Healthy Patient Populations Research Articles

An integrated population pharmacokinetic model of febuxostat in pediatric patients with hyperuricemia including gout and adult population of healthy subjects and patients with renal dysfunction.

The study objective was to validate febuxostat dosage and administration in pediatric patients with hyperuricemia including gout, using an integrated population pharmacokinetic (PopPK) analysis in the Japanese population. Integrated PopPK analysis of febuxostat used a nonlinear mixed-effects modeling (NONMEM) program on plasma febuxostat concentration data for 2611 samples from Japanese pediatric patients with hyperuricemia including gout (n = 29) and from adult subjects who are healthy or have renal dysfunction (n = 113). We described febuxostat pharmacokinetics using an integrated PopPK model applicable both to pediatric patients and to the adult population. The covariates of body weight and eGFR were identified for CL/F and the covariate of fasted/fed status for bioavailability. The range of steady-state exposures (Cmax,ss and AUCτ,ss) for 5, 10, 20, and 30 mg of febuxostat in fed pediatric patients weighing 20 to 40 kg was within that for 10, 20, 40, and 60 mg of febuxostat in fed pediatric patients and adults weighing 40 to 120 kg. Post hoc estimates of CL/F, adjusted by body weight, differed little between pediatric patients and the adult population in the renal function categories of normal, mild dysfunction, and moderate dysfunction. We successfully validated the febuxostat dose that provided the same level of exposure in pediatric patients as in the adult population: half the adult dose for pediatric patients weighing <40 kg and the full adult dose for pediatric patients weighing ≥40 kg. As in adults, the results support the use of febuxostat without dose adjustment in pediatric patients who have mild to moderate renal dysfunction.

Assessing Individual Sensitivity to the Thermal Grill Illusion: A Two-Dimensional Adaptive Psychophysical Approach

In the thermal grill illusion (TGI), the spatial alternation of non-noxious warm and cool temperatures elicits burning sensations that resemble the presence of noxious stimuli. Previous research has largely relied on the use of specific temperature values (i.e., 20°C and 40°C) to study this phenomenon in both healthy individuals and patient populations. However, this methodology fails to account for inter-individual differences in thermal sensitivity, limiting the precision with which TGI responses can be evaluated across diverse populations. To address this gap, we created a Two-Dimensional Thermal Grill Calibration (2D-TGC) protocol, enabling an efficient and precise estimation of the combinations of warm and cool temperatures needed to elicit burning sensations tailored to each individual. By applying the 2D-TGC protocol in 43 healthy participants, we demonstrated key findings: (1) The TGI can be thresholded using an adaptive psychophysical method. (2) Multiple combinations of warm and cool temperatures can elicit this phenomenon. (3) The protocol facilitated the identification of temperature combinations that elicit TGI with varying levels of probability, intensity, and perceived quality ranging from freezing cold to burning hot. (4) TGI responsivity can be quantified as a continuous variable, moving beyond the conventional classification of individuals as responders vs. non-responders based on arbitrary temperature values in the innocuous temperature range. The 2D-TGC offers a comprehensive approach to investigate the TGI across populations with altered thermal sensitivity, and can be integrated with other methods (e.g., neuroimaging) to elucidate the mechanisms responsible for perceptual illusions in the thermo-nociceptive system. PerspectiveThis study reveals that the Thermal Grill Illusion can be accurately measured using psychophysical methods. The innovative Two-Dimensional Thermal Grill Calibration protocol allows for personalized temperature assessments, enhancing our understanding of thermal sensitivity variations and perceptual illusions in the thermo-nociceptive system across different populations.

Radiographic Indicators of Craniocervical Instability: Analyzing Variance of Normative Supine and Upright Imaging in a Healthy Population.

Single-institution retrospective review. To establish baseline ranges and variability of 7 radiographic measurements of the cervical spine in a healthy patient population as potential diagnostic tools for craniocervical instability. Craniocervical instability, common in patients with connective tissue disease such as Ehlers-Danlos Syndrome, often presents with a wide range of symptoms, including neck pain. Current diagnostic methods employ a range of clinical and radiographic features, but diagnostic challenges remain due to missed indications on static imaging and a lack of standardized measurement values and normalized variance. Seventy-two healthy patients with cervical imaging were analyzed. Surgimap software was used to annotate supine computed tomography images, flexion, extension, and neutral x-ray images for measurement. These measurements included the atlanto-dental interval, clival-axial angle, basion-dens interval, basion-axis interval, perpendicular basion to the inferior aspect of C2, also known as Grabb Oakes measurement, and the hard palate to C1 and hard palate to C2. Statistical analysis assessed differences among imaging modalities, and coefficients of variation were calculated for each measurement. Our cohort consisted of a total of 72 patients with a mean age of 64 (SD: 13.54). All measurements except for the basion-axial interval and atlanto-dental interval demonstrated a significant difference between extension and flexion x-ray measurements. clivo-axial angle, hard palate to C1, and hard palate to C2 demonstrated the lowest coefficients of variance across imaging modalities. Understanding normal variance in cervical measurements is invaluable for accurate CCI diagnosis. Using a cohort of healthy patients, this study delineates the distribution and spread of 7 cervical measurements, delineating reference values and variability in these key measurements and highlighting their potential for use as imaging markers for CCI. Level III.

