Vazquez-Benitez, G., Romitti, P. A., Naleway, A. L., Cheetham, T. C., Lipkind, H. S., Klein, N. P., Lee, G., Jackson, M. L., Hambidge, S. J., McCarthy, N., DeStefano, F., Nordin, J. D. 2017

    Abstract

    To examine risks for major structural birth defects in infants after first trimester inactivated influenza vaccine (IIV) exposures.In this observational study, we used electronic health data from 7 Vaccine Safety Datalink sites to examine risks for selected major structural defects in infants after maternal IIV exposure. Vaccine exposures for women with continuous insurance enrollment through pregnancy who delivered singleton live births between 2004 and 2013 were identified from standardized files. Infants with continuous insurance enrollment were followed to 1 year of age. We excluded mother-infant pairs with other exposures that potentially increased their background risk for birth defects. Selected cardiac, orofacial or respiratory, neurologic, ophthalmologic or otologic, gastrointestinal, genitourinary and muscular or limb defects were identified from diagnostic codes in infant medical records using validated algorithms. Propensity score adjusted generalized estimating equations were used to estimate prevalence ratios (PRs).We identified 52 856 infants with maternal first trimester IIV exposure and 373 088 infants whose mothers were unexposed to IIV during first trimester. Prevalence (per 100 live births) for selected major structural birth defects was 1.6 among first trimester IIV exposed versus 1.5 among unexposed mothers. The adjusted PR was 1.02 (95% CI 0.94-1.10). Organ system-specific PRs were similar to the overall PR.First trimester maternal IIV exposure was not associated with an increased risk for selected major structural birth defects in this large cohort of singleton live births.

    View details for DOI 10.1016/j.jpeds.2017.04.039

    View details for PubMedID 28550954

  • Live attenuated influenza vaccine use and safety in children and adults with asthma ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Duffy, J., Lewis, M., Harrington, T., Baxter, R., Belongia, E. A., Jackson, L. A., Jacobsen, S. J., Lee, G. M., Naleway, A. L., Nordin, J., Daley, M. F. 2017; 118 (4): 439-444

    Abstract

    Live attenuated influenza vaccine (LAIV) might increase the risk of wheezing in persons with asthma or children younger than 5 years with a history of recurrent wheezing.To describe the use and assess the safety of LAIV in persons with asthma in the Vaccine Safety Datalink population.We identified persons with asthma using diagnosis codes and medication records in 7 health care organizations over 3 influenza seasons (2008-2009 through 2010-2011) and determined their influenza vaccination rates. Using the self-controlled risk interval method, we calculated the incidence rate ratio of medically attended respiratory events in the 14 days after LAIV compared with 29 to 42 days after vaccination in persons 2 through 49 years old.In our population of 6.3 million, asthma prevalence was 5.9%. Of persons with asthma, approximately 50% received any influenza vaccine but less than 1% received LAIV. The safety study included 12,354 LAIV doses (75% in children; 93% in those with intermittent or mild persistent asthma). The incidence rate ratio for inpatient and emergency department visits for lower respiratory events (including asthma exacerbation and wheezing) was 0.98 (95% confidence interval 0.63-1.51) and the incidence rate ratio for upper respiratory events was 0.94 (95% confidence interval 0.48-1.86). The risk of lower respiratory events was similar for intermittent and mild persistent asthma, across age groups, and for seasonal trivalent LAIV and 2009 H1N1 pandemic monovalent LAIV.LAIV use in asthma was mostly in persons with intermittent or mild persistent asthma. LAIV was not associated with an increased risk of medically attended respiratory adverse events.

    View details for DOI 10.1016/j.anai.2017.01.030

    View details for Web of Science ID 000398936900010

    View details for PubMedID 28390584

  • Identifying birth defects in automated data sources in the Vaccine Safety Datalink PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Kharbanda, E. O., Vazquez-Benitez, G., Romitti, P. A., Naleway, A. L., Cheetham, T. C., Lipkind, H. S., Sivanandam, S., Klein, N. P., Lee, G. M., Jackson, M. L., Hambidge, S. J., Olsen, A., McCarthy, N., DeStefano, F., Nordin, J. D. 2017; 26 (4): 412-420

    Abstract

    The Vaccine Safety Datalink (VSD), a collaboration between the Centers for Disease Control and Prevention and several large healthcare organizations, aims to monitor safety of vaccines administered in the USA. We present definitions and prevalence estimates for major structural birth defects to be used in studies of maternal vaccine safety.In this observational study, we created and refined algorithms for identifying major structural birth defects from electronic healthcare data, conducted formal chart reviews for severe cardiac defects, and conducted limited chart validation for other defects. We estimated prevalence for selected defects by VSD site and birth year and compared these estimates to those in a US and European surveillance system.We developed algorithms to enumerate >50 major structural birth defects from standardized administrative and healthcare data based on utilization patterns and expert opinion, applying criteria for number, timing, and setting of diagnoses. Our birth cohort included 497 894 infants across seven sites. The period prevalence for all selected major birth defects in the VSD from 2004 to 2013 was 1.7 per 100 live births. Cardiac defects were most common (65.4 per 10 000 live births), with one-fourth classified as severe, requiring emergent intervention. For most major structural birth defects, prevalence estimates were stable over time and across sites and similar to those reported in other population-based surveillance systems.Our algorithms can efficiently identify many major structural birth defects in large healthcare datasets and can be used in studies evaluating the safety of vaccines administered to pregnant women. Copyright © 2017 John Wiley & Sons, Ltd.

    View details for DOI 10.1002/pds.4153

    View details for Web of Science ID 000398540200007

    View details for PubMedID 28054412

  • A Pediatric Approach to Ventilator-Associated Events Surveillance INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Cocoros, N. M., Priebe, G. P., Logan, L. K., Coffin, S., Larsen, G., Toltzis, P., Sandora, T. J., Harper, M., Sammons, J. S., Gray, J. E., Goldmann, D., Horan, K., Burton, M., Checchia, P. A., Lakoma, M., Sims, S., Klompas, M., Lee, G. M. 2017; 38 (3): 327-333

    Abstract

    OBJECTIVE Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children. DESIGN Retrospective cohort SETTING Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals PATIENTS Patients ≤18 years old ventilated for ≥1 day METHODS We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models. RESULTS In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on "pediatric VAC with antimicrobial use" (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test ("pediatric PVAP") occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls. CONCLUSIONS We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes. Infect Control Hosp Epidemiol 2017;38:327-333.

    View details for DOI 10.1017/ice.2016.277

    View details for Web of Science ID 000395452000011

    View details for PubMedID 27917737

  • Immunization, Antibiotic Use, and Pneumococcal Colonization Over a 15-Year Period. Pediatrics Lee, G. M., Kleinman, K., Pelton, S., Lipsitch, M., Huang, S. S., Lakoma, M., Dutta-Linn, M., Rett, M., Hanage, W. P., Finkelstein, J. A. 2017; 140 (5)

    Abstract

    Rates of invasive pneumococcal disease have declined since widespread introduction of pneumococcal conjugate vaccines (PCVs) in the United States. We evaluated the impact of immunization status and recent antibiotic use on an individual child's risk of colonization.This study extends previously reported data from children <7 years of age seen for well child or acute care visits in Massachusetts communities. Nasopharyngeal swabs were collected during 6 surveillance seasons from 2000 to 2014. Parent surveys and medical record reviews confirmed immunization status and recent antibiotic use. We estimated the proportions of children colonized with PCV7-included, additional PCV13-included, and non-PCV13 serotypes. Risk factors for colonization with additional PCV13-included and non-PCV13 serotypes were assessed by using generalized linear mixed models adjusted for clustering by community.Among 6537 children, 19A emerged as the predominant serotype in 2004, with substantial reductions in 2014. Among non-PCV serotypes, 15B/C, 35B, 23B, 11A, and 23A were most common in 2014. We observed greater odds for both additional PCV13 and non-PCV13 colonization in younger children, those with more child care exposure, and those with a concomitant respiratory tract infection. Adjusted odds for additional PCV13 colonization was lower (odds ratio 0.48 [95% confidence interval 0.31-0.75]) among children up-to-date for PCV13 vaccines. Recent antibiotic use was associated with higher odds of additional PCV13 colonization but substantially lower odds of non-PCV13 colonization.Despite the success of pneumococcal vaccines in reducing colonization and disease due to targeted serotypes, ongoing community-based surveillance will be critical to evaluate the impact of interventions on pneumococcal colonization and disease.

    View details for DOI 10.1542/peds.2017-0001

    View details for PubMedID 28978716

    View details for PubMedCentralID PMC5654389

  • Maternal and Infant Outcomes After Human Papillomavirus Vaccination in the Periconceptional Period or During Pregnancy. Obstetrics and gynecology Lipkind, H. S., Vazquez-Benitez, G., Nordin, J. D., Romitti, P. A., Naleway, A. L., Klein, N. P., Hechter, R. C., Jackson, M. L., Hambidge, S. J., Lee, G. M., Sukumaran, L., Kharbanda, E. O. 2017; 130 (3): 599–608

    Abstract

    To evaluate whether quadrivalent human papillomavirus vaccine (4vHPV) administered during the periconceptional period or during pregnancy was associated with increased risks for adverse obstetric events, adverse birth outcomes, or selected major structural birth defects.We conducted a retrospective, observational cohort study using administrative and health care data from the Vaccine Safety Datalink. Insured women 13-27 years old with singleton pregnancies and a live birth from January 1, 2007, through September 1, 2013, who received 4vHPV during the periconceptional period (2 weeks before to 2 weeks after their last menstrual period), during pregnancy, or during both periods combined were compared with women who had a live birth during the same time period and received 4vHPV 4-18 months before their last menstrual period. We examined risks of gestational diabetes, hypertensive disorders of pregnancy, chorioamnionitis, preterm birth, small-for-gestational-age birth, and selected major structural birth defects in offspring. We estimated relative risks associated with receipt of 4vHPV during the periconceptional period, during pregnancy, and both exposure periods combined using a generalized linear model with Poisson distribution including a propensity score that included relevant maternal demographic and pregnancy characteristics.Of 92,579 potentially eligible pregnant women, 720 received 4vHPV during the periconceptional period, 638 received 4vHPV during pregnancy, and 8,196 received 4vHPV during the comparison period. Administration of 4vHPV during pregnancy was not associated with increased risk of adverse obstetric events, birth outcomes. Preterm birth occurred in 7.9% of pregnancies with vaccine exposures during pregnancy compared with 7.6% of pregnancies with vaccination in the comparison period (adjusted relative risk 0.97, 95% CI 0.72-1.3). Major structural birth defects were diagnosed in 2.0% of pregnancies with vaccine exposure during pregnancy compared with 1.8% of pregnancies with vaccine exposure during the comparison period (adjusted prevalence ratio 1.0, 95% CI 0.52-1.9). Results were similar for 4vHPV exposure during the periconceptional period.Quadrivalent HPV vaccine inadvertently administered in pregnancy or during the periconceptional period was not associated with adverse pregnancy or birth outcomes.

    View details for DOI 10.1097/AOG.0000000000002191

    View details for PubMedID 28796684

  • Surveillance of pneumococcal colonization and invasive pneumococcal disease reveals shift in prevalent carriage serotypes in Massachusetts' children to relatively low invasiveness. Vaccine Yildirim, I., Little, B. A., Finkelstein, J., Lee, G., Hanage, W. P., Shea, K., Pelton, S. I. 2017; 35 (32): 4002–9

    Abstract

    Following the introduction of pneumococcal conjugate vaccines (PCV), overall nasopharyngeal colonization rates have not changed significantly, however a dramatic and sustained decline in invasive pneumococcal disease (IPD) in children was observed in every setting where the PCVs were implemented. We aimed to describe the differences in invasive disease potential of serotypes that are common colonizers in pre- and post-vaccine eras in order to provide further insight in our understanding of dynamic epidemiology of pneumococcal diseases.Using data from surveillance of nasopharyngeal carriage and enhanced surveillance for IPD, a serotype specific "invasive capacity (IC)" was computed by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children <7years of age in Massachusetts. We have evaluated the serotype specific invasive capacity in two periods; pre-PCV13 (2001/02, 2003/04, 2006/07, 2008/09) and post-PCV13 (2010/11 and 2013/14), and by age groups; <24monthsvs. ≥24months.An approximate 50-fold variation in the point estimate was observed between the serotypes having the highest (7F, 38, 19A, 3, 33F) and the lowest (6C, 35B, 21, 11A, 23B and 23A) computed serotype specific invasive disease potential. In the post-PCV13 era (6C, 35B, 11A, 23B and 23A), 5 of the 7 most common serotypes colonizing the nasopharynx were serotypes with the lowest invasive capacity. Serotype specific invasive capacity trended down in older children for majority of the serotypes, and serotypes 3, 10A and 19A had significantly lower invasive capacity in children older than 24months of age compared to younger children.Invasive capacity differs among serotypes and likely by age. Point estimates of IC for most of the common serotypes colonizing children in Massachusetts in post-PCV13 era were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes.

    View details for DOI 10.1016/j.vaccine.2017.05.077

    View details for PubMedID 28645717

  • Factors Associated With Pediatric Ventilator-Associated Conditions in Six U.S. Hospitals: A Nested Case-Control Study. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Cocoros, N. M., Priebe, G., Gray, J. E., Toltzis, P., Larsen, G. Y., Logan, L. K., Coffin, S., Sammons, J. S., Deakins, K., Horan, K., Lakoma, M., Young, J., Burton, M., Klompas, M., Lee, G. M. 2017; 18 (11): e536–e545

    Abstract

    A newly proposed surveillance definition for ventilator-associated conditions among neonatal and pediatric patients has been associated with increased morbidity and mortality among ventilated patients in cardiac ICU, neonatal ICU, and PICU. This study aimed to identify potential risk factors associated with pediatric ventilator-associated conditions.Retrospective cohort.Six U.S. hospitals PATIENTS:: Children less than or equal to 18 years old ventilated for greater than or equal to 1 day.None.We identified children with pediatric ventilator-associated conditions and matched them to children without ventilator-associated conditions. Medical records were reviewed for comorbidities and acute care factors. We used bivariate and multivariate conditional logistic regression models to identify factors associated with ventilator-associated conditions. We studied 192 pairs of ventilator-associated conditions cases and matched controls (113 in the PICU and cardiac ICU combined; 79 in the neonatal ICU). In the PICU/cardiac ICU, potential risk factors for ventilator-associated conditions included neuromuscular blockade (odds ratio, 2.29; 95% CI, 1.08-4.87), positive fluid balance (highest quartile compared with the lowest, odds ratio, 7.76; 95% CI, 2.10-28.6), and blood product use (odds ratio, 1.52; 95% CI, 0.70-3.28). Weaning from sedation (i.e., decreasing sedation) or interruption of sedation may be protective (odds ratio, 0.44; 95% CI, 0.18-1.11). In the neonatal ICU, potential risk factors included blood product use (odds ratio, 2.99; 95% CI, 1.02-8.78), neuromuscular blockade use (odds ratio, 3.96; 95% CI, 0.93-16.9), and recent surgical procedures (odds ratio, 2.19; 95% CI, 0.77-6.28). Weaning or interrupting sedation was protective (odds ratio, 0.07; 95% CI, 0.01-0.79).In mechanically ventilated neonates and children, we identified several possible risk factors associated with ventilator-associated conditions. Next steps include studying propensity-matched cohorts and prospectively testing whether changes in sedation management, transfusion thresholds, and fluid management can decrease pediatric ventilator-associated conditions rates and improve patient outcomes.

    View details for DOI 10.1097/PCC.0000000000001328

    View details for PubMedID 28914722

  • Research Methods in Healthcare Epidemiology and Antimicrobial Stewardship: Use of Administrative and Surveillance Databases INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Drees, M., Gerber, J. S., Morgan, D. J., Lee, G. M. 2016; 37 (11): 1278-1287

    Abstract

    Administrative and surveillance data are used frequently in healthcare epidemiology and antimicrobial stewardship (HE&AS) research because of their wide availability and efficiency. However, data quality issues exist, requiring careful consideration and potential validation of data. This methods paper presents key considerations for using administrative and surveillance data in HE&AS, including types of data available and potential use, data limitations, and the importance of validation. After discussing these issues, we review examples of HE&AS research using administrative data with a focus on scenarios when their use may be advantageous. A checklist is provided to help aid study development in HE&AS using administrative data. Infect Control Hosp Epidemiol 2016;1-10.

    View details for DOI 10.1017/ice.2016.189

    View details for Web of Science ID 000386404400003

    View details for PubMedID 27572516

  • Febrile Seizure Risk After Vaccination in Children 6 to 23 Months PEDIATRICS Duffy, J., Weintraub, E., Hambidge, S. J., Jackson, L. A., Kharbanda, E. O., Klein, N. P., Lee, G. M., Marcy, S. M., Nakasato, C. C., Naleway, A., Omer, S. B., Vellozzi, C., DeStefano, F. 2016; 138 (1)

    Abstract

    An increased risk of febrile seizure (FS) was identified with concomitant administration of trivalent inactivated influenza vaccine (IIV3) and pneumococcal conjugate vaccine (PCV) 13-valent during the 2010-2011 influenza season. Our objective was to determine whether concomitant administration of IIV3 with other vaccines affects the FS risk.We examined the risk of FS 0 to 1 day postvaccination for all routinely recommended vaccines among children aged 6 through 23 months during a period encompassing 5 influenza seasons (2006-2007 through 2010-2011). We used a population-based self-controlled risk interval analysis with a control interval of 14 to 20 days postvaccination. We used multivariable regression to control for receipt of concomitant vaccines and test for interaction between vaccines.Only PCV 7-valent had an independent FS risk (incidence rate ratio [IRR], 1.98; 95% confidence interval [CI], 1.00 to 3.91). IIV3 had no independent risk (IRR, 0.46; 95% CI, 0.21 to 1.02), but risk was increased when IIV3 was given with either PCV (IRR, 3.50; 95% CI, 1.13 to 10.85) or a diphtheria-tetanus-acellular-pertussis (DTaP)-containing vaccine (IRR, 3.50; 95% CI, 1.52 to 8.07). The maximum estimated absolute excess risk due to concomitant administration of IIV3, PCV, and DTaP-containing vaccines compared with administration on separate days was 30 FS per 100 000 persons vaccinated.The administration of IIV3 on the same day as either PCV or a DTaP-containing vaccine was associated with a greater risk of FS than when IIV3 was given on a separate day. The absolute risk of postvaccination FS with these vaccine combinations was small.

    View details for DOI 10.1542/peds.2016-0320

    View details for Web of Science ID 000378853100046

    View details for PubMedID 27273711

  • Prospective influenza vaccine safety surveillance using fresh data in the Sentinel System PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Yih, W. K., Kulldorff, M., Sandhu, S. K., Zichittella, L., Maro, J. C., Cole, D. V., Jin, R., Kawai, A. T., Baker, M. A., Liu, C., McMahill-Walraven, C. N., Selvan, M. S., Platt, R., Nguyen, M. D., Lee, G. M. 2016; 25 (5): 481-492

    Abstract

    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.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.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.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.

    View details for DOI 10.1002/pds.3908

    View details for Web of Science ID 000375615900001

    View details for PubMedID 26572776

    View details for PubMedCentralID PMC5019152

  • Diagnosing sepsis is subjective and highly variable: a survey of intensivists using case vignettes CRITICAL CARE Rhee, C., Kadri, S. S., Danner, R. L., Suffredini, A. F., Massaro, A. F., Kitch, B. T., Lee, G., Klompas, M. 2016; 20

    Abstract

    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.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.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.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.

    View details for DOI 10.1186/s13054-016-1266-9

    View details for Web of Science ID 000373670400001

    View details for PubMedID 27048508

  • Risk of anaphylaxis after vaccination in children and adults JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY McNeil, M. M., Weintraub, E. S., Duffy, J., Sukumaran, L., Jacobsen, S. J., Klein, N. P., Hambidge, S. J., Lee, G. M., Jackson, L. A., Irving, S. A., King, J. P., Kharbanda, E. O., Bednarczyk, R. A., DeStefano, F. 2016; 137 (3): 868-878

    Abstract

    Anaphylaxis is a potentially life-threatening allergic reaction. The risk of anaphylaxis after vaccination has not been well described in adults or with newer vaccines in children.We sought to estimate the incidence of anaphylaxis after vaccines and describe the demographic and clinical characteristics of confirmed cases of anaphylaxis.Using health care data from the Vaccine Safety Datalink, we determined rates of anaphylaxis after vaccination in children and adults. We first identified all patients with a vaccination record from January 2009 through December 2011 and used diagnostic and procedure codes to identify potential anaphylaxis cases. Medical records of potential cases were reviewed. Confirmed cases met the Brighton Collaboration definition for anaphylaxis and had to be determined to be vaccine triggered. We calculated the incidence of anaphylaxis after all vaccines combined and for selected individual vaccines.We identified 33 confirmed vaccine-triggered anaphylaxis cases that occurred after 25,173,965 vaccine doses. The rate of anaphylaxis was 1.31 (95% CI, 0.90-1.84) per million vaccine doses. The incidence did not vary significantly by age, and there was a nonsignificant female predominance. Vaccine-specific rates included 1.35 (95% CI, 0.65-2.47) per million doses for inactivated trivalent influenza vaccine (10 cases, 7,434,628 doses given alone) and 1.83 (95% CI, 0.22-6.63) per million doses for inactivated monovalent influenza vaccine (2 cases, 1,090,279 doses given alone). The onset of symptoms among cases was within 30 minutes (8 cases), 30 to less than 120 minutes (8 cases), 2 to less than 4 hours (10 cases), 4 to 8 hours (2 cases), the next day (1 case), and not documented (4 cases).Anaphylaxis after vaccination is rare in all age groups. Despite its rarity, anaphylaxis is a potentially life-threatening medical emergency that vaccine providers need to be prepared to treat.

