Humoral and Cell-Mediated Immunity to Pandemic H1N1 Influenza in a Canadian Cohort One Year Post-Pandemic: Implications for Vaccination

We evaluated a cohort of Canadian donors for T cell and antibody responses against influenza A/California/7/2009 (pH1N1) at 8-10 months after the 2nd pandemic wave by flow cytometry and microneutralization assays. Memory CD8 T cell responses to pH1N1 were detectable in 58% (61/105) of donors. These responses were largely due to cross-reactive CD8 T cell epitopes as, for those donors tested, similar recall responses were obtained to A/California 2009 and A/PR8 1934 H1N1 Hviruses. Longitudinal analysis of a single infected individual showed only a small and transient increase in neutralizing antibody levels, but a robust CD8 T cell response that rose rapidly post symptom onset, peaking at 3 weeks, followed by a gradual decline to the baseline levels seen in a seroprevalence cohort post-pandemic. The magnitude of the influenza-specific CD8 T cell memory response at one year post-pandemic was similar in cases and controls as well as in vaccinated and unvaccinated donors, suggesting that any T cell boosting from infection was transient. Pandemic H1-specific antibodies were only detectable in approximately half of vaccinated donors. However, those who were vaccinated within a few months following infection had the highest persisting antibody titers, suggesting that vaccination shortly after influenza infection can boost or sustain antibody levels. For the most part the circulating influenza-specific T cell and serum antibody levels in the population at one year post-pandemic were not different between cases and controls, suggesting that natural infection does not lead to higher long term T cell and antibody responses in donors with pre-existing immunity to influenza. However, based on the responses of one longitudinal donor, it is possible for a small population of pre-existing cross-reactive memory CD8 T cells to expand rapidly following infection and this response may aid in viral clearance and contribute to a lessening of disease severity

The relationship of punishment- and victim-based moral orientation to prosocial, externalizing, and norm trespassing behaviour in delinquent and non-delinquent adolescents:a validation study of the Moral Orientation Measure

This study examined the reliability and validity of the Moral Orientation Measure (MOM), which was administered to 75 juvenile delinquents and 579 non-delinquent adolescents from lower socio-economic and educational backgrounds. Confirmatory factor analysis of a two-factor model, with punishment- and victim-based moral orientation as factors, showed an adequate fit to the data, indicating construct validity of the MOM. Moderate associations between moral orientation and sociomoral reasoning, as well as empathy, were also considered indicative of construct validity. Additional evidence for construct validity was found in only small associations between moral orientation and social desirability and verbal intelligence. Stronger victim-based orientation proved to be associated with less norm trespassing behaviour in non-delinquent adolescents and more prosocial behaviour in juvenile delinquents, which was considered indicative of concurrent validity. The results of this study strengthen the case for the MOM as a reliable and valid instrument to assess moral development in adolescents at risk of behavioural maladjustment, showing that moral orientation is differently associated with morally relevant behaviour in delinquent and non-delinquent adolescents

Influenza-Specific T Cells from Older People Are Enriched in the Late Effector Subset and Their Presence Inversely Correlates with Vaccine Response

T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1+CD57+ influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8+KLRG1+CD57+ population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age

Improving Patient Experience of Wait Times and Courtesy Through Electronic Sign-in and Notification in the Phlebotomy Clinic