Challenges in designing a randomized, double-blind noninferiority trial for treatment of acne: The SD-ACNE trial.

Excessive use of antibiotics has led to development of antibiotic resistance and other antibiotic-associated complications. Dermatologists prescribe more antibiotics per clinician than any other major specialty, with much of this use for acne. Alternative acne treatments are available but are used much less often than antibiotics, at least partially because dermatologists feel that they are less effective. Spironolactone, a hormonal therapy with antiandrogen effects that can address the hormonal pathogenesis of acne, may represent a therapeutic alternative to oral antibiotics for women with acne. However, the comparative effects of spironolactone and oral antibiotics in the treatment of acne have not been definitively studied. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation (SD-ACNE) trial aims to answer whether spironolactone, in addition to standard topical therapy, is noninferior to doxycycline (an oral antibiotic) for women with acne. Several interesting challenges arose in the development of this study, including determining acceptability of the comparative regimens to participating dermatologists, identifying data to support a noninferiority margin, and establishing a process for unblinding participants after they completed the study while maintaining the blind for study investigators. We present the scientific and clinical rationale for the decisions made in the design of the trial, including input from key stakeholders through a Delphi consensus process. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial (NCT04582383) is being conducted at a range of community and academic sites in the United States. To maximize external validity and inform clinical practice, the study is designed with broad eligibility criteria and no prohibition of use of topical medications. Participants in the trial will be randomized to receive either spironolactone 100 mg/day or doxycycline hyclate 100 mg/day for 16 weeks. The primary outcome is the absolute decrease in inflammatory lesion count, and we have established a noninferiority margin of four inflammatory lesions. Secondary outcomes include the percentage of participants achieving Investigator Global Assessment success, change in quality of life, and microbiome changes and diversity. The Spironolactone versus Doxycycline for Acne: A Comparative Effectiveness, Noninferiority Evaluation trial will have substantial implications for the treatment of acne and antibiotic stewardship. In addition, this study will provide important information on the effect of these systemic agents on the development of changes to the microbiome and antibiotic resistance in a healthy population of patients.

Population pharmacokinetic, pharmacodynamic and efficacy modeling of SB12 (proposed eculizumab biosimilar) and reference eculizumab

PurposeTo describe, compare similarity of pharmacokinetic (PK), pharmacodynamic (PD) and efficacy of SB12 and reference eculizumab (ECU) and find clinically significant covariate relationships.MethodsThe PK, PD (terminal complement activity) and efficacy (LDH) data of SB12 and ECU were obtained from 289 subjects from phase I and phase III studies. One- and two-compartment PK models with first-order elimination were evaluated for SB12 and ECU. For PD and efficacy, both direct and indirect models were tested. The impact of covariates on PK, PD and efficacy parameters was assessed. Relationship between PK/PD and PD/efficacy was characterized. This modeling was performed using NONMEM version 7.4 (Icon Development Solutions, Ellicott City, MD, USA).ResultsThe two-compartment model adequately described the PK of SB12 and ECU, and the subject’s weight was chosen as a clinically significant covariate affecting drugs’ clearance and central volume of distribution. Treatment group was not a significant covariate affecting clearance. The direct response model using inhibitory sigmoid Emax and sigmoid Emax relationship well described the PK/PD relationship and PD/efficacy relationship of SB12 and ECU, respectively. Through this modeling, the relationships between PK, PD and efficacy were characterized. There were no differences in PK, PD and efficacy parameters between SB12 and ECU in pooled populations of healthy subjects and paroxysmal nocturnal haemoglobinuria (PNH) patients.ConclusionThe population modeling showed PK, PD and efficacy similarities between SB12 and ECU in pooled population of healthy subjects and PNH patients, supporting the totality of evidence on biosimilarity for SB12.

