Clinical Disposition Research Articles

A preliminary diagnostic accuracy study of quantitative MRI biomarkers for differentiating parotid tumor types.

Differentiating among the different types of parotid tumors on imaging is useful for guiding clinical disposition, which ultimately may lead to surgical management. The goal of this study was to determine whether quantitative T2 signal characteristics and morphologic features on magnetic resonance imaging (MRI) can serve as predictive biomarkers for distinguishing between tumor types. A retrospective review of T2-weighted MRIs in patients with pathology-proven parotid tumors was performed. Quantitative T2 maps and surface regularity measurements of the tumors were obtained via semi-automated regions of interest (ROI). Linear Discriminant Analysis was used to populate the receiver operating characteristics (ROCs) curves for these variables. A P value of <0.05 was considered to be significant. A total of 35 tumors (21 benign and 14 malignant neoplasms) were included in this analysis. For differentiating the benign versus malignant classes of parotid tumors, T2 signal and surface regularity combined yielded an area under the curve of 0.62 (P value: 0.2) through the ROC analysis. However, for the pleomorphic adenomas versus other types of parotid tumors, using both T2 signal and surface regularity yielded an area under the curve of 0.81 (P value: 0.007) through the ROC analysis. T2 signal and surface regularity combined can significantly differentiate pleomorphic adenomas from other types of parotid tumors and can potentially be used as a predictive imaging biomarker.

Prevalence of Behavioral Flags in the Electronic Health Record Among Black and White Patients Visiting the Emergency Department

Behavioral flags in the electronic health record (EHR) are designed to alert clinicians of potentially unsafe or aggressive patients. These flags may introduce bias, and understanding how they are used is important to ensure equitable care. To investigate the incidence of behavioral flags and assess whether there were differences between Black and White patients and whether the flags were associated with differences in emergency department (ED) clinical care. This was a retrospective cohort study of EHR data of adult patients (aged ≥18 years) from 3 Philadelphia, Pennsylvania, EDs within a single health system between January 1, 2017, and December 31, 2019. Secondary analyses excluded patients with sickle cell disease and high ED care utilization. Data were analyzed from February 1 to April 4, 2022. The primary outcome of interest was the presence of an EHR behavioral flag. Secondary measures included variation of flags across sex, race, age, insurance status, triage status, ED clinical care metrics (eg, laboratory, medication, and radiology orders), ED disposition (discharge, admission, or observation), and length of key intervals during ED care. Participating EDs had 195 601 eligible patients (110 890 [56.7%] female patients; 113 638 Black patients [58.1%]; 81 963 White patients [41.9%]; median [IQR] age, 42 [28-60] years), with 426 858 ED visits. Among these, 683 patients (0.3%) had a behavioral flag notification in the EHR (3.5 flags per 1000 patients), and it was present for 6851 ED visits (16 flagged visits per 1000 visits). Patient differences between those with a flag and those without included male sex (56.1% vs 43.3%), Black race (71.2% vs 56.7%), and insurance status, particularly Medicaid insurance (74.5% vs 36.3%). Flag use varied across sites. Black patients received flags at a rate of 4.0 per 1000 patients, and White patients received flags at a rate of 2.4 per 1000 patients (P < .001). Among patients with a flag, Black patients, compared with White patients, had longer waiting times to be placed in a room (median [IQR] time, 28.0 [10.5-89.4] minutes vs 18.2 [7.2-75.1] minutes; P < .001), longer waiting times to see a clinician (median [IQR] time, 42.1 [18.8-105.5] minutes vs 33.3 [15.3-84.5] minutes; P < .001), and shorter lengths of stay (median [IQR] time, 274 [135-471] minutes vs 305 [154-491] minutes; P = .01). Black patients with a flag underwent fewer laboratory (eg, 2449 Black patients with 0 orders [43.4%] vs 441 White patients with 0 orders [36.7%]; P < .001) and imaging (eg, 3541 Black patients with no imaging [62.7%] vs 675 White patients with no imaging [56.2%]; P < .001) tests compared with White patients with a flag. This cohort study found significant differences in ED clinical care metrics, including that flagged patients had longer wait times and were less likely to undergo laboratory testing and imaging, which was amplified in Black patients.

