Differences In Disposition Research Articles

A COMPARISON OF THE EFFICACY AND SAFETY OF ORAL ANTI-DIABETIC DRUGS IN CAUCASIANS AND SOUTH ASIANS

Type 2 diabetes mellitus is more prevalent, and presents differently, in South Asians than Caucasians. This suggests a possible difference in the genetic disposition of South Asians for this condition. Such genetic difference could also confer a difference in the response of patients of different ethnicities to oral antidiabetic drugs (OADs)

Homeless patients tend to have greater psychiatric needs when presenting to the emergency department,

IntroductionHomeless patients tend to visit Emergency Departments (EDs) more frequently than the non-homeless population. The goal of this study was to assess differences in chief complaint, medical conditions, and disposition between homeless patients compared to non-homeless patients presenting to an urban ED. MethodsThis was a retrospective cohort of homeless patients ages ≥18 years compared to non-homeless controls from January 1, 2017 to December 31, 2017. Exclusion criteria were as follows: direct admission to hospital floor, repeat visits, or leaving without being seen. The primary endpoint of this study was to assess differences in chief complaint of homeless versus non-homeless patients upon presentation to the ED. Our secondary endpoints included differences in ED utilization between the two groups, in terms of length of stay, ambulance use, diagnosis, and disposition. ResultsHomeless patients were more likely present to the ED for a psychiatric evaluation (homeless group 34% vs. non-homeless group 4%, p < 0.01) and have a history of a psychiatric diagnosis (56% vs. 10%, p < 0.01) compared to non-homeless controls. Homeless patients also tended to require more ambulance transport (46% vs. 16%, p < 0.01). More homeless patients were transferred to a psychiatric facility (40% vs. 1%, p < 0.01), while the majority of non-homeless patients were discharged home (50% vs. 93%, p < 0.01). ConclusionThis study found that homeless patients had a significantly higher association with psychiatric diagnoses and greater ED utilization than non-homeless. This suggests the importance of increased access to consistent psychiatric care and follow up within the homeless population.

The psychology of privacy in the digital age

AbstractPrivacy is a psychological topic suffering from historical neglect—a neglect that is increasingly consequential in an era of social media connectedness, mass surveillance, and the permanence of our electronic footprint. Despite fundamental changes in the privacy landscape, social and personality psychology journals remain largely unrepresented in debates on the future of privacy. By contrast, in disciplines like computer science and media and communication studies, engaging directly with sociotechnical developments, interest in privacy has grown considerably. In our review of this interdisciplinary literature, we suggest four domains of interest to psychologists. These are as follows: sensitivity to individual differences in privacy disposition, a claim that privacy is fundamentally based in social interactions, a claim that privacy is inherently contextual, and a suggestion that privacy is as much about psychological groups as it is about individuals. Moreover, we propose a framework to enable progression to more integrative models of the psychology of privacy in the digital age and in particular suggest that a group and social relations–based approach to privacy is needed.

Problem based MHM-Strategy to enhance junior high school students mathematical creative problem solving ability and mathematical disposition

This article presents the results of research on the development of mathematics learning with problem based Mathematical Habits of Mind (MHM) strategy to enhance mathematical creative problem solving (MCPS) ability and mathematical disposition. Quasi experimental research with posttest control group design involved 146 eighth grade students from two State Junior High Schools in Subang regency, each consisting of two classes. The instruments used were tests MCPS ability and mathematical disposition. Research data of students pretest, posttes, and normalized gain scores for MCPS ability were analyzed using two-way ANOVA and Mann Whitney. Based on data analysis results, it is found that there is a significant difference in the enhancement of students MCPS ability and mathematical disposition of students between the experimental and control groups at the high and medium school levels. On the other hand, there is a difference in mathematical disposition in terms of school level. Meanwhile, there is an interaction effect between problem-based MHM strategies and school-levels on the student’s mathematical disposition. Conclusion, that the enhancement of MCPS ability of students who were taught with problem-based MHM strategy is significantly greater compared conventional learning in terms of school level.

A Machine Learning Algorithm to Predict Severe Sepsis and Septic Shock: Development, Implementation, and Impact on Clinical Practice.

