Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis.

Background: Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes. Methods: The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated. Results: Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74. Conclusions: To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool

R2Play development: Fostering user-driven technology that supports return-to-play decision-making following pediatric concussion

ObjectiveTo design a multi-domain return-to-play assessment system (R2Play) for youth athletes with concussion.MethodsThe R2Play system was developed using an overarching user-centered approach, the Design Thinking Framework, and research activities included: 1) structured brainstorming within our research team, 2) interviews with clinician and youth sports coaches, 3) building a testable prototype, and 4) interface testing through cognitive walkthroughs with clinician partners.ResultsClinician and coach participants provided feedback on the R2Play concept, which was integrated into the design process and provided future directions for research. Examples of feedback-driven design choices included reducing assessment time, increasing ecological validity by adding in background noise, and developing youth-friendly graphical results screens. Following refinement based on stakeholder feedback, the R2Play system was outlined in detail and a testable prototype was developed. It is made up of two parts: a clinician tablet, and a series of tablet “buttons” that display numbers and letters. Youth athletes run between the buttons to connect a “trail” in ascending alphanumeric order, 1-A-2-B, etc. Their performance across a series of levels of increasing difficulty is logged on the clinician tablet. Initial testing with five clinicians showed the system's interface to have excellent usability with a score of 81% (SD = 8.02) on the System Usability Scale.ConclusionThrough this research, a prototype of the R2Play system was innovated and evaluated by clinician and coach stakeholders. Initial usability was excellent and directions for future iterations were highlighted. Outcomes suggest the potential benefits of using technologies to assist in complex clinical assessment, as well as utilizing a user-centered approach to design

R2Play and Stakeholder Needs: Fostering User-driven Technology to Support Return-to-play Decision-making

Background: Following concussion, return-to-play protocols rely on a battery of single-domain assessments to assess recovery. Yet, single-domain assessments may fail to detect symptoms elicited by the cognitive, physical, and socio-emotional multi-domain demands when an athlete returns to sport.Objective: To bridge this gap by developing the R2Play system, which facilitates the implementation of a multi-domain return-to-play assessment for young athletes. Method: To address this aim, I have: (1) conducted a scoping review of multi-domain assessments; (2) conducted needs-assessment interviews with stakeholders; (3) collaborated with our research team to build a testable prototype; and (4) carried out proof-of-concept testing for R2Play. Results: The current thesis details the development and initial testing of the R2Play system, providing proof-of-concept and outlining next steps based on user feedback. Conclusions: This thesis contributes a prototype of the R2Play system, and highlights the potential of technology in clinical assessment and the benefits of user-centered design.M.Sc

The Teachabi Professional Development Module: A Mixed Method Analysis of Change in Open-Ended Case Study Responses

Background. Educators have limited knowledge of acquired brain injury (ABI). This work evaluates an online professional development module, TeachABI. Objective. To explore and evaluate educators’ knowledge change following completion of TeachABI using a mixed-method approach. Method. Case study responses were analyzed before and after 49 elementary-level educators reviewed TeachABI. Results. After completing TeachABI, educators conceptualized ABI more accurately and were more likely to identify ABI as a factor for classroom challenges, χ^2(1, N=49) = 8.64, p < .01. Teachers described a variety of procedural steps and classroom strategies to support students with ABI. Post-module, educators outlined a greater diversity, z = 4.7, p < .01, and number, t(49) = 3.2, p < .01, d = .46, of steps and a greater number of classroom, z = 3.1. p < .01, r = .5. Conclusions. TeachABI was an effective professional development tool and improved educators’ approaches to the case study

The lived experience of female genital cutting (FGC) in Somali-Canadian women's daily lives.

Many of the Somali women who have immigrated to other countries, including Canada, have experienced Female Genital Circumcision/ Mutilation/ Cutting (FGC). While there is literature on the medical aspects of FGC, we were interested in understanding the daily life experiences and bodily sensations of Somali-Canadian women in the context of FGC. Fourteen women living in the Greater Toronto Area were interviewed. Interview data were analyzed using a phenomenological approach. We found that the memory of the ceremonial cutting was vivid but was frequently described with acceptance and resignation-as something that just is; that was normal given the particular context, familial and cultural, and their young age. Most of the women recounted experiencing pain and discomfort throughout their adult lives but were intent on not noticing or giving the pain any power; they considered themselves healthy. The following themes emerged from our interviews: Every Body Had It: Discussing FGC, I'm Normal Aren't I?, and Feeling in My Body-all themes that work at normalizing their bodies in a society that they know views them as different. They dealt with both pain and pleasure in the context of their busy lives suggesting resilience in spite of the day-to-day difficulties of daily life

Table1_R2Play development: Fostering user-driven technology that supports return-to-play decision-making following pediatric concussion.docx