Love’s place in the spectrum of affect, one of 24 secondary emotions: implications for psychiatry

Love is defined and examined as an emotion, using the psychoevolutionary theory of emotions developed by Robert Plutchik and extended to social psychiatry by Henry Kellerman. This theory posits a fourfold ethogram, representing the valanced adaptive reactions to problems of life which define the eight primary emotions. The problem of identity is addressed by acceptance and disgust; temporality, by joy–happiness and sadness. Using a hierarchical classification system, love is defined as a secondary-level emotion, a mixture of joy and acceptance. Examination of the brain infrastructure of these emotions supports their interpretation as basic emotions. In romantic and other forms of love, there is a global acceptance–incorporation, of the other, together with the joy of sexual pair-bonding. This can rise to the level of a clinical disposition that is both histrionic and manic, akin to a Durkheimian collective effervescence. The emotions of acceptance and joy are in everyday life constrained by ego-defense mechanisms: acceptance is constrained by a more critical, less idealised, view of a potential love object; uninhibited joy of sexuality is defended against by sublimation, in which libidinal energy is deflected into an emphasis on correct and proper behaviour, and purposive and productive activities.

Clinical characteristics, microbiology and outcomes of a cohort of patients treated with ceftolozane/tazobactam in acute care inpatient facilities, Houston, Texas, USA.

Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16-0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa.

What influences psychological functioning in patients with mood disorders? The role of clinical, sociodemographic, and temperamental characteristics in a naturalistic study

BackgroundThe present study aims to assess clinical and psychological correlates of psychological functioning in patients with mood disorders, in a naturalistic setting. In particular, we aimed to describe which sociodemographic, clinical, and temperamental dispositions are more frequently associated with poor psychological functioning, and to describe the association between cognitive and psychological functioning in euthymic patients with major depression and bipolar disorder.MethodsInclusion criteria were as follows: (1) diagnosis of major depression, or bipolar disorder type I or II; (2) age between 18 and 65 years; and (3) being in a stable phase of the disorder. Patients’ psychiatric symptoms, quality of life, affective temperaments, and impulsivity were investigated with validated assessment instruments.Results166 patients have been recruited, mainly female (55.4%), whose mean age was 47.1 ± 14.2 years. 42.6% of individuals reported a diagnosis of major depression. According to regression analyses, poor cognitive performance (p < 0.05), reduced perceived quality of life (p < .0001), lifetime suicide attempts (p < 0.01), and increased trait-related impulsivity (p <0 .001) strongly correlated with poor psychological functioning. Moreover, cyclothymic and irritable dispositions were also associated with poor social functioning (p < 0.01), whereas hyperthymic affective disposition was associated to a better psychological performance (p < 0.01).ConclusionsOur results support the evidence that patients with mood disorders should be assessed for psychological functioning and affective dispositions, to identify patients at higher risk to develop worse long-term outcomes and to develop targeted interventions.

Altered Bioavailability and Pharmacokinetics in Crohn's Disease: Capturing Systems Parameters for PBPK to Assist with Predicting the Fate of Orally Administered Drugs.

Backgrond and ObjectiveCrohn’s disease (CD) is a chronic inflammatory bowel disease that affects a wide age range. Hence, CD patients receive a variety of drugs over their life beyond those used for CD itself. The changes to the integrity of the intestine and its drug metabolising enzymes and transporters (DMETs) can alter the oral bioavailability of drugs. However, there are other changes in systems parameters determining the fate of drugs in CD, and understanding these is essential for dose adjustment in patients with CD.MethodsThe current analysis gathered all the available clinical data on the kinetics of drugs in CD (by March 2021), focusing on orally administered small molecule drugs. A meta-analysis of the systems parameters affecting oral drug pharmacokinetics was conducted. The systems information gathered on intestine, liver and blood proteins and other physiological parameters was incorporated into a physiologically based pharmacokinetic (PBPK) platform to create a virtual population of CD patients, with a view for guiding dose adjustment in the absence of clinical data in CD.ResultsThere were no uniform trends in the reported changes in reported oral bioavailability. The nature of the drug as well as the formulation affected the direction and magnitude of variation in kinetics in CD patients relative to healthy volunteers. Even for the same drug, the reported changes in exposure varied, possibly due to a lack of distinction between the activity states of CD. The highest alteration was seen with S-verapamil and midazolam, 8.7- and 5.3-fold greater exposure, respectively, in active CD patients relative to healthy volunteers. Only one report was available on liver DMETs in CD, and indicated reduced CYP3A4 activity. In a number of reports, mRNA expression of DMETs in the ileum and colon of CD patients was measured, focussing on P-glycoprotein (p-gp) transporter and CYP3A4 enzyme, and showed contradictory results. No data were available on protein expression in duodenum and jejunum despite their dominant role in oral drug absorption.ConclusionThere are currently inadequate dedicated clinical or quantitative proteomic studies in CD to enable predictive PBPK models with high confidence and adequate verification. The PBPK models for CD with the available systems parameters were able to capture the major physiological influencers and the gaps to be filled by future research. Quantification of DMETs in the intestine and the liver in CD is warranted, alongside well-defined clinical drug disposition studies with a number of index drugs as biomarkers of changes in DMETs in these patients, to avoid large-scale dedicated studies for every drug to determine the effects of disease on the drug’s metabolism and disposition and the consequential safety and therapeutic concerns.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-022-01169-4.

