No abstract

Traumatic brain injury (TBI) is linked to long-term symptoms in a sub-set of patients who sustain an injury, but this risk is not universal, leading us and others to question the nature of individual variability in recovery trajectories. Extracellular vesicles (EVs) are a promising, novel avenue to identify blood-based biomarkers for TBI. Here, our aim was to determine if glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) measured 1-year postinjury in EVs could distinguish patients from controls, and whether these biomarkers relate to TBI severity or recovery outcomes. EV GFAP and EV NfL were measured using an ultrasensitive assay in 72 TBI patients and 20 controls. EV GFAP concentrations were elevated in moderate and severe TBI compared to controls (p’s < 0.001) and could distinguish controls from moderate (AUC = 0.86) or severe TBI (AUC = 0.88). Increased EV GFAP and EV NfL levels were associated with lower 1-year Glasgow Outcome Scale–Extended (GOS-E) score (p’s < 0.05). These findings suggest that blood-derived EV concentrations of GFAP and NfL drawn even 1 year after injury are higher in TBI patients compared to controls, and are related to injury severity and poor recovery outcomes, suggesting that TBIs alter the activity of these biomarkers, likely contributing to individual variability in recovery.

Objectives: Musculoskeletal pain is a common emergency department (ED) presentation, and patient-centered care may improve quality of life, treatment satisfaction, and outcomes. Our objective was to investigate the expectations, definitions of success, and priorities of ED patients with musculoskeletal pain. Methods: We conducted a cross-sectional survey of the demographic, clinical, and psychosocial characteristics of adult ED patients (n = 210) with musculoskeletal pain. Patients completed the Patient-Centered Outcomes Questionnaire to quantify usual, desired, expected, and successful levels of pain and interference with daily activities, fatigue, and emotion from 0 (none) to 100 (worst imaginable). They also reported the importance of improvement in each domain. Cluster analysis identified subgroups by importance ratings. Patients were asked their willingness to try various pharmacologic and nonpharmacologic treatments. Fully completed surveys were analyzed (n = 174). Results: Most patients desired 100% resolution in each domain and defined treatment success as substantial (median = 63.2%-76.5%) reductions but expected only moderate (median = 45%-53.7%) improvements across all domains. Patients with previous pain episodes had similar desired levels but less stringent definitions of success and expectations for improvement. Cluster analysis identified three patient subgroups by importance ratings of each domain: (1) multiple domains important (n = 118) with high importance attached to all four domains, (2) pain and function important (n = 34) with high importance primarily for pain and interference with daily activities, and (3) only pain important (n = 22). Regardless of subgroup, there was a high willingness to use a variety of pharmacologic and nonpharmacologic treatments. Discussion: ED patients with musculoskeletal pain have expectations and goals that include addressing impairments in function, improving quality of life, and reducing pain.

To the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacological agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 antihyperglycemic therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from &lt;5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.

Despite the growing momentum behind a movement to augment adoption of continuous glucose monitoring (CGM) in clinical practice and investigation, to the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacologic agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 diabetes therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov listings, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from <5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes’s Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.

Background: Research suggests that women experience greater cardiovascular ischemic effects from stress than men. Visceral adiposity is an endocrine tissue that differs by sex and interacts with stress hormones. We hypothesized that urinary cortisol would be associated with increased cardiovascular events and change in coronary artery calcium score (CAC) in women, and these relationships would vary by central obesity. Methods: In the Multi-Ethnic Study of Atherosclerosis Stress Ancillary study, cortisol was quantified by 12-hour overnight urine collection. Central obesity was estimated by waist-hip ratio (WHR). Multivariable Cox models estimated the relationship between cortisol and cardiovascular events and assessed for moderation by WHR. The relationship between cortisol and change in CAC Agatston score was assessed by Tobit regression models. Results: 918 patients were analyzed with median follow up of 11 years. There was no association between urinary cortisol and cardiovascular events in the cohort. However, in individuals with below median WHR, higher urinary cortisol levels (upper tertile) were associated with higher cardiovascular event rates in the full cohort, women, and men, but not in groups with above median WHR. There was significant moderation by WHR in women, but not men, whereby the association between elevated cortisol and increased cardiovascular events diminished as WHR increased. Urinary cortisol was associated with increased change in CAC in women (P=0.003) but not men, without moderation by WHR. Conclusions: Our study highlights associations between cortisol and subclinical atherosclerosis in women, and moderation of the relationship between cortisol and cardiovascular events by central obesity in both genders.

No abstract

Despite the growing momentum behind a movement to augment adoption of continuous glucose monitoring (CGM) in clinical practice and investigation, to the best of our knowledge, there are no published data on the historical and recent use of CGM in clinical trials of pharmacologic agents used in the treatment of diabetes. We analyzed 2,032 clinical trials of 40 diabetes therapies currently on the market with a study start date between 1 January 2000 and 31 December 2019. According to ClinicalTrials.gov listings, 119 (5.9%) of these trials used CGM. CGM usage in clinical trials has increased over time, rising from <5% before 2005 to 12.5% in 2019. However, it is still low given its inclusion in the American Diabetes’s Association’s latest guidelines and known limitations of A1C for assessing ongoing diabetes care.