Develop and implement a machine learning algorithm to predict severe sepsis and septic shock and evaluate the impact on clinical practice and patient outcomes. Retrospective cohort for algorithm derivation and validation, pre-post impact evaluation. Tertiary teaching hospital system in Philadelphia, PA. All non-ICU admissions; algorithm derivation July 2011 to June 2014 (n = 162,212); algorithm validation October to December 2015 (n = 10,448); silent versus alert comparison January 2016 to February 2017 (silent n = 22,280; alert n = 32,184). A random-forest classifier, derived and validated using electronic health record data, was deployed both silently and later with an alert to notify clinical teams of sepsis prediction. Patients identified for training the algorithm were required to have International Classification of Diseases, 9th Edition codes for severe sepsis or septic shock and a positive blood culture during their hospital encounter with either a lactate greater than 2.2 mmol/L or a systolic blood pressure less than 90 mm Hg. The algorithm demonstrated a sensitivity of 26% and specificity of 98%, with a positive predictive value of 29% and positive likelihood ratio of 13. The alert resulted in a small statistically significant increase in lactate testing and IV fluid administration. There was no significant difference in mortality, discharge disposition, or transfer to ICU, although there was a reduction in time-to-ICU transfer. Our machine learning algorithm can predict, with low sensitivity but high specificity, the impending occurrence of severe sepsis and septic shock. Algorithm-generated predictive alerts modestly impacted clinical measures. Next steps include describing clinical perception of this tool and optimizing algorithm design and delivery.

Peran Interaksi Guru-Siswa dan Gaya Belajar Siswa terhadap Disposisi Berpikir Kritis dalam Pembelajaran Fisika

This study aimed to empirically determine the role of teacher-student interaction and students’ learning styles in students’ disposition toward critical thinking in physics subject. Research participants were high school students of grade XI majoring in natural science. Sampling in this study was done using convenience sampling with sample size of 67 students (25 males and 42 females). Data collection method used in this study was survey using Disposition toward Critical Thinking in Physics Subject Scale, Teacher-student Interaction in Physics Subject Scale, and Learning Styles in Physics Subject Scale. Analysis of covariance with one covariate showed 1) there was a correlation between teacher-student interaction and students’ disposition toward critical thinking in physics subject (F = 37.199; ƞ2p = 0.375; p &lt; 0.01) and 2) there was difference of disposition toward critical thinking in physics subjects between student with diverging, assimilating, accommodating, and converging learning styles (F = 6.870; ƞ2p = 0.249; p &lt; 0.01). Post-hoc test was also done to further analyze the data. The findings are going to help improving quality of learning especially in the subject being studied by fostering wholesome teacher-student interaction and accommodating students’ learning styles.

Sulfolobus acidocaldarius Microvesicles Exhibit Unusually Tight Packing Properties as Revealed by Optical Spectroscopy.

In this study, we used optical spectroscopy to characterize the physical properties of microvesicles released from the thermoacidophilic archaeon Sulfolobus acidocaldarius (Sa-MVs). The most abundant proteins in Sa-MVs are the S-layer proteins, which self-assemble on the vesicle surface forming an array of crystalline structures. Lipids in Sa-MVs are exclusively bipolar tetraethers. We found that when excited at 275 nm, intrinsic protein fluorescence of Sa-MVs at 23 °C has an emission maximum at 303 nm (or 296 nm measured at 75 °C), which is unusually low for protein samples containing multiple tryptophans and tyrosines. In the presence of 10–11 mM of the surfactant n-tetradecyl-β-d-maltoside (TDM), Sa-MVs were disintegrated, the emission maximum of intrinsic protein fluorescence was shifted to 312 nm, and the excitation maximum was changed from 288 nm to 280.5 nm, in conjunction with a significant decrease (>2 times) in excitation band sharpness. These data suggest that most of the fluorescent amino acid residues in native Sa-MVs are in a tightly packed protein matrix and that the S-layer proteins may form J-aggregates. The membranes in Sa-MVs, as well as those of unilamellar vesicles (LUVs) made of the polar lipid fraction E (PLFE) tetraether lipids isolated from S. acidocaldarius (LUVPLFE), LUVs reconstituted from the tetraether lipids extracted from Sa-MVs (LUVMV) and LUVs made of the diester lipids, were investigated using the probe 6-dodecanoyl-2-dimethylaminonaphthalene (Laurdan). The generalized polarization (GP) values of Laurdan in tightly packed Sa-MVs, LUVMV, and LUVPLFE were found to be much lower than those obtained from less tightly packed DPPC gel state, which echoes the previous finding that the GP values from tetraether lipid membranes cannot be directly compared with the GP values from diester lipid membranes, due to differences in probe disposition. Laurdan’s GP and red-edge excitation shift (REES) values in Sa-MVs and LUVMV decrease with increasing temperature monotonically with no sign for lipid phase transition. Laurdan’s REES values are high (9.3–18.9 nm) in the tetraether lipid membrane systems (i.e., Sa-MVs, LUVMV and LUVPLFE) and low (0.4–5.0 nm) in diester liposomes. The high REES and low GP values suggest that Laurdan in tetraether lipid membranes, especially in the membrane of Sa-MVs, is in a very motionally restricted environment, bound water molecules and the polar moieties in the tetraether lipid headgroups strongly interact with Laurdan’s excited state dipole moment, and “solvent” reorientation around Laurdan’s chromophore in tetraether lipid membranes occurs very slowly compared to Laurdan’s lifetime.