Walking on a Balance Beam as a New Measure of Dynamic Balance to Predict Falls in Older Adults and Patients with Neurological Conditions.

Beam walking is a new test to estimate dynamic balance. We characterized dynamic balance measured by the distance walked on beams of different widths in five age groups of healthy adults (20, 30, 40, 50, 60years) and individuals with neurological conditions (i.e., Parkinson, multiple sclerosis, stroke, age: 66.9years) and determined if beam walking distance predicted prospective falls over 12months. Individuals with (n = 97) and without neurological conditions (n = 99, healthy adults, age 20-60) participated in this prospective longitudinal study. Falls analyses over 12months were conducted. The summed distance walked under single (walking only) and dual-task conditions (walking and serial subtraction by 7 between 300 to 900) on three beams (4, 8, and 12-cm wide) was used in the analyses. Additional functional tests comprised grip strength and the Short Physical Performance Battery. Beam walking distance was unaffected on the 12-cm-wide beam in the healthy adult groups. The distance walked on the 8-cm-wide beam decreased by 0.34m in the 20-year-old group. This reduction was ~ 3 × greater, 1.1m, in the 60-year-old group. In patients, beam walking distances decreased sharply by 0.8m on the 8 versus 12cm beam and by additional 1.6m on the 4 versus 8cm beam. Beam walking distance under single and dual-task conditions was linearly but weakly associated with age (R2 = 0.21 for single task, R2 = 0.27 for dual-task). Age, disease, and beam width affected distance walked on the beam. Beam walking distance predicted future falls in the combined population of healthy adults and patients with neurological conditions. Based on receiver operating characteristic curve analyses using data from the entire study population, walking ~ 8.0 of the 12m maximum on low-lying beams predicted future fallers with reasonable accuracy. Balance beam walking is a new but worthwhile measure of dynamic balance to predict falls in the combined population of healthy adults and patients with neurological conditions. Future studies are needed to evaluate the predictive capability of beam walking separately in more homogenous populations. Clinical Trial Registration Number NCT03532984.

A personalized semi-automatic sleep spindle detection (PSASD) framework

BackgroundSleep spindles are distinct electroencephalogram (EEG) patterns of brain activity that have been posited to play a critical role in development, learning, and neurological disorders. Manual scoring for sleep spindles is labor-intensive and tedious but could supplement automated algorithms to resolve challenges posed with either approaches alone. New methodsA Personalized Semi-Automatic Sleep Spindle Detection (PSASD) framework was developed to combine the strength of automated detection algorithms and visual expertise of human scorers. The underlying model in the PSASD framework assumes a generative model for EEG sleep spindles as oscillatory components, optimized to EEG amplitude, with remaining signals distributed into transient and low-frequency components. ResultsA single graphical user interface (GUI) allows both manual scoring of sleep spindles (model training data) and verification of automatically detected spindles. A grid search approach allows optimization of parameters to balance tradeoffs between precision and recall measures. Comparison with existing methodsPSASD outperformed DETOKS in F1-score by 19% and 4% on the DREAMS and P-DROWS-E datasets, respectively. It also outperformed YASA in F1-score by 25% in the P-DROWS-E dataset. Further benchmarking analysis showed that PSASD outperformed four additional widely used sleep spindle detectors in F1-score in the P-DROWS-E dataset. Titration analysis revealed that four 30-second epochs are sufficient to fine-tune the model parameters of PSASD. Associations of frequency, duration, and amplitude of detected sleep spindles matched those previously reported with automated approaches. ConclusionsOverall, PSASD improves detection of sleep spindles in EEG data acquired from both younger healthy and older adult patient populations.