임상간호사의 비판적 사고성향, 간호근무환경이 간호업무성과에 미치는 영향

Objectives This study aims to explore the mediating effect of communication competence in the relationship between clinical thinking disposition and nursing work environment on the nursing performance of clinical nurses. Methods The data were collected from December 1st to December 20th, 2021, using questionnaires administered to 188 nurses working in a general hospital in J province and G city. Then, they were analyzed using the SPSS/23.0 program with descriptive statistics, an independent t-test, one-way ANOVA, Pearson’s correlation coefficient, multiple regression, and the Sobel test. Results The results of the study are as follows. First, there were significant positive relationships for clinical thinking disposition(r=.66, p&lt;.001) and nursing work environment(r=.45, p&lt;.001), and communication competence(r=.72, p&lt;.001) with nursing performance. Second, communication competence mediated the relationship between clinical thinking disposition and nursing performance(z=6.584, p&lt;.001). Third, communication competence mediated the relationship between the nursing work environment and nursing performance(z=5.822, p&lt;.001). Conclusions The results suggest that to improve nursing performance, it is necessary to consider the critical thinking disposition, the creation of a nursing work environment that nurses can perceive positively, and the improvement of communication competence.

Analysis of Patients With Bed Bugs in the Emergency Department.

The objective was to evaluate the clinical characteristics, triage information, diagnostic evaluation, and disposition for emergency department patients with and without bed bug infestation. A retrospective case-control study of patients with and without bed bugs was performed from February 1, 2011, through February 1, 2017. Cases (n = 332) and controls (n = 4,952) were matched by age, sex, and emergency department location. Patient characteristics and clinical information were compared between groups. On univariable and multivariable analysis, patients with bed bugs had higher heart rate, lower systolic blood pressure, higher pain scores, and more frequent tobacco use in the past year. They were also more likely to screen positive in triage for an unsafe home; require an abuse consultation; be diagnosed in the emergency department or inpatient setting with malnutrition, marasmus, and/or cachexia; have more emergency department and hospital visits; and have longer hospital encounter lengths of stay (all p ≤ 0.02). On univariable analysis, patients with bed bugs were also more likely than uninfested controls to be single, be Black, come to the emergency department from home, arrive to the emergency department by ambulance, and not be discharged back to their homes from the hospital.

Methadone pharmacogenetics in vitro and in vivo: Metabolism by CYP2B6 polymorphic variants and genetic variability in paediatric disposition.

Methadone metabolism and clearance are determined principally by polymorphic cytochrome P4502B6 (CYP2B6). Some CYP2B6 allelic variants affect methadone metabolism in vitro and disposition in vivo. We assessed methadone metabolism by CYP2B6 minor variants in vitro. We also assessed the influence of CYP2B6 variants, and P450 oxidoreductase (POR) and CYP2C19 variants, on methadone clearance in surgical patients in vivo. CYP2B6 and P450 oxidoreductase variants were coexpressed with cytochrome b5 . The metabolism of methadone racemate and enantiomers was measured at therapeutic concentrations and intrinsic clearances were determined. Adolescents receiving methadone for surgery were genotyped for CYP2B6, CYP2C19 and POR, and methadone clearance and metabolite formation clearance were determined. In vitro, CYP2B6.4 was more active than wild-type CYP2B6.1. CYPs 2B6.5, 2B6.6, 2B6.7, 2B6.9, 2B6.17, 2B6.19 and 2B6.26 were less active. CYPs 2B6.16 and 2B6.18 were inactive. CYP2B6.1 expressed with POR variants POR.28, POR.5 and P228L had lower rates of methadone metabolism than wild-type reductase. In vivo, methadone clinical clearance decreased linearly with the number of CYP2B6 slow metabolizer alleles, but was not different in CYP2C19 slow or rapid metabolizer phenotypes, or in carriers of the POR*28 allele. Several CYP2B6 and POR variants were slow metabolizers of methadone in vitro. Polymorphisms in CYP2B6, but not CYP2C19 or P450 reductase, affected methadone clearance in vivo. CYP2B6 polymorphisms 516G>T and 983T>C code for canonical loss of function variants and should be assessed when considering genetic influences on clinical methadone disposition. These complementary translational in vitro and in vivo results inform on pharmacogenetic variability affecting methadone disposition in patients.