    View details for DOI 10.1016/j.jaci.2015.07.048

    View details for Web of Science ID 000371897500031

    View details for PubMedID 26452420

    View details for PubMedCentralID PMC4783279

  • Maternal Tdap vaccination: Coverage and acute safety outcomes in the vaccine safety datalink, 2007-2013 VACCINE Kharbanda, E. O., Vazquez-Benitez, G., Lipkind, H. S., Klein, N. P., Cheetham, T. C., Naleway, A. L., Lee, G. M., Hambidge, S., Jackson, M. L., Omeri, S. B., McCarthy, N., Nordin, J. D. 2016; 34 (7): 968-973

    Abstract

    Since October 2012, the combined tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine (Tdap) has been recommended in the United States during every pregnancy.In this observational study from the Vaccine Safety Datalink, we describe receipt of Tdap during pregnancy among insured women with live births across seven health systems. Using a retrospective matched cohort, we evaluated risks for selected medically attended adverse events in pregnant women, occurring within 42 days of vaccination. Using a generalized estimating equation, we calculated adjusted incident rate ratios (AIRR).Our vaccine coverage cohort included 438,487 live births between January 1, 2007 and November 15, 2013. Across the coverage cohort, 14% received Tdap during pregnancy. By 2013, Tdap was administered during pregnancy in 41.7% of live births, primarily in the 3rd trimester. Our vaccine safety cohort included 53,885 vaccinated and 109,253 matched unvaccinated pregnant women. There was no increased risk for a composite outcome of medically attended acute adverse events within 3 days of vaccination. Similarly, across the safety cohort, over a 42 day window, incident neurologic events, thrombotic events, and new onset proteinuria did not differ by maternal receipt of Tdap. Among women receiving Tdap at 20 weeks gestation or later, as compared to their matched controls, there was no increased risk for gestational diabetes or cardiac events while venous thromboembolic events and thrombocytopenia were diagnosed within 42 days of vaccination at slightly decreased rates.Tdap coverage during pregnancy increased from 2007 through 2013, but was still below 50%. No acute maternal safety signals were detected in this large cohort.

    View details for DOI 10.1016/j.vaccine.2015.12.046

    View details for Web of Science ID 000370087500013

    View details for PubMedID 26765288

  • Impact of Hospital Operating Margin on Central Line-Associated Bloodstream Infections Following Medicare's Hospital-Acquired Conditions Payment Policy. Infection control and hospital epidemiology Calderwood, M. S., Vaz, L. E., Tse Kawai, A., Jin, R., Rett, M. D., Grant, P. S., Lee, G. M. 2016; 37 (1): 100-103

    Abstract

    In October 2008, Medicare ceased additional payment for hospital-acquired conditions not present on admission. We evaluated the policy's differential impact in hospitals with high vs low operating margins. Medicare's payment policy may have had an impact on reducing central line-associated bloodstream infections in hospitals with low operating margins. Infect. Control Hosp. Epidemiol. 2015;37(1):100-103.

    View details for DOI 10.1017/ice.2015.250

    View details for PubMedID 26526631

  • Ventilator-Associated Events in Neonates and Children-A New Paradigm CRITICAL CARE MEDICINE Cocoros, N. M., Kleinman, K., Priebe, G. P., Gray, J. E., Logan, L. K., Larsen, G., Sammons, J., Toltzis, P., Miroshnik, I., Horan, K., Burton, M., Sims, S., Harper, M., Coffin, S., Sandora, T. J., Hocevar, S. N., Checchia, P. A., Klompas, M., Lee, G. M. 2016; 44 (1): 14-22

    Abstract

    To identify a pediatric ventilator-associated condition definition for use in neonates and children by exploring whether potential ventilator-associated condition definitions identify patients with worse outcomes.Retrospective cohort study and a matched cohort analysis.Pediatric, cardiac, and neonatal ICUs in five U.S. hospitals.Children 18 years old or younger ventilated for at least 1 day.None.We evaluated the evidence of worsening oxygenation via a range of thresholds for increases in daily minimum fraction of inspired oxygen (by 0.20, 0.25, and 0.30) and daily minimum mean airway pressure (by 4, 5, 6, and 7 cm H2O). We required worsening oxygenation be sustained for at least 2 days after at least 2 days of stability. We matched patients with a ventilator-associated condition to those without and used Cox proportional hazard models with frailties to examine associations with hospital mortality, hospital and ICU length of stay, and duration of ventilation. The cohort included 8,862 children with 10,209 hospitalizations and 77,751 ventilator days. For the fraction of inspired oxygen 0.25/mean airway pressure 4 definition (i.e., increase in minimum daily fraction of inspired oxygen by 0.25 or mean airway pressure by 4), rates ranged from 2.9 to 3.2 per 1,000 ventilator days depending on ICU type; the fraction of inspired oxygen 0.30/mean airway pressure 7 definition yielded ventilator-associated condition rates of 1.1-1.3 per 1,000 ventilator days. All definitions were significantly associated with greater risk of hospital death, with hazard ratios ranging from 1.6 (95% CI, 0.7-3.4) to 6.8 (2.9-16.0), depending on thresholds and ICU type. Each definition was associated with prolonged hospitalization, time in ICU, and duration of ventilation, among survivors. The advisory board of the study proposed using the fraction of inspired oxygen 0.25/mean airway pressure 4 thresholds to identify pediatric ventilator-associated conditions in ICUs.Pediatric patients with ventilator-associated conditions are at substantially higher risk for mortality and morbidity across ICUs, regardless of thresholds used. Next steps include identification of risk factors, etiologies, and preventative measures for pediatric ventilator-associated conditions.

    View details for DOI 10.1097/CCM.0000000000001372

    View details for Web of Science ID 000366605100003

    View details for PubMedID 26524075

  • Febrile Seizures After 2010-2011 Trivalent Inactivated Influenza Vaccine PEDIATRICS Kawai, A. T., Martin, D., Kulldorff, M., Li, L., Cole, D. V., McMahill-Walraven, C. N., Selvam, N., Selvan, M. S., Lee, G. M. 2015; 136 (4): E848-E855

    Abstract

    In the Post-Licensure Rapid Immunization Safety Monitoring Program, we examined risk of febrile seizures (FS) after trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal conjugate vaccine (PCV13) during the 2010-2011 influenza season, adjusted for concomitant diphtheria tetanus acellular pertussis-containing vaccines (DTaP). Assuming children would receive both vaccines, we examined whether same-day TIV and PCV13 vaccination was associated with greater FS risk when compared with separate-day vaccination.We used a self-controlled risk interval design, comparing the FS rate in a risk interval (0-1 days) versus control interval (14-20 days). Vaccinations were identified in claims and immunization registry data. FS were confirmed with medical records.No statistically significant TIV-FS associations were found in unadjusted or adjusted models (incidence rate ratio [IRR] adjusted for age, seasonality, and concomitant PCV13 and DTaP: 1.36, 95% confidence interval [CI] 0.78 to 2.39). Adjusted for age and seasonality, PCV13 was significantly associated with FS (IRR 1.74, 95% CI 1.06 to 2.86), but not when further adjusting for concomitant TIV and DTaP (IRR 1.61, 95% CI 0.91 to 2.82). Same-day TIV and PCV13 vaccination was not associated with excess risk of FS when compared with separate-day vaccination (1.08 fewer FS per 100 000 with same day administration, 95% CI -5.68 to 6.09).No statistically significant increased risk of FS was found for 2010-2011 TIV or PCV13, when adjusting for concomitant vaccines. Same-day TIV and PCV13 vaccination was not associated with more FS compared with separate-day vaccination.

    View details for DOI 10.1542/peds.2015-0635

    View details for Web of Science ID 000362944300009

    View details for PubMedID 26371192

  • Ongoing Attention to Injurious Inpatient Falls and Pressure Ulcers JAMA INTERNAL MEDICINE Lee, G. M., Soumerai, S. B. 2015; 175 (9): 1581-1582

    View details for Web of Science ID 000361059900051

    View details for PubMedID 26348515

  • Impact of the Centers for Medicare and Medicaid Services Hospital-Acquired Conditions Policy on Billing Rates for 2 Targeted Healthcare-Associated Infections INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Kawai, A. T., Calderwood, M. S., Jin, R., Soumerai, S. B., Vaz, L. E., Goldmann, D., Lee, G. M. 2015; 36 (8): 871-877

    Abstract

    The 2008 Centers for Medicare & Medicaid Services hospital-acquired conditions policy limited additional payment for conditions deemed reasonably preventable.To examine whether this policy was associated with decreases in billing rates for 2 targeted conditions, vascular catheter-associated infections (VCAI) and catheter-associated urinary tract infections (CAUTI).Adult Medicare patients admitted to 569 acute care hospitals in California, Massachusetts, or New York and subject to the policy. DESIGN We used an interrupted times series design to assess whether the hospital-acquired conditions policy was associated with changes in billing rates for VCAI and CAUTI.Before the policy, billing rates for VCAI and CAUTI were increasing (prepolicy odds ratio per quarter for VCAI, 1.17 [95% CI, 1.11-1.23]; for CAUTI, 1.19 [1.16-1.23]). The policy was associated with an immediate drop in billing rates for VCAI and CAUTI (odds ratio for change at policy implementation for VCAI, 0.75 [95% CI, 0.69-0.81]; for CAUTI, 0.87 [0.79-0.96]). In the postpolicy period, we observed a decreasing trend in the billing rate for VCAI and a leveling-off in the billing rate for CAUTI (postpolicy odds ratio per quarter for VCAI, 0.98 [95% CI, 0.97-0.99]; for CAUTI, 0.99 [0.97-1.00]).The Centers for Medicare & Medicaid Services hospital-acquired conditions policy appears to have been associated with immediate reductions in billing rates for VCAI and CAUTI, followed by a slight decreasing trend or leveling-off in rates. These billing rates, however, may not correlate with changes in clinically meaningful patient outcomes and may reflect changes in coding practices.

    View details for DOI 10.1017/ice.2015.86

    View details for Web of Science ID 000358391800001

    View details for PubMedID 25906824

  • Impact of Medicare's Hospital-Acquired Condition Policy on Infections in Safety Net and Non-Safety Net Hospitals INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Vaz, L. E., Kleinman, K. P., Kawai, A. T., Jin, R., Kassler, W. J., Grant, P. S., Rett, M. D., Goldmann, D. A., Calderwood, M. S., Soumerai, S. B., Lee, G. M. 2015; 36 (6): 649-655

    Abstract

    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.

    View details for DOI 10.1017/ice.2015.38

    View details for Web of Science ID 000354981400006

    View details for PubMedID 25732568

  • GROUP A STREPTOCOCCAL BACTEREMIA WITHOUT A SOURCE IS ASSOCIATED WITH LESS SEVERE DISEASE IN CHILDREN PEDIATRIC INFECTIOUS DISEASE JOURNAL Gauguet, S., Ahmed, A. A., Zhou, J., Pfoh, E. R., Ahnger-Pier, K. K., Harper, M. B., Ozonoff, A., Wessels, M. R., Lee, G. M. 2015; 34 (4): 447-449

    Abstract

    We analyzed characteristics of 86 Group A streptococcal bacteremia cases at Boston Children's Hospital from 1992 to 2012. Twenty-three percent of children had severe disease, using intensive care unit admission (18), disability (7) or death (2) as indicators. Children with bacteremia without a source (30% of cases) were less likely to have severe disease than children with focal infections in adjusted models.

    View details for DOI 10.1097/INF.0000000000000587

    View details for Web of Science ID 000351007900024

    View details for PubMedID 25319760

  • Stability of the pneumococcal population structure in Massachusetts as PCV13 was introduced BMC INFECTIOUS DISEASES Chang, Q., Stevenson, A. E., Croucher, N. J., Lee, G. M., Pelton, S. I., Lipsitch, M., Finkelstein, J. A., Hanage, W. P. 2015; 15

    Abstract

    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.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.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.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.

    View details for DOI 10.1186/s12879-015-0797-z

    View details for Web of Science ID 000349868300002

    View details for PubMedID 25887323

    View details for PubMedCentralID PMC4336693

  • Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006 VACCINE Abrams, J. Y., Weintraub, E. S., Baggs, J. M., McCarthy, N. L., Schonberger, L. B., Lee, G. M., Klein, N. P., Belongia, E. A., Jackson, M. L., Naleway, A. L., Nordin, J. D., Hambidge, S. J., Belay, E. D. 2015; 33 (2): 382-387

    Abstract

    Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease.Data from the Vaccine Safety Datalink were collected on children aged 0-6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding.A total of 1,721,186 children aged 0-6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1-42 days after vaccination (rate ratio=0.50, 95% CL=0.27-0.92) and 8-42 days after vaccination (rate ratio=0.45, 95% CL=0.22-0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio=0.79, 95% CL=0.64-0.97) and verified Kawasaki disease (rate ratio=0.38, 95% CL=0.20-0.75).Childhood vaccinations' studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease.

    View details for DOI 10.1016/j.vaccine.2014.10.044

    View details for Web of Science ID 000348268500017

    View details for PubMedID 25444786

  • Accuracy of administrative data for surveillance of healthcare-associated infections: a systematic review BMJ OPEN van Mourik, M. S., van Duijn, P. J., Moons, K. G., Bonten, M. J., Lee, G. M. 2015; 5 (8)

    Abstract

    Measuring the incidence of healthcare-associated infections (HAI) is of increasing importance in current healthcare delivery systems. Administrative data algorithms, including (combinations of) diagnosis codes, are commonly used to determine the occurrence of HAI, either to support within-hospital surveillance programmes or as free-standing quality indicators. We conducted a systematic review evaluating the diagnostic accuracy of administrative data for the detection of HAI.Systematic search of Medline, Embase, CINAHL and Cochrane for relevant studies (1995-2013). Methodological quality assessment was performed using QUADAS-2 criteria; diagnostic accuracy estimates were stratified by HAI type and key study characteristics.57 studies were included, the majority aiming to detect surgical site or bloodstream infections. Study designs were very diverse regarding the specification of their administrative data algorithm (code selections, follow-up) and definitions of HAI presence. One-third of studies had important methodological limitations including differential or incomplete HAI ascertainment or lack of blinding of assessors. Observed sensitivity and positive predictive values of administrative data algorithms for HAI detection were very heterogeneous and generally modest at best, both for within-hospital algorithms and for formal quality indicators; accuracy was particularly poor for the identification of device-associated HAI such as central line associated bloodstream infections. The large heterogeneity in study designs across the included studies precluded formal calculation of summary diagnostic accuracy estimates in most instances.Administrative data had limited and highly variable accuracy for the detection of HAI, and their judicious use for internal surveillance efforts and external quality assessment is recommended. If hospitals and policymakers choose to rely on administrative data for HAI surveillance, continued improvements to existing algorithms and their robust validation are imperative.

    View details for DOI 10.1136/bmjopen-2015-008424

    View details for Web of Science ID 000363479100057

    View details for PubMedID 26316651

    View details for PubMedCentralID PMC4554897

  • Cost-Effectiveness of Strategies to Prevent Methicillin-Resistant Staphylococcus aureus Transmission and Infection in an Intensive Care Unit INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Gidengil, C. A., Gay, C., Huang, S. S., Platt, R., Yokoe, D., Lee, G. M. 2015; 36 (1): 17-27

    Abstract

    OBJECTIVE To create a national policy model to evaluate the projected cost-effectiveness of multiple hospital-based strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection. DESIGN Cost-effectiveness analysis using a Markov microsimulation model that simulates the natural history of MRSA acquisition and infection. PATIENTS AND SETTING Hypothetical cohort of 10,000 adult patients admitted to a US intensive care unit. METHODS We compared 7 strategies to standard precautions using a hospital perspective: (1) active surveillance cultures; (2) active surveillance cultures plus selective decolonization; (3) universal contact precautions (UCP); (4) universal chlorhexidine gluconate baths; (5) universal decolonization; (6) UCP + chlorhexidine gluconate baths; and (7) UCP+decolonization. For each strategy, both efficacy and compliance were considered. Outcomes of interest were: (1) MRSA colonization averted; (2) MRSA infection averted; (3) incremental cost per colonization averted; (4) incremental cost per infection averted. RESULTS A total of 1989 cases of colonization and 544 MRSA invasive infections occurred under standard precautions per 10,000 patients. Universal decolonization was the least expensive strategy and was more effective compared with all strategies except UCP+decolonization and UCP+chlorhexidine gluconate. UCP+decolonization was more effective than universal decolonization but would cost $2469 per colonization averted and $9007 per infection averted. If MRSA colonization prevalence decreases from 12% to 5%, active surveillance cultures plus selective decolonization becomes the least expensive strategy. CONCLUSIONS Universal decolonization is cost-saving, preventing 44% of cases of MRSA colonization and 45% of cases of MRSA infection. Our model provides useful guidance for decision makers choosing between multiple available hospital-based strategies to prevent MRSA transmission.

    View details for DOI 10.1017/ice.2014.12

    View details for Web of Science ID 000348588800004

    View details for PubMedID 25627757

    View details for PubMedCentralID PMC4311265

  • Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study PLOS ONE Maro, J. C., Fryback, D. G., Lieu, T. A., Lee, G. M., Martin, D. B. 2014; 9 (12)

    Abstract

    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.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.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.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.

    View details for DOI 10.1371/journal.pone.0115553

    View details for Web of Science ID 000348563300048

    View details for PubMedID 25536228

    View details for PubMedCentralID PMC4275236

  • Evaluation of the Association of Maternal Pertussis Vaccination With Obstetric Events and Birth Outcomes JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Kharbanda, E. O., Vazquez-Benitez, G., Lipkind, H. S., Klein, N. P., Cheetham, T. C., Naleway, A., Omer, S. B., Hambidge, S. J., Lee, G. M., Jackson, M. L., McCarthy, N. L., DeStefano, F., Nordin, J. D. 2014; 312 (18): 1897-1904

    Abstract

    In 2010, due to a pertussis outbreak and neonatal deaths, the California Department of Health recommended that the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) be administered during pregnancy. Tdap is now recommended by the Advisory Committee on Immunization Practices for all pregnant women, preferably between 27 and 36 weeks' gestation. Limited data exist on Tdap safety during pregnancy.To evaluate whether maternal Tdap vaccination during pregnancy is associated with increased risks of adverse obstetric events or adverse birth outcomes.Retrospective, observational cohort study using administrative health care databases from 2 California Vaccine Safety Datalink sites.Of 123,494 women with singleton pregnancies ending in a live birth between January 1, 2010, and November 15, 2012, 26,229 (21%) received Tdap during pregnancy and 97,265 did not.Risks of small-for-gestational-age (SGA) births (<10th percentile), chorioamnionitis, preterm birth (<37 weeks' gestation), and hypertensive disorders of pregnancy were evaluated. Relative risk (RR) estimates were adjusted for site, receipt of another vaccine during pregnancy, and propensity to receive Tdap during pregnancy. Cox regression was used for preterm delivery, and Poisson regression for other outcomes.Vaccination was not associated with increased risks of adverse birth outcomes: crude estimates for preterm delivery were 6.3% of vaccinated and 7.8% of unvaccinated women (adjusted RR, 1.03; 95% CI, 0.97-1.09); 8.4% of vaccinated and 8.3% of unvaccinated had an SGA birth (adjusted RR, 1.00; 95% CI, 0.96-1.06). Receipt of Tdap before 20 weeks was not associated with hypertensive disorder of pregnancy (adjusted RR, 1.09; 95% CI, 0.99-1.20); chorioamnionitis was diagnosed in 6.1% of vaccinated and 5.5% of unvaccinated women (adjusted RR, 1.19; 95% CI, 1.13-1.26).In this cohort of women with singleton pregnancies that ended in live birth, receipt of Tdap during pregnancy was not associated with increased risk of hypertensive disorders of pregnancy or preterm or SGA birth, although a small but statistically significant increased risk of chorioamnionitis diagnosis was observed.

    View details for DOI 10.1001/jama.2014.14825

    View details for Web of Science ID 000344532600019

    View details for PubMedID 25387187

  • Central Line-Associated Bloodstream Infections in Neonates with Gastrointestinal Conditions: Developing a Candidate Definition for Mucosal Barrier Injury Bloodstream Infections INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Coffin, S. E., Klieger, S. B., Duggan, C., Huskins, W. C., Milstone, A. M., Potter-Bynoe, G., Raphael, B., Sandora, T. J., Song, X., Zerr, D. M., Lee, G. M. 2014; 35 (11): 1391-1399

    Abstract

    To develop a candidate definition for central line-associated bloodstream infection (CLABSI) in neonates with presumed mucosal barrier injury due to gastrointestinal (MBI-GI) conditions and to evaluate epidemiology and microbiology of MBI-GI CLABSI in infants.Multicenter retrospective cohort study.Neonatal intensive care units from 14 US children's hospitals and pediatric facilities.A multidisciplinary focus group developed a candidate MBI-GI CLABSI definition based on presence of an MBI-GI condition, parenteral nutrition (PN) exposure, and an eligible enteric organism. CLABSI surveillance data from participating hospitals were supplemented by chart review to identify MBI-GI conditions and PN exposure.During 2009-2012, 410 CLABSIs occurred in 376 infants. MBI-GI conditions and PN exposure occurred in 149 (40%) and 324 (86%) of these 376 neonates, respectively. The distribution of pathogens was similar among neonates with versus without MBI-GI conditions and PN exposure. Fifty-nine (16%) of the 376 initial CLABSI episodes met the candidate MBI-GI CLABSI definition. Subsequent versus initial CLABSIs were more likely to be caused by an enteric organism (22 of 34 [65%] vs 151 of 376 [40%]; P = .009) and to meet the candidate MBI-GI CLABSI definition (19 of 34 [56%] vs 59 of 376 [16%]; P < .01).While MBI-GI conditions and PN exposure were common, only 16% of initial CLABSIs met the candidate definition of MBI-GI CLABSI. The high proportion of MBI-GI CLABSIs among subsequent infections suggests that infants with MBI-GI CLABSI should be a population targeted for further surveillance and interventional research.

    View details for DOI 10.1086/678410

    View details for Web of Science ID 000344316700010

    View details for PubMedID 25333434

    View details for PubMedCentralID PMC4551075

  • Cost Savings of Universal Decolonization to Prevent Intensive Care Unit Infection: Implications of the REDUCE MRSA Trial INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Huang, S. S., Septimus, E., Avery, T. R., Lee, G. M., Hickok, J., Weinstein, R. A., Moody, J., Hayden, M. K., Perlin, J. B., Platt, R., Ray, G. T. 2014; 35: S23-S31

    Abstract

    To estimate and compare the impact on healthcare costs of 3 alternative strategies for reducing bloodstream infections in the intensive care unit (ICU): methicillin-resistant Staphylococcus aureus (MRSA) nares screening and isolation, targeted decolonization (ie, screening, isolation, and decolonization of MRSA carriers or infections), and universal decolonization (ie, no screening and decolonization of all ICU patients).Cost analysis using decision modeling.We developed a decision-analysis model to estimate the health care costs of targeted decolonization and universal decolonization strategies compared with a strategy of MRSA nares screening and isolation. Effectiveness estimates were derived from a recent randomized trial of the 3 strategies, and cost estimates were derived from the literature.In the base case, universal decolonization was the dominant strategy and was estimated to have both lower intervention costs and lower total ICU costs than either screening and isolation or targeted decolonization. Compared with screening and isolation, universal decolonization was estimated to save $171,000 and prevent 9 additional bloodstream infections for every 1,000 ICU admissions. The dominance of universal decolonization persisted under a wide range of cost and effectiveness assumptions.A strategy of universal decolonization for patients admitted to the ICU would both reduce bloodstream infections and likely reduce healthcare costs compared with strategies of MRSA nares screening and isolation or screening and isolation coupled with targeted decolonization.