LIQUID-BIOPSY FOR ASSESSING SEVERITY OF INFLAMMATORY BOWEL DISEASE VIA PLASMA MICROBIAL CELL-FREE DNA

Abstract Plasma cell-free DNA (cfDNA) has emerged as a robust biomarker utilized in multiple applications that span cancer screening, diagnosis and monitoring, prenatal testing, and characterization of organ health post-transplantation. Cell-free DNA-based assays leverage the occurrence of processed extracellular DNA that produce unique signatures to discern a variety of biological states, disease manifestations, as well as forms of cell death. Similar to human cells, microbes produce cfDNA when they turnover, providing evident clinical utility in diagnosing and treating deep-seated infections in immunocompromised patients. Here, we describe the use of plasma microbial cell-free DNA (mcfDNA) as a unique means to assess inflammatory bowel disease type and severity. A total of 392 plasma samples encompassing remission and active (mild, moderate, severe) Crohn’s disease (N=196) and ulcerative colitis (N=196) were provided by the Crohn’s and Colitis Foundation for this study. All samples were derived from patients who had an endoscopic assessment within a 30-day window of plasma collection. Our classifiers, based solely on plasma mcfDNA signatures, are able to discriminate between Crohn’s disease, Ulcerative colitis, or otherwise healthy patient populations with an AUC &amp;gt;0.95. Similarly, a second set of classifiers are able to distinguish between endoscopically validated remission, mild, moderate, and severe disease cases (as determined by Mayo Endoscopic score or Crohn’s disease activity index) with AUCs &amp;gt;0.75. These results correspond to greater than 37% (UC) and 18% (CD) increase in sensitivity in comparison to standard of care measurements via fecal-calprotectin and high sensitivity-C-reactive protein for this cohort. Upon investigation, critical features in our classifiers correspond with well-known signatures from microbes associated with IBD or well-curated from the human microbiome. The use of mcfDNA for IBD diagnosis and assessment of disease severity may provide clinicians and patients a valuable non-invasive means to gain additional insight into disease progression in a routine manner. Further opportunities to leverage these signatures to predict response to therapy, and validate classifier performance on an independent cohort are currently being explored.

Unveiling the reliability of left atrial strain measurement: a dedicated speckle tracking software perspective in controls and cases.

Speckle tracking echocardiography increasingly supports left atrial (LA) strain (LAS) analysis for diagnosis and prognosis of various clinical conditions. Prior limitations, such as the absence of dedicated software, have been overcome by validated ventricular-based software. A newly automated real-time and offline LA-specific software have now become available on echocardiographs and dedicated workstations. This study aimed at comparing LA strain measures obtained from new fully automated software vs. traditional semi-automated ventricular-based methods in different groups of patients. Two operators acquired LA images in a mixed population of healthy individuals and patients with pressure overload (hypertension and aortic stenosis) or pressure-volume overload (mitral regurgitation and heart failure). Subjects with prosthetic valves, heart transplant, or atrial fibrillation were excluded. Strain analysis was performed twice by old semi-automated software and new LA dedicated. LAS was then measured online on the scanning echocardiograph. Overall, 100 patients were analysed (41 healthy subjects, 28 pressure overload, 31 volume overload). LAS proved to be highly reproducible with both software. The dedicated method exhibited slightly superior inter- and intra-operator reproducibility. The online software results showed a nearly perfect reproducibility with offline software [intraclass correlation coefficient = 0.99 [0.99; 1.00]] in addition to being able to save an average of ∼30 s. The recently developed fully automated software for dedicated LAS analysis demonstrates excellent inter- and intra-operator reproducibility, making it a reliable and efficient strain calculation method in routine clinical practice. Another advantage of online LAS calculation is time efficiency.

Traumatic Cardiac Arrest-A Narrative Review.

A paradigm shift in traumatic cardiac arrest (TCA) perception switched the traditional belief of futility of TCA resuscitation to a more optimistic perspective, at least in selected cases. The goal of TCA resuscitation is to rapidly and aggressively treat the common potentially reversible causes of TCA. Advances in diagnostics and therapy in TCA are ongoing; however, they are not always translating into improved outcomes. Further research is needed to improve outcome in this often young and previously healthy patient population.

Reliability and validity of ultrasonography in evaluating the thickness, excursion, stiffness, and strain rate of respiratory muscles in non-hospitalized individuals: a systematic review

ObjectiveTo summarize the reliability and validity of ultrasonography in evaluating the stiffness, excursion, stiffness, or strain rate of diaphragm, intercostals and abdominal muscles in healthy or non-hospitalized individuals.Literature searchPubMed, Embase, SPORTDiscus, CINAHL and Cochrane Library were searched from inception to May 30, 2022.Study selection criteriaCase–control, cross-sectional, and longitudinal studies were included if they investigated the reliability or validity of various ultrasonography technologies (e.g., brightness-mode, motion-mode, shear wave elastography) in measuring the thickness, excursion, stiffness, or strain rate of any respiratory muscles.Data synthesisRelevant data were summarized based on healthy and different patient populations. The methodological quality by different checklist depending on study design. The quality of evidence of each psychometric property was graded by the Grading of Recommendations, Assessment, Development and Evaluations, respectively.ResultsThis review included 24 studies with 787 healthy or non-hospitalized individuals (e.g., lower back pain (LBP), adolescent idiopathic scoliosis (AIS), and chronic obstructive pulmonary disease (COPD)). Both inspiratory (diaphragm and intercostal muscles) and expiratory muscles (abdominal muscles) were investigated. Moderate-quality evidence supported sufficient (intra-class correlation coefficient > 0.7) within-day intra-rater reliability of B-mode ultrasonography in measuring right diaphragmatic thickness among people with LBP, sufficient between-day intra-rater reliability of M-mode ultrasonography in measuring right diaphragmatic excursion in non-hospitalized individuals. The quality of evidence for all other measurement properties in various populations was low or very low. High-quality evidence supported sufficient positive correlations between diaphragm excursion and forced expiratory volume in the first second or forced vital capacity (r > = 0.3) in healthy individuals.ConclusionsDespite the reported sufficient reliability and validity of using ultrasonography to assess the thickness, excursion, stiffness, and strain rate of respiratory muscles in non-hospitalized individuals, further large-scale studies are warranted to improve the quality of evidence regarding using ultrasonography for these measurements in clinical practice. Researchers should establish their own reliability before using various types of ultrasonography to evaluate respiratory muscle functions.Trial registrationPROSPERO NO. CRD42022322945.