Medicaid payer status and other factors associated with hospital length of stay in patients undergoing primary lumbar spine surgery

ObjectiveThe Medicaid patient population and health care costs for spine surgeries among these patients have increased since 2010. Hospital length of stay (LOS) contributes appreciably to hospital costs for patients undergoing primary lumbar spine surgery (PLSS). The aim of this study was to identify independent risk factors for increased LOS in patients undergoing PLSS. Patients and methodsIn a single-center retrospective study, we reviewed demographic and clinical data from electronic medical records for 181 consecutive adult patients who underwent PLSS involving 1–3 levels from July 2014 to July 2017. We performed regression analyses to identify independent risk factors for increased LOS and to quantify their effects as percent changes in LOS. ResultsAmong 181 patients who underwent PLSS, the mean LOS was 3.57 days. Based on the Charlson Comorbidity Index (CCI) and American Society of Anesthesiologist (ASA) classification, patients with Medicaid insurance were healthier than non-Medicaid patients (mean CCI: 0.34 versus 0.65; p = 0.041, ASA: 1.71 versus 1.91; p = 0.046) yet Medicaid patients had a longer LOS compared with non-Medicaid patients (mean LOS: 4.03 versus 3.30 days; p = 0.047). There was no significant difference in discharge disposition between Medicaid and non-Medicaid patients (Home = 82.35 % versus 79.65 %; p = 0.855). Medicaid patients also had significantly less spinal levels involved in their surgery (1.44 versus 1.67; p = 0.027). Multivariable regression modeling identified independent risk factors positively associated with increased LOS as age (+1.0 % per year; p = 0.007), Medicaid insurance status (+28.7 %; p = 0.007), and CCI (10.1 % per increment in CCI; p = 0.030). Fusion surgery also was an independent risk factor for increased LOS when compared with laminectomy (−54.1 %; p < 0.001) or discectomy (−51.3 %; p < 0.001). ConclusionsIncreasing age, Medicaid insurance status, higher CCI, and fusion surgery were independently associated with increased LOS after PLSS. This information is useful for preoperative patient counseling, shared decision-making, and risk stratification and may help to further ongoing discussion regarding contributors to rising health care costs. Findings of increased LOS among Medicaid patients will help direct efforts to identify factors that contribute to this health care expense.

Factors Complicating Discharge to Home following Total Knee Arthroplasty-A Single Institution Initiative.

Recently, with the Medicare bundled payments initiative for total knee arthroplasty (TKA), there has been a move by many institutions to further streamline costs associated with the entire operative and perioperative process. One of these cost-saving strategies has been to favor discharging patients to home with outpatient services as opposed to discharging to the relatively more expensive rehabilitation facilities. Our aim was to determine the success of a teaching institute's initiative in discharging patients to home instead of a rehabilitation facility. Specifically, we evaluated if there were differences in discharge disposition based off of (1) surgeon/patient preference, (2) length of stay, (3) demographics, and (4) postoperative complications. A retrospective review of all patients who had a TKA from 2015 to 2017 at a single teaching institution was performed and assessed discharge to home or to a rehabilitation facility. If they were not discharged to home, we evaluated why that did not happen, stratified the reason they were discharged to a rehabilitation facility into four groups based on (1) physician and occupational health team assessment, (2) patient preference, (3) physician preference, and (4) family or caretaker preference. A total of 229 patients were enrolled in this initiative, with 107 patients (47%) discharged to home with outpatient physical therapy services and 122 (53%) discharged to a rehabilitation facility. Of these, 35 patients (29%) went to these facilities because of physician and occupational health team assessment. However, 31 (25%) patients were due to patient preference, 32 (26%) were because of surgeon's preference, and 24 (20%) were not discharged to home because of family or caretaker preference. There were no differences in length of stay, gender, or complication rates between cohorts. Many patients can be safely discharged to home following TKA at a community teaching institution; however, there continues to be a strong prejudice by patients, physicians, and caretakers to be discharged to a rehabilitation facility despite the home discharge initiative.

PT Achievement in Public Hospitals and Its Effect on Outcomes.

The demand for TKA continues to rise within the United States, while increasing quality measures and cost containment became the basis of reimbursement for hospital systems. Length of stay is a major driver in the cost of TKA. Early mobilization with physical therapy has been shown to increase range of motion and decrease complications, but with mixed results in regards to length of stay. We postulate that initiating physical therapy on post-operative day zero will decrease length of stay in an urban public hospital. Retrospective chart review was performed at a large, urban, public academic medical center to identify patients who have had a primary TKA over the course of a 3-year period. Groups who underwent post-operative day zero therapy were compared with those who initiated physical therapy on post-operative day one. Length of stay was the primary outcome. Patient demographic characteristics and discharge disposition were also collected. There were 98 patients in the post-operative day-one physical therapy cohort and 58 in the post-operative day zero physical therapy group. Hospital length of stay was significantly decreased in the post-operative day zero physical therapy group. (p < 0.01) There was no difference in discharge disposition between the two groups.