    View details for DOI 10.1086/677819

    View details for Web of Science ID 000341939700005

    View details for PubMedID 25222894

  • Health Care-Associated Infections Among Critically III Children in the US, 2007-2012 PEDIATRICS Patrick, S. W., Kawai, A. T., Kleinman, K., Jin, R., Vaz, L., Gay, C., Kassler, W., Goldmann, D., Lee, G. M. 2014; 134 (4): 705-712

    Abstract

    Health care-associated infections (HAIs) are harmful and costly and can result in substantial morbidity for hospitalized children; however, little is known about national trends in HAIs in neonatal and pediatric populations. Our objective was to determine the incidence of HAIs among a large sample of hospitals in the United States caring for critically ill children from 2007 to 2012.In this cohort study, we included NICUs and PICUs located in hospitals reporting data to the Centers for Disease Control and Prevention's National Healthcare Safety Network for central line-associated bloodstream infections (CLABSIs), ventilator-associated pneumonias, and catheter-associated urinary tract infections. We used a time-series design to evaluate changes in HAI rates.A total of 173 US hospitals provided data from NICUs, and 64 provided data from PICUs. From 2007 to 2012, rates of CLABSIs decreased in NICUs from 4.9 to 1.5 per 1000 central-line days (incidence rate ratio (IRR) per quarter = 0.96, 95% confidence interval 0.94-0.97) and in PICUs from 4.7 to 1.0 per 1000 central-line days (IRR per quarter = 0.96 [0.94-0.98]). Rates of ventilator-associated pneumonias decreased in NICUs from 1.6 to 0.6 per 1000 ventilator days (IRR per quarter = 0.97 [0.93-0.99]) and PICUs from 1.9 to 0.7 per 1000 ventilator-days (IRR per quarter = 0.95 [0.92-0.98]). Rates of catheter-associated urinary tract infections did not change significantly in PICUs.Between 2007 and 2012 there were substantial reductions in HAIs among hospitalized neonates and children.

    View details for DOI 10.1542/peds.2014-0613

    View details for Web of Science ID 000343140500053

    View details for PubMedID 25201802

  • The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety VACCINE McNeil, M. M., Gee, J., Weintraub, E. S., Belongia, E. A., Lee, G. M., Glanz, J. M., Nordin, J. D., Klein, N. P., Baxter, R., Naleway, A. L., Jackson, L. A., Omer, S. B., Jacobsen, S. J., DeStefano, F. 2014; 32 (42): 5390-5398

    Abstract

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

    View details for DOI 10.1016/j.vaccine.2014.07.073

    View details for Web of Science ID 000343346200005

    View details for PubMedID 25108215

  • Monovalent H1N1 influenza vaccine safety in pregnant women, risks for acute adverse events VACCINE Nordin, J. D., Kharbanda, E. O., Vazquez-Benitez, G., Lipkind, H., Lee, G. M., Naleway, A. L. 2014; 32 (39): 4985-4992

    Abstract

    To assess risks for acute adverse events and pregnancy complications in pregnant women following monovalent 2009 H1N1 inactivated influenza (MIV) vaccination.Within the Vaccine Safety Datalink, we compared rates of pre-specified medically attended events (MAE) occurring within 42 days of MIV vaccination to those occurring in matched cohorts that at the same gestational age were either unvaccinated or received seasonal trivalent inactivated influenza (TIV) vaccine. Using generalized estimating equation method, with a Poisson distribution and log link, we calculated adjusted incident rate ratios (AIRR).Among 9349 women receiving MIV in any trimester, only one MAE occurred 0-3 days following MIV, an allergic reaction. No cases of Guillain-Barré syndrome, Bell's palsy, or transverse myelitis occurred 1-42 days after MIV. Compared to women receiving TIV and to unvaccinated women, risks for acute MAEs were not increased following MIV for any outcome. Hyperemesis was the most common adverse event in the MIV, TIV, and unvaccinated groups, occurring at a rate of about 4% over a 42-day period in all groups. Over a 42-day window, among all groups, incident gestational diabetes occurred at a rate of 3% and thrombocytopenia occurred at a rate of approximately 0.3%. Among women receiving MIV during pregnancy, increased risks for these and other less common obstetric events were not detected.In this large cohort of pregnant women no acute safety signals were identified within 6 weeks of receipt of MIV.

    View details for DOI 10.1016/j.vaccine.2014.07.017

    View details for Web of Science ID 000341559300015

    View details for PubMedID 25045808

  • Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals: 2014 Update INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Klompas, M., Branson, R., Eichenwald, E. C., Greene, L. R., Howell, M. D., Lee, G., Magill, S. S., Maragakis, L. L., Priebe, G. P., Speck, K., Yokoe, D. S., Berenholtz, S. M. 2014; 35: 915-936

    View details for DOI 10.1086/677144

    View details for Web of Science ID 000341014500012

  • Strategies to prevent ventilator-associated pneumonia in acute care hospitals: 2014 update. Infection control and hospital epidemiology Klompas, M., Branson, R., Eichenwald, E. C., Greene, L. R., Howell, M. D., Lee, G., Magill, S. S., Maragakis, L. L., Priebe, G. P., Speck, K., Yokoe, D. S., Berenholtz, S. M. 2014; 35: S133-54

    View details for PubMedID 25376073

  • Strategies to Prevent Ventilator-Associated Pneumonia in Acute Care Hospitals: 2014 Update INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Klompas, M., Branson, R., Eichenwald, E. C., Greene, L. R., Howell, M. D., Lee, G., Magill, S. S., Maragakis, L. L., Priebe, G. P., Speck, K., Yokoe, D. S., Berenholtz, S. M. 2014; 35 (8): 915-936

    View details for DOI 10.1086/677144

    View details for Web of Science ID 000339046900001

    View details for PubMedID 25026607

  • Timely Versus Delayed Early Childhood Vaccination and Seizures PEDIATRICS Hambidge, S. J., Newcomer, S. R., Narwaney, K. J., Glanz, J. M., Daley, M. F., Xu, S., Shoup, A., Rowhani-Rahbar, A., Klein, N. P., Lee, G. M., Nelson, J. C., Lugg, M., Naleway, A. L., Nordin, J. D., Weintraub, E., DeStefano, F. 2014; 133 (6): E1492-E1499

    Abstract

    Little is known regarding the timing of childhood vaccination and postvaccination seizures.In a cohort of 323 247 US children from the Vaccine Safety Datalink born from 2004 to 2008, we analyzed the association between the timing of childhood vaccination and the first occurrence of seizure with a self-controlled case series analysis of the first doses of individual vaccines received in the first 2 years of life.In infants, there was no association between the timing of infant vaccination and postvaccination seizures. In the second year of life, the incident rate ratio (IRR) for seizures after receipt of the first measles-mumps-rubella vaccine (MMR) dose at 12 to 15 months was 2.65 (95% confidence interval [CI] 1.99-3.55); the IRR after an MMR dose at 16 to 23 months was 6.53 (95% CI 3.15-13.53). The IRR for seizures after receipt of the first measles-mumps-rubella-varicella vaccine (MMRV) dose at 12 to 15 months was 4.95 (95% CI 3.68-6.66); the IRR after an MMRV dose at 16 to 23 months was 9.80 (95% CI 4.35 -22.06).There is no increased risk of postvaccination seizure in infants regardless of timing of vaccination. In year 2, delaying MMR vaccine past 15 months of age results in a higher risk of seizures. The strength of the association is doubled with MMRV vaccine. These findings suggest that on-time vaccination is as safe with regard to seizures as delayed vaccination in the first year of life, and that delayed vaccination in the second year of life is associated with more postvaccination seizures than on-time vaccination.

    View details for DOI 10.1542/peds.2013-3429

    View details for Web of Science ID 000337172600002

    View details for PubMedID 24843064

  • Absence of associations between influenza vaccines and increased risks of seizures, Guillain-Barre syndrome, encephalitis, or anaphylaxis in the 2012-2013 season PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Kawai, A. T., Li, L., Kulldorff, M., Vellozzi, C., Weintraub, E., Baxter, R., Belongia, E. A., Daley, M. F., Jacobsen, S. J., Naleway, A., Nordin, J. D., Lee, G. M. 2014; 23 (5): 548-553

    Abstract

    We conducted weekly surveillance for pre-specified adverse events following receipt of the 2012-2013 influenza vaccines in the Vaccine Safety Datalink (VSD).For each outcome, risk intervals (i.e., period after vaccination with a potentially increased risk) were defined on the basis of biologic plausibility and prior literature. Seizures following inactivated influenza vaccine (IIV) were monitored in children in three age groups (6-23 months, 24-59 months, and 5-17 years) using a self-controlled risk interval design. We also monitored for Guillain-Barré syndrome, encephalitis, and anaphylaxis following IIV in patients ≥6 months of age using a cohort design with historical controls. In the risk intervals following live attenuated influenza vaccine (LAIV), we collected weekly counts of Guillain-Barré syndrome, encephalitis, and anaphylaxis in patients ages 2-49. Among LAIV vaccinees, numbers of expected events based on rates in historical controls were calculated, adjusted for age and site.At the end of surveillance, approximately 3.6 million first doses of IIV and 250 000 first doses of LAIV had been administered in the VSD. No elevated risks were identified in risk intervals following 2012-2013 IIV, as compared with a self-matched control interval or to historical controls. For each outcome, fewer than three events occurred in the risk interval following 2012-2013 LAIV, and we thus were unable to estimate measures of relative risks.No increased risk was identified for any of the pre-specified outcomes following 2012-2013 influenza vaccinations in the VSD. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

    View details for DOI 10.1002/pds.3575

    View details for Web of Science ID 000333948300012

    View details for PubMedID 24497128

  • Impact of 13-Valent Pneumococcal Conjugate Vaccination on Streptococcus pneumoniae Carriage in Young Children in Massachusetts. Journal of the Pediatric Infectious Diseases Society Lee, G. M., Kleinman, K., Pelton, S. I., Hanage, W., Huang, S. S., Lakoma, M., Dutta-Linn, M., Croucher, N. J., Stevenson, A., Finkelstein, J. A. 2014; 3 (1): 23-32

    Abstract

    In April 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 for use in the United States. We evaluated rates of pneumococcal colonization, by serotype and antibiotic resistance, in Massachusetts communities where serial cross-sectional surveillance has been conducted for the past decade.Nasopharyngeal swabs were obtained from children 0 to <7 years of age and seen by primary care providers for well child or acute illness visits in 2001, 2004, 2007, 2009, and 2011. Pneumococcal isolates were serotyped by Quellung reaction and classified as PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F), additional PCV13 serotypes (1, 3, 5, 6A, 7F, 19A), or non-PCV13 serotypes. Changes in colonization and impact of PCV13 were assessed using generalized linear mixed models, adjusting for known risk factors and accounting for clustering by community.Introduction of PCV13 did not affect the rate of overall pneumococcal colonization (31% in 2011). Colonization with non-PCV13 serotypes increased between 2001 and 2011 for all children (odds ratio [OR] per year, 1.12; 95% confidence interval [CI], 1.10, 1.15; P < .0001). 19A remained the second most common serotype in 2011, although a decline from 2009 was observed. Penicillin (7%), erythromycin (28%), ceftriaxone (10%), and clindamycin (10%) nonsusceptibility were commonly identified, concentrated among a small number of serotypes (including 19A, 35B, 15B/C, and 15A). Among healthy children 6-23 months old, colonization with PCV13 serotypes was lower among recipients of PCV13 vaccine (adjusted OR, 0.30; 95% CI, 0.11, 0.78). This effect was not observed in 6- to 23-month-old children with a concomitant respiratory tract infection (adjusted OR 1.36; 95% CI, 0.66, 2.77) or children 2 to <7 years old (adjusted OR, 1.17; 95% CI, 0.58, 2.34).13-Valent pneumococcal conjugate vaccine reduced the prevalence of colonization with PCV13 serotypes among children 6-23 months old, but its efficacy was not shown among older children.

    View details for DOI 10.1093/jpids/pit057

    View details for PubMedID 24567842

  • Intussusception risk after rotavirus vaccination in U.S. infants. New England journal of medicine Yih, W. K., Lieu, T. A., Kulldorff, M., Martin, D., McMahill-Walraven, C. N., Platt, R., Selvam, N., Selvan, M., Lee, G. M., Nguyen, M. 2014; 370 (6): 503-512

    Abstract

    International postlicensure studies have identified an increased risk of intussusception after vaccination with the second-generation rotavirus vaccines RotaTeq (RV5, a pentavalent vaccine) and Rotarix (RV1, a monovalent vaccine). We studied this association among infants in the United States.The study included data from infants 5.0 to 36.9 weeks of age who were enrolled in three U.S. health plans that participate in the Mini-Sentinel program sponsored by the Food and Drug Administration. Potential cases of intussusception and vaccine exposures from 2004 through mid-2011 were identified through procedural and diagnostic codes. Medical records were reviewed to confirm the occurrence of intussusception and the status with respect to rotavirus vaccination. The primary analysis used a self-controlled risk-interval design that included only vaccinated children. The secondary analysis used a cohort design that included exposed and unexposed person-time.The analyses included 507,874 first doses and 1,277,556 total doses of RV5 and 53,638 first doses and 103,098 total doses of RV1. The statistical power for the analysis of RV1 was lower than that for the analysis of RV5. The number of excess cases of intussusception per 100,000 recipients of the first dose of RV5 was significantly elevated, both in the primary analysis (attributable risk, 1.1 [95% confidence interval, 0.3 to 2.7] for the 7-day risk window and 1.5 [95% CI, 0.2 to 3.2] for the 21-day risk window) and in the secondary analysis (attributable risk, 1.2 [95% CI, 0.2 to 3.2] for the 21-day risk window). No significant increase in risk was seen after dose 2 or 3. The results with respect to the primary analysis of RV1 were not significant, but the secondary analysis showed a significant risk after dose 2.RV5 was associated with approximately 1.5 (95% CI, 0.2 to 3.2) excess cases of intussusception per 100,000 recipients of the first dose. The secondary analysis of RV1 suggested a potential risk, although the study of RV1 was underpowered. These risks must be considered in light of the demonstrated benefits of rotavirus vaccination. (Funded by the Food and Drug Administration.).

    View details for DOI 10.1056/NEJMoa1303164

    View details for PubMedID 24422676

  • Do community-level predictors of pneumococcal carriage continue to play a role in the conjugate vaccine era? EPIDEMIOLOGY AND INFECTION Hsu, K. K., Rifas-Shiman, S. L., Shea, K. M., Kleinman, K. P., Lee, G. M., Lakoma, M., Pelton, S. I., Finkelstein, J. A., Huang, S. S. 2014; 142 (2): 379-387

    Abstract

    This paper examined whether previously identified community-level factors (high proportion of crowded households and/or persons below the poverty level) remained associated with childhood pneumococcal carriage in the heptavalent pneumococcal conjugate vaccine (PCV7) era. Using logistic regression, individual factors were used to develop base models to which community-level factors were added to evaluate impact on pneumococcal carriage within two paediatric study cohorts from Massachusetts (urban Boston, outside Boston). Six years after introduction of universal childhood PCV7 vaccination, we found no consistent evidence that census tract characteristics (e.g. population size and density, age and race distribution, percent participating in group childcare, parental education, percent lacking in-unit plumbing, poverty, and community stability) affected odds of pneumococcal carriage when added to individual predictors (e.g. younger age, current respiratory tract infections, and attendance in group childcare). How community-level factors influence pneumococcal carriage continues to change in the era of increasing immunization coverage.

    View details for DOI 10.1017/S0950268813000794

    View details for Web of Science ID 000332524300018

    View details for PubMedID 23731707

    View details for PubMedCentralID PMC3849242

  • Impact of Medicare's Payment Policy on Mediastinitis Following Coronary Artery Bypass Graft Surgery in US Hospitals INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Calderwood, M. S., Kleinman, K., Soumerai, S. B., Jin, R., Gay, C., Platt, R., Kassler, W., Goldmann, D. A., Jha, A. K., Lee, G. M. 2014; 35 (2): 144-151

    Abstract

    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.

    View details for DOI 10.1086/674861

    View details for Web of Science ID 000329873000006

    View details for PubMedID 24442076

  • Post-licensure rapid immunization safety monitoring program (PRISM) data characterization VACCINE Baker, M. A., Michael Nguyen, M., Cole, D. V., Lee, G. M., Lieu, T. A. 2013; 31: K98-K112

    Abstract

    The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program is the immunization safety monitoring component of FDA's Mini-Sentinel project, a program to actively monitor the safety of medical products using electronic health information. FDA sought to assess the surveillance capabilities of this large claims-based distributed database for vaccine safety surveillance by characterizing the underlying data.We characterized data available on vaccine exposures in PRISM, estimated how much additional data was gained by matching with select state and local immunization registries, and compared vaccination coverage estimates based on PRISM data with other available data sources. We generated rates of computerized codes representing potential health outcomes relevant to vaccine safety monitoring. Standardized algorithms including ICD-9 codes, number of codes required, exclusion criteria and location of the encounter were used to obtain the background rates.The majority of the vaccines routinely administered to infants, children, adolescents and adults were well captured by claims data. Immunization registry data in up to seven states comprised between 5% and 9% of data for all vaccine categories with the exception of 10% for hepatitis B and 3% and 4% for rotavirus and zoster respectively. Vaccination coverage estimates based on PRISM's computerized data were similar to but lower than coverage estimates from the National Immunization Survey and Healthcare Effectiveness Data and Information Set. For the 25 health outcomes of interest studied, the rates of potential outcomes based on ICD-9 codes were generally higher than rates described in the literature, which are typically clinically confirmed cases.PRISM program's data on vaccine exposures and health outcomes appear complete enough to support robust safety monitoring.

    View details for DOI 10.1016/j.vaccine.2013.04.088

    View details for Web of Science ID 000329684600012

    View details for PubMedID 24331080

  • Initial Antibiotic Choice in the Treatment of Group A Streptococcal Pharyngitis and Return Visit Rates. Journal of the Pediatric Infectious Diseases Society Gidengil, C. A., Kruskal, B. A., Lee, G. M. 2013; 2 (4): 361-367

    Abstract

    Our objectives were to describe the incidence of return visits for children with Group A Streptococcal (GAS) pharyngitis (ie, clinical treatment failure) and to assess whether initial treatment with amoxicillin or penicillin was associated with the rate of retreatment for GAS pharyngitis.This analysis was a retrospective cohort study of 5533 children 0-17 years from a multisite practice. Eligible visits (n = 6585) were associated with a positive test for GAS, receipt of antibiotics within 7 days, no allergies to penicillins or cephalosporins, and no codiagnoses requiring antibiotic treatment. Retreatment for GAS pharyngitis was defined as an index visit followed by another visit within 1-4 weeks. Five hundred episodes (250 treatment failures and 250 controls) were randomly selected for chart review to validate cases.Amoxicillin or penicillin was the initial antibiotic treatment at 76.1% of visits, and retreatment for GAS pharyngitis occurred after 5.8% of initial visits. Children initially prescribed amoxicillin or penicillin had higher odds of retreatment of GAS pharyngitis even after adjusting for age, sex, symptoms, and community-level covariates such as race, income, and education (odds ratio, 1.51; 95% confidence interval, 1.07-2.13).Retreatment for GAS pharyngitis was uncommon and associated with receipt of amoxicillin or penicillin, although the impact of GAS carriage is unknown. Recommendations for initial treatment of GAS pharyngitis should reflect both individual and societal considerations, including the potential impact on antibiotic resistance in the community.

    View details for DOI 10.1093/jpids/pit043

    View details for PubMedID 26619498

  • Association Between Undervaccination With Diphtheria, Tetanus Toxoids, and Acellular Pertussis (DTaP) Vaccine and Risk of Pertussis Infection in Children 3 to 36 Months of Age JAMA PEDIATRICS Glanz, J. M., Narwaney, K. J., Newcomer, S. R., Daley, M. F., Hambidge, S. J., Rowhani-Rahbar, A., Lee, G. M., Nelson, J. C., Naleway, A. L., Nordin, J. D., Lugg, M. M., Weintraub, E. S. 2013; 167 (11): 1060-1064

    Abstract

    Undervaccination is an increasing trend that potentially places children and their communities at an increased risk for serious infectious diseases.To examine the association between undervaccination and pertussis in children 3 to 36 months of age.Matched case-control study with conditional logistic regression analysis.Eight managed care organizations of the Vaccine Safety Datalink between 2004 and 2010.Each laboratory-confirmed case of pertussis (72 patients) was matched to 4 randomly selected controls (for a total of 288 controls). The case patients were matched to controls by managed care organization site, sex, and age at the index date. The index date was defined as the date of pertussis diagnosis for the case patients.Undervaccination for the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine. Undervaccination was defined as the number of doses of DTaP vaccine that was either missing or delayed by the index date. Case patients and controls could be undervaccinated by 0, 1, 2, 3, or 4 doses of DTaP vaccine. Children undervaccinated by 0 doses were considered age-appropriately vaccinated by the index date.Pertussis.Of the 72 case patients with pertussis, 12 (16.67%) were hospitalized, and 34 (47.22%) were undervaccinated for DTaP vaccine by the date of pertussis diagnosis. Of the 288 matched controls, 64 (22.22%) were undervaccinated for DTaP vaccine. Undervaccination was strongly associated with pertussis. Children undervaccinated for 3 or 4 doses of DTaP vaccine were 18.56 (95% CI, 4.92-69.95) and 28.38 (95% CI, 3.19-252.63) times more likely, respectively, to have received a diagnosis of pertussis than children who were age-appropriately vaccinated.Undervaccination with DTaP vaccine increases the risk of pertussis among children 3 to 36 months of age.