Socioeconomic status is associated with greater hazard of post-discharge mortality than race, gender, and ballistic injury mechanism in a young, healthy, orthopedic trauma population

ObjectivesTo explore the utility of legacy demographic factors and ballistic injury mechanism relative to popular markers of socioeconomic status as prognostic indicators of 10-year mortality following hospital discharge in a young, healthy patient population with isolated orthopedic trauma injuries. MethodsA retrospective cohort study was performed to evaluate patients treated at an urban Level I trauma center from January 1, 2003, through December 31, 2016. Current Procedure Terminology (CPT) codes were used to identify upper and lower extremity fracture patients undergoing operative fixation. Exclusion criteria were selected to yield a patient population of isolated extremity trauma in young, otherwise healthy individuals between the ages of 18 and 65 years. Variables collected included injury mechanism, age, race, gender, behavior risk factors, Area Deprivation Index (ADI), and insurance status. The primary outcome was post-discharge mortality, occurring at any point during the study period. ResultsWe identified 2539 patients with operatively treated isolated extremity fractures. The lowest two quartiles of socioeconomic status (SES) were associated with higher hazard of mortality than the highest SES quartile in multivariable analysis (Quartile 3 HR: 2.2, 95% CI: 1.2–4.1, p = 0.01; Quartile 4 HR: 2.2, 95% CI: 1.1–4.3, p = 0.02). Not having private insurance was associated with higher mortality hazard in multivariable analysis (HR 2.0, 95% CI: 1.3–3.2, p = 0.002). The presence of any behavioral risk factor was associated with higher mortality hazard in univariable analysis (HR: 1.8, p < 0.05), but this difference did not reach statistical significance in multivariable analysis (HR: 1.4, 95%: 0.8–2.3, p = 0.20). Injury mechanism (ballistic versus blunt), gender, and race were not associated with increased hazard of mortality (p > 0.20). ConclusionLow SES is associated with a greater hazard of long-term mortality than ballistic injury mechanism, race, gender, and medically diagnosable behavioral risk factors in a young, healthy orthopedic trauma population with isolated extremity injury.

Identifying Aging-Related Biomarkers and Immune Infiltration Features in Diabetic Nephropathy Using Integrative Bioinformatics Approaches and Machine-Learning Strategies.

Aging plays an essential role in the development of diabetic nephropathy (DN). This study aimed to identify and verify potential aging-related genes associated with DN using bioinformatics analysis. To begin with, we combined the datasets from GEO microarrays (GSE104954 and GSE30528) to find the genes that were differentially expressed (DEGs) across samples from DN and healthy patient populations. By overlapping DEGs, weighted co-expression network analysis (WGCNA), and 1357 aging-related genes (ARGs), differentially expressed ARGs (DEARGs) were discovered. We next performed functional analysis to determine DEARGs' possible roles. Moreover, protein-protein interactions were examined using STRING. The hub DEARGs were identified using the CytoHubba, MCODE, and LASSO algorithms. We next used two validation datasets and Receiver Operating Characteristic (ROC) curves to determine the diagnostic significance of the hub DEARGs. RT-qPCR, meanwhile, was used to confirm the hub DEARGs' expression levels in vitro. In addition, we investigated the relationships between immune cells and hub DEARGs. Next, Gene Set Enrichment Analysis (GSEA) was used to identify each biomarker's biological role. The hub DEARGs' subcellular location and cell subpopulations were both identified and predicted using the HPA and COMPARTMENTS databases, respectively. Finally, drug-protein interactions were predicted and validated using STITCH and AutoDock Vina. A total of 57 DEARGs were identified, and functional analysis reveals that they play a major role in inflammatory processes and immunomodulation in DN. In particular, aging and the AGE-RAGE signaling pathway in diabetic complications are significantly enriched. Four hub DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) were further screened using the interaction network, CytoHubba, MCODE, and LASSO algorithms. The results above were further supported by validation sets, ROC curves, and RT-qPCR. According to an evaluation of immune infiltration, DN had significantly more resting mast cells and delta gamma T cells but fewer regulatory T cells and active mast cells. Four DEARGs have statistical correlations with them as well. Further investigation revealed that four DEARGs were implicated in immune cell abnormalities and regulated a wide range of immunological and inflammatory responses. Furthermore, the drug-protein interactions included four possible therapeutic medicines that target four DEARGs, and molecular docking could make this association practical. This study identified four DEARGs (CCR2, VCAM1, CSF1R, and ITGAM) associated with DN, which might play a key role in the development of DN and could be potential biomarkers in DN.