Epistemic beliefs about the value of integrating information across multiple documents in history

Individual differences in epistemic dispositions may affect learning from multiple-document inquiry tasks by prompting different students to have different task and activity models. Students with epistemic beliefs that are more appropriate for the required activities may view a multiple-document inquiry task as an exercise in corroboration, seeking coherence, and looking for evidence to support claims, whereas students with less-appropriate epistemic beliefs may see the goal as simply finding the “right” answer verbatim within the documents. This paper describes attempts to develop an assessment for this subset of epistemic beliefs about the value of engaging in integration of evidence when learning from multiple documents in history. Across three experiments, the measure was shown to be reliable and valid. It also uniquely predicted multiple-document comprehension in history above and beyond beliefs about the simplicity and certainty of knowledge, and accounted for differences in prior instruction and experience with document-based questions.

177 Disparities in Admission or Transfer for Inpatient Treatment after Emergency Mental Health Visits

While it is widely recognized that disparities exist in access to mental health (MH) care, the emergency department (ED) should serve as the safety net where all patients can access necessary care. We examine whether there are disparities based on patient race/ethnicity and insurance status in disposition to inpatient settings (admission or transfer) for adolescents and young adults with MH ED visits. We perform multivariate regression analysis of all MH ED visits from 2010 to 2014 reported to the Healthcare Cost and Utilization Project’s State emergency department and State Inpatient Discharge Databases for Arizona, Florida, New York, New Jersey, North Carolina, Maryland, Nevada, Kentucky, Rhode Island, and Iowa for 10-29 year olds. MH ED visits were defined as visits with a primary MH or substance abuse diagnosis or a secondary or tertiary diagnosis of suicidal ideation or attempt. We examine the probability that a MH ED visit results in an admission or transfer for further treatment and report predicted probabilities by primary payer and race/ethnicity. Regressions also control for age, sex, year, hospital location, and median income of the patient’s home address. We also perform diagnosis-specific regressions for encounters related to suicide, serious mental illness, substance use, or alcohol use. We report comparisons of predicted probabilities using Bonferroni-corrected critical values. 2.6 million MH ED visits were analyzed. For MH ED visits, the probability of admission or transfer for MH ED visits varied by the patient’s insurance and race/ethnicity (see Table). When all MH ED visits were analyzed, significantly more visits by privately insured (33.1%) than self-pay patients (25.8%) resulted in an inpatient disposition (p<0.01). Disposition after MH ED visits also varied by patient race/ethnicity. A significantly higher proportion of MH ED visits by white patients (34.0%) than black (30.8%, p<0.01), Native American (30.7%, p<0.01) or Hispanic (30.4%, p<0.01) patients resulted in admission or transfer. Differences in disposition were seen for all MH disorders analyzed, including for suicide-related visits. When compared with suicide-related visits by whites, a significantly smaller proportion of suicide-related visits by blacks, Hispanics and Native Americans resulted in admission or transfer (p<0.01 for all comparisons). Suicide-related visits by uninsured patients were significantly less likely than those by patients with private insurance, Medicaid or Medicare to result in admission or transfer (p<0.01 for all comparisons). We demonstrate sizeable disparities in disposition to inpatient settings after MH ED visits based on patient race/ethnicity and insurance status. Psychiatric inpatient beds are limited and socioeconomic disparities in access to this resource are concerning, particularly in ED patients who may have limited access to outpatient psychiatric care. Future research should focus on identifying and mitigating the underlying causes of these disparities.TablePredicted probabilities of ED disposition of admission or transfer.All Mental Health % (95% CI)Suicide-Related % (95% CI)Serious Mental Illness % (95% CI)Alcohol Use % (95% CI)Substance Use % (95% CI)PayerPrivate Insurance33.1 (33.0-33.2)66.4 (66.2-66.7)58.3 (58.0-58.6)7.2 (7.0-7.4)22.8 (22.5-23.0)Medicare36.5 (36.3-36.8)70.9 (70.2-71.6)58.7 (58.2-59.3)11.7 (10.9-12.6)25.9 (24.8-26.9)Medicaid35.7 (35.6-35.8)67.9 (67.7-68.1)58.1 (57.9-58.3)14.6 (14.3-14.9)25.5 (25.2-25.7)Self-Pay25.8 (25.7-25.9)55.2 (54.9-55.5)45.1 (44.7-45.4)5.4 (5.3-5.5)15.3 (15.1-15.6)Race/EthnicityWhite34.0 (33.9-34.0)65.8 (65.6-66.0)57.0 (56.7-57.2)9.5 (9.4-9.7)22.8 (22.6-23.0)Black30.8 (30.7-30.9)62.4 (62.0-62.7)54.6 (54.4-54.9)6.1 (6.0-6.3)15.2 (14.8-15.6)Hispanic30.4 (30.2-30.5)63.2 (62.8-63.6)54.7 (54.4-55.1)7.1 (6.9-7.3)18.8 (18.4-19.3)Asian33.5 (33.1-33.9)67.2 (66.1-68.2)61.6 (60.6-62.6)5.3 (4.7-6.0)19.1 (17.6-20.6)Native American30.7 (30.2-31.3)60.6 (59.3-62.0)57.5 (55.5-59.5)6.1 (5.6-6.5)21.2 (19.4-22.9) Open table in a new tab