Context.— The phlebotomy clinic, which sees on average 900 patients a day, was faced with issues of congestion and noise due to inefficient workflow and processes. The staff called each patient name for his or her turn, and patients were unsure of wait time and position in line. These factors led to unfavorable patient satisfaction regarding wait times and courtesy of the staff. Objective.— To improve patients' experience of wait times and courtesy in the phlebotomy clinic through an electronic sign-in and notification system, redesign of the area, and training of employees. Design.— An electronic sign-in and notification system was implemented in the phlebotomy clinic. Several sign-in stations and whiteboard wall monitors were installed in the clinic, along with a redesign of the patient flow. A Press Ganey survey was given to patients after their visit which included 3 questions related to wait times, courtesy, and information about delays, respectively. The mean responses for each month between March 2016 and December 2018 were aggregated and compared for each measure. Results.— Overall, wait time saw a 7.7% increase in satisfaction score, and courtesy saw a 1.0% increase in satisfaction score during the course of the several interventions that were introduced. The operational efficiency of the clinic also saw a veritable increase because the percent of patients processed within 20 minutes increased by 27%, from 62% (8212 of 13 245 blood draws) to 89% (11 703 of 13 143 blood draws). Conclusions.— The interventions implemented proved to increase the patient satisfaction in each of the measures. The electronic sign-in and whiteboards provided valuable information to both patients and staff. </jats:sec

Inpatient Preanalytic Process Improvements

Context.—Phlebotomy services are a common target for preanalytic improvements. Many new, quality engineering tools have recently been applied in clinical laboratories. However, data on relatively few projects have been published. This example describes a complete application of current, quality engineering tools to improve preanalytic phlebotomy services. Objectives.—To decrease the response time in the preanalytic inpatient laboratory by 25%, to reduce the number of incident reports related to preanalytic phlebotomy, and to make systematic process changes that satisfied the stakeholders. Design.—The Department of Laboratory Medicine, General Services Section, at the University of Texas MD Anderson Cancer Center (Houston) is responsible for inpatient phlebotomy in a 24-hour operation, which serves 689 inpatient beds. The study director was project director of the Division of Pathology and Laboratory Medicine's Quality Improvement Section and was assisted by 2 quality technologists and an industrial engineer from MD Anderson Office of Performance Improvement. Results.—After implementing each solution, using well-recognized, quality tools and metrics, the response time for blood collection decreased by 23%, which was close to meeting the original responsiveness goal of 25%. The response time between collection and arrival in the laboratory decreased by 8%. Applicable laboratory-related incident reports were reduced by 43%. Conclusions.—Comprehensive application of quality tools, such as statistical control charts, Pareto diagrams, value-stream maps, process failure modes and effects analyses, fishbone diagrams, solution prioritization matrices, and customer satisfaction surveys can significantly improve preset goals for inpatient phlebotomy.</jats:p

High Prevalence of Pre-Treatment HIV Drug Resistance in Papua New Guinea: Findings from the First Nationally Representative Pre-Treatment HIV Drug Resistance Study

Abstract Background: Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey.Methods: We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR.Results: A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4%. The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3%. The PDR prevalence rate among people reinitiating ART was 42.4%. Conclusions: PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG.</jats:p

High prevalence of pre-treatment HIV drug resistance in Papua New Guinea: findings from the first nationally representative pre-treatment HIV drug resistance study

Abstract Background Determining the prevalence of pre-treatment HIV drug resistance (PDR) is important to assess the effectiveness of first-line therapies. To determine PDR prevalence in Papua New Guinea (PNG), we conducted a nationally representative survey. Methods We used a two-stage cluster sampling method to recruit HIV treatment initiators with and without prior exposure to antiretroviral therapies (ART) in selected clinics. Dried blood spots were collected and tested for PDR. Results A total of 315 sequences were available for analysis. The overall PDR prevalence rate was 18.4% (95% CI 13.8–24.3%). The prevalence of PDR to non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs) was 17.8% (95% CI 13.6–23.0%) and of PDR to nucleoside reverse transcriptase inhibitors (NRTIs) was 6.3% (95% CI 1.6–17.1%). The PDR prevalence rate among people reinitiating ART was 42.4% (95% CI 29.1–56.4%). Conclusions PNG has a high PDR prevalence rate, especially to NNRTI-based first-line therapies. Our findings suggest that removing NNRTIs as part of first-line treatment is warranted and will lead to improving viral suppression rates in PNG. </jats:sec