    View details for DOI 10.1001/jamapediatrics.2013.2353

    View details for Web of Science ID 000329842300019

    View details for PubMedID 24019039

  • International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines VACCINE Dodd, C. N., Romio, S. A., Black, S., Vellozzi, C., Andrews, N., Sturkenboom, M., Zuber, P., Hua, W., Bonhoeffer, J., Buttery, J., Crawford, N., Deceuninck, G., de Vries, C., De Wals, P., Gutierrez-Gimeno, M. V., Heijbel, H., Hughes, H., Hur, K., Hviid, A., Kelman, J., Kilpi, T., Chuang, S. K., Macartney, K., Rett, M., Lopez-Callada, V. R., Salmon, D., Sanchez, F. G., Sanz, N., Silverman, B., Storsaeter, J., Thirugnanam, U., van der Maas, N., Yih, K., Zhang, T., Izurieta, H. 2013; 31 (40): 4448-4458

    Abstract

    The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which has been an influenza vaccine safety concern since the swine flu pandemic of 1976, using a common protocol among high and middle-income countries. The primary objective of this project was to demonstrate the feasibility and utility of global collaboration in the assessment of vaccine safety, including countries both with and without an established infrastructure for vaccine active safety surveillance. A second objective, included a priori, was to assess the risk of GBS following pH1N1 vaccination.The primary analysis used the self-controlled case series (SCCS) design to estimate the relative incidence (RI) of GBS in the 42 days following vaccination with pH1N1 vaccine in a pooled analysis across databases and in analysis using a meta-analytic approach.We found a relative incidence of GBS of 2.42 (95% CI 1.58-3.72) in the 42 days following exposure to pH1N1 vaccine in analysis of pooled data and 2.09 (95% CI 1.28-3.42) using the meta-analytic approach.This study demonstrates that international collaboration to evaluate serious outcomes using a common protocol is feasible. The significance and consistency of our findings support a conclusion of an association between 2009 H1N1 vaccination and GBS. Given the rarity of the event the relative incidence found does not provide evidence in contradiction to international recommendations for the continued use of influenza vaccines.

    View details for DOI 10.1016/j.vaccine.2013.06.032

    View details for Web of Science ID 000324510500027

    View details for PubMedID 23770307

  • Health and Economic Burden of Post-Partum Staphylococcus aureus Breast Abscess PLOS ONE Branch-Elliman, W., Lee, G. M., Golen, T. H., Gold, H. S., Baldini, L. M., Wright, S. B. 2013; 8 (9)

    Abstract

    To determine the health and economic burdens of post-partum Staphylococcus aureus breast abscess.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.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.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.

    View details for DOI 10.1371/journal.pone.0073155

    View details for Web of Science ID 000324481600055

    View details for PubMedID 24039877

    View details for PubMedCentralID PMC3764182

  • Inactivated Influenza Vaccine During Pregnancy and Risks for Adverse Obstetric Events OBSTETRICS AND GYNECOLOGY Kharbanda, E. O., Vazquez-Benitez, G., Lipkind, H., Naleway, A., Lee, G., Nordin, J. D. 2013; 122 (3): 659-667

    Abstract

    To compare risks for adverse obstetric events between females who did and did not receive trivalent inactivated influenza vaccine during pregnancy.This retrospective, observational cohort study was conducted at seven Vaccine Safety Datalink sites. Pregnancies were identified from administrative and claims data using a validated algorithm. Females vaccinated while pregnant from 2002 to 2009 were matched one-to-two with replacement to unvaccinated pregnant females. Using a generalized estimating equation method with a Poisson distribution and log link, we evaluated the association of trivalent inactivated influenza vaccine with 13 outcomes. Given our large sample size and multiple comparisons (19 contrasts), a cutoff for significance of P<.005 was selected a priori.Our cohort included 74,292 vaccinated females matched on age, site, and pregnancy start date with 144,597 unvaccinated females. We did not observe increased risks within 42 days of vaccination for hyperemesis, chronic hypertension, gestational hypertension, gestational diabetes, proteinuria, or urinary tract infection. Using a risk window from vaccination through pregnancy end, we did not observe increased risks after vaccination for proteinuria, urinary tract infection, gestational hypertension, preeclampsia or eclampsia, chorioamnionitis, puerperal infection, venous complications, pulmonary embolism, or peripartum cardiomyopathy. A reduced risk for gestational diabetes after vaccination was detected (adjusted hazard rate ratio 0.88, 95% confidence interval 0.83-0.93), likely as a result of healthy vaccine bias or earlier detection among vaccinees.In this large cohort, influenza vaccination during pregnancy was not associated with increased risks for medically attended adverse obstetric events.II.

    View details for DOI 10.1097/AOG.0b013e3182a1118a

    View details for Web of Science ID 000330444300023

    View details for PubMedID 23921876

  • Mortality Rates and Cause-of-Death Patterns in a Vaccinated Population AMERICAN JOURNAL OF PREVENTIVE MEDICINE McCarthy, N. L., Weintraub, E., Vellozzi, C., Duffy, J., Gee, J., Donahue, J. G., Jackson, M. L., Lee, G. M., Glanz, J., Baxter, R., Lugg, M. M., Naleway, A., Omer, S. B., Nakasato, C., Vazquez-Benitez, G., De Stefano, F. 2013; 45 (1): 91-97

    Abstract

    Determining the baseline mortality rate in a vaccinated population is necessary to be able to identify any unusual increases in deaths following vaccine administration. Background rates are particularly useful during mass immunization campaigns and in the evaluation of new vaccines.Provide background mortality rates and describe causes of death following vaccination in the Vaccine Safety Datalink (VSD).Analyses were conducted in 2012. Mortality rates were calculated at 0-1 day, 0-7 days, 0-30 days, and 0-60 days following vaccination for deaths occurring between January 1, 2005, and December 31, 2008. Analyses were stratified by age and gender. Causes of death were examined, and findings were compared to National Center for Health Statistics (NCHS) data.Among 13,033,274 vaccinated people, 15,455 deaths occurred between 0 and 60 days following vaccination. The mortality rate within 60 days of a vaccination visit was 442.5 deaths per 100,000 person-years. Rates were highest in the group aged ≥85 years, and increased from the 0-1-day to the 0-60-day interval following vaccination. Eleven of the 15 leading causes of death in the VSD and NCHS overlap in both systems, and the top four causes of death were the same in both systems.VSD mortality rates demonstrate a healthy vaccinee effect, with rates lowest in the days immediately following vaccination, most apparent in the older age groups. The VSD mortality rate is lower than that in the general U.S. population, and the causes of death are similar.

    View details for DOI 10.1016/j.amepre.2013.02.020

    View details for Web of Science ID 000320827500011

    View details for PubMedID 23790993

  • Guillain-Barre Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011 PLOS ONE Greene, S. K., Rett, M. D., Vellozzi, C., Li, L., Kulldorff, M., Marcy, S. M., Daley, M. F., Belongia, E. A., Baxter, R., Fireman, B. H., Jackson, M. L., Omer, S. B., Nordin, J. D., Jin, R., Weintraub, E. S., Vijayadeva, V., Lee, G. M. 2013; 8 (6)

    Abstract

    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.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.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.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.

    View details for DOI 10.1371/journal.pone.0067185

    View details for Web of Science ID 000321424400082

    View details for PubMedID 23840621

    View details for PubMedCentralID PMC3694016

  • Population genomics of post-vaccine changes in pneumococcal epidemiology NATURE GENETICS Croucher, N. J., Finkelstein, J. A., Pelton, S. I., Mitchell, P. K., Lee, G. M., Parkhill, J., Bentley, S. D., Hanage, W. P., Lipsitch, M. 2013; 45 (6): 656-?

    Abstract

    Whole-genome sequencing of 616 asymptomatically carried Streptococcus pneumoniae isolates was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates showed 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 before the introduction of the vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the decrease in pneumococcal disease rates after the vaccine's introduction.

    View details for DOI 10.1038/ng.2625

    View details for Web of Science ID 000319563900013

    View details for PubMedID 23644493

    View details for PubMedCentralID PMC3725542

  • Risk of adverse events following oseltamivir treatment in influenza outpatients, Vaccine Safety Datalink Project, 20072010 PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Greene, S. K., Li, L., Shay, D. K., Fry, A. M., Lee, G. M., Jacobsen, S. J., Baxter, R., Irving, S. A., Jackson, M. L., Naleway, A. L., Nordin, J. D., Narwaney, K. J., Lieu, T. A. 2013; 22 (4): 335-344

    Abstract

    An association between the influenza antiviral medication oseltamivir and neuropsychiatric events has been suggested by post-marketing case reports in Japan. This possible association was not supported by cohort studies in the U.S. conducted prior to the 2009 influenza A (H1N1) pandemic, when usage rates were comparatively low. We assessed oseltamivir safety before and during the pandemic using biologically plausible risk intervals, particularly focusing on psychiatric events.Outpatients with influenza episodes from January 2007 through June 2010 were identified using diagnosis codes and positive tests at eight health care systems (sites) in the Vaccine Safety Datalink Project. Oseltamivir-treated and untreated patients were matched according to calendar week, age, sex, site, and propensity for treatment. Within this matched cohort, conditional logistic regression models were used to estimate the risk of four neuropsychiatric and five other adverse events (AEs) during pre-specified risk intervals.Among 27,684 matched pairs, no associations were identified between oseltamivir treatment and any pre-defined AE. The absolute risks of incident psychiatric events in the 1-7 day risk interval were 0.126% for oseltamivir-treated and 0.105% for untreated patients (odds ratio = 1.21, 95% confidence interval [CI]: 0.74, 1.97; risk difference = 0.022%, 95% CI: -0.035%, 0.078%); the most common diagnosis was unspecified anxiety state. Results were similar for 1-14 and 1-2 day risk intervals and for pediatric/adolescent subgroups.Consistent with prior U.S. cohort studies, no evidence was identified for an increased risk of neuropsychiatric or other AEs following oseltamivir treatment. Safety should be prospectively monitored to inform antiviral medication usage recommendations.

    View details for DOI 10.1002/pds.3363

    View details for Web of Science ID 000317009200001

    View details for PubMedID 23129321

  • A Population-Based Cohort Study of Undervaccination in 8 Managed Care Organizations Across the United States JAMA PEDIATRICS Glanz, J. M., Newcomer, S. R., Narwaney, K. J., Hambidge, S. J., Daley, M. F., Wagner, N. M., McClure, D. L., Xu, S., Rowhani-Rahbar, A., Lee, G. M., Nelson, J. C., Donahue, J. G., Naleway, A. L., Nordin, J. D., Lugg, M. M., Weintraub, E. S. 2013; 167 (3): 274-281

    Abstract

    OBJECTIVES To examine patterns and trends of undervaccination in children aged 2 to 24 months and to compare health care utilization rates between undervaccinated and age-appropriately vaccinated children. DESIGN Retrospective matched cohort study. SETTING Eight managed care organizations of the Vaccine Safety Datalink. PARTICIPANTS Children born between 2004 and 2008. MAIN EXPOSURE Immunization records were used to calculate the average number of days undervaccinated. Two matched cohorts were created: 1 with children who were undervaccinated for any reason and 1 with children who were undervaccinated because of parental choice. For both cohorts, undervaccinated children were matched to age-appropriately vaccinated children by birth date, managed care organization, and sex. MAIN OUTCOME MEASURES Rates of undervaccination, specific patterns of undervaccination, and health care utilization rates. RESULTS Of 323 247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P < .001). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89- 0.90). In contrast, undervaccinated children had increased inpatient admission rates compared with age-appropriately vaccinated children (IRR, 1.21; 95% CI, 1.18-1.23). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR, 0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR, 0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children. CONCLUSIONS Undervaccination appears to be an increasing trend. Undervaccinated children appear to have different health care utilization patterns compared with age-appropriately vaccinated children.

    View details for DOI 10.1001/jamapediatrics.2013.502

    View details for Web of Science ID 000316799500010

    View details for PubMedID 23338829

  • Accuracy of Hospital Administrative Data in Reporting Central Line-Associated Bloodstream Infections in Newborns PEDIATRICS Patrick, S. W., Davis, M. M., Sedman, A. B., Meddings, J. A., Hieber, S., Lee, G. M., Stillwell, T. L., Chenoweth, C. E., Espinosa, C., Schumacher, R. E. 2013; 131: S75-S80

    Abstract

    Central line-associated bloodstream infections (CLABSIs) are a significant source of morbidity and mortality in the NICU. In 2010, Medicaid was mandated not to pay hospitals for treatment of CLABSI; however, the source of CLABSI data for this policy was not specified. Our objective was to evaluate the accuracy of hospital administrative data compared with CLABSI confirmed by an infection control service.We evaluated hospital administrative and infection control data for newborns admitted consecutively from January 1, 2008, to December 31, 2010. Clinical and demographic data were collected through chart review. We compared cases of CLABSI identified by administrative data (International Classification of Diseases, Ninth Revision, Clinical Modification 999.31) with infection control data that use national criteria from the Centers for Disease Control and Prevention as the gold standard. To ascertain the nature possible deficiencies in the administrative data, each patient's medical record was searched to determine if clinical phrases that commonly refer to CLABSI appeared.Of 2920 infants admitted to the NICU during our study period, 52 were identified as having a CLABSI: 42 by infection control data only, 7 through hospital administrative data only, and 3 appearing in both. Against the gold standard, hospital administrative data were 6.7% sensitive and 99.7% specific, with a positive predictive value of 30.0% and a negative predictive value of 98.6%. Only 48% of medical records indicated a CLABSI.Our findings from a major children's hospital NICU indicate that International Classification of Diseases, Ninth Revision, Clinical Modification code 993.31 is presently not accurate and cannot be used reliably to compare CLABSI rates in NICUs.

    View details for DOI 10.1542/peds.2012-1427i

    View details for Web of Science ID 000317269700008

    View details for PubMedID 23457153

  • Maternal Safety of Trivalent Inactivated Influenza Vaccine in Pregnant Women OBSTETRICS AND GYNECOLOGY Nordin, J. D., Kharbanda, E. O., Benitez, G. V., Nichol, K., Lipkind, H., Naleway, A., Lee, G. M., Hambidge, S., Shi, W., Olsen, A. 2013; 121 (3): 519-525

    Abstract

    To estimate the risks for medically attended events occurring within 42 days of receiving trivalent inactivated influenza vaccine and to evaluate specific risks of first-trimester vaccination.This retrospective observational cohort study compared rates of medically attended adverse events in trivalent inactivated influenza-vaccinated and unvaccinated pregnant women in the Vaccine Safety Datalink. Using a Poisson distribution and log link, we calculated maternal adjusted incident rate ratios for composite safety outcomes for the full cohort and the subset vaccinated during the first trimester.The cohort included 75,906 vaccinated (28.4% in the first trimester) and 147,992 unvaccinated women matched by age, site, and pregnancy start date. In the first 3 days after vaccination, trivalent inactivated influenza vaccine was not associated with increased risk of specified medically attended events, including allergic reactions, cellulitis, and seizures (full cohort adjusted incident rate ratio 1.12, 95% confidence interval [CI] 0.81-1.55; P=.48; first-trimester adjusted incident rate ratio .97, 95% CI 0.53-1.78; P=.93). In the first 42 days, no incident cases of Guillain-Barré syndrome, optic neuritis, transverse myelitis, or Bells palsy were identified. Trivalent inactivated influenza vaccine was not associated with thrombocytopenia (full cohort adjusted incident rate ratio 0.90, 95% CI 0.68--1.19; P=.45; first-trimester adjusted incident rate ratio 0.56, 95% CI 0.22-1.39; P=.21) or an acute neurologic event (full cohort adjusted incident rate ratio 0.92, 95% CI 0.54-1.6; P=.75; first-trimester adjusted incident rate ratio 1.05, 95% CI 0.46-2.38; P=.91).Receipt of trivalent inactivated influenza vaccine during pregnancy was not associated with increased risk of adverse events in the 42 days after vaccination, supporting its safety for the mother.

    View details for DOI 10.1097/AOG.0b013e3182831b83

    View details for Web of Science ID 000316607600005

    View details for PubMedID 23635613

  • The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy PEDIATRIC TRANSPLANTATION Lo, M. S., Lee, G. M., Gunawardane, N., Burchett, S. K., Lachenauer, C. S., Lehmann, L. E. 2013; 17 (2): 133-143

    Abstract

    RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 1993-2006 for transplant recipients, and 2000-2005 for patients with cancer. RSV was the most common respiratory virus identified. There were 17 (10% of all patients) deaths overall, of which 12 were at least partly attributed to the presence of a RVI. In multivariate models, LRT symptoms in the absence of upper respiratory symptoms on presentation (OR 10.2 [2.3, 45.7], p = 0.002) and adenoviral infection (OR 3.7 [1.1, 12.6], p = 0.034) were significantly associated with poor outcome, defined as death or disability related to RVI. All of the deaths occurred in patients who had received either solid organ or HSCT. There were no infections resulting in death or disability in the cancer chemotherapy group.

    View details for DOI 10.1111/petr.12022

    View details for Web of Science ID 000315467000014

    View details for PubMedID 23228170

  • Nonpayment for Preventable Infections in U.S. Hospitals Reply NEW ENGLAND JOURNAL OF MEDICINE Lee, G. M., Soumerai, S. B., Jha, A. K. 2013; 368 (2): 191-192

    View details for Web of Science ID 000313238100026

    View details for PubMedID 23301746

  • Including catheter-associated urinary tract infections in the 2008 CMS payment policy: a qualitative analysis. Urologic nursing Palmer, J. A., Lee, G. M., Dutta-Linn, M. M., Wroe, P., Hartmann, C. W. 2013; 33 (1): 15-23

    Abstract

    The study presented in this article addresses the impact of the 2008 nonpayment policy of the Centers for Medicare and Medicaid Services (CMS) on catheter-associated urinary tract infections (CAUTIs) from the perspective of infection preventionists. With rich qualitative data, it sheds light on the day-to-day impact of this recent health policy on CAUTI prevention.

    View details for PubMedID 23556374

    View details for PubMedCentralID PMC3998716

  • Clinical practice guideline for the diagnosis and management of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Shulman, S. T., Bisno, A. L., Clegg, H. W., Gerber, M. A., Kaplan, E. L., Lee, G., Martin, J. M., Van Beneden, C. 2012; 55 (10): 1279-1282

    Abstract

    The guideline is intended for use by healthcare providers who care for adult and pediatric patients with group A streptococcal pharyngitis. The guideline updates the 2002 Infectious Diseases Society of America guideline and discusses diagnosis and management, and recommendations are provided regarding antibiotic choices and dosing. Penicillin or amoxicillin remain the treatments of choice, and recommendations are made for the penicillin-allergic patient, which now include clindamycin.

    View details for DOI 10.1093/cid/cis847

    View details for PubMedID 23091044

  • Success Of Program Linking Data Sources To Monitor H1N1 Vaccine Safety Points To Potential For Even Broader Safety Surveillance HEALTH AFFAIRS Salmon, D., Yih, W. K., Lee, G., Rosofsky, R., Brown, J., Vannice, K., Tokars, J., Roddy, J., Ball, R., Gellin, B., Lurie, N., Koh, H., Platt, R., Lieu, T. 2012; 31 (11): 2518-2527

    Abstract

    In response to the 2009 H1N1 pandemic and subsequent vaccination program, the Department of Health and Human Services and collaborators developed the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) Program as a demonstration project to detect rare adverse events rapidly. The program monitored three million people who had received the H1N1 vaccine by linking data from large private health plans and from public immunization registries that had originally not been designed to share data, and on a larger scale than had been previously attempted. The program generated safety data in two weeks rather than three to six monty 10ths-the standard time frame achievable using health plan data. PRISM substantially contributed to the understanding of the safety of H1N1 vaccines. Its use in the case of H1N1 highlights the necessity of proactive planning, scalable infrastructure, and public-private partnerships in tracking adverse events after vaccination in epidemics. It also illustrates how data could be integrated to produce policy-relevant information for other medical products.

    View details for DOI 10.1377/hlthaff.2012.0104

    View details for Web of Science ID 000311026900020

    View details for PubMedID 23129683

  • Effect of Nonpayment for Preventable Infections in US Hospitals NEW ENGLAND JOURNAL OF MEDICINE Lee, G. M., Kleinman, K., Soumerai, S. B., Tse, A., Cole, D., Fridkin, S. K., Horan, T., Platt, R., Gay, C., Kassler, W., Goldmann, D. A., Jernigan, J., Jha, A. K. 2012; 367 (15): 1428-1437

    Abstract

    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.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.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.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. (Funded by the Agency for Healthcare Research and Quality.).

    View details for DOI 10.1056/NEJMsa1202419

    View details for Web of Science ID 000309652700009

    View details for PubMedID 23050526

  • Trends in Antibiotic Use in Massachusetts Children, 2000-2009 PEDIATRICS Greene, S. K., Kleinman, K. P., Lakoma, M. D., Rifas-Shiman, S. L., Lee, G. M., Huang, S. S., Finkelstein, J. A. 2012; 130 (1): 15-22

    Abstract

    Antibiotic use rates have declined dramatically since the 1990s. We aimed to determine if, when, and at what level the decline in antibiotic-dispensing rates ended and which diagnoses contributed to the trends.Antibiotic dispensings and diagnoses were obtained from 2 health insurers for 3- to <72-month-olds in 16 Massachusetts communities from 2000 to 2009. Population-based antibiotic-dispensing rates per person-year (p-y) were determined according to year (September-August) for 3 age groups. Fit statistics were used to identify the most likely year for a change in trend. Rates for the first and last years were compared according to antibiotic category and associated diagnosis.From 2000-2001 to 2008-2009, the antibiotic-dispensing rate for 3- to <24-month-olds decreased 24% (2.3-1.8 antibiotic dispensings per p-y); for 24- to <48-month-olds, it decreased 18% (1.6-1.3 antibiotic dispensings per p-y); and for 48- to <72-month-olds, it decreased 20% (1.4-1.1 antibiotic dispensings per p-y). For 3- to <48-month-olds, rates declined until 2004-2005 and remained stable thereafter; the downward trend for 48- to <72-month-olds ended earlier in 2001-2002. Among 3- to <24-month-olds, first-line penicillin use declined 26%. For otitis media, the dispensing rate decreased 14% and the diagnosis rate declined 9%, whereas the treatment fraction was stable at 63%.The downward trend in antibiotic dispensings to young children in these communities ended by 2004-2005. This trend was driven by a declining otitis media diagnosis rate. Continued monitoring of population-based dispensing rates will support efforts to avoid returning to previous levels of antibiotic overuse.