Impact of timing of palliative care consults on disposition to type of hospice care.

50 Background: The 2018 ASCO palliative care guidelines recommend palliative care team (PCT) involvement within 8 weeks for patients with an advanced cancer diagnosis. However, the optimal timing and impact of PCT consults on patient disposition in the inpatient setting has not been established. We investigated whether the timing of PCT involvement for in-patients with an advanced cancer diagnosis affected disposition to a home or inpatient hospice setting. Methods: We queried Hahnemann University Hospital’s Palliative Care In-patient database from 2016-2018 for patients with advanced cancer diagnosis, estimated life expectancy of &lt; 6 months, and recommendation for hospice. Dates of admission, initial PCT consult, discharge to an outpatient vs an inpatient hospice setting/in hospital death were examined. We then examined differences in hospice disposition and timing of PCT consults to determine the ideal consult time. Chi square analysis was used to determine differences in hospice disposition setting and timing of PCT consult. Results: We observed that 75% of PCT consults in our hospital are placed &lt;10 days of admission. We also found that a statistically significant higher percentage of patients were discharged to a home hospice setting (35.1%) when using a PCT consult time of &lt;10 days (p&lt;0.01). Only 17.5% were discharged home when PCT was consulted &gt;10 days after admission. We examined other cut-off times for consultation, but the difference in outcome was not statistically significant. Conclusions: Our findings show that a statistically significant higher percentage of patients went to a home hospice setting if PCT was consulted &lt;10 days of admission. This suggests that early PCT involvement can result in more patients being discharged to a home hospice setting and by extension improve the quality of end of life care for patients. We aim to implement criteria for appropriate timing of PCT consults at our institution and measure post implementation data with the goal of increasing the number of patients discharged to a home hospice setting. [Table: see text]

Critical Thinking Disposition, Professional Self-Concept and Clinical Competence in Nursing Students

본 연구는 간호대학생의 비판적 사고성향과 전문직 자아개념 및 임상수행능력과의 관련성을 규명하고 임상수행능력에 영향을 미치는 변수를 확인하고자 수행되었다. 연구대상자는 4년제 간호학과 학생 267명이며, 자료는 구조화된 설문지를 이용하여 수집되었으며 수집된 자료는 SPSS 21.0 Version을 사용하여 기술통계, 독립 t-검정, 분산분석, 피어슨 상관관계와 단계적 다중회귀분석으로 분석하였다. 연구결과 간호대학생의 특성에 따른 비판적 사고성향은 학년, 성적, 간호학과 만족도, 임상수행만족도, 실습동료와의 관계에서 유의한 차이가 있는 것으로 나타났으며, 전문직 자아개념 정도는 성별, 성적, 간호학과 만족도, 임상수행만족도, 실습동료와의 관계에서 유의한 차이가 있는 것으로 나타났다. 또한 임상수행능력 정도는 학년, 성적, 간호학과 만족도, 임상수행만족도에서 유의한 차이를 보였다. 그리고 임상수행능력은 비판적 사고성향(r=.523, p<.05), 간호전문직 자아개념(r=.551, p<.01)과 유의한 순 상관관계를 가지며, 전문직 자아개념은 비판적 사고성향((r=.631, p<.01)과 유의한 순 상관관계가 있었다. 비판적 사고성향(β=.609, p=.001)과 전문직 자아개념(β=.885, p=.001)이 임상수행능력의 영향요인으로 나타났으며 총설명력은 35.5%이었다. 이러한 영향요인들을 고려하여 간호대학생의 비판적 사고성향과 간호전문직 자아개념을 향상시키는 중재프로그램의 개발 및 적용이 필요하다.The purpose of this study was to identify the relationships among critical thinking disposition, professional self-concept and clinical competence in nursing students, and to identify the effective factor on clinical competence for nursing students. The participants in the study were 267 nursing students and a questionnaire survey was conducted. Statistical processing was performed with SPSS 21.0 version and the data were analyzed using descriptive statistics, independent t-test, variance analysis, Pearson correlation coefficients, stepwise regression analysis. The result showed an significant difference in critical thinking disposition with year, GPA, major satisfaction, clinical performance satisfaction, relationships with student colleagues. Professional self-concept had a significant difference with sex, GPA, major satisfaction, clinical performance satisfaction, relationships with student colleagues and clinical competence with year, GPA, major satisfaction, clinical performance satisfaction. There was a positive correlation among critical thinking disposition and clinical competence, professional self-concept. The effective factors on clinical competence were critical thinking disposition and professional self-concept. The regression model explained 35.5%. The study findings suggest that to develop and apply the effective learning program with achievement level of critical thinking disposition and professional self-concept for nursing students.