Physiologically-based pharmacokinetic modeling for single and multiple dosing regimens of ceftriaxone in healthy and chronic kidney disease populations: a tool for model-informed precision dosing.

Introduction: Ceftriaxone is one of commonly prescribed beta-lactam antibiotics with several label and off-label clinical indications. A high fraction of administered dose of ceftriaxone is excreted renally in an unchanged form, and it may accumulate significantly in patients with impaired renal functions, which may lead to toxicity. Methods: In this study, we employed a physiologically-based pharmacokinetic (PBPK) modeling, as a tool for precision dosing, to predict the biological exposure of ceftriaxone in a virtually-constructed healthy and chronic kidney disease patient populations, with subsequent dosing optimizations. We started developing the model by integrating the physicochemical properties of the drug with biological system information in a PBPK software platform. A PBPK model in an adult healthy population was developed and evaluated visually and numerically with respect to experimental pharmacokinetic data. The model performance was evaluated based on the fold error criteria of the predicted and reported values for different pharmacokinetic parameters. Then, the model was applied to predict drug exposure in CKD patient populations with various degrees of severity. Results: The developed PBPK model was able to precisely describe the pharmacokinetic behavior of ceftriaxone in adult healthy population and in mild, moderate, and severe CKD patient populations. Decreasing the dose by approximately 25% in mild and 50% in moderate to severe renal disease provided a comparable exposure to the healthy population. Based on the simulation of multiple dosing regimens in severe CKD population, it has been found that accumulation of 2g every 24h is lower than the accumulation of 1g every 12h dosing regimen. Discussion: In this study, the observed concentration time profiles and pharmacokinetic parameters for ceftriaxone were successfully reproduced by the developed PBPK model and it has been shown that PBPK modeling can be used as a tool for precision dosing to suggest treatment regimens in population with renal impairment.

Normal range of intraoperative three-dimensionally derived right ventricular free-wall strain in coronary artery bypass surgery patients.

Data on intraoperative three-dimensionally derived right ventricular free-wall strain (3D-RV FWS) is sparse. We sought to evaluate the normal range of intraoperative 3D-RV FWS in patients scheduled for coronary artery bypass graft (CABG) surgery and compared to conventional echocardiographic parameters. Prospective observational study. A total of 150 patients with preserved left and right ventricular (RV) function and sinus rhythm, without significant heart valve disease or pulmonary hypertension undergoing isolated on-pump CABG surgery, with an uneventful, complication-free intraoperative course. 3D-RV FWS analysis and conventional echocardiographic assessment of RV function were performed intraoperatively in anesthetized and ventilated patients using transesophageal echocardiography (TEE). TomTec 4D RV-Function 2.0 software for assessment of 3D-RV FWS and three-dimensional right ventricular ejection fraction (3D-RV EF). Philips QLAB 10.8 was used to evaluate tissue velocity of the tricuspid annulus (RV S´), tricuspid annular systolic excursion (TAPSE), and RV fractional area change (FAC). All echocardiographic measurements were performed under stable hemodynamic conditions and predefined fluid management without any vasoactive support or pacing. The prospective observational study was performed in a single university hospital setting. Assessment of 3D-RV FWS was feasible in 95% of patients. No included patient experienced any serious perioperative complication. In our group of patients, median values with interquartile range (IQR) for 3D-RV FWS and 3D-RV EF were -25.2 (IQR -29.9 to -21.8) and 46.3% (IQR 41.0%-50.1%), respectively. RV FAC, RV S´, and TAPSE accounted for 39.7% (IQR 34.5%-44.4%), 14.8cm/s (IQR 11.8-19.0cm/s), and 22mm (IQR 20-25mm). The normal range (2.5% to 97.5% percentile) for 3D-RV FWS was -37.1 to -12.8. There was no relevant correlation of 3D-RV FWS to postoperative outcome in this group of CABG patients. We present distribution values for intraoperative 3D-RV FWS and conventional parameters of RV function assessment in a healthy on-pump CABG patient population without serious perioperative complications. We observed no correlations of these parameters with any of the outcome parameters considered. Therefore, we consider these values to be intraoperative TEE-assessed normal values, which can be expected in on-pump CABG patients.