    View details for DOI 10.1542/peds.2011-3137

    View details for Web of Science ID 000305905900038

    View details for PubMedID 22732172

    View details for PubMedCentralID PMC3382917

  • Risk of Confirmed Guillain-Barre Syndrome Following Receipt of Monovalent Inactivated Influenza A (H1N1) and Seasonal Influenza Vaccines in the Vaccine Safety Datalink Project, 2009-2010 AMERICAN JOURNAL OF EPIDEMIOLOGY Greene, S. K., Rett, M., Weintraub, E. S., Li, L., Yin, R., Amato, A. A., Ho, D. T., Sheikh, S. I., Fireman, B. H., Daley, M. F., Belongia, E. A., Jacobsen, S. J., Baxter, R., Lieu, T. A., Kulldorff, M., Vellozzi, C., Lee, G. M. 2012; 175 (11): 1100-1109

    Abstract

    An increased risk of Guillain-Barré syndrome (GBS) following administration of the 1976 swine influenza vaccine led to a heightened focus on GBS when monovalent vaccines against a novel influenza A (H1N1) virus of swine origin were introduced in 2009. GBS cases following receipt of monovalent inactivated (MIV) and seasonal trivalent inactivated (TIV) influenza vaccines in the Vaccine Safety Datalink Project in 2009-2010 were identified in electronic data and confirmed by medical record review. Within 1-42 days following vaccination, 9 cases were confirmed in MIV recipients (1.48 million doses), and 8 cases were confirmed in TIV-only recipients who did not also receive MIV during 2009-2010 (1.72 million doses). Five cases following MIV and 1 case following TIV-only had an antecedent respiratory infection, a known GBS risk factor; furthermore, unlike TIV, MIV administration was concurrent with heightened influenza activity. In a self-controlled risk interval analysis comparing GBS onset within 1-42 days following MIV with GBS onset 43-127 days following MIV, the risk difference was 5.0 cases per million doses (95% confidence interval: 0.5, 9.5). No statistically significant increased GBS risk was found within 1-42 days following TIV-only vaccination versus 43-84 days following vaccination (risk difference = 1.1 cases per million doses, 95% confidence interval: -3.1, 5.4). Further evaluation to assess GBS risk following both vaccination and respiratory infection is warranted.

    View details for DOI 10.1093/aje/kws195

    View details for Web of Science ID 000305082300002

    View details for PubMedID 22582210

  • Surveillance for Adverse Events Following Receipt of Pandemic 2009 H1N1 Vaccine in the Post-Licensure Rapid Immunization Safety Monitoring (PRISM) System, 2009-2010 AMERICAN JOURNAL OF EPIDEMIOLOGY Yih, W. K., Lee, G. M., Lieu, T. A., Ball, R., Kulldorff, M., Rett, M., Wahl, P. M., McMahill-Walraven, C. N., Platt, R., Salmon, D. A. 2012; 175 (11): 1120-1128

    Abstract

    The Post-Licensure Rapid Immunization Safety Monitoring (PRISM) system is a cohort-based active surveillance network initiated by the US Department of Health and Human Services to supplement preexisting and other vaccine safety monitoring systems in tracking the safety of monovalent pandemic 2009 H1N1 influenza vaccine in the United States during 2009-2010. PRISM investigators conducted retrospective analysis to determine whether 2009 H1N1 vaccination was associated with increased risk of any of 14 prespecified outcomes. Five health insurance and associated companies with 38 million members and 9 state/city immunization registries contributed records on more than 2.6 million doses of 2009 H1N1 vaccine. Data on outcomes came from insurance claims. Complementary designs (self-controlled risk interval, case-centered, and current-vs.-historical comparison) were used to optimize control for confounding and statistical power. The self-controlled risk interval analysis of chart-confirmed Guillain-Barré syndrome found an elevated but not statistically significant incidence rate ratio following receipt of inactivated 2009 H1N1 vaccine (incidence rate ratio = 2.50, 95% confidence interval: 0.42, 15.0) and no cases following live attenuated 2009 H1N1 vaccine. The study did not control for infection prior to Guillain-Barré syndrome, which may have been a confounder. The risks of other health outcomes of interest were generally not significantly elevated after 2009 H1N1 vaccination.

    View details for DOI 10.1093/aje/kws197

    View details for Web of Science ID 000305082300004

    View details for PubMedID 22582207

  • Perceived impact of the Medicare policy to adjust payment for health care-associated infections AMERICAN JOURNAL OF INFECTION CONTROL Lee, G. M., Hartmann, C. W., Graham, D., Kassler, W., Linn, M. D., Krein, S., Saint, S., Goldmann, D. A., Fridkin, S., Horan, T., Jernigan, J., Jha, A. 2012; 40 (4): 314-319

    Abstract

    In 2008, the Centers for Medicare and Medicaid Services (CMS) ceased additional payment for hospitalizations resulting in complications deemed preventable, including several health care-associated infections. We sought to understand the impact of the CMS payment policy on infection prevention efforts.A national survey of infection preventionists from a random sample of US hospitals was conducted in December 2010.Eighty-one percent reported increased attention to HAIs targeted by the CMS policy, whereas one-third reported spending less time on nontargeted HAIs. Only 15% reported increased funding for infection control as a result of the CMS policy, whereas most reported stable (77%) funding. Respondents reported faster removal of urinary (71%) and central venous (50%) catheters as a result of the CMS policy, whereas routine urine and blood cultures on admission occurred infrequently (27% and 13%, respectively). Resource shifting (ie, less time spent on nontargeted HAIs) occurred more commonly in large hospitals (odds ratio, 2.3; 95% confidence interval: 1.0-5.1; P = .038) but less often in hospitals where front-line staff were receptive to changes in clinical processes (odds ratio, 0.5; 95% confidence interval: 0.3-0.8; P = .005).Infection preventionists reported greater hospital attention to preventing targeted HAIs as a result of the CMS nonpayment policy. Whether the increased focus and greater engagement in HAI prevention practices has led to better patient outcomes is unclear.

    View details for DOI 10.1016/j.ajic.2011.11.003

    View details for Web of Science ID 000303418400008

    View details for PubMedID 22541855

    View details for PubMedCentralID PMC3998719

  • Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011 VACCINE Tse, A., Tseng, H. F., Greene, S. K., Vellozzi, C., Lee, G. M. 2012; 30 (11): 2024-2031

    Abstract

    In fall 2010 in the southern hemisphere, an increased risk of febrile seizures was noted in young children in Australia in the 24 h after receipt of trivalent inactivated influenza vaccine (TIV) manufactured by CSL Biotherapies. Although the CSL TIV vaccine was not recommended for use in young children in the US, during the 2010-2011 influenza season near real-time surveillance was conducted for febrile seizures in the 0-1 days following first dose TIV in a cohort of 206,174 vaccinated children ages 6 through 59 months in the Vaccine Safety Datalink Project. On a weekly basis, surveillance was conducted with the primary approach of a self-controlled risk interval design and the secondary approach of a current vs. historical vaccinee design. Sequential statistical methods were employed to account for repeated analyses of accumulating data. Signals for seizures based on computerized data were identified in mid November 2010 using a current vs. historical design and in late December 2010 using a self-controlled risk interval design. Further signal evaluation was conducted with chart-confirmed febrile seizure cases using only data from the primary approach (i.e. self-controlled risk interval design). The magnitude of the incidence rate ratio and risk difference comparing risk of seizures in the 0-1 days vs. 14-20 days following TIV differed by receipt of concomitant 13-valent pneumococcal conjugate vaccine (PCV13). Among children 6-59 months of age, the incidence rate ratio (IRR) for TIV adjusted for concomitant PCV13 was 2.4 (95% CI 1.2, 4.7) while the IRR for PCV13 adjusted for concomitant TIV was 2.5 (95% CI 1.3, 4.7). The IRR for concomitant TIV and PCV13 was 5.9 (95% CI 3.1, 11.3). Risk difference estimates varied by age due to the varying baseline risk for seizures in young children, with the highest estimates occurring at 16 months (12.5 per 100,000 doses for TIV without concomitant PCV13, 13.7 per 100,000 doses for PCV13 without concomitant TIV, and 44.9 per 100,000 doses for concomitant TIV and PCV13) and the lowest estimates occurring at 59 months (1.1 per 100,000 doses for TIV without concomitant PCV13, 1.2 per 100,000 doses for PCV13 without concomitant TIV, and 4.0 per 100,000 doses for concomitant TIV and PCV13). Incidence rate ratio and risk difference estimates were lower for children receiving TIV without concomitant PCV13 or PCV13 without concomitant TIV. Because of the importance of preventing influenza and pneumococcal infections and associated complications, our findings should be placed in a benefit-risk framework to ensure that population health benefits are maximized.

    View details for DOI 10.1016/j.vaccine.2012.01.027

    View details for Web of Science ID 000302662800016

    View details for PubMedID 22361304

  • Pneumococcal Carriage and Antibiotic Resistance in Young Children Before 13-valent Conjugate Vaccine PEDIATRIC INFECTIOUS DISEASE JOURNAL Wroe, P. C., Lee, G. M., Finkelstein, J. A., Pelton, S. I., Hanage, W. P., Lipsitch, M., Stevenson, A. E., Rifas-Shiman, S. L., Kleinman, K., Dutta-Linn, M. M., Hinrichsen, V. L., Lakoma, M., Huang, S. S. 2012; 31 (3): 249-254

    Abstract

    We sought to measure trends in Streptococcus pneumoniae carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent 7-valent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent PCV (PCV13).We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children aged <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008-2009 and compared with similar studies performed in 2001, 2003-2004, and 2006-2007. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006-2007 and 2008-2009) were evaluated.We collected nasopharyngeal specimens from 1011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008-2009, newly targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin-nonsusceptible S. pneumoniae. In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with penicillin-nonsusceptible S. pneumoniae carriage.Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted.

    View details for DOI 10.1097/INF.0b013e31824214ac

    View details for Web of Science ID 000300706700010

    View details for PubMedID 22173142

    View details for PubMedCentralID PMC3288953

  • The Medicare Policy of Payment Adjustment for Health Care-Associated Infections: Perspectives on Potential Unintended Consequences MEDICAL CARE RESEARCH AND REVIEW Hartmann, C. W., Hoff, T., Palmer, J. A., Wroe, P., Dutta-Linn, M. M., Lee, G. 2012; 69 (1): 45-61

    Abstract

    In 2008, the Centers for Medicare & Medicaid Services introduced a new policy to adjust payment to hospitals for health care-associated infections (HAIs) not present on admission. Interviews with 36 hospital infection preventionists across the United States explored the perspectives of these key stakeholders on the potential unintended consequences of the current policy. Responses were analyzed using an iterative coding process where themes were developed from the data. Participants' descriptions of unintended impacts of the policy centered around three themes. Results suggest the policy has focused more attention on targeted HAIs and has affected hospital staff; relatively fewer systems changes have ensued. Some consequences of the policy, such as infection preventionists having less time to devote to HAIs other than those in the policy or having less time to implement prevention activities, may have undesirable effects on HAI rates if hospitals do not recognize and react to potential time and resource gaps.

    View details for DOI 10.1177/1077558711413606

    View details for Web of Science ID 000300442500002

    View details for PubMedID 21810797

    View details for PubMedCentralID PMC3998710

  • Guillain-Barre Syndrome Incidence in a Large United States Cohort (2000-2009) NEUROEPIDEMIOLOGY Shui, I. M., Rett, M. D., Weintraub, E., Marcy, M., Amato, A. A., Sheikh, S. I., Ho, D., Lee, G. M., Yih, W. K. 2012; 39 (2): 109-115

    Abstract

    We describe the incidence of Guillain-Barré syndrome (GBS) in a large United States cohort.Between 2000 and 2009, we identified visits with an ICD-9 code for GBS (357.0) from all persons with continuous enrollment for at least 1 year. The primary case definition was restricted to emergency department and inpatient visits. We calculated age-standardized rates and used multivariate Poisson regression to assess variation in rates by sex, age, season and year of diagnosis. We tabulated descriptive characteristics and the positive predictive value (PPV) for a subset of the visits with available medical record review.1,619 visits with the GBS ICD-9 code were identified from 50,290,898 person-years of observation. After considering the PPV (55%) for record-reviewed visits, the age-standardized incidence rate was approximately 1.72/100,000 person-years. The rate was 40% higher for males and increased by 50% for every 10-year increase in age. The rate was 15% higher in winter and spring compared with summer. Rates were higher in more recent years.GBS rates are higher in males and increase considerably with age. The potential reasons for differences in rates by season and the increased rates in more recent years should be further investigated.

    View details for DOI 10.1159/000339248

    View details for Web of Science ID 000308731000006

    View details for PubMedID 22846726

  • Financing and systems barriers to seasonal influenza vaccine delivery in community settings VACCINE Penfold, R. B., Rusinak, D., Lieu, T. A., Shefer, A., Messonnier, M., Lee, G. M. 2011; 29 (52): 9632-9639

    Abstract

    Recommendations for annual seasonal influenza vaccination have expanded to now include >300 million children and adults each year. Community settings have become increasingly important venues for influenza vaccination. We sought to identify barriers to and solutions for expanding influenza vaccination in community settings.Semi-structured telephone interviews were conducted from 01/09 to 06/10 with a range of stakeholders involved in influenza vaccination, including health plans, medical services firms, retail based clinics, pharmacies, schools, and state and local public health immunization programs. Participants (n=65) were asked about barriers and feasible solutions to influenza vaccine delivery to children and adults in community settings. Key themes were identified through iterative coding using a grounded theory approach.Stakeholders identified specific financial barriers to influenza vaccine delivery in 3 major areas: purchase and distribution, delivery, and reimbursement. Limited purchasing power, the uncertain nature of public demand, and unpredictable timing of influenza vaccine supply were important barriers to enhance delivery in community settings. Barriers to delivery included complexities in running off-site clinics, especially in school settings, the need to manage publicly vs. privately purchased vaccines separately, and state-to-state variability in requirements for credentialing, physician oversight, and reporting. Reimbursement barriers included a protracted credentialing process, the need to determine insurance eligibility at point-of-service, and lack of a billing infrastructure in off-site clinics. Opportunities to mitigate financial barriers to influenza vaccine delivery in community settings focused on coordination across providers and the role of public health as a "trusted broker" to overcome existing challenges.Financial and systems barriers hamper the optimal use of community settings to effectively deliver influenza vaccines. Public health partners at the federal, state, and local levels are well-positioned to facilitate the engagement of all stakeholders in this important and complex vaccine delivery system.

    View details for DOI 10.1016/j.vaccine.2011.10.041

    View details for Web of Science ID 000298623000014

    View details for PubMedID 22036886

  • Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to 13 valent conjugate vaccination VACCINE Hanage, W. P., Bishop, C. J., Lee, G. M., Lipsitch, M., Stevenson, A., Rifas-Shiman, S. L., Pelton, S. I., Huang, S. S., Finkelstein, J. A. 2011; 29 (48): 8877-8881

    Abstract

    As part of an ongoing study of the response of the Streptococcus pneumoniae population to conjugate vaccination, we applied multi-locus sequence typing (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts children. We found 94 distinct sequence types (STs), including 19 that had not been previously recorded, and a xpt allele containing a large insertion. Comparison with a similar sample collected in 2007 revealed no significant overall difference in the ST composition (p=0.51) suggesting that the population has reached a new equilibrium following the introduction of 7 valent vaccination in 2000. Within serotypes, a large and statistically significant increase (p=0.014 Fisher's Exact test) was noted in the prevalence of the major multiresistant clone ST 320, which is apparently outcompeting ST 199 among serotype 19A strains. This sample will be used as a baseline to study the future evolution of the pneumococcal population in Massachusetts following introduction of vaccines with higher valency.

    View details for DOI 10.1016/j.vaccine.2011.09.075

    View details for Web of Science ID 000297601200015

    View details for PubMedID 21964059

    View details for PubMedCentralID PMC3221484

  • Making the CMS Payment Policy for Healthcare-Associated Infections Work: Organizational Factors That Matter JOURNAL OF HEALTHCARE MANAGEMENT Hoff, T., Hartmann, C. W., Soerensen, C., Wroe, P., Dutta-Linn, M., Lee, G. 2011; 56 (5): 319-335

    Abstract

    Healthcare-associated infections (HAIs) are among the most common adverse events in hospitals, and the morbidity and mortality associated with them are significant. In 2008, the Centers for Medicare and Medicaid Services (CMS) implemented a new financial policy that no longer provides payment to hospitals for services related to certain infections not present on admission and deemed preventable. At present, little is known about how this policy is being implemented in hospital settings. One key goal of the policy is for it to serve as a quality improvement driver within hospitals, providing the rationale and motivation for hospitals to engage in greater infection-related surveillance and prevention activities. This article examines the role organizational factors, such as leadership and culture, play in the effectiveness of the CMS policy as a quality improvement (QI) driver within hospital settings. Between late 2009 and early 2010, interviews were conducted with 36 infection preventionists working at a national sample of 36 hospitals. We found preliminary evidence that hospital executive behavior, a proactive infection control (IC) culture, and clinical staff engagement played a favorable role in enhancing the recognition, acceptance, and significance of the CMS policy as a QI driver within hospitals. We also found several other contextual factors that may impede the degree to which the above factors facilitate links between the CMS policy and hospital QI activities.

    View details for Web of Science ID 000295067100007

    View details for PubMedID 21991680

    View details for PubMedCentralID PMC3998712

  • H1N1 and Seasonal Influenza Vaccine Safety in the Vaccine Safety Datalink Project AMERICAN JOURNAL OF PREVENTIVE MEDICINE Lee, G. M., Greene, S. K., Weintraub, E. S., Baggs, J., Kulldorff, M., Fireman, B. H., Baxter, R., Jacobsen, S. J., Irving, S., Daley, M. F., Yin, R., Naleway, A., Nordin, J. D., Li, L., McCarthy, N., Vellozzi, C., DeStefano, F., Lieu, T. A. 2011; 41 (2): 121-128

    Abstract

    The emergence of pandemic H1N1 influenza virus in early 2009 prompted the rapid licensure and use of H1N1 monovalent inactivated (MIV) and live, attenuated (LAMV) vaccines separate from seasonal trivalent inactivated (TIV) and live, attenuated (LAIV) influenza vaccines. A robust influenza immunization program in the U.S. requires ongoing monitoring of potential adverse events associated with vaccination.To prospectively conduct safety monitoring of H1N1 and seasonal influenza vaccines during the 2009-2010 season.The Vaccine Safety Datalink (VSD) Project monitors ∼9.2 million members in eight U.S. medical care organizations. Electronic data on vaccines and pre-specified adverse events were updated and analyzed weekly for signal detection from November 2009 to April 2010 using either a self-controlled design or a current versus historical comparison. Statistical signals were further evaluated using alternative approaches to identify temporal clusters and to control for time-varying confounders.As of May 1, 2010, a total of 1,345,663 MIV, 267,715 LAMV, 2,741,150 TIV, and 157,838 LAIV doses were administered in VSD. No significant associations were noted during sequential analyses for Guillain-Barré syndrome, most other neurologic outcomes, and allergic and cardiac events. For MIV, a statistical signal was observed for Bell's palsy for adults aged ≥25 years on March 31, 2010, using the self-controlled approach. Subsequent analyses revealed no significant temporal cluster. Case-centered logistic regression adjusting for seasonality demonstrated an OR for Bell's palsy of 1.26 (95% CI=0.97, 1.63).No major safety problems following H1N1 or seasonal influenza vaccines were detected in the 2009-2010 season in weekly sequential analyses. Seasonality likely contributed to the Bell's palsy signal following MIV. Prospective safety monitoring followed by rigorous signal refinement is critical to inform decision-making by regulatory and public health agencies.

    View details for DOI 10.1016/j.amepre.2011.04.004

    View details for Web of Science ID 000292958900002

    View details for PubMedID 21767718

  • Safety of Trivalent Inactivated Influenza Vaccine in Children Aged 24 to 59 Months in the Vaccine Safety Datalink ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Glanz, J. M., Newcomer, S. R., Hambidge, S. J., Daley, M. F., Narwaney, K. J., Xu, S., Lee, G. M., Baggs, J., Klein, N. P., Nordin, J. D., Naleway, A. L., Belongia, E. A., Weintraub, E. S. 2011; 165 (8): 749-755

    Abstract

    To evaluate the safety of trivalent inactivated influenza vaccine (TIV) in children aged 24 to 59 months and to evaluate the risk of medically attended events (MAEs) in a subcohort of children who had multiple annual doses of TIV over their lifetimes.Self-controlled screening study.Seven US managed care organizations from October 1, 2002, to March 31, 2006.Children aged 24 to 59 months who received at least 1 TIV dose (66 283 children and 91 692 TIV doses).Vaccination with TIV.Medically attended events in inpatient and emergency department settings in one of the following risk windows: 0 to 2, 1 to 14, or 1 to 42 days after vaccination. All MAEs that met the screening criteria of incidence rate ratios (IRRs) exceeding 1.0 and P ≤ .05 or IRRs exceeding 2.0 and P < .20 underwent medical record review. A secondary analysis examined the risk of MAEs in children who had multiple annual lifetime TIV doses.Nine diagnoses met the screening criteria. After medical record review, gastrointestinal tract symptoms (IRR, 1.18; 95% confidence interval [CI], 1.10-1.25), gastrointestinal tract disorders (7.70; 1.11-53.52), and fever (1.71; 1.64-1.80) remained significantly associated with vaccination. None of the events seemed to be serious, and none had complications. In the secondary analysis, there was an apparent dose response for vaccine and allergic reactions in the 1- to 3-day risk window.There was no evidence of serious MAEs following vaccination with TIV among children aged 24 to 59 months. Further studies are warranted to evaluate the risk of MAEs in children with multiple lifetime TIV doses.