Abstract 5381: Combinatory effect of EZH2 inhibitor and dopamine D1 receptor agonist enhance inhibition of triple negative breast cancer cell growth

Abstract Treatment for Triple Negative Breast Cancer remains a challenge due to its aggressive behavior; poor clinical outcome and disposition to therapeutic resistance. The diverse clinical and molecular characteristics drives high level of heterogeneity in breast cancer. Overall change in the epigenome triggers oncogenic activity of enhancer of zeste homolog 2 (EZH2) causing changes in gene expression that leads to cancer progression. EZH2 is the catalytic member of the Polycomb group protein complex that provides the active site for covalent methylation reactions. High expression of EZH2 is strongly associated with aggressive TNBC phenotypes, compared to other non-TNBCs. Development of resistance to EZH2 inhibitors limit their therapeutic use. Studies have shown that dopamine receptor (DR) agonists and antagonists alter TNBC cell growth in both in vitro and in vivo models. Our objective was to investigate if a combination of a D1R agonist with an EZH2 inhibitor was effective to attenuate TNBC cell proliferation. Docking studies were performed using Schrodinger software and visualization software to determine the affinity of GSK126 and SKF38393 towards EZH2. TNBC cells were treated individually and combined with EZH2 inhibitor, GSK126, and D1 agonist SKF38393 for cell viability and immunoprecipitation. Insilco analysis using docking studies revealed that SKF38393 actively interacts in the same region where GSK126 binds to EZH2 i.e. the catalytic site. Combination treatment of TNBC cells with GSK126 and SKF38393 caused synergistic inhibition of cell viability, suppressed the H3K27 trimethylation activity, and inhibited invasion of TNBC cells. Immunoprecipitation of EZH2 in the presence of GSK126 and SKF38393 dissociated the association between EZH2, EED, and SUZ12 in MDA-MB-231 cells. We report that combination of GSK126 and SKF38393 may have an enhanced efficacy in inhibiting the catalytic function of EZH2. The combined treatment of TNBC cells with GSK126 and SKF38393 inhibit TNBC proliferation by disrupting EZH2 functions. (This work is supported by DOD: W81XWH2010065, for Eswar Shankar) Citation Format: Prem Prakash Kushwaha, Shiv Verma, Gautham Sarathy, Anmol Kumar, Sanjay Gupta, Bhuvaneswari Ramaswamy, Sarmila Majumder, Eswar Shankar. Combinatory effect of EZH2 inhibitor and dopamine D1 receptor agonist enhance inhibition of triple negative breast cancer cell growth [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5381.

The Effect of Clinical Nurses' Critical Thinking Disposition and Communication Ability on Patient Safety Competency

Purpose: This study was conducted to identify the influence of critical thinking disposition and communication ability on patient safety competence among clinical nurses. Methods: A cross-sectional descriptive study was conducted using a self-reported questionnaire. In total, 139 nurses were recruited from a tertiary care hospital and general hospital in Gyeonggi Province. Data were collected from March 5, 2019 to March 29, 2019 and analyzed using descriptive statistics, independent t-test, one-way analysis of variance, the Scheffé test, Pearson’ correlation coefficients, and hierarchical multiple regression with SPSS version 25.0. Results: The item mean score for patient safety competence was 3.83±0.40 (range, 1~5). Clinical nurses who were female, older, had higher education, and had more clinical experiences showed higher patient safety competence. Hierarchical multiple regression analysis showed that healthy skepticism and objectivity (as subscales of clinical thinking disposition) and communication ability explained 28% and 3% of variance in patient safety competence; the model predicted approximately 38% of the variance in patient safety competence (F=6.69, p&lt;.001). Conclusion: Clinical nurses’ patient safety competence was associated with healthy skepticism and objectivity, among the subscales of clinical thinking disposition, and communication ability. These were also found to be the major factors that influenced patient safety competence. Thus, it is necessary to develop educational programs to improve clinical nurses’ critical thinking disposition and communication skills.