Prevalence and significance of T-wave inversion on the electrocardiogram of patients with marfan syndrome

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Cardiac risk in the young charity, and Robert Luff Foundation. Background The 12-lead ECG is used as a screening tool in healthy individuals and patient populations, and pathological T-wave inversion (TWI) warrant further investigation for heart disease. Marfan syndrome (MFS) can be associated with valvular disease and a cardiomyopathy-like phenotype but there are limited data on the ECG of this cohort. Purpose We aimed to characterize the ECG of MFS patients, with particular emphasis on the prevalence and significance of TWI. Methods The study population included consecutive MFS patients, aged ≥18 years old, free of cardiothoracic surgery, seen in our Aortopathy clinic between 2015 and 2019. We collected information on demographics, MFS systemic score, body habitus (height, weight and body mass index-BMI), medical treatment and echocardiographic data. Chest deformities were defined as presence of pectus excavatum (PE), pectus carinatum (PC) or chest wall asymmetry (CA). The ECG was systematically analysed based on established criteria. The presence of TWI and its localisation were recorded. Results 116 MFS patients were included (mean age 39±15 years, females 60%, Caucasian 89%, BMI 25±6 Kg/m2). 44% of patients were on beta-blocker. Chest deformities were present in 42% of the patients (PE 18%, PC 22%, CW 2%) and scoliosis in 59% of them. Echocardiography revealed a mean aortic root was 38.1±4.8mm but no evidence of significant cardiomyopathy in any of the patients. Four individuals exhibited moderate mitral regurgitation. ECG abnormalities are summarised in Figure 1. Anterior TWI was present in 10.3%, inferior TWI in 4.3% and lateral in 3.4%. Age, ethnicity, BMI, scoliosis, or valvular pathology were not associated with TWI. However, anterior TWI was more common in females compared to males (14.5% versus 4.3%) and in patients with PE compared to those without (31.3% vs 8%, p=0.003). Conclusion Pathological TWI were present in almost a fifth of MFS patients. Anterior TWI were more frequently present in females and in patients with pectus excavatum and are likely to represent a benign trait. The exact significance of other TWI remains to be elucidated

DeepCOVNet Model for COVID-19 Detection Using Chest X-Ray Images.

COVID-19 is an epidemic disease that has threatened all the people at worldwide scale and eventually became a pandemic It is a crucial task to differentiate COVID-19-affected patients from healthy patient populations. The need for technology enabled solutions is pertinent and this paper proposes a deep learning model for detection of COVID-19 using Chest X-Ray (CXR) images. In this research work, we provide insights on how to build robust deep learning based models for COVID-19 CXR image classification from Normal and Pneumonia affected CXR images. We contribute a methodical escort on preparation of data to produce a robust deep learning model. The paper prepared datasets by refactoring, using images from several datasets for ameliorate training of deep model. These recently published datasets enable us to build our own model and compare by using pre-trained models. The proposed experiments show the ability to work effectively to classify COVID-19 patients utilizing CXR. The empirical work, which uses a 3 convolutional layer based Deep Neural Network called "DeepCOVNet" to classify CXR images into 3 classes: COVID-19, Normal and Pneumonia cases, yielded an accuracy of 96.77% and a F1-score of 0.96 on two different combination of datasets.

