Resolution of Clinical Signs of Ventilator-Associated Pneumonia in Trauma Patients

Objectives: The ATS/IDSA Ventilator-Associated Pneumonia (VAP) guidelines suggest that clinical improvement of VAP should be apparent within 3–6 days. This study evaluated resolution of clinical signs of VAP in trauma patients after diagnosis. Methods: Critically injured adults admitted to the trauma intensive care unit (ICU) from June 1, 2006, to December 31, 2007, and subsequently given a diagnosis of VAP were retrospectively assessed. Clinical signs, including derangements of maximum temperature (Tmax), white blood cell (WBC) count, and PaO2/FiO2, were evaluated on days 1–16 after VAP diagnosis. Data are presented as mean ± SD unless otherwise stated. Clinical parameters after VAP were compared using repeated-measures ANOVA with the Tukey test for multiple comparisons. Results: A total of 82 patients were identified. Data for the 34 patients without concurrent infections are presented. Demographic data include: Age 46 ± 17 years; 71% men; 94% blunt trauma; median (IQR) Injury Severity Score 29.5 (24–38); duration of mechanical ventilation 33 ± 27 days; ICU length of stay (LOS) 39 ± 25 days; hospital LOS 53 ± 33 days. Clinical signs following VAP diagnosis: Tmax (°F): Day 1=101.8 ± 1.3, Day 3=101.1 ± 1.1, Day 6=101.1 ± 1.4, Day 16=100.1 ± 3. Compared to Day 1, there was a significant reduction in Tmax at days 10, 11, 12, 13, 14, and 16 (p\u3c0.05 for all). WBC count (cells per microliter): day 1 = 12.9 ± 5, day 3 = 13.7 ± 5, day 6 = 14.4 ± 5, and day 16 = 13.8 ± 6. There was no significant difference in WBC on days 1–16 (p=0.42). PaO2/FiO2: day 1 = 232 ± 108, day 3 = 200 ± 87, day 6 = 218 ± 104, day 16 = 246 ± 126. Differences in PaO2/FiO2 on days 1–16 did not reach statistical significance (p=0.06). Conclusion: Improvement of clinical parameters after a VAP diagnosis is delayed in trauma patients. Alternative methods for determining resolution should be investigated. Published in To be published in Critical Care Medicine’s December 2009 supplement

EFFECTS OF SIX WEEKS OF TRAINING ON INTERSEGMENTAL COORDINATION IN THE ROWING STROKE OF NOVICE INTERCOLLEGIATE ROWERS

The purpose of the study was to examine changes in coordination during the rowing stroke after 1 and 6 weeks of practice. Initially 11 healthy, females who had elected to join a college rowing program volunteered to participate in both testing sessions: Only 3 participants were still on the novice team at wk 6, thus N=3. Participants were video taped on a land ergometer in 2D using the Peak Motion Measurement System. SPC was assessed between adjacent 2-segment combinations of the T-S (trunk-shoulder), K-T (knee-trunk), and S-E (shoulder-elbow) to quantify intersegmental coordination. Mean changes in T-S (78.7% v 74.6 %), K-T (66.5% v 102.9%) and S-E (88.2% v 71.3%) showed that the rowing stroke is primarily a simultaneous pattern. However. individual SPC (shared positive contribution) changes varied indicating that 6 wks is not a long enough for coordination to develop in novice rowers

Resolution of Clinical Signs in Trauma Intensive Care Unit Patients Following Diagnosis of Ventilator-Associated Pneumonia

PURPOSE: The ATS/IDSA Ventilator-Associated Pneumonia (VAP) guidelines suggest that clinical improvement of VAP should be apparent within 3-6 days. Anecdotally, such improvement has not been noted in trauma patients at our institution. The current study was conducted to evaluate resolution of clinical signs of VAP following diagnosis. METHODS: Critically injured adults admitted to the trauma intensive care unit (TICU) from 6/1/06-12/31/07 and subsequently diagnosed with VAP were retrospectively reviewed. Clinical signs, including derangements of maximum temperature (Tmax), white blood cell (WBC) count and Pa02/FiO2, were evaluated on days 1-16 following VAP diagnosis. Data are presented as mean ± SD unless otherwise stated. Clinical parameters following VAP were compared using repeated measures ANOVA with the Tukey test for multiple comparisons. RESULTS: A total of 82 patients were identified. Data for the 34 patients without concurrent infections are presented. Demographic data include: Age 46 ± 17 years; 71% males; 94% blunt trauma; median (IQR) Injury Severity Score 29.5 (24 to 38); duration of mechanical ventilation 33 ± 27 days; ICU length of stay (LOS) 39 ± 25 days; hospital LOS 53 ± 33 days. Clinical signs following VAP diagnosis (Figure): Tmax (°F): Day 1=101.8 ± 1.3, Day 3=101.1 ± 1.1, Day 6=101.1 ± 1.4, Day 16=100.1 ± 3. Compared to Day 1, there was a significant reduction in Tmax at Days 10, 11, 12, 13, 14 and 16 (p \u3c 0.05 for all). WBC count (cells/μL): Day 1=12.9 ± 5, Day 3=13.7 ± 5, Day 6=14.4 ± 5, Day 16=13.8 ± 6. There was no significant difference in WBC count on Days 1-16 (p=0.42). PaO2/FiO2: Day 1=232 ± 108, Day 3=200 ± 87, Day 6=218 ± 104, Day 16=246 ± 126. Differences in PaO2/FiO2 on Days 1-16 did not reach statistical significance (p=0.06). CONCLUSIONS: In trauma patients, improvement of clinical parameters following diagnosis of VAP is delayed beyond the 3-6 day timeframe suggested in the ATS/IDSA guidelines. Alternative methods for determining resolution of VAP in trauma patients should be investigated. METHODS INTRODUCTIO

