bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring expanded interdisciplinary roles in goals of care conversations in a national goals of care initiative: A qualitative approach
Authors: Ma Jessica E , Haverfield Marie , Lorenz Karl A , Bekelman David B , Brown-Johnson Cati , Lo Natalie , Foglia Mary Beth , Lowery Jill S , Walling Anne M , Giannitrapani Karleen F 
Published: June 2021

Background: The United States Veterans Health Administration National Center for Ethics in Health Care implemented the Life-Sustaining Treatment Decisions Initiative throughout the Veterans Health Administration health care system in 2017. This policy encourages goals of care conversations, referring to conversations about patient’s treatment and end-of-life wishes for life-sustaining treatments, among Veterans with serious illnesses. A key component of the initiative is expanding interdisciplinary provider roles in having goals of care conversations. Aim: Use organizational role theory to explore medical center experiences with expanding interdisciplinary roles in the implementation of a goals of care initiative. Design: A qualitative thematic analysis of semi-structured interviews. Setting/participants: Initial participants were recruited using purposive sampling of local medical center champions. Snowball sampling identified additional participants. Participants included thirty-one interdisciplinary providers from 12 geographically diverse initiative pilot and spread medical centers. Results: Five themes were identified. Expanding provider roles in goals of care conversations (1) involves organizational culture change; (2) is influenced by medical center leadership; (3) is supported by provider role readiness; (4) benefits from cross-disciplinary role agreement; and (5) can “overwhelm” providers. Conclusions: Organizational role theory is a helpful framework for exploring interdisciplinary roles in a goals of care initiative. Support and recognition of provider role expansion in goals of care conversations was important for the adoption of a goals of care initiative. Actionable strategies, including multi-level leadership support and the use of interdisciplinary champions, facilitate role change and have potential to strengthen uptake of a goals of care initiative.
Peak and Per-Step Tibial Bone Stress During Walking and Running in Female and Male Recreational Runners
Authors: Meardon Stacey A. , Derrick Timothy R. , Willson John D. , Baggaley Michael , Steinbaker C. Ryan , Marshall Margaret , Willy Richard W. 
Published: June 2021

Background: Athletes, especially female athletes, experience high rates of tibial bone stress injuries (BSIs). Knowledge of tibial loads during walking and running is needed to understand injury mechanisms and design safe running progression programs. Purpose: To examine tibial loads as a function of gait speed in male and female runners. Study Design: Controlled laboratory study. Methods: Kinematic and kinetic data were collected on 40 recreational runners (20 female, 20 male) during 4 instrumented gait speed conditions on a treadmill (walk, preferred run, slow run, fast run). Musculoskeletal modeling, using participant-specific magnetic resonance imaging and motion data, was used to estimate tibial stress. Peak tibial stress and stress-time impulse were analyzed using 2-factor multivariate analyses of variance (speed*sex) and post hoc comparisons (α = .05). Bone geometry and tibial forces and moments were examined. Results: Peak compression was influenced by speed ( P < .001); increasing speed generally increased tibial compression in both sexes. Women displayed greater increases in peak tension ( P = .001) and shear ( P < .001) than men when transitioning from walking to running. Further, women displayed greater peak tibial stress overall ( P < .001). Compressive and tensile stress-time impulse varied by speed ( P < .001) and sex ( P = .006); impulse was lower during running than walking and greater in women. A shear stress-time impulse interaction ( P < .001) indicated that women displayed greater impulse relative to men when changing from a walk to a run. Compared with men, women displayed smaller tibiae ( P < .001) and disproportionately lower tibial forces ( P≤ .001-.035). Conclusion: Peak tibial stress increased with gait speed, with a 2-fold increase in running relative to walking. Women displayed greater tibial stress than men and greater increases in stress when shifting from walking to running. Sex differences appear to be the result of smaller bone geometry in women and tibial forces that were not proportionately lower, given the womens’ smaller stature and lower mass relative to men. Clinical Relevance: These results may inform interventions to regulate running-related training loads and highlight a need to increase bone strength in women. Lower relative bone strength in women may contribute to a sex bias in tibial BSIs, and female runners may benefit from a slower progression when initiating a running program.
Defining Critical Glenoid Bone Loss in Posterior Shoulder Capsulolabral Repair
Authors: Arner Justin W. , Ruzbarsky Joseph J. , Midtgaard Kaare , Peebles Liam , Bradley James P. , Provencher Matthew T. 
Published: June 2021