ObjectiveTo design a multi-domain return-to-play assessment system (R2Play) for youth athletes with concussion.MethodsThe R2Play system was developed using an overarching user-centered approach, the Design Thinking Framework, and research activities included: 1) structured brainstorming within our research team, 2) interviews with clinician and youth sports coaches, 3) building a testable prototype, and 4) interface testing through cognitive walkthroughs with clinician partners.ResultsClinician and coach participants provided feedback on the R2Play concept, which was integrated into the design process and provided future directions for research. Examples of feedback-driven design choices included reducing assessment time, increasing ecological validity by adding in background noise, and developing youth-friendly graphical results screens. Following refinement based on stakeholder feedback, the R2Play system was outlined in detail and a testable prototype was developed. It is made up of two parts: a clinician tablet, and a series of tablet “buttons” that display numbers and letters. Youth athletes run between the buttons to connect a “trail” in ascending alphanumeric order, 1-A-2-B, etc. Their performance across a series of levels of increasing difficulty is logged on the clinician tablet. Initial testing with five clinicians showed the system's interface to have excellent usability with a score of 81% (SD = 8.02) on the System Usability Scale.ConclusionThrough this research, a prototype of the R2Play system was innovated and evaluated by clinician and coach stakeholders. Initial usability was excellent and directions for future iterations were highlighted. Outcomes suggest the potential benefits of using technologies to assist in complex clinical assessment, as well as utilizing a user-centered approach to design.</p

Evaluating the discriminating capacity of cell death (apoptotic) biomarkers in sepsis

Abstract Background Sepsis biomarker panels that provide diagnostic and prognostic discrimination in sepsis patients would be transformative to patient care. We assessed the mortality prediction and diagnostic discriminatory accuracy of two biomarkers reflective of cell death (apoptosis), circulating cell-free DNA (cfDNA), and nucleosomes. Methods The cfDNA and nucleosome levels were assayed in plasma samples acquired in patients admitted from four emergency departments with suspected sepsis. Subjects with non-infectious systemic inflammatory response syndrome (SIRS) served as controls. Samples were acquired at enrollment (T0) and 24 h later (T24). We assessed diagnostic (differentiating SIRS from sepsis) and prognostic (28-day mortality) predictive power. Models incorporating procalcitonin (diagnostic prediction) and APACHE II scores (mortality prediction) were generated. Results Two hundred three subjects were included (107 provided procalcitonin measurements). Four subjects exhibited uncomplicated sepsis, 127 severe sepsis, 35 septic shock, and 24 had non-infectious SIRS. There were 190-survivors and 13 non-survivors. Mortality prediction models using cfDNA, nucleosomes, or APACHEII yielded AUC values of 0.61, 0.75, and 0.81, respectively. A model combining nucleosomes with the APACHE II score improved the AUC to 0.84. Diagnostic models distinguishing sepsis from SIRS using procalcitonin, cfDNA(T0), or nucleosomes(T0) yielded AUC values of 0.64, 0.65, and 0.63, respectively. The three parameter model yielded an AUC of 0.74. Conclusions To our knowledge, this is the first head-to-head comparison of cfDNA and nucleosomes in diagnosing sepsis and predicting sepsis-related mortality. Both cfDNA and nucleosome concentrations demonstrated a modest ability to distinguish sepsis survivors and non-survivors and provided additive diagnostic predictive accuracy in differentiating sepsis from non-infectious SIRS when integrated into a diagnostic prediction model including PCT and APACHE II. A sepsis biomarker strategy incorporating measures of the apoptotic pathway may serve as an important component of a sepsis diagnostic and mortality prediction tool

Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province

<div><p>Melioidosis is a severe infectious disease caused by the gram-negative soil bacterium <i>Burkholderia pseudomallei</i>. Melioidosis is well known to be a major cause of morbidity and mortality in Southeast Asia, particularly in Thailand. However, melioidosis remains underreported in surrounding areas such as Cambodia. We report a case series of melioidosis in seven patients from Takeo Province, Cambodia. The patients, aged 24–65 years, were enrolled from May 2014 to May 2015 during a one year prospective study of sepsis at Takeo Provincial Hospital. They presented with fever, rigors, dyspnea, fatigue, diaphoresis, productive cough, and skin abscesses. Six of the seven patients were also hyponatremic. <i>B</i>. <i>pseudomallei</i> was cultured from the blood of six patients and the sputum of one patient. In this manuscript, we provide a detailed description of the clinical presentation, case management and laboratory confirmation of <i>B</i>. <i>pseudomallei</i>, as well as discuss the difficulties of identifying and treating melioidosis in low resource settings.</p></div

Study site.

<p>We used DIVA-GIS (<a href="http://diva-gis.org/" target="_blank">http://diva-gis.org/</a>) to create a map of Cambodia and surrounding areas. The red H indicates Takeo Provincial Hospital, the study site for this work. Dots indicate the location of the home village of seven melioidosis patients. Map is reflective of Cambodian Provincial borders during the time of patient enrollment.</p

Clinical isolate characteristics.

<p>Clinical isolate characteristics.</p