Influence of Patient Weight on Prehospital Advanced Airway Procedure Success Rates.

OBJECTIVE: Previous investigations of the relationship between obesity and difficult airway management have provided mixed results. Almost universally, these studies were conducted in the hospital setting, and the influence of patient body weight on successful prehospital airway management remains unclear. Because patient weight could be one readily identifiable risk factor for problematic airway interventions, we sought to evaluate this relationship. METHODS: We conducted a retrospective analysis using the 2020 ESO Data Collaborative dataset. The inclusion criteria consisted of adult patients weighing >30kg with an attempted orotracheal intubation (OTI) and/or blind insertion airway device (BIAD) placement. Separate logistic regression models were developed to determine the influence of weight (dichotomized at 100 kg) on cumulative procedure success for OTI and BIAD, and linear regression models were used to identify trends for each across weight strata. RESULTS: A total of 45,344 patients met inclusionary criteria, among which 40,668(89.7%) suffered from a medical emergency, followed by 3,130(6.9%) with traumatic injuries, and 1,546(3.4%) attributable to a combined medical-trauma etiology. Cardiac arrest occurred either prior to EMS arrival or at some point during EMS care in 38,210(84.3%) patients. OTI was attempted in 18,153(40.0%) patients, while 21,597(47.6%) had a BIAD attempt and 5,594(12.3%) had both airway types attempted. The overall cumulative insertion success rates for OTI and BIAD were 79.5% and 92.7%, respectively. Altogether, 2,711(6.0%) had no advanced airway of any type successfully placed, which represents the overall failed advanced airway rate. After controlling for patient age, sex, minority status, and call type (medical vs. trauma), weight >100kg was associated with decreased likelihood of cumulative OTI success (OR = 0.64, p < 0.001), but higher likelihood of cumulative BIAD success (OR = 1.31, p < 0.001). Cumulative OTI success was associated with a negative 0.6% linear trend per 5 kg of body weight (p < 0.001) while cumulative BIAD success had a 0.2% positive trend (p < 0.001). CONCLUSION: This retrospective analysis of a national EMS database revealed that increasing patient weight was negatively associated with intubation success. A positive, but smaller, linear trend was observed for BIAD placement. Patient weight may be an easily identifiable predictor of difficult oral intubation and may be a consideration when selecting an airway management strategy.

Estimated Cost-Effectiveness of Implementing a Statewide Tranexamic Acid Protocol for the Management of Suspected Hemorrhage in the Prehospital Setting.

INTRODUCTION: Hemorrhage is responsible for up to 40% of all traumatic deaths. The seminal CRASH-2 trial demonstrated a reduction in overall mortality following early tranexamic acid (TXA) administration to bleeding trauma patients. Following publication of the trial results, TXA has been incorporated into many prehospital trauma protocols. However, the cost-effectiveness of widespread TXA adoption by EMS is unknown. OBJECTIVE: To estimate the cost-effectiveness of statewide implementation of a TXA protocol. METHODS: The North Carolina Trauma Registry was queried to identify potential TXA patients using the a priori criteria of age ≥18 years, suspected hemorrhage, penetrating or blunt injury, and prehospital blood pressure <90 mmHg and heart rate >110 bpm. Using life tables adjusted for age, sex, and race, and the absolute risk reductions in mortality with early TXA administration reported in the literature, the life-years gained were calculated for each potential life saved. Implementation costs consisted of initial stocking, training, and replacement costs. Projected reduction in hospitalization costs were based on estimates reported in the literature. Economic analyses were conducted from societal and state EMS system perspectives. To assess the robustness of the model, univariate and bivariate sensitivity analyses were performed on selected input variables. RESULTS: Based on the TXA inclusionary criteria, 159 patients could potentially receive TXA per year. In the base-case scenario with a projected absolute mortality reduction of 3%, an additional 4.8 lives per year in NC would be saved, with an estimated 191 total life-years gained. The statewide implementation and operation cost was $305,122 in year 1, and continued operating costs were $6,042 in years 2 and 3, yielding a cost per life saved of $63,967 in year 1 and $1,267 in years 2 and 3. The cost per life-year gained was $1,595 in year 1 and $32 in years 2 and 3. Annual hospitalization costs would potentially be reduced by $1,828,072. CONCLUSION: Previous studies have demonstrated the clinical effectiveness of early TXA administration to patients with hemorrhage. Our modeling of the financial implications and clinical benefits of implementing a statewide TXA protocol suggests that prehospital TXA is a cost-effective treatment.

The synergistic effects of saxagliptin and metformin on CD34+ endothelial progenitor cells in early type 2 diabetes patients: a randomized clinical trial.

