Effect of High-Dose Vitamin D Supplementation on Upper Respiratory Tract Infection Symptom Severity in Healthy Children.

Background: Observational studies support the role of vitamin D in reducing viral upper respiratory tract infection (URTI) symptom severity in adults and children. This study assessed whether wintertime high-dose vitamin D supplementation (2000 IU/day) reduces URTI symptom severity compared with standard-dose (400 IU/day) supplementation in preschool children. Secondary objectives were to assess effects of high-dose supplementation on outpatient physician visits, emergency department (ED) visits and antibiotic prescriptions for URTI.

DNA methylation patterns are related to co-morbidity status and circulating C-reactive protein levels in the nursing home elderly.

Elderly residents of long-term care commonly exhibit a number of age-related health deficits, including impaired physical and cognitive function, chronic illnesses, and chronic inflammation. Given our previous data relating the phenotype and function of innate and adaptive leukocytes from the nursing home elderly to chronic conditions and inflammatory biomarkers, we hypothesized that these factors would influence the regulatory programming of immune cells, thereby contributing to immune dysfunction. Since DNA methylation represents both an important regulatory mechanism of cells as well as a biomarker of health and disease, we sought to characterize the methylome of peripheral blood mononuclear cells (PBMCs) from the nursing home elderly (n=23; 82-98years old, 70% female), and compare these patterns to pathological factors such as dementia, co-morbidity score and frailty, and immune-related factors such as serum C-reactive protein (CRP) and cytokine levels and varicella-zoster virus (VZV) vaccine responsiveness.

Serum C-Reactive Protein and Congestive Heart Failure as Significant Predictors of Herpes Zoster Vaccine Response in Elderly Nursing Home Residents.

Background: Elderly long-term care residents often exhibit a myriad of risk factors for immune dysfunction, including chronic inflammation and multiple comorbid conditions, which undoubtedly contribute to their enhanced susceptibility to infection. Hence, understanding the factors required for optimal vaccine responsiveness is critical.

Methods: We examined 187 elderly nursing home residents (aged 80-102 years) and 50 community-dwelling seniors (aged 60-75 years) immunized with the live-attenuated varicella-zoster virus (VZV) vaccine.

Effect of High-Dose vs Standard-Dose Wintertime Vitamin D Supplementation on Viral Upper Respiratory Tract Infections in Young Healthy Children.

Importance: Epidemiological studies support a link between low 25-hydroxyvitamin D levels and a higher risk of viral upper respiratory tract infections. However, whether winter supplementation of vitamin D reduces the risk among children is unknown.

Objective: To determine whether high-dose vs standard-dose vitamin D supplementation reduces the incidence of wintertime upper respiratory tract infections in young children.

Immunogenicity of Varicella Vaccine and Immunologic Predictors of Response in a Cohort of Elderly Nursing Home Residents.

Background:  Little is known about the immunogenicity of live-attenuated Oka/Merck varicella zoster virus (VZV)-containing vaccine (hereafter, "varicella vaccine") in frail nursing homes residents nor about immune phenotypes associated with a response.

Methods:  A cohort of 190 frail nursing home residents aged 80-102 years and a cohort of 50 community-dwelling seniors aged 60-75 years (a comparison group) received varicella vaccine. Interferon γ (IFN-γ) enzyme-linked immunospot assays were performed before and 6 weeks after vaccination.

Infection management and multidrug-resistant organisms in nursing home residents with advanced dementia.

Importance: Infection management in advanced dementia has important implications for (1) providing high-quality care to patients near the end of life and (2) minimizing the public health threat posed by the emergence of multidrug-resistant organisms (MDROs).

Design, Setting, And Participants: Prospective cohort study of 362 residents with advanced dementia and their health care proxies in 35 Boston area nursing homes for up to 12 months.

Main Outcomes And Measures: Data were collected to characterize suspected infections, use of antimicrobial agents (antimicrobials), clinician counseling of proxies about antimicrobials, proxy preference for the goals of care, and colonization with MDROs (methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and multidrug-resistant gram-negative bacteria).