Elderly adults with isolated hip fractures- orthogeriatric care versus standard care: A practice management guideline from the Eastern Association for the Surgery of Trauma.

Elderly patients commonly suffer isolated hip fractures, causing significant morbidity and mortality. The use of orthogeriatrics (OG) management services, in which geriatric specialists primarily manage or co-manage patients after admission, may improve outcomes. We sought to provide recommendations regarding the role of OG services. Using GRADE methodology with meta-analyses, the Practice Management Guidelines Committee of the Eastern Association for the Surgery of Trauma conducted a systematic review of the literature from January 1, 1900, to August 31, 2017. A single Population, Intervention, Comparator and Outcome (PICO) question was generated with multiple outcomes: Should geriatric trauma patients 65 years or older with isolated hip fracture receive routine OG management, compared with no-routine OG management, to decrease mortality, improve discharge disposition, improve functional outcomes, decrease in-hospital medical complications, and decrease hospital length of stay? Forty-five articles were evaluated. Six randomized controlled trials and seven retrospective case-control studies met the criteria for quantitative analysis. For critical outcomes, retrospective case-control studies demonstrated a 30-day mortality benefit with OG (OR, 0.78 [0.67, 0.90]), but this was not demonstrated prospectively or at 1 year. Functional outcomes were superior with OG, specifically improved score on the Short Physical Performance Battery at 4 months (mean difference [MD], 0.78 [0.28, 1.29]), and improved score on the Mini Mental Status Examination with OG at 12 months (MD, 1.57 [0.40, 2.73]). Execution of activities of daily living was improved with OG as measured by two separate tests at 4 and 12 months. There was no difference in discharge disposition. Among important outcomes, the OG group had fewer hospital-acquired pressure ulcers (OR, 0.30 [0.15, 0.60]). There was no difference in other complications or length of stay. Overall quality of evidence was low. In geriatric patients with isolated hip fracture, we conditionally recommend an OG care model to improve patient outcomes. Systematic review/meta-analysis, level III.

Atropselective Disposition of 2,2',3,4',6-Pentachlorobiphenyl (PCB 91) and Identification of Its Metabolites in Mice with Liver-Specific Deletion of Cytochrome P450 Reductase.

Hepatic cytochrome P450 enzymes metabolize chiral polychlorinated biphenyls (PCBs) to hydroxylated metabolites (OH-PCBs). Animal models with impaired metabolism of PCBs are one approach to study how the atropselective oxidation of PCBs to OH-PCBs contributes to toxic outcomes, such as neurodevelopmental disorders, following PCB exposure. We investigated the disposition of PCB 91, a para-substituted PCB congener, in mice with a liver-specific deletion of the cytochrome P450 reductase (cpr) gene (KO mice). KO mice and wild-type (WT) mice were exposed orally to racemic PCB 91 (30 mg/kg b.w.). Levels and enantiomeric fractions of PCB 91 and its hydroxylated metabolites were determined in tissues 3 days after PCB exposure and in excreta on days 1-3 after PCB exposure. PCB 91, but not OH-PCB levels were higher in KO compared to WT mice. The elevated fat and protein content in the liver of KO mice resulted in the hepatic accumulation of PCB 91. OH-PCBs were detected in blood, liver, and excreta samples of KO and WT mice. 2,2',3,4',6-Pentachlorobiphenyl-5-ol (5-91) was the major metabolite. A considerable percent of the total PCB 91 dose (%TD) was excreted with the feces as 5-91 (23%TD and 31%TD in KO and WT mice, respectively). We tentatively identified glucuronide and sulfate metabolites present in urine samples. The PCB 91 atropisomer eluting first on the chiral column (E1-PCB 91) displayed genotype-dependent atropisomeric enrichment, with a more pronounced atropisomeric enrichment observed in WT compared to KO mice. E1-atropisomers of 5-91 and 2,2',3,4',6-pentachlorobiphenyl-4-ol (4-91) were enriched in blood and liver, irrespective of the genotype; however, the extent of the enrichment of E1-5-91 was genotype dependent. These differences in atropselective disposition are consistent with slower metabolism of PCB 91 in KO compared to WT mice and the accumulation of the parent PCB in the fatty liver of KO mice.