    View details for Web of Science ID 000293342900010

    View details for PubMedID 21810637

  • Epidemiology and Risk Factors for Clostridium difficile Infection in Children PEDIATRIC INFECTIOUS DISEASE JOURNAL Sandora, T. J., Fung, M., Flaherty, K., Helsing, L., Scanlon, P., Potter-Bynoe, G., Gidengil, C. A., Lee, G. M. 2011; 30 (7): 580-584

    Abstract

    Pediatric Clostridium difficile infection (CDI)-related hospitalizations are increasing. We sought to describe the epidemiology of pediatric CDI at a quaternary care hospital.Nested case-control study within a cohort of children <18 years tested for C. difficile between January and August 2008. The study included patients who were ≥ 1 year with a positive test and diarrhea; those without diarrhea (ie, presumed colonization) were excluded. Two unmatched controls per case were randomly selected from patients ≥ 1 year with a negative test. Potential predictors of CDI included age, gender, comorbidities, prior hospitalization, receipt of C. difficile-active antibiotics in the prior 24 hours, and recent (≤ 4 weeks) exposure to antibiotics or acid-blocking medications. Multivariate logistic regression models were created to identify independent predictors of CDI.Of 1891 tests performed, 263 (14%) were positive in 181 children. Ninety-five patients ≥ 1 year with CDI were compared with 238 controls. In multivariate analyses, predictors of CDI included solid organ transplant (odds ratio [OR], 8.09; 95% confidence interval [CI], 2.10-31.12), lack of prior hospitalization (OR, 8.43; 95% CI, 4.39-16.20), presence of gastrostomy or jejunostomy (G or J) tube (OR, 3.32; 95% CI 1.71-6.42), and receipt of fluoroquinolones (OR, 17.04; 95% CI, 5.86-49.54) or nonquinolone antibiotics (OR, 2.23; 95% CI, 1.18-4.20) in the past 4 weeks. Receipt of C. difficile-active antibiotics within 24 hours before testing was associated with a lower odds of CDI (OR, 0.22; 95% CI, 0.09-0.58).Recent antibiotic exposure and certain comorbid conditions (solid organ transplant, presence of a gastrostomy or jejunostomy tube) were associated with CDI. Diagnostic testing has less utility in patients being treated with C. difficile-active antibiotics.

    View details for DOI 10.1097/INF.0b013e31820bfb29

    View details for Web of Science ID 000291675100012

    View details for PubMedID 21233782

  • Near real-time vaccine safety surveillance with partially accrued data PHARMACOEPIDEMIOLOGY AND DRUG SAFETY Greene, S. K., Kulldorff, M., Yin, R., Yih, W. K., Lieu, T. A., Weintraub, E. S., Lee, G. M. 2011; 20 (6): 583-590

    Abstract

    The Vaccine Safety Datalink (VSD) Project conducts near real-time vaccine safety surveillance using sequential analytic methods. Timely surveillance is critical in identifying potential safety problems and preventing additional exposure before most vaccines are administered. For vaccines that are administered during a short period, such as influenza vaccines, timeliness can be improved by undertaking analyses while risk windows following vaccination are ongoing and by accommodating predictable and unpredictable data accrual delays. We describe practical solutions to these challenges, which were adopted by the VSD Project during pandemic and seasonal influenza vaccine safety surveillance in 2009/2010.Adjustments were made to two sequential analytic approaches. The Poisson-based approach compared the number of pre-defined adverse events observed following vaccination with the number expected using historical data. The expected number was adjusted for the proportion of the risk window elapsed and the proportion of inpatient data estimated to have accrued. The binomial-based approach used a self-controlled design, comparing the observed numbers of events in risk versus comparison windows. Events were included in analysis only if they occurred during a week that had already passed for both windows.Analyzing data before risk windows fully elapsed improved the timeliness of safety surveillance. Adjustments for data accrual lags were tailored to each data source and avoided biasing analyses away from detecting a potential safety problem, particularly early during surveillance.The timeliness of vaccine and drug safety surveillance can be improved by properly accounting for partially elapsed windows and data accrual delays.

    View details for DOI 10.1002/pds.2133

    View details for Web of Science ID 000292601300004

    View details for PubMedID 21538670

  • Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program PEDIATRICS Salmon, D. A., Akhtar, A., Mergler, M. J., Vannice, K. S., Izurieta, H., Ball, R., Lee, G. M., Vellozzi, C., Garman, P., Cunningham, F., Gellin, B., Koh, H., Lurie, N. 2011; 127: S78-S86

    Abstract

    The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1-vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines.

    View details for DOI 10.1542/peds.2010-1722L

    View details for Web of Science ID 000296918100012

    View details for PubMedID 21502251

  • Financing vaccines for adolescents: a position paper of the society for adolescent health and medicine. journal of adolescent health Kharbanda, E. O., Lee, G. M., Koenigs, L. 2011; 48 (3): 320-321

    Abstract

    An increasing number of vaccines are now recommended for adolescents. These vaccines may greatly improve the health of adolescents and their communities. However, adolescent vaccine coverage rates lag behind those for infants and behind goals set by Healthy People 2010 [1]. Financial constraints have been reported to be a significant obstacle to immunizing adolescents and young adults [2]. At the Society for Adolescent Health and Medicine, we believe that to achieve increased vaccine coverage in this age group, financial barriers to immunization must be removed.

    View details for DOI 10.1016/j.jadohealth.2010.12.025

    View details for PubMedID 21338909

  • Serotype specific invasive capacity and persistent reduction in invasive pneumococcal disease VACCINE Yildirim, I., Hanage, W. P., Lipsitch, M., Shea, K. M., Stevenson, A., Finkelstein, J., Huang, S. S., Lee, G. M., Kleinman, K., Pelton, S. I. 2010; 29 (2): 283-288

    Abstract

    Defining the propensity of Streptococcus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific "invasive capacity (IC)" by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes.

    View details for DOI 10.1016/j.vaccine.2010.10.032

    View details for Web of Science ID 000287057300017

    View details for PubMedID 21029807

    View details for PubMedCentralID PMC3139683

  • Physicians' opinions about critical attributes of a potential group A streptococcal vaccine VACCINE Gerber, M. A., Brown, H. W., Lee, G., Tanz, R. R., Temte, J. L., Van Beneden, C. A. 2010; 28 (44): 7155-7160

    Abstract

    A group A streptococcal (GAS) vaccine, while not currently available, offers the possibility of a more effective approach; however, barriers to its implementation are likely to exist. The objectives of this study were to describe the attitudes of physicians about the importance of preventing GAS-associated conditions and to identify potential barriers to vaccine implementation. Surveys were sent to randomly selected physicians from the AAP and the AAFP. The GAS conditions believed by respondents to be most important to prevent among pediatric patients were ARF (31%) followed by STSS (24%) and pharyngitis (20%). Pediatricians and family physicians identified similar factors that would encourage routine use of a GAS vaccine. Less than half of pediatricians and only a third of family physicians would recommend a GAS vaccine if it could not be given concurrently with other immunizations or if there were strong parental resistance to the vaccine. This descriptive study provides important information about the anticipated use of a GAS vaccine by primary care physicians in the United States.

    View details for DOI 10.1016/j.vaccine.2010.08.071

    View details for Web of Science ID 000283980400004

    View details for PubMedID 20817014

  • Higher Prevalence of Pharyngeal than Nasal Staphylococcus aureus Carriage in Pediatric Intensive Care Units JOURNAL OF CLINICAL MICROBIOLOGY Nakamura, M. M., McAdam, A. J., Sandora, T. J., Moreira, K. R., Lee, G. M. 2010; 48 (8): 2957-2959

    Abstract

    Sensitive detection of Staphylococcus aureus colonization is important for epidemiologic studies, infection control, and decolonization measures. We examined the sensitivity of nasal and pharyngeal sampling for S. aureus colonization in 331 children admitted to intensive care units. Pharyngeal screening was more sensitive than nasal screening (92.6% versus 63.1%, P < 0.0001).

    View details for DOI 10.1128/JCM.00547-10

    View details for Web of Science ID 000280550500048

    View details for PubMedID 20573867

  • Re-emergence of the type 1 pilus among Streptococcus pneumoniae isolates in Massachusetts, USA VACCINE Regev-Yochay, G., Hanage, W. P., Trzcinski, K., Rifas-Shiman, S. L., Lee, G., Bessolo, A., Huang, S. S., Pelton, S. I., McAdam, A. J., Finkelstein, J. A., Lipsitch, M., Malley, R. 2010; 28 (30): 4842-4846

    Abstract

    Pneumococcal type 1 pilus proteins have been proposed as potential vaccine candidates. Following conjugate pneumococcal vaccination, the prevalence of the pneumococcal type 1 pilus declined dramatically, a decline associated with the elimination of vaccine-type (VT) strains. Here we show that between 2004 and 2007, there has been a significant increase in pilus prevalence, now exceeding rates from the pre-conjugate vaccine era. This increase is primarily due to non-VT strains. These emerging piliated non-VT strains are mostly novel clones, with some exceptions. The rise in pilus type 1 frequency across multiple distinct genetic backgrounds suggests that the pilus may confer an intrinsic advantage.

    View details for DOI 10.1016/j.vaccine.2010.04.042

    View details for Web of Science ID 000280345700023

    View details for PubMedID 20434550

    View details for PubMedCentralID PMC2897942

  • Outpatient urticaria diagnosis codes have limited predictive value for same-day influenza vaccine adverse event detection JOURNAL OF CLINICAL EPIDEMIOLOGY Moore, K. M., Duddy, A., Lee, G. M., Velentgas, P., Burwen, D. R., Platt, R., Brown, J. S. 2010; 63 (4): 407-411

    Abstract

    To assess the predictive value of claims-based outpatient urticaria diagnosis codes to identify potential vaccine-related adverse events (AEs) when recorded on the same day as influenza vaccination.Health plan members with outpatient claims for influenza vaccination and urticaria on the same day between October 1, 2002, and December 31, 2007, were eligible for inclusion. Electronic medical records (EMRs) for 50 eligible patients with the most recent visits of interest occurring at a large group practice were sampled for review.EMRs were available and reviewed for 42 of 50 patients. An influenza vaccination was confirmed in all reviewed medical charts. Urticaria occurring on the day of influenza vaccination was confirmed for 40% of participants (17/42); 3 confirmed urticaria diagnoses were potential AEs and 14 urticaria events occurred before vaccination. Among those with unconfirmed diagnoses, 17 had no evidence of urticaria on physical examination on the day of interest (4 had evidence of a nonurticarial rash and 13 had no evidence of rash on examination) and 8 had insufficient information to make a clinical determination.Outpatient diagnosis codes for urticaria found in health insurance claims data are limited in their predictive value to identify same-day vaccine AEs.

    View details for DOI 10.1016/j.jclinepi.2009.08.002

    View details for Web of Science ID 000275588900009

    View details for PubMedID 19889513

  • Preferences for health outcomes associated with Group A Streptococcal disease and vaccination HEALTH AND QUALITY OF LIFE OUTCOMES Lee, G. M., Salomon, J. A., Gay, C., Hammitt, J. K. 2010; 8

    Abstract

    A 26-valent Group A Streptococcus (GAS) vaccine candidate has been developed that may provide protection against pharyngitis, invasive disease and rheumatic fever. However, recommendations for the use of a new vaccine must be informed by a range of considerations, including parents' preferences for different relevant health outcomes. Our objectives were to: (1) describe parent preferences for GAS disease and vaccination using willingness-to-pay (WTP) and time trade-off (TTO) methods; and (2) understand how parents' implied WTP for a quality-adjusted life year (QALY) gained might vary depending on the particular health outcome considered (e.g. averted GAS disease vs. vaccine adverse events).Telephone interviews were conducted with parents of children diagnosed with GAS pharyngitis at 2 pediatric practice sites in the Boston metropolitan area. WTP and TTO (trading parental longevity for child's health) questions for 2 vaccine and 4 disease-associated health states were asked using a randomly selected opening bid, followed by a 2nd bid and a final open-ended question about the amount willing to pay or trade. Descriptive analyses included medians and interquartile ranges for WTP and TTO estimates. The Wilcoxon signed-rank test was used to assess differences in WTP/QALY values for vaccine adverse events vs. disease states.Of 119 respondents, 100 (84%) and 96 (81%) provided a complete set of responses for WTP and TTO questions, respectively. The median WTP and discounted (at 3% per year) TTO values to avoid each health state were as follows: local reaction, $30, 0.12 days; systemic reaction, $50, 0.22 days; impetigo, $75, 1.25 days; strep throat, $75, 2.5 days; septic arthritis, $1,000, 6.6 days; and toxic shock syndrome, $3,000, 31.0 days. The median WTP/QALY was significantly higher for vaccine adverse events (approximately $60,000/QALY) compared to disease states ($18,000 to $36,000/QALY).Parents strongly prefer to prevent GAS disease in children compared to vaccine adverse events. However, implied WTP/QALY ratios were higher for the prevention of vaccine adverse events. Regret for errors of commission vs. omission may differ and should be considered by vaccine policymakers.

    View details for DOI 10.1186/1477-7525-8-28

    View details for Web of Science ID 000276380200001

    View details for PubMedID 20226042

    View details for PubMedCentralID PMC2848145

  • TEST CHARACTERISTICS OF COMMERCIAL INFLUENZA ASSAYS FOR DETECTING PANDEMIC INFLUENZA A (H1N1) IN CHILDREN PEDIATRIC INFECTIOUS DISEASE JOURNAL Sandora, T. J., Smole, S. C., Lee, G. M., Chung, S., Williams, L., McAdam, A. J. 2010; 29 (3): 261-262

    Abstract

    We assessed the test characteristics of 2 influenza antigen tests, a rapid immunoassay and a direct fluorescence antibody (DFA) assay, in detecting pandemic influenza A (H1N1) in children up to 18 years of age, using polymerase chain reaction as the standard. The sensitivities of BinaxNOW (59.6%) and direct fluorescence antibody (57.3%) were similar. The specificity of each test was >99%.

    View details for DOI 10.1097/INF.0b013e3181be9f9c

    View details for Web of Science ID 000275136000014

    View details for PubMedID 19935118

  • Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project AMERICAN JOURNAL OF EPIDEMIOLOGY Greene, S. K., Kulldorff, M., Lewis, E. M., Li, R., Yin, R., Weintraub, E. S., Fireman, B. H., Lieu, T. A., Nordin, J. D., Glanz, J. M., Baxter, R., Jacobsen, S. J., Broder, K. R., Lee, G. M. 2010; 171 (2): 177-188

    Abstract

    The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06-2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillain-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety.

    View details for DOI 10.1093/aje/kwp345

    View details for Web of Science ID 000273224700005

    View details for PubMedID 19965887

    View details for PubMedCentralID PMC2878099

  • Active Influenza Vaccine Safety Surveillance Potential Within a Healthcare Claims Environment MEDICAL CARE Brown, J. S., Moore, K. M., Braun, M. M., Ziyadeh, N., Chan, K. A., Lee, G. M., Kulldorff, M., Walker, A. M., Platt, R. 2009; 47 (12): 1251-1257

    Abstract

    Rapid safety assessment of novel vaccines, especially those targeted against pandemic influenza, is a public health priority.Assess the feasibility of using healthcare claims data to rapidly detect influenza vaccine adverse events using sequential analytic methods.Retrospective pilot study simulating prospective surveillance using 6 cumulative monthly administrative claims data extracts. The first included encounters occurring in October; each subsequent extract included an additional month of encounters. Ten adverse events were evaluated, comparing postvaccination rates during the 2006-2007 influenza season to those expected based on rates observed in the prior season.Members of a large, multistate health insurer who had a claim for influenza vaccination during the 2005-2006 or 2006-2007 influenza seasons.The completeness of monthly claims extracts.Most vaccinations and outcomes were identified early in the 2006-2007 season; about 50% of vaccinations and short latency events were identified in the second monthly data extract, which would typically become available by mid-December, and 80% of vaccinations and events were identified in the third extract. With respect to overall claims lag, approximately 90% of vaccinations and events were identified within 1 to 2 months after vaccination, regardless of vaccination month.This study suggests that administrative claims data might contribute to same season influenza vaccine safety surveillance in large, defined populations, especially during a threat of pandemic influenza. Based on our previous work, we believe this method could be applied to multiple health plans' data to monitor a large portion of the US population.

    View details for Web of Science ID 000272488100009

    View details for PubMedID 19786905

  • Uptake of meningococcal conjugate vaccine among adolescents in large managed care organizations, United States, 2005: Demand, supply and seasonality BMC INFECTIOUS DISEASES Lorick, S. A., Fishbein, D., Weintraub, E., Wortley, P. M., Lee, G. M., Zhou, F., Davis, R. 2009; 9

    Abstract

    In February 2005, the US Advisory Committee on Immunization Practices recommended the new meningococcal conjugate vaccine (MCV4) for routine use among 11- to 12-year-olds (at the preadolescent health-care visit), 14- to 15-year-olds (before high-school entry), and groups at increased risk. Vaccine distribution started in March; however, in July, the manufacturer reported inability to meet demand and widespread MCV4 shortages were reported. Our objectives were to determine early uptake patterns among target (11-12 and 14-15 year olds) and non-target (13- plus 16-year-olds) age groups. A post hoc analysis was conducted to compare seasonal uptake patterns of MCV4 with polysaccharide meningococcal (MPSV4) and tetanus diphtheria (Td) vaccines.We analyzed data for adolescents 11-16 years from five managed care organizations participating in the Vaccine Safety Datalink (VSD). For MCV4, we estimated monthly and cumulative coverage during 2005 and calculated risk ratios. For MPSV4 and Td, we combined 2003 and 2004 data and compared their seasonal uptake patterns with MCV4.Coverage for MCV4 during 2005 among the 623,889 11-16 years olds was 10%. Coverage for 11-12 and 14-15 year olds was 12% and 11%, respectively, compared with 8% for 13- plus 16-year-olds (p < 0.001). Of the 64,272 MCV4 doses administered from March-December 2005, 73% were administered June-August. Fifty-nine percent of all MPSV4 doses and 38% of all Td doses were administered during June-August.A surge in vaccine uptake between June and August was observed among adolescents for MCV4, MPSV4 and Td vaccines. The increase in summer-time vaccinations and vaccination of non-targeted adolescents coupled with supply limitations likely contributed to the reported shortages of MCV4 in 2005.

    View details for DOI 10.1186/1471-2334-9-175

    View details for Web of Science ID 000272386900001

    View details for PubMedID 19887009

    View details for PubMedCentralID PMC2781813

  • Infection prevention and control in health-care facilities in which hematopoietic cell transplant recipients are treated BONE MARROW TRANSPLANTATION Yokoe, D., Casper, C., Dubberke, E., Lee, G., Munoz, P., Palmore, T., Sepkowitz, K., Young, J. H., Donnelly, J. P. 2009; 44 (8): 495-507

    View details for DOI 10.1038/bmt.2009.261

    View details for Web of Science ID 000271247300008

    View details for PubMedID 19861984

  • Safe living after hematopoietic cell transplantation BONE MARROW TRANSPLANTATION Yokoe, D., Casper, C., Dubberke, E., Lee, G., Munoz, P., Palmore, T., Sepkowitz, K., Young, J. H., Donnelly, J. P. 2009; 44 (8): 509-519

    View details for DOI 10.1038/bmt.2009.262

    View details for Web of Science ID 000271247300009

    View details for PubMedID 19861985

  • Epidemiology and risk factors for Staphylococcus aureus colonization in children in the post-PCV7 era BMC INFECTIOUS DISEASES Lee, G. M., Huang, S. S., Rifas-Shiman, S. L., Hinrichsen, V. L., Pelton, S. I., Kleinman, K., Hanage, W. P., Lipsitch, M., McAdam, A. J., Finkelstein, J. A. 2009; 9

    Abstract

    The incidence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) has risen dramatically in the U.S., particularly among children. Although Streptococcus pneumoniae colonization has been inversely associated with S. aureus colonization in unvaccinated children, this and other risk factors for S. aureus carriage have not been assessed following widespread use of the heptavalent pneumococcal conjugate vaccine (PCV7). Our objectives were to (1) determine the prevalence of S. aureus and MRSA colonization in young children in the context of widespread use of PCV7; and (2) examine risk factors for S. aureus colonization in the post-PCV7 era, including the absence of vaccine-type S. pneumoniae colonization.Swabs of the anterior nares (S. aureus) were obtained from children enrolled in an ongoing study of nasopharyngeal pneumococcal colonization of healthy children in 8 Massachusetts communities. Children 3 months to <7 years of age seen for well child or sick visits in primary care offices from 11/03-4/04 and 10/06-4/07 were enrolled. S. aureus was identified and antibiotic susceptibility testing was performed. Epidemiologic risk factors for S. aureus colonization were collected from parent surveys and chart reviews, along with data on pneumococcal colonization. Multivariate mixed model analyses were performed to identify factors associated with S. aureus colonization.Among 1,968 children, the mean age (SD) was 2.7 (1.8) years, 32% received an antibiotic in the past 2 months, 2% were colonized with PCV7 strains and 24% were colonized with non-PCV7 strains. The prevalence of S. aureus colonization remained stable between 2003-04 and 2006-07 (14.6% vs. 14.1%), while MRSA colonization remained low (0.2% vs. 0.9%, p = 0.09). Although absence of pneumococcal colonization was not significantly associated with S. aureus colonization, age (6-11 mo vs. > or =5 yrs, OR 0.39 [95% CI 0.24-0.64]; 1-1.99 yrs vs. > or =5 yrs, OR 0.35 [0.23-0.54]; 2-2.99 yrs vs. > or =5 yrs, OR 0.45 [0.28-0.73]; 3-3.99 yrs vs. > or =5 yrs, OR 0.53 [0.33-0.86]) and recent antibiotic use were significant predictors in multivariate models.In Massachusetts, S. aureus and MRSA colonization remained stable from 2003-04 to 2006-07 among children <7 years despite widespread use of pneumococcal conjugate vaccine. S. aureus nasal colonization varies by age and is inversely correlated with recent antibiotic use.

    View details for DOI 10.1186/1471-2334-9-110

    View details for Web of Science ID 000268570600001

    View details for PubMedID 19594890

  • Continued Impact of Pneumococcal Conjugate Vaccine on Carriage in Young Children PEDIATRICS Huang, S. S., Hinrichsen, V. L., Stevenson, A. E., Rifas-Shiman, S. L., Kleinman, K., Pelton, S. I., Lipsitch, M., Hanage, W. P., Lee, G. M., Finkelstein, J. A. 2009; 124 (1): E1-E11

    Abstract

    The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7).Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000-2001 and 2003-2004 and in 8 communities in 2006-2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates.We collected 678, 988, and 972 specimens during the sampling periods in 2000-2001, 2003-2004, and 2006-2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006-2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted.The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.