Clinical characteristics, hospital course, and disposition of patients with nontraumatic spinal cord injury in a large private health care system in the United States

Objectives: To evaluate the clinical characteristics, hospital courses, outcomes after hospitalization, and factors associated with outcomes in patients with nontraumatic spinal cord injuries (NTSCI). Design: Retrospective analysis. Setting: A large for-profit United States health care system. Participants: 2807 inpatients with NTSCI between 2014 and 2020 were identified using International Classification of Disease codes. Main Outcome Measure: Demographic, clinical characteristics, hospital course, and disposition data collected from electronic health record. Results: The mean age was 57.91 ± 16.41 years with 69.83% being male. Incomplete cervical level injury was the most common injury type, spinal stenosis was the most common diagnostic etiology and central cord syndrome was the most common clinical syndrome. The average length of stay was 9.52 ± 15.8 days, with the subgroup of 1308 (46.6%) patients who were discharged home demonstrating a shorter length of stay (6.42 ± 10.24 days). Falls were the most common hospital-acquired complication (n = 424, 15.11%) and 83 patients deceased. There were increased odds of non-home discharge among patients with the following characteristics: older age, Medicare insurance, non-black racial minority, increased Charlson Comorbidity Index (CCI), intensive care unit (ICU) stay, use of steroid or anticoagulant medications, and hospital-acquired pulmonary complications. Increased in-hospital mortality was observed in those with Medicaid insurance, ICU stay, increased CCI, diagnosis of degenerative spine disease, other unspecified level of injury, and hospital-acquired pulmonary complications. Conclusions: NTSCI in this sample were predominantly incomplete cervical central SCIs. Increased CCI, ICU stay, and hospital-acquired pulmonary complications were associated with poorer outcomes after acute care hospitalization among patients with NTSCI.

COVID-19 severity and age increase the odds of delirium in hospitalized adults with confirmed SARS-CoV-2 infection: a cohort study

BackgroundDespite recognition of the neurologic and psychiatric complications associated with SARS-CoV-2 infection, the relationship between coronavirus disease 19 (COVID-19) severity on hospital admission and delirium in hospitalized patients is poorly understood. This study sought to measure the association between COVID-19 severity and presence of delirium in both intensive care unit (ICU) and acute care patients by leveraging an existing hospital-wide systematic delirium screening protocol. The secondary analyses included measuring the association between age and presence of delirium, as well as the association between delirium and safety attendant use, restraint use, discharge home, and length of stay.MethodsIn this single center retrospective cohort study, we obtained electronic medical record (EMR) data using the institutional Epic Clarity database to identify all adults diagnosed with COVID-19 and hospitalized for at least 48-h from February 1-July 15, 2020. COVID-19 severity was classified into four groups. These EMR data include twice-daily delirium screenings of all patients using the Nursing Delirium Screening Scale (non-ICU) or CAM-ICU (ICU) per existing hospital-wide protocols.ResultsA total of 99 patients were diagnosed with COVID-19, of whom 44 patients required ICU care and 17 met criteria for severe disease within 24-h of admission. Forty-three patients (43%) met criteria for delirium at any point in their hospitalization. Of patients with delirium, 24 (56%) were 65 years old or younger. After adjustment, patients meeting criteria for the two highest COVID-19 severity groups within 24-h of admission had 7.2 times the odds of having delirium compared to those in the lowest category [adjusted odds ratio (aOR) 7.2; 95% confidence interval (CI) 1.9, 27.4; P = 0.003]. Patients > 65 years old had increased odds of delirium compared to those < 45 years old (aOR 8.7; 95% CI 2.2, 33.5; P = 0.003). Delirium was associated with increased odds of safety attendant use (aOR 4.5; 95% CI 1.0, 20.7; P = 0.050), decreased odds of discharge home (aOR 0.2; 95% CI 0.06, 0.6; P = 0.005), and increased length of stay (aOR 7.5; 95% CI 2.0, 13; P = 0.008).ConclusionsWhile delirium is common in hospitalized patients of all ages with COVID-19, it is especially common in those with severe disease on hospital admission and those who are older. Patients with COVID-19 and delirium, compared to COVID-19 without delirium, are more likely to require safety attendants during hospitalization, less likely to be discharged home, and have a longer length of stay. Individuals with COVID-19, including younger patients, represent an important population to target for delirium screening and management as delirium is associated with important differences in both clinical care and disposition.