AIMS: Type 2 diabetes is associated with endothelial dysfunction leading to cardiovascular disease. CD34+ endothelial Progenitor Cells (EPCs) are responsible for endothelial repair and neo-angiogenesis and can be used as a cardiovascular disease risk biomarker. This study investigated whether the addition of saxagliptin, a DPP-IV inhibitor, to metformin, may reduce cardiovascular disease risk in addition to improving glycemic control in Type 2 diabetes patients. METHODS: In 12 week, double-blind, randomized placebo-controlled trial, 42 subjects already taking metformin 1-2 grams/day were randomized to placebo or saxagliptin 5 mg. Subjects aged 40-70 years with diabetes for < 10 years, with no known cardiovascular disease, BMI 25-39.9, HbA1C 6-9% were included. We evaluated EPCs number, function, surface markers and gene expression, in addition to arterial stiffness, blood biochemistries, resting energy expenditure, and body composition parameters. A mixed model regression to examine saxagliptin vs placebo, accounting for within-subject autocorrelation, was done with SAS (p < 0.05). RESULTS: Although there was no significant increase in CD34+ cell number, CD31+ cells percentage increased. Saxagliptin increased migration (in response to SDF1α) with a trend of higher colony formation count. MNCs cytometry showed higher percentage of CXCR4 double positivity for both CD34 and CD31 positive cells, indicating a functional improvement. Gene expression analysis showed an upregulation in CD34+ cells for antioxidant SOD1 (p < 0.05) and a downregulation in CD34- cells for IL-6 (p < 0.01). For arterial stiffness, both augmentation index and systolic blood pressure measures went down in saxagliptin subjects (p < 0.05). CONCLUSION: Saxagliptin, in combination with metformin, can help improve endothelial dysfunction in early diabetes before macrovascular complications appear. Trial registration Trial is registered under clinicaltrials.gov, NCT02024477.

Effects of a ballet-based dance intervention on gait variability and balance confidence of people with Parkinson's.

BACKGROUND: Dance has shown to be beneficial for people with Parkinson's. However, there is a lack of research on ballet for this population. The present study aimed to determine the effect of weekly ballet classes on gait variability and balance confidence for people with Parkinson's. METHODS: The study follows a non-randomised, controlled project evaluation design. A group of 19 people with Parkinson's who were already involved in weekly ballet classes volunteered for this research. A control group of 13 people with Parkinson's were asked to not participate in dance classes across the duration of the study. RESULTS: The study did not demonstrate significant effects of weekly ballet classes on gait variability or balance confidence. CONCLUSIONS: These findings differ from recent studies that suggest dancing can improve balance and gait for this population. There is a need to examine the optimal ballet class frequency required to elicit any potential positive change.

Use of p53-Silenced Endothelial Progenitor Cells to Treat Ischemia in Diabetic Peripheral Vascular Disease.

BACKGROUND: Peripheral vascular disease is a major diabetes mellitus-related complication. In this study, we noted that expressions of proapoptotic p53 gene and its downstream cascade gene such as p21 are upregulated in hyperglycemia. Therefore, we investigated whether p53- and p21-silenced endothelial progenitor cells (EPCs) were able to survive in hyperglycemic milieu, and whether transplantation of either p53 knockout (KO) or p21KO or p53- and p21-silenced EPCs could improve collateral vessel formation and blood flow in diabetic vaso-occlusive peripheral vascular disease mouse models. METHODS AND RESULTS: We transplanted p53 and p21KO mouse EPCs (mEPCs) into streptozotocin-induced diabetic (type 1 diabetes mellitus model) C57BL/6J and db/db (B6.BKS(D)-Leprdb/J) (type 2 model) post-femoral artery occlusion. Similarly, Ad-p53-silenced and Ad-p21-silenced human EPCs (CD34+) cells were transplanted into streptozotocin-induced diabetic NOD.CB17-Prkdcscid/J mice. We measured blood flow at 3, 7, and 10 days and hindlimb muscles were obtained postsacrifice for mRNA estimation and CD31 staining. Enhanced blood flow was noted with delivery of p53 and p21KO mEPCs in streptozotocin-induced diabetic C57BL/6J mice. Similar results were obtained when human Ad-p53shEPCs(CD34+) and Ad-p21shEPCs(CD34+) were transplanted into streptozotocin-induced nonobese diabetic severe combined immunodeficiency mice. Gene expression analysis of p53 and p21KO EPCs transplanted hindlimb muscles showed increased expression of endothelial markers such as endothelial nitric oxide synthase, vascular endothelial growth factor A, and platelet endothelial cell adhesion molecule 1. Similarly, quantitative reverse transcriptase polymerase chain reaction of human Ad-p53shEPCs (CD34+)- and Ad-p21shEPCs (CD34+)-transplanted hindlimb muscles also showed increased expression of endothelial markers such as vascular endothelial growth factor A, noted primarily in the p53-silenced EPCs group. However, such beneficial effect was not noted in the db/db type 2 diabetic mouse models. CONCLUSIONS: Transient silencing of p53 using adenoviral vector in EPCs may have a therapeutic role in diabetic peripheral vascular disease.

Probability of Return of Spontaneous Circulation as a Function of Timing of Vasopressor Administration in Out-of-Hospital Cardiac Arrest.