    View details for DOI 10.1542/peds.2008-3099

    View details for Web of Science ID 000267448100057

    View details for PubMedID 19564254

    View details for PubMedCentralID PMC2782668

  • Financial Barriers to Implementing Combination Vaccines: Perspectives From Pediatricians and Policy Makers CLINICAL PEDIATRICS Gidengil, C. A., Rusinak, D., Allred, N. J., Luff, D., Lee, G. M., Lieu, T. A. 2009; 48 (5): 539-547

    Abstract

    To describe the factors that affect the use of new combination vaccines, the authors conducted qualitative interviews with pediatricians (n = 7), state immunization program managers (n = 7), and health insurance plan representatives (n = 6 plans). Respondents from each group identified reduction in pain and potentially increased immunization coverage as key benefits of new combination vaccines. For several pediatricians, low reimbursement for cost of vaccine doses and potential loss of fees for vaccine administration were barriers to using combination vaccines. For most state immunization programs, the higher cost of combination vaccines relative to separate vaccines was an important consideration but not a barrier to adoption. Most insurers were not aware of the financial issues for providers, but some had changed or were willing to change reimbursement to support the use of new combination vaccines. Financial issues for pediatric practices that purchase and provide vaccines for children may be an important barrier to offering combination vaccines.

    View details for DOI 10.1177/0009922808330773

    View details for Web of Science ID 000265954800012

    View details for PubMedID 19318705

  • Vaccine Financing in the United States An Emerging Crisis ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Lee, G. M., Lieu, T. A. 2009; 163 (5): 485-487

    View details for Web of Science ID 000265789000016

    View details for PubMedID 19414698

  • Adverse Events After Administration of Tetanus-Diphtheria-Acellular Pertussis Vaccine to Healthcare Workers INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY Sandora, T. J., Pfoh, E., Lee, G. M. 2009; 30 (4): 389-391

    Abstract

    Healthcare workers who received the tetanus-diphtheria-acellular pertussis (Tdap) vaccine were surveyed about adverse events. Local adverse events were more common among women and among those who received the Tdap vaccine less than 5 years after they had received the tetanus-diphtheria vaccine. Systemic adverse events were more common among healthcare workers aged less than 30 years. These findings provide guidance for counseling of healthcare workers who receive Tdap vaccine.

    View details for DOI 10.1086/596201

    View details for Web of Science ID 000263897700014

    View details for PubMedID 19239376

  • Influenza Vaccination in Adolescents With High-Risk Conditions PEDIATRICS Nakamura, M. M., Lee, G. M. 2008; 122 (5): 920-928

    Abstract

    We assessed influenza vaccination rates from 1992 to 2002, individual continuity of vaccination, and missed opportunities for vaccination in adolescents with high-risk conditions.We performed a retrospective observational study of 18 703 adolescents with high-risk conditions who were enrolled in a large health maintenance organization and received care at a multisite practice for >or=1 influenza season and the preceding year, between 1992 and 2002, was performed. Subjects were identified as having a high-risk condition if they had >or=1 visit with an associated International Classification of Diseases, Ninth Revision, Clinical Modification code during the season or previous year. Influenza vaccination rates were compared by season in logistic regression analyses, using generalized estimating equations for repeated measurements of subjects enrolled for multiple seasons. Vaccination continuity was measured for adolescents who were enrolled for 4 consecutive seasons (1999-2002) as the number of seasons during which vaccine was received. Missed opportunities were defined as visits during the first 4 months of influenza season at which an unvaccinated adolescent did not receive vaccine.For adolescents with high-risk conditions, influenza vaccination rates varied from 8.3% to 15.4%. Rates improved significantly from 1992 to 1993, from 8.3% to 12.8%, and again in 2001, reaching 15.4%. Only 11.1% of those enrolled continuously from 1999 to 2002 received vaccine during all 4 seasons. According to season from 1992 to 2002, 45.7% to 53.6% of unvaccinated subjects had >or=1 missed opportunity.Influenza vaccination rates in adolescents with high-risk conditions improved from 1992 to 2002 but were still low in recent years. Individual vaccination continuity was poor. Numerous opportunities already exist for improving coverage.

    View details for DOI 10.1542/peds.2007-3032

    View details for Web of Science ID 000260542500002

    View details for PubMedID 18977969

  • Adolescent immunizations: Missed opportunities for prevention PEDIATRICS Lee, G. M., Lorick, S. A., Pfoh, E., Kleinman, K., Fishbein, D. 2008; 122 (4): 711-717

    Abstract

    The goals were (1) to describe immunization rates for tetanus-diphtheria, hepatitis B, and measles-mumps-rubella vaccines among 13-year-old adolescents; (2) to identify missed opportunities for tetanus-diphtheria immunization among adolescents 11 to 17 years of age; and (3) to evaluate the association between preventive care use and tetanus-diphtheria immunization.Adolescents born between January 1, 1986, and December 31, 1991, and enrolled in Harvard Pilgrim Health Care and Harvard Vanguard Medical Associates for >or=1 year in 1997-2004 were included. Immunization rates for tetanus-diphtheria, hepatitis B, and measles-mumps-rubella were assessed at 13 years of age. Missed opportunities for tetanus-diphtheria immunization within 14 days after a health care visit were measured. Multivariate models were used to determine predictors of timeliness of tetanus-diphtheria vaccination, particularly the use of preventive care services. RESULTS. A total of 23,987 eligible adolescents were enrolled in Harvard Pilgrim Health Care and Harvard Vanguard Medical Associates between 1997 and 2004. Among 13-year-old adolescents in the most recent birth cohort, 84%, 74%, and 67% were up to date for tetanus-diphtheria, hepatitis B, and measles-mumps-rubella, respectively. When the analysis was limited to those with >or=1 vaccine received before 2 years of age (a proxy measure for complete records), 92%, 82%, and 85% were up to date for tetanus-diphtheria, hepatitis B, and measles-mumps-rubella, respectively. Missed opportunities for tetanus-diphtheria immunization occurred at 84% of all health care visits. Adolescents who did not seek preventive care were less likely to receive tetanus-diphtheria in a timely manner.Adolescent immunization rates lag far behind childhood rates, and missed opportunities are common. Additional strategies are needed to increase the use of preventive services among adolescents and to enable providers to vaccinate adolescents at every opportunity.

    View details for DOI 10.1542/peds.2007-2857

    View details for Web of Science ID 000259812600003

    View details for PubMedID 18829792

  • Cost-effectiveness of adult pertussis vaccination in Germany VACCINE Lee, G. M., Riffelmann, M., von Konig, C. H. 2008; 26 (29-30): 3673-3679

    Abstract

    The incidence of pertussis in adults is high despite good childhood vaccination coverage. An adult formulation of an acellular pertussis vaccine is licensed and available for use in Germany.To evaluate the potential health benefits, risks, costs and cost-effectiveness of routine pertussis vaccination programs for German adults.A Markov model was used to simulate health states and immunity levels associated with pertussis disease and vaccination. The following strategies were evaluated: (1) no adult pertussis vaccination, (2) one-time adult vaccination at 20-64 years, and (3) adult vaccination with decennial boosters. Our main outcome measures were costs (2006 Euros), cases prevented, incremental cost per case prevented and incremental cost per quality-adjusted life year (QALY) saved. We performed sensitivity analyses for key assumptions in the model including disease incidence, vaccine cost, vaccine efficacy, disease costs and frequency of adverse events. Future costs and benefits were discounted at 3%.At a disease incidence of 165 per 100,000, the one-time adult vaccination strategy would prevent 498,000 cases, and the decennial adult vaccination strategy would prevent 1 million cases. Approximately 31 million adults ( approximately 62% of the cohort) would be vaccinated with a one-time adult vaccination strategy for a total program cost of 366 million Euros, while a decennial vaccination strategy would cost 687 million Euros. The one-time adult vaccination strategy resulted in CE ratios of 5800 Euros per QALY saved, or 160 Euros per pertussis case prevented. The decennial booster strategy cost 7200 Euros per QALY saved, or 200 Euros per case prevented. The results were most sensitive to assumptions about disease incidence and vaccine cost.Routine vaccination of German adults aged 20-64 years with Tdap is cost-effective.

    View details for DOI 10.1016/j.vaccine.2008.04.068

    View details for Web of Science ID 000257649000017

    View details for PubMedID 18538901

  • Tetanus-diphtheria-acellular pertussis vaccination of adults in the USA EXPERT REVIEW OF VACCINES Gidengil, C. A., Sandora, T. J., Lee, G. M. 2008; 7 (5): 621-634

    Abstract

    Pertussis is an important cause of morbidity and mortality, and its incidence has been increasing in adolescents and adults over the past two decades. Waning immunity in adolescents and adults may be partially responsible. Adults can suffer significant illness from pertussis and its complications, such as pneumonia, rib fractures and syncope. Moreover, adults serve as a source of disease for infants, who are more vulnerable to severe complications and even death. The economic burden of pertussis is substantial, in terms of both medical and nonmedical costs. Fortunately, the burden of pertussis disease can now be safely and effectively reduced by vaccinating adults with tetanus-diphtheria-acellular pertussis (Tdap) vaccine. Further research is needed to elucidate the role of vaccination in pregnant women and those over 65 years of age, and also to determine whether further booster doses of Tdap are needed.

    View details for DOI 10.1586/14760584.7.5.621

    View details for Web of Science ID 000257617400015

    View details for PubMedID 18564017

  • Pertussis vaccination for health care workers CLINICAL MICROBIOLOGY REVIEWS Sandora, T. J., Gidengil, C. A., Lee, G. M. 2008; 21 (3): 426-434

    Abstract

    Pertussis, an acute respiratory infection caused by Bordetella pertussis, classically manifests as a protracted cough illness. The incidence of pertussis in the United States has been increasing in recent years. Immunity wanes after childhood vaccination, leaving adolescents and adults susceptible to infection. The transmission of pertussis in health care settings has important medical and economic consequences. Acellular pertussis booster vaccines are now available for use and have been recommended for all adolescents and adults. These vaccines are safe, immunogenic, and effective. Health care workers are a priority group for vaccination because of their increased risk of acquiring infection and the potential to transmit pertussis to high-risk patients. Health care worker vaccination programs are likely to be cost-effective, but further research is needed to determine the acceptability of pertussis vaccines among health care workers, the duration of immunity after booster doses, and the impact of vaccination on the management of pertussis exposures in health care settings.

    View details for DOI 10.1128/CMR.00003-08

    View details for Web of Science ID 000258667400002

    View details for PubMedID 18625679

    View details for PubMedCentralID PMC2493083

  • Burden and economic cost of group A streptococcal pharyngitis PEDIATRICS Pfoh, E., Wessels, M. R., Goldmann, D., Lee, G. M. 2008; 121 (2): 229-234

    Abstract

    Our aim was to describe the morbidity, medical costs, and nonmedical costs associated with group A streptococcal pharyngitis in school-aged children.Our study population included parents of children diagnosed as having group A streptococcal pharyngitis at 2 pediatric practice sites in the Boston, Massachusetts, metropolitan area. Telephone interviews were conducted with parents of eligible children, who were asked questions about health care utilization, medications, and time missed from work or school, for calculation of medical and nonmedical costs associated with illness.One hundred thirty-five parents completed interviews between October 2005 and January 2006. Older children were significantly more likely to present with headache, compared with those < or = 5 years of age. No significant differences between older and younger children were found for rates of sore throat, fever, abdominal pain/nausea/vomiting, or rash. Children missed a mean of 1.9 days (range: 0-7 days) of school/day care, and 42% of parents missed a mean of 1.8 days of work. A second parent or caregiver also missed a mean of 1.5 days in 14% of families. The total societal cost per case of group A streptococcal pharyngitis was $205 (medical: $118; nonmedical: $87).The societal cost of group A streptococcal pharyngitis is substantial, with almost one half being attributable to nonmedical costs. Through extrapolation from this experience, the total cost of group A streptococcal pharyngitis among children in the United States ranges from $224 to $539 million per year.

    View details for DOI 10.1542/peds.2007-0484

    View details for Web of Science ID 000252877600001

    View details for PubMedID 18245412

  • Projected cost-effectiveness of new vaccines for adolescents in the United States PEDIATRICS Ortega-Sanchez, I. R., Lee, G. M., Jacobs, R. J., Prosser, L. A., Molinari, N., Zhang, X., Baine, W. B., McCauley, M. M., Miller, T. 2008; 121: S63-S78

    Abstract

    Economic assessments that guide policy making on immunizations are becoming increasingly important in light of new and anticipated vaccines for adolescents. However, important considerations that limit the utility of these assessments, such as the diversity of approaches used, are often overlooked and should be better understood.Our goal was to examine economic studies of adolescent vaccines and compare cost-effectiveness outcomes among studies on a particular vaccine, across adolescent vaccines, and between new adolescent vaccines versus vaccines that are recommended for young children.A systematic review of economic studies on immunizations for adolescents was conducted. Studies were identified by searching the Medline, Embase, and EconLit databases. Each study was reviewed for appropriateness of model design, baseline setup, sensitivity analyses, and input variables (ie, epidemiologic, clinical, cost, and quality-of-life impact). For comparison, the cost-effectiveness outcomes reported in key studies on vaccines for younger children were selected.Vaccines for healthy adolescents were consistently found to be more costly than the health care or societal cost savings they produced and, in general, were less cost-effective than vaccines for younger children. Among the new vaccines, pertussis and human papillomavirus vaccines were more cost-effective than meningococcal vaccines. Including herd-immunity benefits in studies significantly improved the cost-effectiveness estimates for new vaccines. Differences in measurements or assumptions limited further comparisons.Although using the new adolescent vaccines is unlikely to be cost-saving, vaccination programs will result in sizable health benefits.

    View details for DOI 10.1542/peds.2007-1115H

    View details for Web of Science ID 000253781900008

    View details for PubMedID 18174323

  • Gaps in vaccine financing for underinsured children in the United States JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Lee, G. M., Santoli, J. M., Hannan, C., Messonnier, M. L., Sabin, J. E., Rusinak, D., Gay, C., Lett, S. M., Lieu, T. A. 2007; 298 (6): 638-643

    Abstract

    The number of new vaccines recommended for children and adolescents has nearly doubled during the past 5 years, and the cost of fully vaccinating a child has increased dramatically in the past decade. Anecdotal reports from state policy makers and clinicians suggest that new gaps have arisen in financial coverage of vaccines for children who are underinsured (ie, have private insurance that does not cover all recommended vaccines). In 2000, approximately 14% of children were underinsured for vaccines in the United States.To describe variation among states in the provision of new vaccines to underinsured children and to identify barriers to state purchase and distribution of new vaccines.A 2-phase mixed-methods study of state immunization program managers in the United States. The first phase included 1-hour qualitative telephone interviews conducted from November to December 2005 with 9 program managers chosen to represent different state vaccine financing policies. The second phase incorporated findings from phase 1 to develop a national telephone and paper-based survey of state immunization program managers that was conducted from January to June 2006.Percentage of states in which underinsured children are unable to receive publicly purchased vaccines in the private or public sectors.Immunization program managers from 48 states (96%) participated in the study. Underinsured children were not eligible to receive publicly purchased meningococcal conjugate or pneumococcal conjugate vaccines in the private sector in 70% and 50% of states, respectively, or in the public sector in 40% and 17% of states, respectively. Due to limited financing for new vaccines, 10 states changed their policies for provision of publicly purchased vaccines between 2004 and early 2006 to restrict access to selected new vaccines for underinsured children. The most commonly cited barriers to implementation in underinsured children were lack of sufficient federal and state funding to purchase vaccines.The current vaccine financing system has resulted in gaps for underinsured children in the United States, many of whom are now unable to receive publicly purchased vaccines in either the private or public sectors. Additional strategies are needed to ensure financial coverage for all vaccines, particularly new vaccines, among this vulnerable population.

    View details for Web of Science ID 000248574800024

    View details for PubMedID 17684186

  • Varicella vaccination in adults: Is it cost-effective? Editorial commentary CLINICAL INFECTIOUS DISEASES Lee, G. M. 2007; 44 (8): 1049-1050

    View details for DOI 10.1086/512744

    View details for Web of Science ID 000244928200005

    View details for PubMedID 17366447

  • Cost effectiveness of pertussis vaccination in adults AMERICAN JOURNAL OF PREVENTIVE MEDICINE Lee, G. M., Murphy, T. V., Lett, S., Cortese, M. M., Kretsinger, K., Schauer, S., Lieu, T. A. 2007; 32 (3): 186-193

    Abstract

    Prior economic analyses have reached disparate conclusions about whether vaccinating adults against pertussis would be cost effective. Newly available data on pertussis incidence were used to evaluate the cost effectiveness of one-time adult vaccination and adult vaccination with decennial boosters.A Markov model was used to calculate the health benefits, risks, costs, and cost effectiveness of the following strategies: (1) no adult pertussis vaccination, (2) one-time adult vaccination at 20-64 years, and (3) adult vaccination with decennial boosters. The impact of the severity of pertussis illness, vaccine adverse events, and herd immunity on model outcomes were also examined.At a disease incidence of 360 per 100,000, the one-time adult vaccination strategy would prevent 2.8 million cases, and the decennial vaccination strategy would prevent 8.3 million cases. As disease incidence varied from 10 to 500 per 100,000, the one-time adult vaccination strategy was projected to prevent 79,000 to 3.8 million adult pertussis cases, while the decennial vaccination program would prevent 239,000 to 11.4 million cases. A one-time adult vaccination strategy would result in 106 million people vaccinated, or approximately 64% of the adult cohort, for a total program cost of $2.1 billion, while a decennial vaccination strategy would cost $6.7 billion. The one-time and decennial booster vaccination strategies result in cost-effectiveness ratios of <$50,000 per quality-adjusted life year saved if disease incidence in adults were greater than 120 cases per 100,000 population.Routine vaccination of adults aged 20 to 64 years with combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis is cost effective if pertussis incidence in this age group is greater than 120 per 100,000 population.

    View details for DOI 10.1016/j.amepre.2006.10.016

    View details for Web of Science ID 000244730000002

    View details for PubMedID 17296470

  • Preventing tetanus, diphtheria, and pertussis among adults: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine recommendations of the Advisory Committee on Immunization Practices (ACIP) and recommendation of ACIP, supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC), for use of Tdap among health-care personnel. MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports Kretsinger, K., Broder, K. R., Cortese, M. M., Joyce, M. P., Ortega-Sanchez, I., Lee, G. M., Tiwari, T., Cohn, A. C., Slade, B. A., Iskander, J. K., Mijalski, C. M., Brown, K. H., Murphy, T. V. 2006; 55 (RR-17): 1-37

    Abstract

    On June 10, 2005, a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) formulated for use in adults and adolescents was licensed in the United States for persons aged 11-64 years (ADACEL, manufactured by sanofi pasteur, Toronto, Ontario, Canada). Prelicensure studies demonstrated safety and efficacy, inferred through immunogenicity, against tetanus, diphtheria, and pertussis when Tdap was administered as a single booster dose to adults. To reduce pertussis morbidity among adults and maintain the standard of care for tetanus and diphtheria prevention and to reduce the transmission of pertussis to infants and in health-care settings, the Advisory Committee on Immunization Practices (ACIP) recommends that: 1) adults aged 19-64 years should receive a single dose of Tdap to replace tetanus and diphtheria toxoids vaccine (Td) for booster immunization against tetanus, diphtheria, and pertussis if they received their last dose of Td >or=10 years earlier and they have not previously received Tdap; 2) intervals shorter than 10 years since the last Td may be used for booster protection against pertussis; 3) adults who have or who anticipate having close contact with an infant aged <12 months (e.g., parents, grandparents aged <65 years, child-care providers, and health-care personnel) should receive a single dose of Tdap to reduce the risk for transmitting pertussis. An interval as short as 2 years from the last Td is suggested; shorter intervals can be used. When possible, women should receive Tdap before becoming pregnant. Women who have not previously received Tdap should receive a dose of Tdap in the immediate postpartum period; 4) health-care personnel who work in hospitals or ambulatory care settings and have direct patient contact should receive a single dose of Tdap as soon as feasible if they have not previously received Tdap. An interval as short as 2 years from the last dose of Td is recommended; shorter intervals may be used. These recommendations for use of Tdap in health-care personnel are supported by the Healthcare Infection Control Practices Advisory Committee (HICPAC). This statement 1) reviews pertussis, tetanus and diphtheria vaccination policy in the United States; 2) describes the clinical features and epidemiology of pertussis among adults; 3) summarizes the immunogenicity, efficacy, and safety data of Tdap; and 4) presents recommendations for the use of Tdap among adults aged 19-64 years.

    View details for PubMedID 17167397

  • Changing epidemiology of acute rheumatic fever in the United States CLINICAL INFECTIOUS DISEASES Lee, G. M., Wessels, M. R. 2006; 42 (4): 448-450

    View details for Web of Science ID 000234742800002

    View details for PubMedID 16421786

  • Quality of life for children and adolescents: Impact of HIV infection and antiretroviral treatment PEDIATRICS Lee, G. M., Gortmaker, S. L., MCINTOSH, K., Hughes, M. D., Oleske, J. M. 2006; 117 (2): 273-283

    Abstract

    HIV/AIDS mortality rates in the United States are declining; pediatric HIV has become a chronic disease, with quality of life (QoL) outcomes assuming greater importance.To compare QoL among HIV-infected and uninfected children and to assess the impact of different antiretroviral regimens on QoL among HIV-infected children.Perinatally exposed, HIV-infected (N = 1847) and uninfected (N = 712) children and adolescents were studied. Among infected children, 1283 were available for the antiretroviral regimen analysis. QoL domain scores were assessed for subjects 6 months to 4 years, 5 to 11 years, and 12 to 21 years of age, and the impact of infection status and alternative treatment regimens on QoL domains was evaluated.HIV infection was associated with significantly worse mean adjusted scores for functional status among children 6 months to 4 years of age and health perceptions, physical resilience, physical functioning, and social/role functioning among those 5 to 11 years of age. However, uninfected children 5 to 11 years of age reported significantly worse psychological functioning. HIV-infected children (5-11 years of age) and adolescents (12-21 years of age) receiving no antiretroviral treatment had worse health perceptions. Adolescents receiving no antiretroviral agents also had worse symptoms. When antiretroviral regimens were compared, adolescents receiving protease inhibitor plus nonnucleoside reverse transcriptase inhibitor-containing therapy had worse symptoms, compared with those receiving protease inhibitor-containing therapy; otherwise, no significant differences were found.Generally parents of HIV-infected children 6 months to 4 years and 5 to 11 years of age generally reported lower mean QoL scores than did parents of uninfected children, although worse psychological functioning was reported for uninfected children. HIV-infected adolescents not receiving antiretroviral treatment had worse health perceptions and symptoms. We found no consistent QoL differences among children receiving different antiretroviral regimens.

