Pilot comparison of the ease of swallowing of single tablet antiretroviral regimens.

Daily adherence to lifelong antiretroviral therapy (ART) is required to achieve long term treatment success. However, patient preferences for ART tablet size have not been well studied. Our study assessed factors associated with the ease of swallowing (EoS) and tolerability of two placebo tablets representing and matching B/F/TAF (BPT) and DTG/ABC/3TC (DPT). Fifty ART-naïve patients were randomized into a two-period cross-over study. Likert scale (1-5) questionnaires were administered to assess patient factors influencing the ease of swallowing, adherence, home medications, medication preferences and perceptions. Comparisons were done using Student t-tests and ordinal regression. Participants were 64% female, 61% white, mean age 43 years, and taking a mean (median) of 4(1) pills/day. BPT was reported to be easier than DPT with ease of swallowability 1.76 vs. 2.42 (p < 0.001) (1 = very easy). DPT tablet was correctly perceived as larger than BPT (p < 0.001); with both tablets perceived as smaller than actual size (p < 0.001). EoS of either tablet was positively associated with the EoS of the largest home tablet medication (p = 0.021, p = 0.03). Patient's perceptions of EoS can affect their medication adherence, especially in HIV, and should be considered in treatment regimens.

Structural and functional, empirical and modeled connectivity in the cerebral cortex of the rat.

Connectomics data from animal models provide an invaluable opportunity to reveal the complex interplay between structure and function in the mammalian brain. In this work, we investigate the relationship between structural and functional connectivity in the rat brain cortex using a directed anatomical network generated from a carefully curated meta-analysis of published tracing data, along with resting-state functional MRI data obtained from a group of 14 anesthetized Wistar rats. We found a high correspondence between the strength of functional connections, measured as blood oxygen level dependent (BOLD) signal correlations between cortical regions, and the weight of the corresponding anatomical links in the connectome graph (maximum Spearman rank-order correlation ρ=0.48). At the network-level, regions belonging to the same functionally defined community tend to form more mutual weighted connections between each other compared to regions located in different communities. We further found that functional communities in resting-state networks are enriched in densely connected anatomical motifs. Importantly, these higher-order structural subgraphs cannot be explained by lower-order topological properties, suggesting that dense structural patterns support functional associations in the resting brain. Simulations of brain-wide resting-state activity based on neural mass models implemented on the empirical rat anatomical connectome demonstrated high correlation between the simulated and the measured functional connectivity (maximum Pearson correlation ρ=0.53), further suggesting that the topology of structural connections plays an important role in shaping functional cortical networks.

Increased histone-DNA complexes and endothelial-dependent thrombin generation in severe COVID-19.

Coagulopathy in severe COVID-19 is common but poorly understood. The purpose of this study was to determine how SARS-CoV-2 infection impacts histone levels, fibrin structure, and endogenous thrombin potential in the presence and absence of endothelial cells. We studied individuals with SARS-CoV-2 infection and acute respiratory distress syndrome at the time of initiation of mechanical ventilation compared to healthy controls. Circulating histone-DNA complexes were elevated in the plasma of COVID-19 patients relative to healthy controls (n=6, each group). Using calibrated automated thrombography, thrombin generation was altered in COVID-19 patient plasma samples. Despite having increased endogenous thrombin potential, patient plasma samples exhibited prolonged lag times and times to peak thrombin in the presence of added tissue factor and PCPS. Strikingly different results were observed when endothelial cells were used in place of tissue factor and PCPS. While healthy control plasma samples did not generate measurable thrombin after 60 min, plasma samples from COVID-19+ patients formed thrombin (mean lag time ~20 min). Consistent with the observed alterations in thrombin generation, clots from COVID-19 subjects exhibited a denser fibrin network, thinner fibers and lower fibrin resolvability. Elevated histones, aberrant fibrin formation, and increased endothelial-dependent thrombin generation may contribute to coagulopathy in COVID-19.

Dense and dangerous: The tissue plasminogen activator-resistant fibrinolysis shutdown phenotype is due to abnormal fibrin polymerization.