MP67-20 FEASIBILITY OF OUTPATIENT ROBOT ASSISTED LAPAROSCOPIC PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP67-20 FEASIBILITY OF OUTPATIENT ROBOT ASSISTED LAPAROSCOPIC PROSTATECTOMY Kyle Szymanski, Hunter Lacouture, Jonathan Zakrajsek, Riley Gillette, Katie Colborn, Paul Maroni, Austin Derosa, and Janet Kukreja Kyle SzymanskiKyle Szymanski More articles by this author , Hunter LacoutureHunter Lacouture More articles by this author , Jonathan ZakrajsekJonathan Zakrajsek More articles by this author , Riley GilletteRiley Gillette More articles by this author , Katie ColbornKatie Colborn More articles by this author , Paul MaroniPaul Maroni More articles by this author , Austin DerosaAustin Derosa More articles by this author , and Janet KukrejaJanet Kukreja More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003330.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Research demonstrates the benefits of robotic-assisted prostatectomies (RARP) in regard to blood loss and post-operative recovery, there is a paucity in the literature regarding RARP as an outpatient procedure. With minimal operating room capacity during COVID-19, advances in minimally invasive surgical techniques and a relatively healthy patient population, outpatient RARP may be feasible. The aim of our study was to demonstrate the safety and feasibility of RARP as a same day outpatient procedure. METHODS: A retrospective cohort study at a single institution was performed by four fellowship trained surgeons who routinely perform RARP. Patients were identified through billing records who underwent RARP between January 2019 and December 2021. Patients were divided into two cohorts, inpatient (one stay past midnight) and outpatient (defined as same day surgery with no stay past midnight). Individual surgeons admission necessity during COVID-19 limitations. We then extracted data using the electronic health record (EHR). The two groups were then compared using standard statistical methods for cohort studies. Statistical significance was defined as p<0.05. RESULTS: Over a two-year period, a total of 497 RARP were performed with 139 (28%) outpatient cases. There was no difference in baseline demographics between the cohorts. There was a statistically significant difference in estimated blood loss (142 vs 102 mLs, p≤0.001) and operative time (193 vs 180 mins, p=0.004) in the inpatient vs outpatient cohorts, respectively. There was no significant difference in cancer stage, prostate size, or node/margin positivity between cohorts. There was a higher rate of readmissions (5% vs 0%, p=0.007) and number of ED presentations (0.15 vs 0.05, p=0.019) in the inpatient group. There was no difference in complication rates between the groups. Importantly, there was no significant difference in burden on the clinical staff demonstrated by no difference in number of phone calls to clinic, number of EHR messages, or opioid prescriptions on discharge. CONCLUSIONS: Overall, our data suggests that in a well selected patient group, RARP can safely be performed as an outpatient procedure with no significant differences on clinic staff workload or oncologic outcomes. While there was no pre-defined “algorithm” to determine outpatient vs inpatient surgery, the similarity in demographics and pre-operative characteristics between the groups lends support to performing this procedure as an outpatient with inpatient admission being reserved for select patients. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e951 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kyle Szymanski More articles by this author Hunter Lacouture More articles by this author Jonathan Zakrajsek More articles by this author Riley Gillette More articles by this author Katie Colborn More articles by this author Paul Maroni More articles by this author Austin Derosa More articles by this author Janet Kukreja More articles by this author Expand All Advertisement PDF downloadLoading ...

Reference values for accelerometer metrics and associations with cardiorespiratory fitness: a prospective cohort study of healthy adults and patients with heart failure

Reference values for accelerometer metrics and associations with cardiorespiratory fitness: a prospective cohort study of healthy adults and patients with heart failure

Effects of Gandharva Veda Music on Mood States, Health, and Brain Functioning

Background and Objectives: This paper explores effects of Gandharva Veda music--traditional North Indian music-- on emotional and physical well-being. Hypothesis: Gandharva Veda music balances the mind and body. Materials and Methods: A professional Gandharvan performed 16 live and two online concerts.&amp;nbsp; Mood states were assessed with the Profile of Mood states (POMS) at the live concerts, emotional and physiological balance were assessed during the online concerts using a traditional Ayurveda diagnostic technique called &amp;ldquo;pulse diagnosis,&amp;rdquo; and the EEG of a single Gandharvan was recorded while she played a raga. Results: In the first study (n=1,800), Gandharva Veda music led to significant decreases of negative emotions and significant increases of positive emotions. In the second study, 78 Ayurveda students reported significantly higher levels of vibrant health and significant lowers level of physiological blockages after the ragas. In the last study, high theta1 and alpha1 coherence patterns were seen both during &amp;nbsp;meditation practice and when the Gandharvan played the ragas, along with higher 12 &amp;ndash; 50 Hz coherence during the ragas. Discussion: The responses on the POMS and pulse reading support the prediction that Gandharva Veda music creates a healthy influence for the listener. Also, the coexistence of higher alpha1 coherence, a marker of inner silence, and higher 12-50 Hz coherence, a marker of goal-oriented performance suggests that playing Gandharva Veda music may culture inner silence as the performer plays complex musical passages. Conclusion: Future research is warranted to explore the application of Gandharva Veda music across a wider population of healthy and clinical patients.