The Esophageal Pressure-Guided Ventilation 2 (EPVent2) trial protocol: a multicentre, randomised clinical trial of mechanical ventilation guided by transpulmonary pressure

Introduction: Optimal ventilator management for patients with acute respiratory distress syndrome (ARDS) remains uncertain. Lower tidal volume ventilation appears to be beneficial, but optimal management of positive end-expiratory pressure (PEEP) remains unclear. The Esophageal Pressure-Guided Ventilation 2 Trial (EPVent2) aims to examine the impact of mechanical ventilation directed at maintaining a positive transpulmonary pressure (PTP) in patients with moderate-to-severe ARDS. Methods and analysis EPVent2 is a multicentre, prospective, randomised, phase II clinical trial testing the hypothesis that the use of a PTP-guided ventilation strategy will lead to improvement in composite outcomes of mortality and time off the ventilator at 28 days as compared with a high-PEEP control. This study will enrol 200 study participants from 11 hospitals across North America. The trial will utilise a primary composite end point that incorporates death and days off the ventilator at 28 days to test the primary hypothesis that adjusting ventilator pressure to achieve positive PTP values will result in improved mortality and ventilator-free days. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approvals of the protocol as well as informed consent documents were also obtained from the Institutional Review Board of each participating institution prior to enrolling study participants at each respective site. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to PubMed Central in accordance with the National Institute of Health Public Access Policy. Trial registration number ClinicalTrials.gov under number NCT01681225

Ten years of lesbian health survey research in the UK West Midlands

Abstract Background Very little is known about the physical health needs of lesbian and bisexual women in the UK; most research has looked at mental or sexual health only. This article reports the results of four surveys carried out in the West Midlands between 1995 and 2005. Methods The first two surveys were conducted in 1995–6 by a volunteer group, with participants from a lesbian health conference (n = 69) and in a convenience sample from a wide range of relevant groups and venues (n = 354). The second two surveys were commissioned by the West Midlands South Strategic Health Authority in partnership with the Gay Men's Health Network and were conducted in 2002 (n = 449) and 2005 (n = 166) and again used convenience sampling methods including the internet. Results The mean age of respondents varied between 29–33 years and 5–7% were from a non-white ethnic background. The smoking rates varied from 42% o 55%, being twice the West Midlands regional average of 21% for women aged 16 or more. Similarly, problems with alcohol were reported in 25–37% of respondents, higher than the West Midlands regional average of 7% for women aged 16+. The prevalence of any mental health problem varied between 31–35% and any suicide attempt between 20–31%. Only 29–45% had revealed their sexual orientation to their GP and of these, approximately 50% had experienced a positive reaction. Conclusion The results suggest health needs that current UK health services may not be meeting. There is a need to identify and target specific health measures for lesbians and bisexual women in order to ensure improved physical and mental health in the longer term.</p

Recommended Revisions to the National SEP‐1 Sepsis Quality Measure: A commentary by the Society of Infectious Diseases Pharmacists on the Infectious Diseases Society of America Position Paper

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154912/1/phar2384.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154912/2/phar2384_am.pd

Epidural Hematoma Following Cervical Spine Surgery.

STUDY DESIGN: A multicentered retrospective case series. OBJECTIVE: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. METHODS: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. RESULTS: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment (P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. CONCLUSION: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements

Pituitary stem cells produce paracrine WNT signals to control the expansion of their descendant progenitor cells

In response to physiological demand, the pituitary gland generates new hormonesecreting cells from committed progenitor cells throughout life. It remains unclear to what extent pituitary stem cells (PSCs), which uniquely express SOX2, contribute to pituitary growth and renewal. Moreover, neither the signals that drive proliferation nor their sources have been elucidated. We have used genetic approaches in the mouse, showing that the WNT pathway is essential for proliferation of all lineages in the gland. We reveal that SOX2+ stem cells are a key source of WNT ligands. By blocking secretion of WNTs from SOX2+ PSCs in vivo, we demonstrate that proliferation of neighbouring committed progenitor cells declines, demonstrating that progenitor multiplication depends on the paracrine WNT secretion from SOX2+ PSCs. Our results indicate that stem cells can hold additional roles in tissue expansion and homeostasis, acting as paracrine signalling centres to coordinate the proliferation of neighbouring cells