BACKGROUND: Both hyperfibrinolysis and fibrinolysis shutdown can occur after severe trauma. The subgroup of trauma patients with fibrinolysis shutdown resistant to tissue plasminogen activator (t-PA)-mediated fibrinolysis have increased mortality. Fibrin polymerization and structure may influence fibrinolysis subgroups in trauma, but fibrin architecture has not been characterized in acutely injured subjects. We hypothesized that fibrin polymerization measured in situ will correlate with fibrinolysis subgroups. METHODS: Blood samples were collected from trauma patients and noninjured controls. We selected samples across a range of fibrinolysis phenotypes (shutdown, physiologic, hyperfibrinolysis) and t-PA sensitivities (sensitive, physiologic, resistant) determined by thrombelastography. Plasma clots were created in situ with fluorescent fibrinogen and imaged using confocal microscopy for analysis of clot architecture in three dimensions. For each clot, we quantified the fiber resolvability, a metric of fiber distinctness or clarity, by mapping the variance of fluorescence intensity relative to background fluorescence. We also determined clot porosity by measuring the size and distribution of the gaps between fibrin fibers in three-dimensional space. We compared these measures across fibrinolysis subgroups. RESULTS: Fiber resolvability was significantly lower in all trauma subgroups compared with controls (n = 35 and 5, respectively; p < 0.05). We observed markedly different patterns of fibrin architecture among trauma patients stratified by fibrinolysis subgroup. Subjects with t-PA-resistant fibrinolysis shutdown exhibited abnormal, densely packed fibrin clots nearly devoid of pores. Individuals with t-PA-hypersensitive fibrinolysis shutdown had highly irregular clots with pores as large as 2500 µm to 20,000 µm, versus 78 µm to 1250 µm in noninjured controls. CONCLUSION: Fiber resolvability was significantly lower in trauma patients than controls, and subgroups of fibrinolysis differ in the porosity of the fibrin clot structure. The dense fibrin network in the t-PA-resistant group may prevent access to plasmin, suggesting a mechanism for thrombotic morbidity after injury.

Diagnostic Performance of Carbon Monoxide Testing by Pulse Oximetry in the Emergency Department.

BACKGROUND: Carbon monoxide (CO) exposure causes roughly 40,000 emergency department (ED) visits annually and is commonly misdiagnosed. Whereas the standard method of carboxyhemoglobin (HbCO) measurement utilizes blood gas analysis, a noninvasive, FDA-cleared alternative exists. We evaluated the performance of pulse oximetry (SpCO) for identification of CO exposure in ED patients. METHODS: We compared pulse oximetry to blood HbCO levels in a prospective observational study of adult and pediatric subjects recruited from the ED. Nurses screened a convenience sample of patients and referred those with SpCO ≥ 10% to research staff. Researchers also approached individuals who presented with signs and symptoms of CO toxicity. We determined diagnostic performance with a Bland-Altman analysis and calculated sensitivity and specificity for detection of elevated HbCO at thresholds of ≥ 10% and ≥ 15%. To optimize the potential sensitivity of SpCO for detection of CO toxicity, research technicians performed 3 SpCO readings within 5 min of the blood draw for laboratory measurement. A positive SpCO test was defined as any SpCO ≥ 10%. RESULTS: 42,000 patients were screened, 212 were evaluated, and 126 subjects were enrolled. Median HbCO level was 6% (range 1.6-21.9%). Limits of agreement were -10.3% and 8.1%. Of 23 individuals with elevated HbCO ≥ 10%, 13 were not suspected based on clinical assessment. Critically elevated HbCO was present in 6 individuals. Based on our a priori threshold of 10% for a positive test, pulse oximetry identified 14 of 23 subjects with HbCO ≥ 10%, with a sensitivity of 61% (95% CI 39-80%) and a specificity of 86% (95% CI 78-92%), and 5 of 6 subjects with HbCO ≥ 15%, with a sensitivity of 83% (95% CI 36-100%) and a specificity of 81% (95% CI 73-87%). CONCLUSIONS: Pulse oximetry underestimated HbCO and produced false negative results (ie, SpCO < 10% for all three measurements) in 17% of ED subjects with elevated HbCO ≥ 15%. Triage screening with pulse oximetry detected cases of elevated HbCO that were not suspected by the clinical provider.

Rapidly growing, multifocal, benign choroid plexus tumor in an infant: case report.

Choroid plexus papillomas (CPPs) are rare, benign tumors that can arise in young children. Most pediatric patients present with signs of hydrocephalus and require immediate treatment. The natural history of choroid plexus tumors in children without hydrocephalus is poorly defined. In this report, the authors present the very rare case of a child without hydrocephalus but with two intraventricular choroid plexus tumors discovered shortly after birth. Initial imaging had been performed for seizures and showed agenesis of the corpus callosum and enhancing tumors in the third and left lateral ventricles. Sequential imaging demonstrated rapid growth of both tumors. The lateral tumor was removed when the child was 3 months of age. A histological examination of the specimen showed benign features with an elevated mitotic rate. Given the patient's age of under 3 years, the diagnosis was WHO grade I CPP. The third ventricle tumor grew rapidly. A second surgery was performed and this tumor was resected. Again, the pathological diagnosis was WHO grade I CPP. The authors present this rare case and discuss the current relevant literature.

Accuracy of Point-of-Care Testing for Anemia in the Emergency Department.

