Stefan Gravenstein

Seasonal Influenza in Adults and Children—Diagnosis, Treatment, Chemoprophylaxis, and Institutional Outbreak Management: Clinical Practice Guidelines of the Infectious Diseases Society of America

Guidelines for the treatment of persons with influenza virus infection were prepared by an Expert Panel of the Infectious Diseases Society of America. The evidence-based guidelines encompass diagnostic issues, treatment and chemoprophylaxis with antiviral medications, and issues related to institutional outbreak management for seasonal (interpandemic) influenza. They are intended for use by physicians in all medical specialties with direct patient care, because influenza virus infection is common in communities during influenza season and may be encountered by practitioners caring for a wide variety of patients.

Influenza estacional en adultos y niños—Diagnóstico, tratamiento, quimioprofilaxis y control de brotes institucionales: Guías de práctica clínica de la Sociedad de Enfermedades Infecciosas de Estados Unidos de América

Abstract Un Grupo de Expertos de la Sociedad de Enfermedades Infecciosas de los Estados Unidos de América elaboró las guias para el tratamiento de personas infectadas por el virus de la influenza. Estas guias basadas en datos y pruebas cientificas comprenden el diagnóstico, el tratamiento y la quimioprofilaxis con medicamentos antivirales, además de temas relacionados con el control de brotes de influenza estacional (interpandémicas) en ámbitos institucionales. Están destinadas a los médicos de todas las especialidades a cargo de la atención directa de pacientes porque los médicos generales que atienden una gran variedad de casos son los que se enfrentan con la influenza, frecuente en el ámbito comunitario durante la temporada de influenza.

Age-related impaired type 1 T cell responses to influenza: reduced activation ex vivo, decreased expansion in CTL culture in vitro, and blunted response to influenza vaccination in vivo in the elderly.

The objective of this study was to analyze the changes in the type 1 T cell response, including the CD4+ Th1 and CD8+ T cell responses, to influenza in the elderly compared with those in young adults. PBMC activated ex vivo with influenza virus exhibited an age-related decline in type 1 T cell response, shown by the decline in the frequency of IFN-γ-secreting memory T cells specific for influenza (IFN-γ+ ISMT) using ELISPOT or intracellular cytokine staining. The reduced frequency of IFN-γ+ ISMT was accompanied by a reduced level of IFN-γ secretion per cell in elderly subjects. Tetramer staining, combined with IFN-γ ELISPOT, indicated that the decline in IFN-γ+, influenza M1-peptide-specific T cells was not due to attrition of the T cell repertoire, but, rather, to the functional loss of ISMT with age. In addition, the decline in type 1 T cell response was not due to an increase in Th2 response or defects in APCs from the elderly. The expansion of influenza-specific CD8+ T cells in CTL cultures was reduced in the elderly. Compared with young subjects, frail elderly subjects also exhibited a blunted and somewhat delayed type 1 T cell response to influenza vaccination, which correlated positively with the reduced IgG1 subtype and the total Ab response. Taken together, these data demonstrate that there is a decline in the type 1 T cell response to influenza with age that may help explain the age-related decline in vaccine efficacy and the increases in influenza morbidity and mortality.

Immunization of healthy adults with a single recombinant pneumococcal surface protein A (PspA) variant stimulates broadly cross-reactive antibodies to heterologous PspA molecules.

Pneumococcal surface protein A (PspA) is a highly variable protein found on all strains of pneumococci. To be successful, a PspA-based vaccine for S. pneumoniae must induce antibodies that are broadly cross-reactive. To address whether cross-reactive antibodies could be induced in man, we evaluated serum from adults immunized with recombinant clade 2 PspA from strain Rx1. Immunization with 5-125 microg rPspA lead to a significant increase in circulating anti-PspA antibodies, as well as antibodies reactive to heterologous rPspA molecules. Increased binding of post-immune sera to 37 pneumococcal strains expressing a variety of PspA and capsule types was observed, versus pre-immune sera. The extent of cross-clade reactivity of human anti-rPspA followed roughly the amount of sequence homology to the non-clade 2 antigens. It is hypothesized that priming of humans by natural exposure to S. pneumoniae contributes to the breadth of the cross-reactivity of antibody to PspA.

Clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Diseases Society of America.

Residents of long-term care facilities (LTCFs) are at great risk for infection. Most residents are older and have multiple comorbidities that complicate recognition of infection; for example, typically defined fever is absent in more than one-half of LTCF residents with serious infection. Furthermore, LTCFs often do not have the on-site equipment or personnel to evaluate suspected infection in the fashion typically performed in acute care hospitals. In recognition of the differences between LTCFs and hospitals with regard to hosts and resources present, the Infectious Diseases Society of America first provided guidelines for evaluation of fever and infection in LTCF residents in 2000. The guideline presented here represents the second edition, updated by data generated over the intervening 8 years. It focuses on the typical elderly person institutionalized with multiple chronic comorbidities and functional disabilities (e.g., a nursing home resident). Specific topic reviews and recommendations are provided with regard to what resources are typically available to evaluate suspected infection, what symptoms and signs suggest infection in a resident of an LTCF, who should initially evaluate the resident with suspected infection, what clinical evaluation should be performed, how LTCF staff can effectively communicate about possible infection with clinicians, and what laboratory tests should be ordered. Finally, a general outline of how a suspected outbreak of a specific infectious disease should be investigated in an LTCF is provided.

Long-Term Use of Oseltamivir for the Prophylaxis of Influenza in a Vaccinated Frail Older Population

OBJECTIVES To investigate the efficacy of once-daily oral oseltamivir for 6 weeks (Tamiflu) in prophylaxis against laboratory-confirmed clinical influenza in frail older subjects living in homes for seniors and to determine the safety and tolerability of long-term oseltamivir. DESIGN Double-blind, placebo-controlled, parallel-group, randomized, multicenter study. SETTING Thirty-one residential homes for seniors across United States and Europe. PARTICIPANTS Five hundred forty-eight frail older occupants (mean age 81 years, >80% vaccinated). INTERVENTION Prophylaxis with oseltamivir 75 mg or placebo once daily for 6 weeks, beginning when influenza was detected locally. MEASUREMENTS The primary efficacy endpoint was laboratory-confirmed clinical influenza. RESULTS Oseltamivir administration resulted in a 92% reduction in the incidence of laboratory-confirmed clinical influenza compared with placebo (placebo 12/272 (4.4%), oseltamivir 1/276 (0.4%); P = .002). Of subjects vaccinated against influenza, oseltamivir was 91% effective in preventing laboratory-confirmed clinical influenza (placebo 11/218 (5.0%), oseltamivir 1/222 (0.5%); P = .003). Oseltamivir use was associated with a significant reduction in the incidence of secondary complications (placebo 7/272 (2.6%), oseltamivir 1/276 (0.4%); P = .037). Although nearly all subjects were taking concomitant medication both before and during the study, oseltamivir was well tolerated. A similar incidence of adverse events, including gastrointestinal effects, occurred in both groups. There was no suppression of antibody response in oseltamivir recipients. CONCLUSION Oral oseltamivir 75 mg once daily for 6 weeks effectively prevented clinical influenza in vaccinated frail older subjects using significant concomitant medications in a residential care setting. The treatment was well tolerated and provided additional protection to that afforded by vaccination.