Resolution of Clinical and Laboratory Abnormalities after Diagnosis of Ventilator-Associated Pneumonia in Trauma Patients

Background: Guidelines advise that patients with ventilator-associated pneumonia (VAP) should respond clinically by Day 3 of antibiotics. White blood cell (WBC) count, maximum temperature (Tmax), and PaO2:FIO2 ratio are all said to respond significantly by Day 6. Resolution of abnormalities has not been evaluated in trauma patients. Methods: Retrospective review of trauma patients with VAP. The WBC count, Tmax, and PaO2:FIO2 were evaluated for 16 days after diagnosis. Patients were grouped into uncomplicated VAP, complicated VAP (those with inadequate empirical therapy [IEAT], VAP relapse/superinfection, or acute respiratory distress syndrome), and concurrent infection +VAP (those also infected at another site). Results: There were 126 patients (uncomplicated VAP= 29, complicated VAP = 69, and concurrent infection + VAP = 28). The mean Tmax in patients with uncomplicated VAP decreased significantly from diagnosis to Day 4 (Day 1: 39 – 0.5°C vs. Day 4: 38.6 – 0.7°C; p = 0.028) but never normalized. Their WBC counts and PaO2:FIO2 did not change significantly over the 16-day follow-up and never normalized.When comparing the three groups, the probability of resolving all three abnormalities was not different (p = 0.5). Conclusions: Clinical and laboratory abnormalities in critically injured patients with VAP do not resolve as quickly as suggested in the guidelines. Future studies should evaluate new methods to determine the response to antibiotic therapy in critically injured patients with VAP

Pathology caused by persistent murine norovirus infection.

Subclinical infection of murine norovirus (MNV) was detected in a mixed breeding group of WT and Stat1(-/-) mice with no outward evidence of morbidity or mortality. Investigations revealed the presence of an attenuated MNV variant that did not cause cytopathic effects in RAW264.7 cells or death in Stat1(-/-) mice. Histopathological analysis of tissues from WT, heterozygous and Stat1(-/-) mice revealed a surprising spectrum of lesions. An infectious molecular clone was derived directly from faeces (MNV-O7) and the sequence analysis confirmed it was a member of norovirus genogroup V. Experimental infection with MNV-O7 induced a subclinical infection with no weight loss in Stat1(-/-) or WT mice, and recapitulated the clinical and pathological picture of the naturally infected colony. Unexpectedly, by day 54 post-infection, 50 % of Stat1(-/-) mice had cleared MNV-O7. In contrast, all WT mice remained infected persistently. Most significantly, this was associated with liver lesions in all the subclinically infected WT mice. These data confirmed that long-term persistence in WT mice is established with specific variants of MNV and that despite a subclinical presentation, active foci of acute inflammation persist within the liver. The data also showed that STAT1-dependent responses are not required to protect mice from lethal infection with all strains of MNV

Women versus men with chronic atrial fibrillation: insights from the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY)

BACKGROUND: Gender-based clinical differences are increasingly being identified as having significant influence on the outcomes of patients with cardiovascular disease (CVD), including atrial fibrillation (AF). OBJECTIVE: To perform detailed clinical phenotyping on a cohort of hospitalised patients with chronic forms of AF to understand if gender-based differences exist in the clinical presentation, thrombo-embolic risk and therapeutic management of high risk patients hospitalised with chronic AF. METHODS: We are undertaking the Standard versus Atrial Fibrillation spEcific managemenT studY (SAFETY) - a multi-centre, randomised controlled trial of an AF-specific management intervention versus usual care. Extensive baseline profiling of recruited patients was undertaken to identify gender-specific differences for risk delineation. RESULTS: We screened 2,438 patients with AF and recruited 335 into SAFETY. Of these, 48.1% were women who were, on average, 5 years older than their male counterparts. Women and men displayed divergent antecedent profiles, with women having a higher thrombo-embolic risk but being prescribed similar treatment regimens. More women than men presented to hospital with co-morbid thyroid dysfunction, depression, renal impairment and obesity. In contrast, more men presented with coronary artery disease (CAD) and/or chronic obstructive pulmonary disease (COPD). Even when data was age-adjusted, women were more likely to live alone (odds ratio [OR] 2.33; 95% confidence interval [CI] 1.47 to 3.69), have non-tertiary education (OR 2.69; 95% CI 1.61 to 4.48) and be symptomatic (OR 1.93; 95% CI 1.06 to 3.52). CONCLUSION: Health care providers should be cognisant of gender-specific differences in an attempt to individualise and, hence, optimise the management of patients with chronic AF and reduce potential morbidity and mortality.Jocasta Ball, Melinda J. Carrington, Kathryn A. Wood, Simon Stewart (the SAFETY Investigators