Background: Although critical bone loss for anterior instability is well defined, a clinically significant threshold of posterior bone loss has not been elucidated. Hypothesis: Patients with failed arthroscopic posterior shoulder capsulolabral repair will have increased posterior glenoid bone loss with a defined critical threshold. Study Design: Case control study; Level of evidence, 3. Methods: Athletes older than 18 years with unidirectional posterior instability treated with arthroscopic repair were evaluated at 2-year minimum follow-up. Failure was defined as revision surgery, American Shoulder and Elbow Surgeons (ASES) score of <60, or subjective stability score of >5. Magnetic resonance imaging (MRI) measurements from 19 patients with failed arthroscopic posterior shoulder capsulolabral repair were compared with 56 patients whose surgery was successful. MRI measures included glenoid version, labral version, glenoid width, labral width, percentage bone loss using the circle technique, labral height, percent subluxation, and recently described measures of defect slope, bone loss angle, and defect length. The P value threshold was set at .05, and a multivariable logistic regression analysis was performed for evaluation of risk of surgical failure. Results: Smaller glenoid width and greater percentage glenoid bone loss (25.5 ± 0.68 mm vs 28.8 ± 0.47 mm; P < .001; 6.8% ± 0.64% vs 4.6% ± 0.43%; P = .008) were seen in those patients with failed surgery. There was no difference in glenoid version or other measurements between the failures and nonfailures. A cutoff of 11% glenoid bone loss resulted in a 10.4 times statistically higher surgical failure rate, while a 15% bone loss resulted in a 24.4 times statistically higher failure rate. Six patients had >11% bone loss (range, 11.1 to 19.3) and 1 patient had >15% bone loss. Conclusion: Risk factors for failure of arthroscopic posterior shoulder capsulolabral repair include smaller glenoid bone width and greater percentage of glenoid bone loss. A threshold of 11% posterior glenoid bone loss implicated a 10 times higher surgical failure rate, while a threshold of 15% led to a 25 times higher surgical failure rate. Surgical failure of posterior capsulolabral repair, however, is relatively rare as it is an overall successful intervention.
Critical Care Utilization and Outcomes of Interhospital Medical Transfers at Lower Risk of Death
Authors: Baig Saqib H. , Gorth Deborah J. , Yoo Erika J. 
Published: June 2021

Purpose: To evaluate utilization and mortality outcomes of interhospital transferred critically-ill medical patients with lower predicted risk of hospital mortality. Materials & Methods: Multisite retrospective cohort analysis of patients with Acute Physiology and Chronic Health Evaluation (APACHE) IV-a predicted mortality of ≤20% from 335 ICUs in 208 hospitals in the Philips eICU database between 2014-2015. Differences in length-of-stay (LOS) and mortality between transferred and local patients were evaluated using negative binomial logistic regression and logistic regression, respectively. Stratified analyses were conducted for subgroups of predicted mortality: 0%-5%, 6%-10%, 11%-15%, and 16%-20%. Results: Transfers had a higher risk of longer ICU and hospital LOS across all risk strata (IRR 1.12; 95% CI 1.09-1.16, P < 0.001 and IRR 1.11; 95% CI 1.07-1.14, P < 0.001 respectively). Mortality was higher among transfers, largely driven by the 6%-10% mortality risk strata (OR 1.30; 95% CI 1.09-1.54, P = 0.003). Conclusions: Interhospital transfer of critically-ill medical patients with lower illness severity is associated with higher ICU and hospital utilization and increased mortality. Better understanding of factors driving patient selection for and characteristics of interhospital transfer for this population will have an impact on ICU resource utilization, care efficiency, and hospital quality.
COVID-19 Experiences and Social Distancing: Insights From the Theory of Planned Behavior
Authors: Frounfelker Rochelle L. , Santavicca Tara , Li Zhi Yin , Miconi Diana , Venkatesh Vivek , Rousseau Cecile 
Published: June 2021

Purpose: The objective of this study is to identify the relationship between COVID-19 experiences, perceived COVID-19 behavioral control, social norms and attitudes, and future intention to follow social distancing guidelines. Design: This is a cross-sectional study. Setting: Participants responded to an on-line survey in June 2020. Subjects: The study included 3,183 residents within Quebec, Canada aged 18 and over. Measures: Measures include perceived COVID-19 related discrimination, fear of COVID-19 infection, prior exposure to COVID-19, and prior social distancing behavior. Participants self-reported attitudes, perceived behavioral control, and perceived norms related to social distancing. Finally, we measured social distancing behavioral intention. Analysis: We evaluated a theory of planned behavior (TPB) measurement model of social distancing using confirmatory factor analysis (CFA). The association between COVID-19 perceived discrimination, fear of infection, previous social distancing behavior, exposure to COVID-19, TPB constructs and behavioral intentions to social distance were estimated using SEM path analysis. Results: TPB constructs were positively associated with intention to follow social distancing guidelines. Fear of COVID-19 infection and prior social distancing behavior were positively associated with behavioral intentions. In contrast, perceived discrimination was negatively associated with the outcome. Associations between fear of COVID-19, perceived COVID-19 discrimination and behavioral intentions were partially mediated by constructs of TPB. Conclusions: COVID-19 prevention efforts designed to emphasize positive attitudes, perceived control, and social norms around social distancing should carefully balance campaigns that heighten fear of infection along with anti- discrimination messaging.
Trends and Predictors of Palliative Care Consultation Among Patients Admitted for LVAD: A Retrospective Analysis From the Nationwide Inpatient Sample Database From 2006-2014
Authors: Quelal Karol , Olagoke Olankami , Shahi Anoj , Torres Andrea , Ezegwu Olisa , Golzar Yasmeen 
Published: June 2021