The Care Transitions Intervention: Translating From Efficacy to Effectiveness

BACKGROUND Well-executed communication among hospital providers, patients, and receiving providers at the time of hospital discharge contributes to better health outcomes and lower overall health care costs. The Care Transitions Intervention has reduced 30-day hospital readmissions by 30% in a randomized controlled trial in an integrated health system but requires real-world testing to establish effectiveness in other settings. We hypothesized that coaching would reduce 30-day readmission rates for fee-for-service Medicare beneficiaries, even in open, urban health care delivery systems. METHODS This was a quasi-experimental prospective cohort study. From January 1, 2009, through June 30, 2010, coaches recruited a convenience sample of fee-for-service Medicare patients in 6 Rhode Island hospitals to receive the Care Transitions Intervention. We paired coaching data with Medicare claims and enrollment data and used logistic regression to compare the odds of 30-day readmission for the intervention group vs internal and external control groups. RESULTS Compared with individuals who did not receive any part of the intervention (20.0% readmission rate), 30-day readmissions were fewer for participants who received coaching (12.8%; odds ratio, 0.61; 95% confidence interval, 0.42-0.88). Individuals in the internal control group (declined to participate or were lost to follow-up before completing a home visit) had readmission rates similar to those of the external control group (18.6%; odds ratio, 0.94, 95% confidence interval, 0.77-1.14). CONCLUSIONS The Care Transitions Intervention appears to be effective in this real-world implementation. This finding underscores the opportunity to improve health outcomes beginning at the time of discharge in open health care settings.

Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood.

Dendritic cells (DC) are potent antigen-presenting cells that initiate and regulate T-cell responses. In this study, the numbers and functional cytokine secretions of plasmacytoid and myeloid DC (pDC and mDC, respectively) in peripheral blood from young and elderly subjects were compared. Overall, pDC numbers in peripheral blood were lower in healthy elderly compared with healthy young subjects (p = 0.016). In response to influenza virus stimulation, isolated pDC from healthy elderly subjects secreted less interferon (IFN)-alpha compared with those from healthy young subjects. The decline in IFN-alpha secretion was associated with a reduced proportion of pDC that expressed Toll-like receptor-7 or Toll-like receptor-9. In contrast, there was little difference in the numbers and cytokine secretion function between healthy young and healthy elderly subjects (p = 0.82). However, in peripheral blood from frail elderly subjects, the numbers of mDC were severely depleted as compared with either healthy young or elderly subjects (p = 0.014 and 0.007, respectively). Thus, aging was associated with the numerical and functional decline in pDC, but not mDC, in healthy young versus elderly subject group comparisons, while declining health in the elderly can profoundly impact mDC negatively. Because of the importance of pDC for antiviral responses, the age-related changes in pDC likely contribute to the impaired immune response to viral infections in elderly persons, especially when combined with the mDC dysfunction occurring in those with compromised health.

Drawing clocks and driving cars.

AbstractOBJECTIVE: The purpose of the study was to determine whether a new method of scoring the Clock Drawing Test (CDT) is a reliable and valid method for identifying older adults with declining driving competence. DESIGN: Prospective cohort study. SETTING: An outpatient driving evaluation clinic. PARTICIPANTS: One hundred nineteen community-dwelling, active drivers with a valid driver’s license, aged 60 and older referred for driving evaluation. MAIN OUTCOME MEASURES: The CDT and a driving test using a STISIM Drive simulator. RESULTS: The CDT showed a high level of accuracy in predicting driving simulation outcome (area under the receiver-operator curve, 0.90; 95% confidence interval, 0.82 to 0.95). CDT scoring scales were comparable and all correlations between CDT scores and driving performance were negative, implying that as the CDT score decreases, the number of errors increases. Interrater reliability of CDT scores was 0.95. Subjects scoring less than 5 out of 7 points on the CDT made significantly more driving errors, hazardous and in total (P<.001). CONCLUSIONS: The CDT can help establish problems with executive function and indicate the need for a formal driving evaluation. Our CDT scoring scale is a reliable, valid, and time-effective screening tool for identifying elderly drivers in need of further evaluation.

Efficacy of an Influenza Hemagglutinin‐Diphtheria Toxoid Conjugate Vaccine in Elderly Nursing Home Subjects During an Influenza Outbreak

To compare the efficacy of an influenza hemagglutinin‐diphtheria toxoid conjugate vaccine with the commercially available influenza hemagglutinin‐subunit vaccine in preventing influenza in older adults living in a nursing home.