    View details for DOI 10.1542/peds.2005-0323

    View details for Web of Science ID 000235491100002

    View details for PubMedID 16452344

  • Antibiotic treatment of children with sore throat JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Linder, J. A., Bates, D. W., Lee, G. M., Finkelstein, J. A. 2005; 294 (18): 2315-2322

    Abstract

    Of children with sore throat, 15% to 36% have pharyngitis caused by group A beta-hemolytic streptococci (GABHS). Performance of a GABHS test prior to antibiotic prescribing is recommended for children with sore throat. Penicillin, amoxicillin, erythromycin, and first-generation cephalosporins are the recommended antibiotics for treatment of sore throat due to GABHS.To measure rates of antibiotic prescribing and GABHS testing and to evaluate the association between testing and antibiotic treatment for children with sore throat.Analysis of visits by children aged 3 to 17 years with sore throat to office-based physicians, hospital outpatient departments, and emergency departments in the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, 1995 to 2003 (N = 4158) and of a subset of visits with GABHS testing data (n = 2797).National rates of antibiotic prescribing, prescribing of antibiotics recommended and not recommended for GABHS, and GABHS testing.Physicians prescribed antibiotics in 53% (95% confidence interval [CI], 49%-56%) of an estimated 7.3 million annual visits for sore throat and nonrecommended antibiotics to 27% (95% CI, 24%-31%) of children who received an antibiotic. Antibiotic prescribing decreased from 66% of visits in 1995 to 54% of visits in 2003 (P = .01 for trend). This decrease was attributable to a decrease in the prescribing of recommended antibiotics (49% to 38%; P = .002). Physicians performed a GABHS test in 53% (95% CI, 48%-57%) of visits and in 51% (95% CI, 45%-57%) of visits at which an antibiotic was prescribed. GABHS testing was not associated with a lower antibiotic prescribing rate overall (48% tested vs 51% not tested; P = .40), but testing was associated with a lower antibiotic prescribing rate for children with diagnosis codes for pharyngitis, tonsillitis, and streptococcal sore throat (57% tested vs 73% not tested; P<.001).Physicians prescribed antibiotics to 53% of children with sore throat, in excess of the maximum expected prevalence of GABHS. Although there was a decrease in the proportion of children receiving antibiotics between 1995 and 2003, this was due to decreased prescribing of agents recommended for GABHS. Although GABHS testing was associated with a lower rate of antibiotic prescribing for children with diagnosis codes of pharyngitis, tonsillitis, and streptococcal sore throat, GABHS testing was underused.

    View details for Web of Science ID 000233089700023

    View details for PubMedID 16278359

  • Randomized, controlled trial of a multifaceted intervention including alcohol-based hand sanitizer and hand-hygiene education to reduce illness transmission in the home PEDIATRICS Sandora, T. J., Taveras, E. M., Shih, M. C., Resnick, E. A., Lee, G. M., Ross-Degnan, D., GOLDMANN, D. A. 2005; 116 (3): 587-594

    Abstract

    Good hand hygiene may reduce the spread of infections in families with children who are in out-of-home child care. Alcohol-based hand sanitizers rapidly kill viruses that are commonly associated with respiratory and gastrointestinal (GI) infections. The objective of this study was to determine whether a multifactorial campaign centered on increasing alcohol-based hand sanitizer use and hand-hygiene education reduces illness transmission in the home.A cluster randomized, controlled trial was conducted of homes of 292 families with children who were enrolled in out-of-home child care in 26 child care centers. Eligible families had > or =1 child who was 6 months to 5 years of age and in child care for > or =10 hours/week. Intervention families received a supply of hand sanitizer and biweekly hand-hygiene educational materials for 5 months; control families received only materials promoting good nutrition. Primary caregivers were phoned biweekly and reported respiratory and GI illnesses in family members. Respiratory and GI-illness-transmission rates (measured as secondary illnesses per susceptible person-month) were compared between groups, adjusting for demographic variables, hand-hygiene practices, and previous experience using hand sanitizers.Baseline demographics were similar in the 2 groups. A total of 1802 respiratory illnesses occurred during the study; 443 (25%) were secondary illnesses. A total of 252 GI illnesses occurred during the study; 28 (11%) were secondary illnesses. The secondary GI-illness rate was significantly lower in intervention families compared with control families (incidence rate ratio [IRR]: 0.41; 95% confidence interval [CI]: 0.19-0.90). The overall rate of secondary respiratory illness was not significantly different between groups (IRR: 0.97; 95% CI: 0.72-1.30). However, families with higher sanitizer usage had a marginally lower secondary respiratory illness rate than those with less usage (IRR: 0.81; 95% CI: 0.65-1.09).A multifactorial intervention emphasizing alcohol-based hand sanitizer use in the home reduced transmission of GI illnesses within families with children in child care. Hand sanitizers and multifaceted educational messages may have a role in improving hand-hygiene practices within the home setting.

    View details for DOI 10.1542/peds.2005-0199

    View details for Web of Science ID 000231576600029

    View details for PubMedID 16140697

  • Pertussis in adolescents and adults: Should we vaccinate? PEDIATRICS Lee, G. M., Lebaron, C., Murphy, T. V., Lett, S., Schauer, S., Lieu, T. A. 2005; 115 (6): 1675-1684

    Abstract

    The incidence of reported pertussis among adolescents, adults, and young infants has increased sharply over the past decade. Combined acellular pertussis vaccines for adolescents and adults are available in Canada, Australia, and Germany and may soon be considered for use in the United States.To evaluate the potential health benefits, risks, and costs of a national pertussis vaccination program for adolescents and/or adults.The projected health states and immunity levels associated with pertussis disease and vaccination were simulated with a Markov model. The following strategies were examined from the health care payer and societal perspectives: (1) no vaccination; (2) 1-time adolescent vaccination; (3) 1-time adult vaccination; (4) adult vaccination with boosters; (5) adolescent and adult vaccination with boosters; and (6) postpartum vaccination. Data on disease incidence, costs, outcomes, vaccine efficacy, and adverse events were based on published studies, recent unpublished clinical trials, and expert panel input.Cases prevented, adverse events, costs (in 2004 US dollars), cost per case prevented, and cost per quality-adjusted life-year (QALY) saved.One-time adolescent vaccination would prevent 30800 cases of pertussis (36% of projected cases) and would result in 91000 vaccine adverse events (67% local reactions). If pertussis vaccination cost $15 and vaccine coverage was 76%, then 1-time adolescent vaccination would cost $1100 per case prevented (or $1200 per case prevented) or $20000 per QALY (or $23000 per QALY) saved, from the societal (or health care payer) perspective. With a threshold of $50000 per QALY saved, the adolescent and adult vaccination with boosters strategy became potentially cost-effective from the societal perspective only if 2 conditions were met simultaneously, ie, (1) the disease incidence for adolescents and adults was > or =6 times higher than base-case assumptions and (2) the cost of vaccination was less than $10. Adult vaccination strategies were more costly and less effective than adolescent vaccination strategies. The results were sensitive to assumptions about disease incidence, vaccine efficacy, frequency of vaccine adverse events, and vaccine costs.Routine pertussis vaccination of adolescents results in net health benefits and may be relatively cost-effective.

    View details for DOI 10.1542/peds.2004-2509

    View details for Web of Science ID 000229504800029

    View details for PubMedID 15930232

  • Illness transmission in the home: A possible role for alcohol-based hand gels PEDIATRICS Lee, G. M., Salomon, J. A., Friedman, J. F., Hibberd, P. L., Ross-Degnan, D., Zasloff, E., Bediako, S., GOLDMANN, D. A. 2005; 115 (4): 852-860

    Abstract

    The widespread use of child care has altered the epidemiology of respiratory and gastrointestinal (GI) infection in the community. Our primary objective was to measure transmission of respiratory and GI illnesses among families with children enrolled in child care. We also sought to examine potential predictors of reduced illness transmission in the home in a secondary analysis.We performed an observational, prospective cohort study to determine transmission rates for respiratory and GI illnesses within families with at least 1 child between 6 months and 5 years of age enrolled in child care. A survey about family beliefs and practices was mailed at the beginning of the study. Symptom diaries were provided for families to record the timing and duration of respiratory and GI illnesses. To ensure the accuracy of symptom diaries, biweekly telephone calls were performed to review illnesses recorded by participants. Families with > or =4 weeks of data recorded were included in the analysis. Families were recruited from 5 pediatric practices in the metropolitan Boston area. Of 261 families who agreed to participate in the study, 208 were available for analysis. Secondary transmission rates for respiratory and GI illnesses were measured as illnesses per susceptible person-month.We observed 1545 respiratory and 360 GI illnesses in 208 families from November 2000 to May 2001. Of these, 1099 (71%) respiratory and 297 (83%) GI illnesses were considered primary illnesses introduced into the home. The secondary transmission rates for respiratory and GI illnesses were 0.63 and 0.35 illnesses per susceptible person-month, respectively. Only two thirds of respondents correctly believed that contact transmission was important in the spread of colds, and fewer than half believed that it was important in the spread of stomach flus. Twenty-two percent of respondents reported use of alcohol-based hand gels all, most, or some of the time; 33% reported always washing their hands after blowing or wiping a nose. In multivariate models, use of alcohol-based hand gels had a protective effect against respiratory illness transmission in the home.In homes with young children enrolled in child care, illness transmission to family members occurs frequently. Alcohol-based hand gel use was associated with reduced respiratory illness transmission in the home.

    View details for DOI 10.1542/peds.2004-0856

    View details for Web of Science ID 000228107900023

    View details for PubMedID 15805355

  • Health-state valuations for pertussis: methods for valuing short-term health states. Health and quality of life outcomes Lee, G. M., Salomon, J. A., LeBaron, C. W., Lieu, T. A. 2005; 3: 17-?

    Abstract

    The incidence of reported adolescent and adult pertussis continues to rise in the United States. Acellular pertussis vaccines for adolescents and adults have been developed and may be available soon for use in the U.S. Our objectives were: (1) to describe patient valuations of pertussis disease and vaccination; and (2) to compare valuations for short-term and long-term health states associated with pertussis.We conducted telephone surveys with 515 adult patients and parents of adolescent patients with pertussis in Massachusetts to determine valuations of pertussis-related health states for disease and vaccination using time trade-off (TTO) and contingent valuation (CV) techniques. Respondents were randomized to complete either a short-term or long-term TTO exercise. Discrimination between health states for each valuation technique was assessed using Tukey's method, and valuations for short-term vs. long-term health states were compared using the Wilcoxon rank-sum test.Three hundred three (59%) and 309 (60%) respondents completed and understood the TTO and CV exercises, respectively. Overall, respondents gave lower valuations (lower TTO and higher CV values) to avoid a given state for adolescent/adult disease compared to vaccine adverse events. Infant complications due to pertussis were considered worse than adolescent/adult disease, regardless of the method of valuation. The short-term TTO resulted in lower mean valuations and larger mean differences between health states than the long-term TTO exercise.Pertussis was considered worse than adverse events due to vaccination. Short-term health-state valuation is better able to discriminate among health states, which is useful for cost-utility analysis.

    View details for PubMedID 15780145

  • Societal costs and morbidity of pertussis in adolescents and adults CLINICAL INFECTIOUS DISEASES Lee, G. M., Lett, S., Schauer, S., Lebaron, C., Murphy, T. V., Rusinak, D., Lieu, T. A. 2004; 39 (11): 1572-1580

    Abstract

    Since the 1980s, the reported incidence of pertussis among adolescents and adults has been steadily increasing. To understand whether the benefits of an acellular pertussis vaccine formulated for adolescents and adults might offset its costs, policy makers will need information about morbidity and societal (medical and nonmedical) costs of pertussis.Adolescents (age, 10-17 years) and adults (age, >or=18 years) with confirmed pertussis illness were identified by the Massachusetts enhanced pertussis surveillance system. We evaluated medical costs in a cohort of patients who had confirmed pertussis during the period of January 1998 through December 2000; nonmedical costs, by means of prospective interviews, in a cohort of patients who had confirmed pertussis during the period of December 2001 through January 2003; and morbidity in both cohorts. Our main outcome measures were mean costs per case, in 2002 US dollars.In the analysis of medical costs, 1679 adolescents and 936 adults were found to have mean costs of 242 dollars and 326 dollars, respectively (P<.05). In interviews with 314 adolescents and 203 adults, adults had significantly higher nonmedical costs (447 dollars) than those of adolescents (155 dollars). A total of 83% of adolescents missed a mean of 5.5 days from school (range, 0.4-32 days), and 61% of adults missed a mean of 9.8 days from work (range, 0.1-180 days) because of pertussis. Thirty-eight percent of adolescents and 61% of adults were still coughing at the time of the interview, which occurred an average of 106 days and 94 days, respectively, after cough onset.Pertussis causes significant morbidity in and costs for adolescents and adults, with time losses comprising the largest proportion of the cost. Societal costs should be considered when making decisions about potential vaccine use in the future.

    View details for Web of Science ID 000227492100002

    View details for PubMedID 15578353

  • Child care center policies and practices for management of ill children AMBULATORY PEDIATRICS Friedman, J. F., Lee, G. M., Kleinman, K. P., Finkelstein, J. A. 2004; 4 (5): 455-460

    Abstract

    The objectives of this study were to 1) describe child care staff knowledge and beliefs regarding upper respiratory tract infections and antibiotic indications and 2) evaluate child care staff reported reasons for a) exclusion from child care, b) referral to a health care provider, and c) recommending antibiotics for an ill child.A longitudinal study based in randomly selected child care centers in Massachusetts. Staff completed a survey to assess knowledge regarding common infections. For six weeks, staff completed a record of absences each day, describing the reason for an absence, and advice given to the parents regarding exclusion, referral to a health care provider, and obtaining antibiotics. Exclusions for the specific illness/symptom were defined as appropriate or inappropriate based on national guidelines.A large proportion of child care staff incorrectly believed that antibiotics are indicated for bronchitis (80.5%) and green rhinorrhea (80.5%) in children. For 82.2% of absences, the circumstances or reasons for the absence were discussed with a child care staff member. Of 538 absences due to illness that child care staff discussed with parents, there were 45 inappropriate exclusions (8.4% of illnesses discussed), 91 appropriate exclusions (16.9% of illnesses discussed), and 402 cases (74.7%) in which no recommendation for exclusion was made.Misconceptions regarding the need for antibiotics for URIs are common among child care staff. However, day care staff do not pressure parents to seek medical attention or antibiotics.

    View details for Web of Science ID 000224035900011

    View details for PubMedID 15369413

  • Acute care and antibiotic seeking for upper respiratory tract infections for children in day care - Parental knowledge and day care center policies ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Friedman, J. F., Lee, G. M., Kleinman, K. P., Finkelstein, J. A. 2003; 157 (4): 369-374

    Abstract

    Children who attend day care are high consumers of antibiotics. Studies suggest that physicians prescribe unnecessary antibiotics for upper respiratory tract infections (URIs) for children who attend day care on the basis of perceived pressure from parents and/or day care centers.To determine both parental and day care-level predictors of acute care and antibiotic seeking for children who attend day care.We conducted a day care center-based cross-sectional survey of parents and day care center staff. Two hundred eleven parents of children attending 36 day care centers in Massachusetts completed a survey. Day care center staff completed a separate survey addressing their day care center's policies for ill children.Few parents reported day care staff pressure to seek care from a physician (3.9%) or antibiotics (1.9%). In multivariate models, higher parental knowledge about URIs was related to decreased acute care seeking for 3 upper respiratory symptoms (clear rhinorrhea, green rhinorrhea, and cough) in the absence of fever (odds ratios and 95% confidence intervals: 0.45 [0.31-0.65], 0.66 [0.52-0.85], and 0.57 [0.45-0.72], respectively). Parent-reported acute care seeking was not related to a day care center's polices for exclusion or physician clearance for these illnesses. Similar results were also found for the parental belief that antibiotics expedite return to day care for these symptoms.Although it has been suggested that inappropriate day care center policies for exclusion motivate parental acute care and antibiotic seeking, this study suggests that parental knowledge is a more important predictor of these reported behaviors than are day care center policies.

    View details for Web of Science ID 000182096100012

    View details for PubMedID 12695233

  • Misconceptions about colds and predictors of health service utilization PEDIATRICS Lee, G. M., Friedman, J. F., Ross-Degnan, D., Hibberd, P. L., GOLDMANN, D. A. 2003; 111 (2): 231-236

    Abstract

    Colds accounted for 1.6 million emergency department (ED) visits and 25 million ambulatory visits by children and adults in 1998. Although most colds are caused by viruses and do not require medical intervention, many families seek health care for the treatment of colds. Parental misconceptions about the cause and appropriate treatment of colds may contribute to unnecessary health service utilization. The objective of this study was to determine predictors of reported ED use and ambulatory care use for colds among families with young children.This study was an observational, prospective cohort study to determine attack rates for respiratory illnesses within families that have at least 1 child who is 6 months to 5 years of age and enrolled in out-of-home child care. Families were randomly selected from 5 pediatric practices in Massachusetts and were considered eligible when the child was enrolled in child care with at least 5 other children for >or=10 hours per week. Enrolled families were asked to complete a survey that assessed knowledge about colds, antibiotic indications, and frequency of health service utilization. Predictors of self-reported use of health care services were assessed in multivariate logistic regression models.Of the 261 families enrolled in the study, 197 families (75%) returned completed surveys. Although 93% of parents understood that viruses caused colds, 66% of parents also believed that colds were caused by bacteria. Fifty-three percent believed that antibiotics were needed to treat colds. Parents reported that they would visit the ED (23%) or their doctor's office (60%) when their child had a cold. Predictors of ED use on multivariate analysis included Medicaid insurance (odds ratio [OR]: 17.6 [2.2-139.3]), history of wheezing (OR: 18.3 [4.4-75.8]), and belief that antibiotics treat colds (OR: 4.2 [1.4-12.9]). Predictors of ambulatory care use included parent younger than 30 years (OR: 10.0 [1.6-64.3]), history of wheezing (OR: 5.6 [1.1-29.7]), and belief that antibiotics treat colds (OR: 3.8 [1.7-8.5]).Misconceptions about the appropriate treatment of colds are predictive of increased health service utilization. Targeted educational interventions for families may reduce inappropriate antibiotic-seeking behavior and unnecessary health service utilization for colds.

    View details for Web of Science ID 000180709100017

    View details for PubMedID 12563044

  • Management of febrile children in the age of the conjugate pneumococcal vaccine: A cost-effectiveness analysis PEDIATRICS Lee, G. M., Fleisher, G. R., Harper, M. B. 2001; 108 (4): 835-844

    Abstract

    The optimal practice management of highly febrile 3- to 36-month-old children without a focal source has been controversial. The recent release of a conjugate pneumococcal vaccine may reduce the rate of occult bacteremia and alter the utility of empiric testing and treatment. The objective of this study was to determine the cost-effectiveness of 6 different management strategies of febrile 3- to 36-month-old children at current and declining rates of occult pneumococcal bacteremia.A cost-effectiveness (CE) analysis was performed to compare the strategies of "no work-up," "clinical judgment," "blood culture," "blood culture + treatment," "complete blood count (CBC) + selective blood culture and treatment," and "CBC and blood culture + selective treatment." A hypothetical cohort of 100 000 children who were 3 to 36 months of age and had a fever of >/=39 degrees C and no source of infection was modeled for each strategy. Our main outcome measures were cases of meningitis prevented, life-years saved compared with "no work-up," total cost (1999 dollars), and incremental CE ratios.When compared with "no work-up," the strategy of "CBC + selective blood culture and treatment" using a white blood cell (WBC) cutoff of 15 x 10(9)/L prevents 48 cases of meningitis, saves 86 life-years per 100 000 patients, and is less costly at the current rate of bacteremia (1.5%). Using the strategy of "CBC + selective blood culture and treatment" with a lower WBC cutoff of 10 x 10(9)/L costs an additional $72 300 per life-year saved. If the rate of bacteremia declines to 0.5%, then the incremental CE ratio of "clinical judgment" compared with "no work-up" is $38 000 per life-year saved; however, strategies that include empiric testing or treatment result in CE ratios greater than $300 000 per life-year saved."CBC + selective blood culture and treatment" using a WBC cutoff of 15 x 10(9)/L is cost-effective at the current rate of pneumococcal bacteremia. If the rate of occult bacteremia falls below 0.5% with widespread use of the conjugate pneumococcal vaccine, then strategies that use empiric testing and treatment should be eliminated.

    View details for Web of Science ID 000171319600022

    View details for PubMedID 11581433

  • Risk of bacteremia for febrile young children in the post-Haemophilus influenzae type b era ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Lee, G. M., Harper, M. B. 1998; 152 (7): 624-628

    Abstract

    To determine the risk for bacteremia, in the post-Haemophilus influenzae type b era, in a prospective cohort of well-appearing febrile children 3 to 36 months of age with no obvious source of infection; and to compare the predictive abilities of objective criteria in identification of children with occult pneumococcal bacteremia from those at risk.All children seen from 1993 through 1996, 3 to 36 months of age with a temperature of 39.0 degrees C or higher, no identified source of infection (except otitis media), and discharged to home were considered to be at risk for occult bacteremia and included in the study.Urban pediatric emergency department.Of 199868 patient visits to the emergency department, 1911 children were considered to be at risk for occult bacteremia. Blood cultures were obtained from 9465 (79%). A total of 149 blood cultures contained pathogenic organisms, indicating a rate of occult bacteremia of 1.57% (95% confidence intervals: 1.32%-1.83%). White blood cell count and absolute neutrophil count were the best predictors for occult pneumococcal bacteremia. Using a white blood cell count cutoff value of 15 cells x 10(9)/L (sensitivity, 86%; specificity, 77%; and positive predictive value, 5.1%) would result in the treatment of approximately 19 nonbacteremic children for each bacteremic child treated.The prevalence of occult bacteremia in children 3 to 36 months old with temperatures of 39.0 degrees C or higher and no obvious source of infection is 1.6%. The white blood cell and absolute neutrophil counts are the most accurate predictors of occult pneumococcal bacteremia and when available should be used if presumptive antibiotic therapy is being considered.

    View details for Web of Science ID 000074610000002

    View details for PubMedID 9667531