Background: Left ventricular assist devices (LVADs) are an essential part of advanced heart failure (HF) management, either as a bridge to transplantation or destination therapy. Patients with advanced HF have a poor prognosis and may benefit from palliative care consultation (PCC). However, there is scarce data regarding the trends and predictors of PCC among patients undergoing LVAD implantation. Aim: This study aims to assess the incidence, trends, and predictors of PCC in LVAD recipients using the United States Nationwide Inpatient Sample (NIS) database from 2006 until 2014. Methods: We conducted a weighted analysis on LVAD recipients during their index hospitalization. We compared those who had PCC with those who did not. We examined the trend in palliative care utilization and calculated adjusted odds ratios (aOR) to identify demographic, social, and hospital characteristics associated with PCC using multivariable logistic regression analysis. Results: We identified 20,675 admissions who had LVAD implantation, and of them 4% had PCC. PCC yearly rate increased from 0.6% to 7.2% (P < 0.001). DNR status (aOR 28.30), female sex (aOR 1.41), metastatic cancer (aOR: 3.53), Midwest location (aOR 1.33), and small-sized hospitals (aOR 2.52) were positive predictors for PCC along with in-hospital complications. Differently, Black (aOR 0.43) and Hispanic patients (aOR 0.25) were less likely to receive PCC. Conclusion: There was an increasing trend for in-hospital PCC referral in LVAD admissions while the overall rate remained low. These findings suggest that integrative models to involve PCC early in advanced HF patients are needed to increase its generalized utilization.
Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder
Authors: Waters Kristin 
Published: June 2021

Objective To provide an overview of the efficacy and safety of lemborexant in the treatment of insomnia disorder by assessing the currently available literature. Data Sources A literature search of PubMed was performed (2010 to March 2021) using the following search terms: lemborexant, sleep, orexin Study Selection and Data Extraction All relevant English-language studies were reviewed and considered, with a focus on phase 3 trials. Data Synthesis The efficacy and safety of lemborexant in the treatment of insomnia disorder in adults was demonstrated in 2 phase 3 trials. Lemborexant significantly reduced latency to persistent sleep compared with placebo. The first study also demonstrated a significant reduction compared with the active control zolpidem ER. Somnolence and headache were relatively common, but the marked adverse effects associated with other medications commonly used to treat insomnia, such as cognitive and psychomotor impairment and complex sleep-related behaviors, were not observed. Relevance to Patient Care and Clinical Practice Although nonpharmacological therapy is considered first-line treatment for insomnia disorder, pharmacological treatment is most commonly utilized. Lemborexant is a viable pharmacological treatment option for patients who are unable to tolerate the adverse effects associated with the most commonly prescribed medications for insomnia, such as benzodiazepines and sedative-hypnotics (Z drugs). This is especially true for geriatric patients, who may be more sensitive to these adverse effects. Conclusion Lemborexant can be recommended to treat insomnia disorder when pharmacological treatment is warranted. It has demonstrated efficacy in clinical trials and is likely better tolerated than most currently available treatment options.
Impact of Interferons and Biological Drug Inhibitors of IL-2 and IL-6 on Small-Molecule Drug Metabolism Through the Cytochrome P450 System
Authors: White C. Michael , Sicignano Dakota J. , Smith Kimberly 
Published: June 2021