INTRODUCTION: Vasopressors (epinephrine and vasopressin) are associated with return of spontaneous circulation (ROSC). Recent retrospective studies reported a greater likelihood of ROSC when vasopressors were administered within the first 10 minutes of arrest. However, it is unlikely that the relationship between ROSC and the timing of vasopressor administration is a binary function (i.e., ≤10 vs. >10 minutes). More likely, this relationship is a function of time measured on a continuum, with diminishing effectiveness even within the first 10 minutes of arrest, and potentially, some lingering benefit beyond 10 minutes. However, this relationship remains undefined. OBJECTIVE: To develop a model describing the likelihood of ROSC as a function of the call receipt to vasopressor interval (CRTVI) measured on a continuum. METHODS: We conducted a retrospective study of cardiac arrest using the North Carolina Prehospital Care Reporting System (PREMIS). Inclusionary criteria were all adult patients suffering a witnessed, nontraumatic arrest during January-June 2012. Chi-square and t-tests were used to analyze the relationships between ROSC and CRTVI; patient age, race, and gender; endotracheal intubation (ETI); automated external defibrillator (AED) use; presenting cardiac rhythm; and bystander cardiopulmonary resuscitation (CPR). A multivariate logistic regression model calculated the odds ratio (OR) of ROSC as a function of CRTVI while controlling for potential confounding variables. RESULTS: Of the 1,122 patients meeting inclusion criteria, 542 (48.3%) experienced ROSC. ROSC was less likely with increasing CRTVI (OR = 0.96, p < 0.01). Compared to patients with shockable rhythms, patients with asystole (OR = 0.42, p < 0.01) and pulseless electrical activity (OR = 0.52, p < 0.01) were less likely to achieve ROSC. Males (OR = 0.64, p = 0.02) and patients receiving bystander CPR (OR = 0.42, p < 0.01) were less likely to attain ROSC, although emergency medical services response times were significantly longer among patients receiving bystander CPR. Race, age, ETI, and AED were not predictors of ROSC. CONCLUSIONS: We found that time to vasopressor administration is significantly associated with ROSC, and the odds of ROSC declines by 4% for every 1-minute delay between call receipt and vasopressor administration. These results support the notion of a time-dependent function of vasopressor effectiveness across the entire range of administration delays rather than just the first 10 minutes. Large, prospective studies are needed to determine the relationship between the timing of vasopressor administration and long-term outcomes.

Dance for Parkinson's: a new framework for research on its physical, mental, emotional, and social benefits.

Parkinson's is a neurodegenerative disease commonly associated with symptoms such as tremor, rigidity, bradykinesia, freezing during gait, motor control deficits and instability. These physical symptoms can cause a myriad of psychological problems including depression, feelings of loneliness, and low self-esteem. Current research suggests pharmacological interventions do not sufficiently address all symptoms and thus alternative therapies have been deemed an important part of treatment for people with Parkinson's. Dance has shown to be a beneficial activity for this population. Upon reviewing recent dance for Parkinson's studies it is clear that there are developing trends with respect to overall approach. The tendency to place more emphasis on changes to clinical signs is creating a gap whereby research neglects to look at how dance is influencing a particular individual in all aspects of their life. There is a need for a framework that allows for and encourages the analysis of the dancing experience for people with Parkinson's on a variety of levels including physically, mentally, emotionally, and socially. With such a framework it would be possible to triangulate the information gathered to draw stronger conclusions that are more meaningful to the people with Parkinson's. This paper would like to propose the use of the World Health Organization's International Classification of Functioning, Disability, and Health as a possible framework for dance for Parkinson's research.

A mixed-methods study into ballet for people living with Parkinson's.

Background: Parkinson's is a neurological disease that is physically debilitating and can be socially isolating. Dance is growing in popularity for people with Parkinson's and claims have been made for its benefits. The paper details a mixed-methods study that examined a 12-week dance project for people with Parkinson's, led by English National Ballet. Methods: The effects on balance, stability and posture were measured through the Fullerton Advanced Balance Scale and a plumb-line analysis. The value of participation and movement quality were interpreted through ethnographic methods, grounded theory and Effort analysis. Results: Triangulation of results indicates that people were highly motivated, with 100% adherence, and valued the classes as an important part of their lives. Additionally, results indicated an improvement in balance and stability, although not in posture. Conclusions: Dancing may offer benefit to people with Parkinson's through its intellectual, artistic, social and physical aspects. The paper suggests that a range of research methods is fundamental to capture the importance of multifaceted activity, such as dance, to those with Parkinson's.

Impaired regulation of electron transport chain subunit genes by nuclear respiratory factor 2 in multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease. Recently, decreased expression of nuclear encoded electron transport chain genes was found in neurons in MS cortex. To understand the transcriptional mechanisms responsible for the coordinate down regulation of these genes, we performed electrophoretic mobility shifts with nuclear extracts isolated from gray matter from nonlesion areas of postmortem MS and control cortex. Nine tissue blocks from eight different MS brains and six matched control blocks from five control brains were analyzed. We identified a decrease in a transcription factor complex containing nuclear respiratory factor 2 (NRF-2) in nuclear extracts isolated from MS cortex. This decrease is correlated with decreased expression of electron transport chain subunit genes and increased oxidative damage measured by increased anti-nitrotyrosine immunoreactivity. We conclude that in MS cortex a chronic increase in oxidative stress leads to aberrant regulation of transcription of genes involved in energy metabolism.