Interactive narration with a child: impact of prosody and facial expressions

International audienceIntelligent Virtual Agents are suitable means for interactive sto-rytelling for children. The engagement level of child interaction with virtual agents is a challenging issue in this area. However, the characteristics of child-agent interaction received moderate to little attention in scientific studies whereas such knowledge may be crucial to design specific applications. This article proposes a Wizard of Oz platform for interactive narration. An experimental study in the context of interactive story-telling exploiting this platform is presented to evaluate the impact of agent prosody and facial expressions on child participation during storytelling. The results show that the use of the virtual agent with prosody and facial expression modalities improves the engagement of children in interaction during the narrative sessions

Muscle Loss Is Associated with Overall Survival in Patients with Metastatic Colorectal Cancer Independent of Tumor Mutational Status and Weight Loss

Background: Survival in patients with metastatic colorectal cancer (mCRC) has been associated with tumor mutational status, muscle loss, and weight loss. We sought to explore the combined effects of these variables on overall survival. Materials and methods: We performed an observational cohort study, prospectively enrolling patients receiving chemotherapy for mCRC. We retrospectively assessed changes in muscle (using computed tomography) and weight, each dichotomized as >5% or ≤5% loss, at 3, 6, and 12 months after diagnosis of mCRC. We used regression models to assess relationships between tumor mutational status, muscle loss, weight loss, and overall survival. Additionally, we evaluated associations between muscle loss, weight loss, and tumor mutational status. Results: We included 226 patients (mean age 59 ± 13 years, 53% male). Tumor mutational status included 44% wild type, 42% RAS-mutant, and 14% BRAF-mutant. Patients with >5% muscle loss at 3 and 12 months experienced worse survival controlling for mutational status and weight (3 months hazard ratio, 2.66; p 5% muscle loss with BRAF-mutational status at 6 and 12 months. Weight loss was not associated with survival nor mutational status. Conclusion: Increased muscle loss at 3 and 12 months may identify patients with mCRC at risk for decreased overall survival, independent of tumor mutational status. Specifically, >5% muscle loss identifies patients within each category of tumor mutational status with decreased overall survival in our sample. Our findings suggest that quantifying muscle loss on serial computed tomography scans may refine survival estimates in patients with mCRC. Implications for practice: In this study of 226 patients with metastatic colorectal cancer, it was found that losing >5% skeletal muscle at 3 and 12 months after the diagnosis of metastatic disease was associated with worse overall survival, independent of tumor mutational status and weight loss. Interestingly, results did not show a significant association between weight loss and overall survival. These findings suggest that muscle quantification on serial computed tomography may refine survival estimates in patients with metastatic colorectal cancer beyond mutational status

'Everyday memory' impairments in autism spectrum disorders

‘Everyday memory’ is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead Behavioural Memory Test (RBMT) and a standard word recall task (Children’s Auditory Verbal Learning Test-2: CAVLT-2). The ASD group showed significant impairments on the RBMT, including in prospective memory, alongside impaired performance on the CAVLT-2. Social and communication ability was significantly associated with prospective remembering in an everyday memory context but not with the CAVLT-2. The complex nature of everyday memory and its relevance to ASD is discussed

Toward Improved Environmental Stability of Polymer:Fullerene and Polymer:Nonfullerene Organic Solar Cells: A Common Energetic Origin of Light- and Oxygen-Induced Degradation

With the emergence of nonfullerene electron acceptors resulting in further breakthroughs in the performance of organic solar cells, there is now an urgent need to understand their degradation mechanisms in order to improve their intrinsic stability through better material design. In this study, we present quantitative evidence for a common root cause of light-induced degradation of polymer:nonfullerene and polymer:fullerene organic solar cells in air, namely, a fast photo-oxidation process of the photoactive materials mediated by the formation of superoxide radical ions, whose yield is found to be strongly controlled by the lowest unoccupied molecular orbital (LUMO) levels of the electron acceptors used. Our results elucidate the general relevance of this degradation mechanism to both polymer:fullerene and polymer:nonfullerene blends and highlight the necessity of designing electron acceptor materials with sufficient electron affinities to overcome this challenge, thereby paving the way toward achieving long-term solar cell stability with minimal device encapsulation