Pharmacogenomic test that predicts response to inhaled corticosteroids in adults with asthma likely to be cost-saving

Aim: To identify the clinical and economic circumstances under which a pharmacogenomic test that predicts response to inhaled corticosteroids might be a cost-effective option for individuals with asthma. Materials & methods: We synthesized published data on clinical and economic outcomes to project 10-year costs, quality-adjusted life-years and cost–effectiveness of pharmacogenomic testing for inhaled corticosteroid response. We assumed the pharmacogenomic test cost was $500 with a sensitivity and specificity of 84 and 98%, respectively. These were varied in sensitivity analyses. Results: Both strategies, pharmacogenomic testing for inhaled corticosteroid response and no testing conferred 7.1 quality-adjusted life-years. Compared with no testing, pharmacogenomic testing costs less. Conclusion: Pharmacogenomic testing for asthma is cost-saving and noninferior in improving health

Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys

African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIVagmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms

Guillain-Barré Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009–2011

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

Inhibition of Adaptive Immune Responses Leads to a Fatal Clinical Outcome in SIV-Infected Pigtailed Macaques but Not Vervet African Green Monkeys

African green monkeys (AGM) and other natural hosts for simian immunodeficiency virus (SIV) do not develop an AIDS-like disease following SIV infection. To evaluate differences in the role of SIV-specific adaptive immune responses between natural and nonnatural hosts, we used SIVagmVer90 to infect vervet AGM and pigtailed macaques (PTM). This infection results in robust viral replication in both vervet AGM and pigtailed macaques (PTM) but only induces AIDS in the latter species. We delayed the development of adaptive immune responses through combined administration of anti-CD8 and anti-CD20 lymphocyte-depleting antibodies during primary infection of PTM (n = 4) and AGM (n = 4), and compared these animals to historical controls infected with the same virus. Lymphocyte depletion resulted in a 1-log increase in primary viremia and a 4-log increase in post-acute viremia in PTM. Three of the four PTM had to be euthanized within 6 weeks of inoculation due to massive CMV reactivation and disease. In contrast, all four lymphocyte-depleted AGM remained healthy. The lymphocyte-depleted AGM showed only a trend toward a prolongation in peak viremia but the groups were indistinguishable during chronic infection. These data show that adaptive immune responses are critical for controlling disease progression in pathogenic SIV infection in PTM. However, the maintenance of a disease-free course of SIV infection in AGM likely depends on a number of mechanisms including non-adaptive immune mechanisms

Immunization, Antibiotic Use, and Pneumococcal Colonization Over a 15-Year Period.

BackgroundRates 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.MethodsThis 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.ResultsAmong 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.ConclusionsDespite 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

Immunization, Antibiotic Use, and Pneumococcal Colonization Over a 15-Year Period.

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

Impact of Medicare’s Hospital-Acquired Condition Policy on Infections in Safety Net and Non–Safety Net Hospitals

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

C-B5-02: H1N1 Vaccine Safety Monitoring in the Vaccine Safety Datalink Project: New Challenges and Useful Lessons

Background and Aims: The worldwide introduction of influenza A (H1N1) vaccines in fall 2009 has raised widespread public questions about the safety of these new vaccines. The Vaccine Safety Datalink Project, a collaboration among CDC and eight health care systems in the HMORN, began accelerated monitoring of this vaccine’s safety in early fall 2009