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

Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder.

BackgroundWe evaluated the orexin receptor antagonist filorexant (MK-6096) for treatment augmentation in patients with major depressive disorder.MethodsWe conducted a 6-week, double-blind, placebo-controlled, parallel-group, Phase II, proof-of-concept study. Patients with major depressive disorder (partial responders to ongoing antidepressant therapy) were randomized 1:1 to once-daily oral filorexant 10 mg or matching placebo.ResultsDue to enrollment challenges, the study was terminated early, resulting in insufficient statistical power to detect a prespecified treatment difference; of 326 patients planned, 129 (40%) were randomized and 128 took treatment. There was no statistically significant difference in the primary endpoint of change from baseline to week 6 in Montgomery Asberg Depression Rating Scale total score; the estimated treatment difference for filorexant-placebo was -0.7 (with negative values favoring filorexant) (P=.679). The most common adverse events were somnolence and suicidal ideation.ConclusionsThe interpretation of the results is limited by the enrollment, which was less than originally planned, but the available data do not suggest efficacy of orexin receptor antagonism with filorexant for the treatment of depression. (Clinical Trial Registry: clinicaltrials.gov: NCT01554176)

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

Trailblazers in Cancer Research : The Next Generation – The British Association of Cancer Research Early Career Conference

ACKNOWLEDGEMENTS We thank Mrs Janet Alexander and Ms Barbora Gaborova for their invaluable help with this conference's organisation, marketing, and administration.Peer reviewe

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

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men.

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment

Trailblazers in cancer research: the next generation – the British Association of Cancer Research early-career conference

The inaugural ‘British Association of Cancer Research (BACR) Early Career Conference, Trailblazers in Cancer Research 2023’, was a 2-day meeting held in Manchester, UK. Recognising the disruption caused by the COVID-19 pandemic to early-career researchers (ECRs), the BACR executive committee organised an in-person conference to address the lack of network and training opportunities during this time. The conference brought together PhD students and post-doctoral researchers from across the UK and beyond, who shared their outstanding contributions to cancer research. The meeting incorporated several cutting-edge cancer themes, including ‘Cancer Cell Signalling and The Tumour Microenvironment’; ‘Emerging Approaches in Cancer Treatment’; ‘Cancer Omics and Lifestyle’, and ‘Nutrition and Cancer’. Alongside showcasing world-class cancer research, the meeting included a career-focused session which allowed industrial and non-academic speakers to provide vital insight into alternative career paths aside from the familiar ‘academic’ route. Importantly, the conference also introduced delegates to Patient Public Involvement in cancer research, an area of limited experience for many. Overall, the BACR Trailblazers Conference was hugely successful and presented an excellent platform for collaboration and networking among ECRs in cancer research