Influence of a Novel Multidisciplinary Cognitive Impairment Intervention on Post-Acute Care in an Inpatient Community-Based HFrEF Cohort

Background Cognitive impairment (CI) is a strong predictor of six-month mortality and risk for re-admission in older hospitalized heart failure (HF) patients. We sought to develop a novel, multidisciplinary CI inpatient intervention to improve post-acute care discharge planning and reduce 30-day hospital re-admissions. Methods From July 2016 to July 2018 at a large, community-based hospital, we developed a CI inpatient screening program using the Mini-Cog test for eligible patients over the age of 65 admitted with a primary diagnosis of HF. The Mini-Cog is a three word recall and clock drawing test, scored between 0 and 5 points. A score of 2 or below identifies CI. In May 2017, Mini-Cog (+) patients received a multidisciplinary CI intervention led by palliative care nurses and speech therapists which included: a) family meeting b) goals of care discussion c) family-directed HF education and d) speech therapy evaluation. We compared the pre-intervention cohort (10 months prior to intervention) with the post-intervention cohort (15 months after intervention) with respect to discharge disposition and 30-day re-admission rates. Results We screened 740 patients for CI, of which 11.4% were Mini-Cog (+). In Mini-Cog (+) patients, the CI intervention increased the percentage of home health discharges (46% vs 20%, p=0.02, OR 3.4) and decreased the percentage of home discharges (44% vs 15%, p=0.008, OR 0.23), while rates of skilled nursing and hospice discharges were not significantly different (29% vs 26%, p=0.93 and 7% vs 8%, p=1.0), respectively). In the Mini-Cog (-) patients, there were no significant differences in pre vs post intervention cohort discharge disposition. In the combined pre and post intervention cohorts, a greater percentage of Mini-cog (+) patients were discharged to skilled nursing facilities and hospice compared to Mini-cog (-) patients (36.9% vs 19.8%, P Conclusions CI represents an important marker of HF post-acute care morbidity and mortality. Our CI multi-disciplinary intervention had a significant impact on discharge disposition with increased utilization of home health services. While not achieving statistical significance likely due to inadequate power, our intervention numerically lowered rates of 30-day re-admissions in a high-risk CI impaired population. Moreover, re-admission rates were similar to those noted in the Mini-Cog (-) group in this high-risk population. Hence, we believe these data justify further validation of this novel, multi-disciplinary approach in a larger multi-center study.

Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry.

Efavirenz (more specifically the S-enantiomer) is a cornerstone antiretroviral therapy for treatment of HIV infection. The major primary metabolite is S-8-hydroxyefavirenz, which does not have antiretroviral activity but is neurotoxic. Cytochrome P450 2B6 (CYP2B6) is the major enzyme catalyzing S-8-hydroxyefavirenz formation. CYP2B6 genetics and drug interactions are major determinants of clinical efavirenz disposition and dose adjustment. In addition, as a prototypic CYP2B6 substrate, S-efavirenz and analogs can inform on the structure, activity, catalytic mechanisms, and stereoselectivity of CYP2B6. Metabolism of R-efavirenz by CYP2B6 remains unexplored. This investigation assessed S-efavirenz metabolism by clinically relevant CYP2B6 genetic variants. This investigation also evaluated R-efavirenz hydroxylation by wild-type CYP2B6.1 and CYP2B6 variants. S-Efavirenz 8-hydroxylation by wild-type CYP2B6.1 and variants exhibited positive cooperativity and apparent cooperative substrate inhibition. On the basis of Clmax values, relative activities for S-efavirenz 8-hydroxylation were in the order CYP2B6.4 > CYP2B6.1 ≈ CYP2B6.5 ≈ CYP2B6.17 > CYP2B6.6 ≈ CYP2B6.7 ≈ CYP2B6.9 ≈ CYP2B6.19 ≈ CYP2B6.26; CYP2B6.16 and CYP2B6.18 showed minimal activity. Rates of R-efavirenz metabolism were approximately 1/10 those of S-efavirenz for wild-type CYP2B6.1 and variants. On the basis of Clmax values, there was 14-fold enantioselectivity (S > R-efavirenz) for wild-type CYP2B6.1, and 5- to 22-fold differences for other CYP2B6 variants. These results show that both CYP2B6 516G > T (CYP2B6*6 and CYP2B6*9) and 983T > C (CYP2B6*16 and CYP2B6*18) polymorphisms cause canonical diminishment or loss-of-function variants for S-efavirenz 8-hydroxylation, provide a mechanistic basis for known clinical pharmacogenetic differences in efavirenz disposition, and may predict additional clinically important variant alleles. Efavirenz is the most stereoselective CYP2B6 drug substrate yet identified and may be a useful probe for the CYP2B6 active site and catalytic mechanisms. SIGNIFICANCE STATEMENT: Clinical disposition of the antiretroviral S-efavirenz is affected by CYP2B6 polymorphisms. Expressed CYP2B6 with 516G>T (CYP2B6*6 and CYP2B6*9), and 983T>C (CYP2B6*16 and CYP2B6*18) polymorphisms had a diminishment or loss of function for efavirenz 8-hydroxylation. This provides a mechanistic basis for efavirenz clinical pharmacogenetics and may predict additional clinically important variant alleles. Efavirenz metabolism showed both cooperativity and cooperative substrate inhibition. With greater than 10-fold enantioselectivity (S- vs. R- metabolism), efavirenz is the most stereoselective CYP2B6 drug substrate yet identified. These findings may provide mechanistic insights.