Clinical and Nonclinical Disposition and In Vitro Drug-Drug Interaction Potential of Felcisetrag, a Highly Selective and Potent 5-HT4 Receptor Agonist.

Background and ObjectiveFelcisetrag (previously TAK-954 or TD-8954) is a highly selective and potent 5-HT4 receptor agonist in clinical development for prophylaxis and treatment of postoperative gastrointestinal dysfunction (POGD). The rat, dog, and human absorption, distribution, metabolism, and excretion (ADME) properties of felcisetrag were investigated.MethodsThe metabolism and victim and perpetrator drug interaction potentials towards cytochrome P450s (CYP) and transporters were determined using in vitro models. The excretion, metabolite profile, and pharmacokinetics were determined during unlabeled and radiolabeled ADME studies in rat and dog for comparison with human. Due to a low clinical dose (0.5 mg) and radioactivity (~ 1.5 μCi), a combination of liquid scintillation counting and accelerator mass spectrometry was used for analysis of samples in this study.ResultsThe ADME properties, including metabolite profile, for felcisetrag are generally conserved across species. Felcisetrag is primarily cleared through renal excretion (0.443) and metabolism in humans (0.420), with intact parent as the predominant species in circulation. There are multiple metabolites, each representing < 10% of the circulating radioactivity, confirming no metabolites in safety testing (MIST) liabilities. Metabolites were also detected in animals. The potential for major CYP- and transporter-based drug–drug interaction (DDI) of felcisetrag as a victim or perpetrator is considered to be low.ConclusionsFelcisetrag is primarily cleared in humans through renal excretion. Although the metabolism of felcisetrag is primarily through CYP3A, the potential for clinically relevant DDI as a victim is significantly reduced as metabolism plays a minor role in the overall clearance.Graphical Supplementary InformationThe online version contains supplementary material available at 10.1007/s13318-021-00751-8.

Endovascular thrombectomy with and without preceding intravenous thrombolysis for treatment of large vessel anterior circulation stroke: A cross-sectional analysis of 50,000 patients

IntroductionThe safety and efficacy of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) for large vessel occlusion stroke remains a highly contested and unanswered clinical question. We aim to characterize the clinical profile, complications, and discharge disposition of EVT patients treated with and without preceding IVT using a large, nationally-representative sample. MethodsThe National Inpatient Sample was queried from 2015 to 2018 to identify adult patients with anterior circulation stroke treated with EVT with and without preceding IVT. Multivariable logistic regression analysis and propensity-score matching were employed to assess adjusted associations with clinical endpoints and to address confounding by indication for IVT, respectively. ResultsAmong 48,525 patients identified, 40.7% (n = 19,735) received IVT prior to EVT. On unadjusted analysis, patients treated with IVT bridging therapy experienced higher rates of intracranial hemorrhage (26% vs. 24%, p = 0.003) and routine discharge to home with or without services (33% vs. 27%, p < 0.001), a lower frequency of thromboembolic complications (3% vs. 5%, p < 0.001), and lower rates of extended hospital stays (eLOS) (20% vs. 24%, p < 0.001). Multivariable logistic regression analysis adjusting for demographic and baseline clinical characteristics demonstrated independent associations of IVT bridging therapy with intracranial hemorrhage (aOR 1.28, 95% CI 1.15, 1.43; p < 0.001), thromboembolic complications (aOR 0.66, 95% CI 0.53, 0.83; p < 0.001), routine discharge (aOR 1.27, 95% CI 1.15, 1.40; p < 0.001), and eLOS (aOR 0.76, 95% CI 0.68, 0.85; p < 0.001). Sensitivity testing confirmed these findings. ConclusionPreceding IVT was associated with favorable functional outcomes following endovascular therapy. Prospective randomized clinical trials are warranted for further evaluation.