BACKGROUND: Pulse oximetry has become the standard of care in emergency medicine, operating rooms, and medical wards for the monitoring of oxygenation, but the use of pulse oximetry for assessment of hemoglobin (Hb) is controversial. The purpose of this study was to compare the accuracy and precision of 2 point-of-care Hb measurement devices, the Pronto-7 and the HemoCue 201+, to laboratory testing. METHODS: We studied a convenience sample of patients in the emergency department who required a complete blood count. We excluded patients in critical condition or those with elevated methemoglobin, impaired perfusion, or finger deformities. Each subject provided 2 capillary samples for measurement with the HemoCue 201+ and 2 consecutive readings with the Pronto-7. We used Bland-Altman analysis to compare the performance of the point-of-care devices to laboratory measurements. We also determined the diagnostic performance for the detection of anemia by sex (Hb < 11.6 g/dL for females, Hb < 13.8 g/dL for males). RESULTS: 201 of the 350 subjects enrolled (57%) were female. Mean (SD) age was 50.9 (19.0) y. Complete data were available for 297 (84.9%) of the Pronto-7 readings and 323 (92.3%) of the HemoCue 201+ readings. Mean (SD) laboratory Hb was 13.1 g/dL (2.3). Mean bias (Bland-Altman limits of agreement) for the Pronto-7 was -0.52 g/dL (-3.29 to 2.25), and for the HemoCue 201+ the mean bias was -0.98 g/dL (-3.57 to 1.61). Sensitivity and specificity for diagnosis of anemia were 81.6% (95% CI 72.5-88.7) and 75.4% (95% CI 68.8-81.1) for the Pronto-7 and 99.1% (95% CI 94.8-100.0) and 71.0% (95% CI 64.4-76.9) for HemoCue 201+. CONCLUSION: Both devices provided clinically useful methods to screen for anemia.

Personalized drinking feedback intervention for veterans of the wars in Iraq and Afghanistan: a randomized controlled trial.

OBJECTIVE: Research has shown that U.S. military veterans are at risk relative to the general adult population for excessive alcohol consumption, and veterans of the wars in Afghanistan and Iraq (Operation Enduring Freedom [OEF], Operation Iraqi Freedom [OIF], and Operation New Dawn [OND]) particularly so. The purpose of this study was to examine the efficacy of a brief personalized drinking feedback intervention tailored for veterans. METHOD: All veterans who presented to the OEF/OIF/OND Seamless Transition Clinic at the Harry S. Truman Memorial Veterans' Hospital (Columbia, MO) were eligible to participate. Participants were 325 veterans (93% male; 82% White, 75% Army, M(age) = 32.20 years) who were randomly assigned to one of two conditions: personalized drinking feedback (PDF) or educational information (EDU). Those in the PDF condition received personalized information about their alcohol use, including social norms comparisons, risks associated with reported drinking levels, and a summary of their alcohol-related problems. Follow-up assessments were completed at 1 and 6 months after intervention (response rates = 93% and 86%, respectively). RESULTS: Results indicated a significant (p < .05) Omnibus Group × Time effect for estimated peak blood alcohol concentration, although tests of simple main effects did not indicate between-group differences at the individual follow-up points. Among baseline abstainers, those in the PDF condition were more likely than those in the EDU condition to remain an abstainer at 6-month follow-up (p < .05). CONCLUSIONS: These findings provide preliminary support for the efficacy of a brief, inexpensive alcohol prevention/intervention for young adult military veterans.

Personality and injury risk among professional hockey players.

BACKGROUND: Although much is known about risk for athletic injury, research on the roles of individual differences in personality and temperament on athletic injury has lagged. We hypothesized that professional athletes with high sensation-seeking and extraversion scores, and with low effortful control scores, would experience more injuries over the course of a season, would have more severe injuries, and would miss more total days of play. METHODS: Prospective design with questionnaire report at time one and injury tracking throughout an 18-week athletic season. SETTING: Professional hockey team in the United States. PARTICIPANTS: Eighteen professional hockey players (ages 21-33). MEASUREMENTS: Players completed self-report personality (Sensation-Seeking Scale, Form V) and temperament (the Adult Temperament Questionnaire) measures. Quantity and severity of injury, as well as playing time missed, were tracked for 18 weeks. RESULTS: On average, players experienced almost 6 injuries causing a loss of 10 playing days through the season. Those players scoring high on Boredom Susceptibility and Total Sensation-Seeking incurred more total injuries. Those scoring high on temperamental neutral perceptual sensitivity suffered more severe injuries. CONCLUSIONS: Athletes who suffered more injuries reported a preference for stimulating environments and boredom with non-stimulating environments. Injury severity was not correlated with sensation-seeking but was related to temperamental perceptual sensitivity. Implications for identification of injury-prone athletes, pre-injury training, and post-injury treatment are discussed.