Characterization of the in vitro CYP450 mediated metabolism of the polymorphic CYP2D6 probe drug codeine in horses

Despite their widespread popularity as sport and companion animals and published and anecdotal reports of vast difference in drug disposition and pharmacokinetics between individuals, studies describing equine drug metabolism are limited. It has been theorized that similar to humans, members of the CYP2D family in horses may be polymorphic in nature leading to differences in metabolism of substrates. This study aims to build on the limited current knowledge regarding P450 mediated metabolism in horses by describing the metabolism of the polymorphic CYP2D6 probe drug codeine in vitro. Codeine, at varying substrate concentrations, was incubated with equine liver microsomes (±UDPGA) and a panel of baculovirus expressed recombinant equine P450s. Parent drug and metabolite concentrations were determined using LC-MS/MS. Incubation of codeine in equine liver microsomes generated norcodeine, morphine, codeine glucuronide and morphine 3- and 6- glucuronide. In recombinant P450 assays, the newly described CYP2D82 was responsible for catalyzing the biotransformation of codeine to morphine (Km of 247.4 μM and a Vmax of 1.6 pmol/min/pmol P450). CYP2D82 is 80% homologous to the highly polymorphic CYP2D6 enzyme, which is responsible for biotransformation of codeine to morphine in humans. CYP3A95, which shares 79% sequence homology with human CYP3A4 and CYP2D50 catalyzed the conversion of codeine to norcodeine (Km of 104.1 and 526.9 μM, Vmax of 2.8 and 2.6 pmol/min/pmol P450). In addition to describing the P450 mediated metabolism of codeine, the current study offers a candidate probe drug that could be used in vivo to study the functional implications of polymorphisms in the CYP2D gene in horses.

Improving Tracheostomy Decannulation Rate In Trauma Patients.

Objectives:Identify the effect of a multidisciplinary tracheostomy decannulation protocol in the trauma population.Design:Single-center retrospective review.Setting:American College of Surgeons level 1 trauma center; large academic associated community hospital.Patients:Adult trauma patients who required a tracheostomy.Interventions:A tracheostomy decannulation protocol empowering respiratory therapists to move patients toward tracheostomy decannulation.Measurements Main Results:Tracheostomy decannulation rate, time to tracheostomy decannulation, length of stay, and reintubation and recannulation rates. A total of 252 patients met inclusion criteria during the study period with 134 presenting after the tracheostomy decannulation protocol was available. Since the tracheostomy decannulation protocol was implemented, patients managed by the tracheostomy decannulation protocol had a 50% higher chance of tracheostomy decannulation during the hospital stay (p < 0.001). The time to tracheostomy decannulation was 1 day shorter with the tracheostomy decannulation protocol (p = 0.54). There was no difference in time to discharge after ventilator liberation (p = 0.91) or in discharge disposition (p = 0.66). When comparing all patients, the development of a tracheostomy decannulation protocol, regardless if a patient was managed by the tracheostomy decannulation protocol, resulted in an 18% higher chance of tracheostomy decannulation (p = 0.003). Time to tracheostomy decannulation was 5 days shorter in the postintervention period (p = 0.07). There was no difference in discharge disposition (p = 0.88) but the time to discharge after ventilator liberation was shorter post protocol initiation (p = 0.04).Conclusions:In a trauma population, implementation of a tracheostomy decannulation protocol significantly improves tracheostomy decannulation rates during the same hospital stay. A larger population will be required to identify patient predictive factors for earlier successful tracheostomy decannulation.