Obstructive sleep apnea confers lower mortality risk in acute ischemic stroke patients treated with endovascular thrombectomy: National Inpatient Sample analysis 2010–2018

BackgroundObstructive sleep apnea (OSA) portends increased morbidity and mortality following acute ischemic stroke (AIS). Evaluation of OSA in the setting of AIS treated with endovascular mechanical thrombectomy (MT) has not...

Effectiveness of Telehealth in Rural and Remote Emergency Departments: Systematic Review.

BackgroundEmergency telehealth has been used to improve access of patients residing in rural and remote areas to specialist care in the hope of mitigating the significant health disparities that they experience. Patient disposition decisions in rural and remote emergency departments (EDs) can be complex and largely dependent on the expertise and experience available at local (receiving-end) hospitals. Although there has been some synthesis of evidence of the effectiveness of emergency telehealth in clinical practice in rural and remote EDs for nonacute presentations, there has been limited evaluation of the influence of contextual factors such as clinical area and acuity of presentation on these findings.ObjectiveThe aims of this systematic review are to examine the outcome measures used in studying the effectiveness of telehealth in rural and remote EDs and to analyze the clinical context in which these outcome measures were used and interpreted.MethodsThe search strategy used Medical Subject Headings and equivalent lists of subject descriptors to find articles covering 4 key domains: telehealth or telemedicine, EDs, effectiveness, and rural and remote. Studies were selected using the Population, Intervention, Comparator, Outcomes of Interest, and Study Design framework. This search strategy was applied to MEDLINE (Ovid), Cochrane Library, Scopus, CINAHL, ProQuest, and EconLit, as well as the Centre for Reviews and Dissemination databases (eg, National Health Service Economic Evaluation Database) for the search period from January 1, 1990, to May 23, 2020. Qualitative synthesis was performed on the outcome measures used in the included studies, in particular the clinical contexts within which they were interpreted.ResultsA total of 21 full-text articles were included for qualitative analysis. Telehealth use in rural and remote EDs demonstrated effectiveness in achieving improved or equivalent clinical effectiveness, appropriate care processes, and—depending on the context—improvement in speed of care, as well as favorable service use patterns. The definition of effectiveness varied across the clinical areas and contexts of the studies, and different measures have been used to affirm the safety and clinical effectiveness of telehealth in rural and remote EDs. The acuity of patient presentation emerged as a dominant consideration in the interpretation of interlinking time-sensitive clinical effectiveness and patient disposition measures such as transfer and discharge rates, local hospital admission, length of stay, and ED length of stay. These, together with clinical area and acuity of presentation, are the outcome determination criteria that emerged from this review.ConclusionsEmergency telehealth studies typically use multiple outcome measures to determine the effectiveness of the services. The outcome determination criteria that emerged from this analysis are useful when defining the favorable direction for each outcome measure of interest. The findings of this review have implications for emergency telehealth service design and policies.Trial RegistrationPROSPERO CRD42019145903; https://tinyurl.com/ndmkr8ry

Understanding the Accuracy of Clinician Provided Estimated Discharge Dates.

Discharge planning is a vital tool in managing hospital capacity, which is essential for maintaining hospital throughput for surgical postoperative admissions. Early discharge planning has been effective in reducing length of stay and hospital readmissions. Between 2014 and 2017, Vanderbilt University Medical Center (VUMC) implemented a tool in the electronic health record (EHR) requiring providers to input the patient's estimated discharge date on each hospital day. We hypothesized discharge estimates would be more accurate, on average, for surgical patients compared to non-surgical patients because treatment plans are known in advance of surgical admissions. We also analyzed the data to identify factors associated with more accurate discharge estimates. In this retrospective observational study, via an analysis of covariance (ANCOVA) approach, we identified factors associated with more accurate discharge estimates for admitted adult patients at VUMC. The primary outcome was the difference between estimated and actual discharge date, and the primary exposure of interest was whether the patient underwent surgery while admitted to the hospital. A total of 304,802 date of discharge estimate entries from 68,587 inpatient encounters met inclusion criteria. After controlling for measured confounding, we found the discharge estimates were more precise as the difference between estimated and actual discharge date narrowed; for each additional day closer to discharge, prediction accuracy improved by .67days (95% confidence interval [CI], 0.66 to 0.67; p < 0.001), on average. No difference was observed on the primary outcome in patients undergoing surgery compared with non-surgical treatment (0.02days; 95% CI, 0.00 to 0.03; p = 0.111). Faculty members were found to perform best among all clinicians in predicting estimated discharge date with a 0.24-day better accuracy (95% CI, 0.20 to 0.27; p < 0.001), on average, than other staff. Weekend and holiday, specific clinical teams, staff types, and discharge dispositions were associated with the variability in estimated versus actual discharge date (p < 0.001). Given the widespread variation in current efforts to improve discharge planning and the recommended approach of assigning a discharge date early in the hospital stay, understanding provider estimated discharge dates is an important tool in hospital capacity management. While we did not determine a difference in discharge estimates among surgical and non-surgical patients, we found estimates were more accurate as discharge came nearer and identified notable trends in provider inputs and patient factors. Assessing factors that impact variability in discharge accuracy can allow hospitals to design targeted interventions to improve discharge planning and reduce unnecessary hospital days.

