Impact of Hospital Operating Margin on Central Line-Associated Bloodstream Infections Following Medicare's Hospital-Acquired Conditions Payment Policy.

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.

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. Original submitted 19 November 2014; Revision submitted 23 February 2015.

Impact of Medicare's Hospital-Acquired Condition policy on infections in safety net and non-safety net hospitals.

BACKGROUND: Policymakers may wish to align healthcare payment and quality of care while minimizing unintended consequences, particularly for safety net hospitals. OBJECTIVE: 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. DESIGN: Interrupted time-series design. SETTING AND PARTICIPANTS: 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. RESULTS: 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). CONCLUSIONS: 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.

Pharmacogenomic test that predicts response to ß2-agonists in adults with asthma is cost effective.

BACKGROUND: Pharmacogenomic tests that predict which asthma patients are likely to respond to ß2-agonists hold promise to improve care for asthma. OBJECTIVE: To identify the clinical and economic circumstances under which a pharmacogenomic test that predicts response to ß2-agonists might or might not be an appropriate, cost-effective option. METHODS: We synthesized published data on clinical and economic outcomes in adults 18-35 to project 10-year costs, quality-adjusted life years and cost-effectiveness of pharmacogenomic testing for ß2-agonist response. RESULTS: Pharmacogenomic testing for ß2-agonist response conferred a cost-effectiveness ratio of $13,700 per quality-adjusted life year gained compared with no testing. CONCLUSION: Pharmacogenomic testing for ß2-agonist response in individuals with asthma is potentially cost effective and should be pursued by test developers.

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.

Guillain-Barré syndrome incidence in a large United States cohort (2000-2009).

BACKGROUND/AIM: We describe the incidence of Guillain-Barré syndrome (GBS) in a large United States cohort. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Suppression of adaptive immune responses during primary SIV infection of sabaeus African green monkeys delays partial containment of viremia but does not induce disease.

One of the most puzzling observations in HIV research is the lack of pathogenicity in most nonhuman primate species that are natural hosts of simian immunodeficiency virus (SIV) infection. Despite this, natural hosts experience a level of viremia similar to humans infected with HIV or macaques infected with SIV. To determine the role of adaptive immune responses in viral containment and lack of disease, we delayed the generation of cellular and humoral immune responses by administering anti-CD8- and anti-CD20 lymphocyte-depleting antibodies to sabaeus African green monkeys (Chlorocebus sabaeus) before challenge with SIV(sab9315BR). In vivo lymphocyte depletion during primary infection resulted in a brief elevation of viremia but not in disease. Based on the magnitude and timing of SIV-specific CD8(+) T-cell responses in the lymphocyte-depleted animals, CD8(+) T-cell responses appear to contribute to viral containment in natural hosts. We found no evidence for a contribution of humoral immune responses in viral containment. These studies indicate that natural hosts have developed mechanisms in addition to classic adaptive immune responses to cope with this lentiviral infection. Thus, adaptive immune responses in natural hosts appear to be less critical for viral containment than in HIV infection.

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 SIV(agmVer90) 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.

Simian immunodeficiency virus (SIV)-specific CD8+ T-cell responses in vervet African green monkeys chronically infected with SIVagm.

African green monkeys (AGM) do not develop overt signs of disease following simian immunodeficiency virus (SIV) infection. While it is still unknown how natural hosts like AGM can cope with this lentivirus infection, a large number of investigations have shown that CD8(+) T-cell responses are critical for the containment of AIDS viruses in humans and Asian nonhuman primates. Here we have compared the phenotypes of T-cell subsets and magnitudes of SIV-specific CD8(+) T-cell responses in vervet AGM chronically infected with SIVagm and rhesus monkeys (RM) infected with SIVmac. In comparison to RM, vervet AGM exhibited weaker signs of immune activation and associated proliferation of CD8(+) T cells as detected by granzyme B, Ki-67, and programmed death 1 staining. By gamma interferon enzyme-linked immunospot assay and intracellular cytokine staining, SIV Gag- and Env-specific immune responses were detectable at variable but lower levels in vervet AGM than in RM. These observations demonstrate that natural hosts like SIV-infected vervet AGM develop SIV-specific T-cell responses, but the disease-free course of infection does not depend on the generation of robust CD8(+) T-cell responses.

Contribution of CD8+ T cells to containment of viral replication and emergence of mutations in Mamu-A*01-restricted epitopes in Simian immunodeficiency virus-infected rhesus monkeys.

Here, we investigated the containment of virus replication in simian immunodeficiency virus (SIV) infection by CD8(+) lymphocytes. Escape mutations in Mamu-A*01 epitopes appeared first in SIV Tat TL8 and then in SIV Gag p11C. The appearance of escape mutations in SIV Gag p11C was coincident with compensatory changes outside of the epitope. Eliminating CD8(+) lymphocytes from rhesus monkeys during primary infection resulted in more rapid disease progression that was associated with preservation of canonical epitopes. These results confirm the importance of cytotoxic T cells in controlling viremia and the constraint on epitope sequences that require compensatory changes to go to fixation.

Increased loss of CCR5+ CD45RA- CD4+ T cells in CD8+ lymphocyte-depleted Simian immunodeficiency virus-infected rhesus monkeys.

Previously we have shown that CD8(+) T cells are critical for containment of simian immunodeficiency virus (SIV) viremia and that rapid and profound depletion of CD4(+) T cells occurs in the intestinal tract of acutely infected macaques. To determine the impact of SIV-specific CD8(+) T-cell responses on the magnitude of the CD4(+) T-cell depletion, we investigated the effect of CD8(+) lymphocyte depletion during primary SIV infection on CD4(+) T-cell subsets and function in peripheral blood, lymph nodes, and intestinal tissues. In peripheral blood, CD8(+) lymphocyte-depletion changed the dynamics of CD4(+) T-cell loss, resulting in a more pronounced loss 2 weeks after infection, followed by a temporal rebound approximately 2 months after infection, when absolute numbers of CD4(+) T cells were restored to baseline levels. These CD4(+) T cells showed a markedly skewed phenotype, however, as there were decreased levels of memory cells in CD8(+) lymphocyte-depleted macaques compared to controls. In intestinal tissues and lymph nodes, we observed a significantly higher loss of CCR5(+) CD45RA(-) CD4(+) T cells in CD8(+) lymphocyte-depleted macaques than in controls, suggesting that these SIV-targeted CD4(+) T cells were eliminated more efficiently in CD8(+) lymphocyte-depleted animals. Also, CD8(+) lymphocyte depletion significantly affected the ability to generate SIV Gag-specific CD4(+) T-cell responses and neutralizing antibodies. These results reemphasize that SIV-specific CD8(+) T-cell responses are absolutely critical to initiate at least partial control of SIV infection.