DO IT Trial: vitamin D Outcomes and Interventions in Toddlers - a TARGet Kids! randomized controlled trial.

Background: Vitamin D levels are alarmingly low (<75 nmol/L) in 65-70% of North American children older than 1 year. An increased risk of viral upper respiratory tract infections (URTI), asthma-related hospitalizations and use of anti-inflammatory medication have all been linked with low vitamin D. No study has determined whether wintertime vitamin D supplementation can reduce the risk of URTI and asthma exacerbations, two of the most common and costly illnesses of early childhood.

Challenges in assessing nursing home residents with advanced dementia for suspected urinary tract infections.

Objectives: To describe the presentation of suspected urinary tract infections (UTIs) in nursing home (NH) residents with advanced dementia and how they align with minimum criteria to justify antimicrobial initiation.

Design: Twelve-month prospective study.

Setting: Twenty-five NHs.

The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced by age.

As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence that these global changes impact virus-specific CD8+ T cell immunity in the elderly is lacking. To gain further insight into the functionality of virus-specific CD8+ T cells in older individuals, we interrogated a cohort of individuals who were acutely infected with West Nile virus (WNV) and chronically infected with Epstein Barr virus (EBV) and Cytomegalovirus (CMV).

Effects of school closure on incidence of pandemic influenza in Alberta, Canada.

Background: Control of pandemic influenza by social-distancing measures, such as school closures, is a controversial aspect of pandemic planning. However, investigations of the extent to which these measures actually affect the progression of a pandemic have been limited.

Objective: To examine correlations between the incidence of pandemic H1N1 (pH1N1) influenza in Alberta, Canada, in 2009 and school closures or weather changes, and to estimate the effects of school closures and weather changes on pH1N1 transmission.

Prognosis of West Nile virus associated acute flaccid paralysis: a case series.

Introduction: Little is known about the long-term health related quality of life outcomes in patients with West Nile virus associated acute flaccid paralysis. We describe the quality of life scores of seven patients with acute flaccid paralysis who presented to hospital between 2003 and 2006, and were followed for up to two years.

Case Presentations: Between 2003 and 2006, 157 symptomatic patients with West Nile virus were enrolled in a longitudinal cohort study of West Nile virus in Canada.

Surface phenotype and functionality of WNV specific T cells differ with age and disease severity.

West Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inadequate antiviral T cell immunity was involved in neurologic sequelae and the more severe outcomes associated with age. We previously reported the discovery of six HLA-A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in naturally infected individuals being SVG9 (Env) and SLF9 (NS4b).

Identification of CD8+ T cell epitopes in the West Nile virus polyprotein by reverse-immunology using NetCTL.

Background: West Nile virus (WNV) is a growing threat to public health and a greater understanding of the immune response raised against WNV is important for the development of prophylactic and therapeutic strategies.

Methodology/principal Findings: In a reverse-immunology approach, we used bioinformatics methods to predict WNV-specific CD8(+) T cell epitopes and selected a set of peptides that constitutes maximum coverage of 20 fully-sequenced WNV strains. We then tested these putative epitopes for cellular reactivity in a cohort of WNV-infected patients.

Research preparedness paves the way to respond to pandemic H1N1 2009 influenza virus.

The international community has been preparing for an influenza pandemic because of the threat posed by H5N1 avian influenza. Over the past several years, Canada has dedicated funding to boost capacity for research, and public health and health care system readiness and response in the event of a pandemic. The current H1N1/09 influenza pandemic is now testing our readiness.

Hand hygiene in the intensive care unit: prospective observations of clinical practice.

Introduction: Adherence to hand hygiene recommendations in the intensive care unit (ICU) is variable and moderate, at best.

Objectives: To measure adherence to hand hygiene recommendations among ICU clinicians in a prospective observational study in 6 multidisciplinary ICUs among 4 hospitals.

Patients And Methods: We observed 115 clinicians (64 nurses, 21 respiratory therapists, 18 residents and 12 physicians) during 1 patient encounter, each.

Deciphering epitope specificities within polyserum using affinity selection of random peptides and a novel algorithm based on pattern recognition theory.