High prevalence of subclinical tuberculosis in HIV-1-infected persons without advanced immunodeficiency: implications for TB screening

Background The prevalence of asymptomatic tuberculosis (TB) in recently diagnosed HIV-1-infected persons attending pre-antiretroviral therapy (ART) clinics is not well described. In addition, it is unclear if the detection of Mycobacterium tuberculosis in these patients clearly represents an early asymptomatic phase leading to progressive disease or transient excretion of bacilli. Objective To describe the prevalence and outcome of subclinical TB disease in HIV-1-infected persons not eligible for ART. Methods The study was conducted in 274 asymptomatic ART-naive HIV-1-infected persons in Khayelitsha Day Hospital, Cape Town, South Africa. All participants were screened for TB using a symptom screen and spoligotyping was performed to determine genotypes. Results The prevalence of subclinical TB disease was 8.5% (95% CI 5.1% to 13.0%) (n = 18; median days to culture positivity 17 days), with 22% of patients being smear-positive. Spoligotyping showed a diverse variety of genotypes with all paired isolates being of the same spoligotype, effectively excluding cross-contamination. 56% of patients followed up developed symptoms 3 days to 2 months later. All were well and still in care 6-12 months after TB diagnosis; 60% were started on ART. A positive tuberculin skin test (OR 4.96, p = 0.064), low CD4 count (OR 0.996, p = 0.06) and number of years since HIV diagnosis (OR 1.006, p = 0.056) showed trends towards predicting TB disease. Conclusion This study found a high prevalence but good outcome (retained in care) of subclinical TB disease in HIV-1-infected persons. The results suggest that, in high HIV/TB endemic settings, a positive HIV-1 test should prompt TB screening by sputum culture irrespective of symptoms, particularly in those with a positive tuberculin skin test, longer history of HIV infection and low CD4 count. Operational difficulties in resource-constrained settings with respect to screening with TB culture highlight the need for rapid and affordable point-of-care tests to identify persons with clinical and subclinical TB disease.Immunogenetics and cellular immunology of bacterial infectious disease

Point-of-sale tobacco advertising in Beirut, Lebanon following a national advertising ban

Abstract Background The objective of this study was to conduct an audit of point-of-sale (POS) tobacco advertising and assess compliance with an advertising ban in a large district of Beirut, Lebanon. Methods The audit was conducted 3 months following the ban on tobacco advertising. Trained students observed all tobacco retail outlets (n = 100) and entered data into a web-based form using iPad® technology. Presence of tobacco advertisements was assessed to determine compliance with the national advertising ban. Results Among the 100 tobacco retail outlets, 62% had tobacco advertisements, including 7% with a tobacco brand logo as part of the main exterior store sign. Conclusions POS tobacco advertising is widespread in Beirut despite the national advertising ban. These findings point to an urgent need for the enforcement of the advertisement ban with tobacco retail outlets in Lebanon

The Calcineurin Inhibitor Tacrolimus Specifically Suppresses Human T Follicular Helper Cells.

BACKGROUND: T follicular helper (Tfh) cells are key players in the production of antibody-producing B cells via the germinal center reaction. Therapeutic strategies targeting Tfh cells are important where antibody formation is implicated in disease, such as transplant rejection and autoimmune diseases. We investigated the impact of the immunosuppressive agent tacrolimus on human Tfh cell differentiation and function in transplant recipients. METHODS: Paired blood and lymph node (LN) samples were obtained from 61 transplant recipients immediately prior to organ implantation. Living-donor recipients received a week of tacrolimus prior to kidney transplantation. Deceased-donor recipients served as controls, as tacrolimus was not administered until after the transplant operation. Flow cytometry was used to compare LN and circulating cell subsets. RESULTS: The calcineurin inhibitor (CNIs) tacrolimus specifically suppresses both LN Tfh cells and circulating Tfh cells, but not their regulatory counterparts or other CD4 T cell subsets. CONCLUSION: Our findings suggest that CNIs may have a more important role in the prevention of antibody formation than previously understood and, therefore, have potential for antibody-associated conditions in which aberrant Tfh function has been implicated in disease