High overall mortality of Mycobacterium genavense infections and impact of antimycobacterial therapy: Systematic review and individual patient data meta-analysis

IntroductionMycobacterium genavense is a fastidious slow growing mycobacterium (SGM) that causes disseminated infections in immunocompromised hosts. It has been described in HIV-positive individuals and increasingly in patients without HIV. The infections are difficult to treat and the optimal antimycobacterial regimen is still unknown. MethodsAn individual patient data meta-analysis was conducted aiming at including all hitherto published cases of infection with M. genavense. Clinical manifestations, microbiological data, dispositions and immunosuppression were recorded. Antimycobacterial therapies and mortality were analyzed by logistic regression and time-to-event analysis. ResultsWe included 223 patients with infection due to M. genavense published from 1992 to 2021. While the majority was HIV positive (n = 171, 76.7%), 52 patients were non-HIV-patients (23.3%), 36 of whom received immunosuppressive therapy (69%). We could confirm the bacterium's tropism for the gastrointestinal tract with abdominal pain, hepato-/splenomegaly and abdominal lymphadenopathy being major clinical manifestations. More than 90% of patients received antimycobacterial therapy. The regimens consisted mainly of macrolides, rifamycins and ethambutol. Overall mortality was high, but in logistic regression and time-to-event analysis a macrolide containing regimen was associated with better outcomes. ConclusionIn this first individual patient data meta-analysis of infections with M. genavense we confirm its tropism for the gastrointestinal tract. The high overall mortality underlines the clinical relevance of infection with this bacterium for the individual patient. In addition, our data give a hint that a macrolide containing regimen is associated with better survival.

Impact of Hyponatremia on Morbidity, Mortality, and Resource Utilization in Portal Hypertensive Ascites: A Nationwide Analysis

Ascites and hyponatremia are important milestones of worsening portal hypertension in those with cirrhosis. The objective of our study was to evaluate the differences in clinical characteristics, resource utilization, and disposition of hospitalized cirrhotic patients with ascites with and without hyponatremia. The National Inpatient Sample (NIS) database was used to identify all adult hospitalized patients with a diagnosis of cirrhosis and ascites with or without hyponatremia from 2016 to 2017 using ICD-10 codes. During the study period, 10,187 (7.6%) hospitalized patients with cirrhosis had ascites and hyponatremia and 34,555 (24.3%) had ascitesbut no hyponatremia. Elixhauser comorbidity score, excluding liver disease, was higher in hyponatremic patients (median 21 vs. 12, P<0.001). Acute kidney injury (50.3% vs. 32.8%, P < 0.001) and sepsis (16.8% vs. 11.8%, P<0.001) were more common in hyponatremic patients compared to those without hyponatremia. Similarly, acute respiratory failure, coagulopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, acute (on chronic) liver failure, and liver cancer were more common in hyponatremic patients. Hyponatremia patients had a higher number of inpatient procedures, longer (6 days vs. 4 days, P<0.001) hospital stay, and had higher hospital charges ($97,327 vs. $72,278, P<0.01) than those without hyponatremia. Inpatient mortality was 38% higher in hyponatremic patients (9.8% vs. 7.1%, P<0.001) compared to those without hyponatremia. Additionally, hyponatremic patients were less likely to have routine home discharges with self-care. In conclusion, using a large and diverse national cohort of unselected patients, we were able to show that hyponatremia in patients with cirrhosis and ascites is associated with poor clinical outcomes and increased resource utilization.