While numerous strategies have been developed to map epitope specificities for monoclonal antibodies, few have been designed for elucidating epitope specificity within complex polysera. We have developed a novel algorithm based on pattern recognition theory that can be used to characterize the breadth of epitope specificities within a polyserum based on affinity selection of random peptides. To attribute these random peptides to a specific epitope, the sequences of the affinity-selected peptides were matched against a database of random peptides selected using well-described monoclonal antibodies.

A novel computer algorithm improves antibody epitope prediction using affinity-selected mimotopes: a case study using monoclonal antibodies against the West Nile virus E protein.

Understanding antibody function is often enhanced by knowledge of the specific binding epitope. Here, we describe a computer algorithm that permits epitope prediction based on a collection of random peptide epitopes (mimotopes) isolated by antibody affinity purification. We applied this methodology to the prediction of epitopes for five monoclonal antibodies against the West Nile virus (WNV) E protein, two of which exhibit therapeutic activity in vivo.

The memory T cell response to West Nile virus in symptomatic humans following natural infection is not influenced by age and is dominated by a restricted set of CD8+ T cell epitopes.

We examined the West Nile virus (WNV)-specific T cell response in a cohort of 52 patients with symptomatic WNV infections, including neuroinvasive and non-invasive disease. Although all virus proteins were shown to contain T cell epitopes, certain proteins, such as E, were more commonly targeted by the T cell response. Most patients exhibited reactivity toward 3-4 individual WNV peptides; however, several patients exhibited reactivity toward >10 individual peptides.

Comparing estimates of influenza-associated hospitalization and death among adults with congestive heart failure based on how influenza season is defined.

Background: There is little consensus about how the influenza season should be defined in studies that assess influenza-attributable risk. The objective of this study was to compare estimates of influenza-associated risk in a defined clinical population using four different methods of defining the influenza season.

Methods: Using the Studies of Left Ventricular Dysfunction (SOLVD) clinical database and national influenza surveillance data from 1986-87 to 1990-91, four definitions were used to assess influenza-associated risk: (a) three-week moving average of positive influenza isolates is at least 5%, (b) three-week moving average of positive influenza isolates is at least 10%, (c) first and last positive influenza isolate are identified, and (d) 5% of total number of positive isolates for the season are obtained.

Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome.

It is not understood how immune inflammation influences the pathogenesis of severe acute respiratory syndrome (SARS). One area of strong controversy is the role of interferon (IFN) responses in the natural history of SARS. The fact that the majority of SARS patients recover after relatively moderate illness suggests that the prevailing notion of deficient type I IFN-mediated immunity, with hypercytokinemia driving a poor clinical course, is oversimplified.

Pneumonia and lower respiratory infections in nursing home residents: predictors of hospitalization and mortality.

Objectives: To compare predictors of hospitalization and death in nursing home residents with pneumonia and other lower respiratory infections (LRIs).

Design: A nested cohort study.

Setting: Nine nursing homes in southern Ontario.

Interobserver reliability of radiologists' interpretations of mobile chest radiographs for nursing home-acquired pneumonia.

Objectives: To determine the interobserver reliability of radiologists' interpretations of mobile chest radiographs for nursing home-acquired pneumonia.

Design: A cross-sectional reliability study.

Setting: Nursing homes and an acute care hospital.

Pneumonia in nursing homes and long-term care facilities.

This article reviews the epidemiology of pneumonia in residents of nursing homes and other long-term care facilities (LTCFs). Streptococcus pneumoniae is the most important cause of pneumonia in residents of nursing homes and LTCFs. Factors suggestive of aspiration are the most important risk factors for pneumonia in this population.

Nursing home-acquired pneumonia: an emergency department treatment algorithm.

Nursing home-acquired pneumonia (NHAP) is a leading cause of morbidity, hospitalization, and mortality among older nursing home residents. Too often, these patients are erroneously grouped with cases of community-acquired and hospital-acquired pneumonia. Yet, they differ in terms of most common pathogens, significant underlying disease, impaired functional and cognitive status, and poor nutrition.