Objective: Assess the impact of interferons and interleukin (IL)-2 and IL-6 inhibitors on cytochrome P450 (CYP) drug metabolism in human subjects. Data Sources: PubMed search from 1980 to March 31, 2021, limited to human subjects and English language via search strategy: (biological drug names) [AND] (cytochrome [OR] CYP metabolism). Study Selection and Data Extraction: Narrative review of human studies assessing biological drugs in select classes that affect CYP drug metabolism. Data Synthesis: Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients; have minimal impact on CYP3A4 (midazolam and dapsone), CYP2C9 (tolbutamide), or CYP2C19 (mephenytoin) metabolism; and increase CYP2D6 (debrisoquine, dextromethorphan) metabolism. Biological IL-2 inhibitors (basiliximab, daclizumab) have no effect on metabolism via CYP1A2 (caffeine), CYP2C9 (s-warfarin), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam, tacrolimus) but may enhance CYP3A4 (cyclosporin) metabolism over time. IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine). Relevance to Patient Care and Clinical Practice: Patients using interferons, IL-2, or IL-6 blocking drugs at steady state with CYP substrates could have altered drug metabolism and experience adverse events. With interferons and biological anti-inflammatory drugs, some isoenzymes will be inhibited, whereas others will be enhanced, and the magnitude of the effect can sometimes be significant. In clinical practice, clinicians may consider these metabolic changes as an additive effect to a patient’s entire disease and medication profile when determining risk/benefit of treatment. Conclusions: Interferon therapy or inflammatory suppression via IL-2 or IL-6 can alter steady-state concentrations of CYP-metabolized small-molecule drugs.
Real world use of FLT3 inhibitors for treatment of FLT3+ acute myeloid leukemia (AML): A single center, propensity-score matched, retrospective cohort study
Authors: Bazzell Brian G , Marini Bernard L , Benitez Lydia L , Bixby Dale , Burke Patrick , Pettit Kristen , Perissinotti Anthony J 
Published: June 2021

Background Patients diagnosed with acute myeloid leukemia with a FLT3 mutation (FLT3+ AML) have historically had poor outcomes. While the addition of the FLT3 inhibitors to induction therapy has been shown to improve survival outcomes in FLT3+ AML, interactions and overlapping toxicities between FLT3 inhibitors and standard of care medications used during induction therapy (e.g. azole antifungals, anthracyclines) and logistical barriers have complicated their use. To avoid these concerns, our institution has opted to defer initiation of midostaurin until after completion of induction therapy. However, to our knowledge no study confirming the effectiveness of this strategy for real world FLT3 inhibitor use has been published. Methods We performed a single center, propensity-score matched, retrospective cohort study characterizing efficacy and safety of our strategy for use of FLT3 inhibitors in the treatment of FLT3+ AML. The primary outcome was median event-free survival (EFS), while secondary endpoints included median overall survival (OS), overall response rate (ORR), 30-day mortality, duration of neutropenia, duration of thrombocytopenia, consolidation cycle delays, documented infections, and all-cause hospital readmission. Results A total of 83 FLT3+ AML patients treated with intensive induction therapy were included in the study, of whom 48 were propensity-score matched and analyzed. Baseline characteristics were similar between the patients who received a FLT3 inhibitor after induction therapy and the historical control arm. Median EFS was not significantly different but compared favorably between the FLT3 inhibitor cohort and historical controls (not reached vs 8 months, p = 0.343) with 18-month EFS of 54% and 43% for the two cohorts, respectively. Similarly, no significant differences were noted with regard to median OS (not reached vs 28.7 months, p = 0.752), ORR (79.2% vs 79.2%), or safety outcomes between groups. Conclusion Compared to historical controls, addition of a FLT3 inhibitor to intensive chemotherapy post-induction may improve EFS or OS in a real world patient cohort with longer follow-up and a larger sample size. The omission of midostaurin in induction allowed for the use of an azole antifungal and the intensification of anthracycline dose may have contributed to high remission rates in both groups.
RNA Binding Protein-Based Model for Prognostic Prediction of Colorectal Cancer
Authors: Li Ting , Hui Wenjia , Halike Halina , Gao Feng 
Published: June 2021

Background: Colorectal cancer (CRC) is a kind of gastrointestinal tumor with serious high morbidity and mortality. Several reports have implicated the disorder of RNA-binding proteins (RBPs) in plenty of tumors, associating it to tumorigenesis and disease progression. The study is intended to construct novel prognostic biomarkers associated with CRC patients. Methods: Data of gene expression was acquired from the TCGA database, prognosis-related genes were selected. Besides, we analyzed GO and KEGG pathways. Univariate and multivariate Cox analyses were performed to generate a prognostic-related gene signature, which was evaluated by the Kaplan-Meier (K-M) and the Receiver Operating Characteristic (ROC) curve. The independent prognostic factor was established by survival analysis. GSE38832 dataset was used to validate the signature. Finally, expression of 8 genes was further confirmed by qRT-PCR in SW480 and SW620 cell lines. Results: We obtained 224 differentially expressed RBPS in total, of which 78 were downregulated and 146 were upregulated. Univariate COX analysis was conducted in the TCGA cohort to select 13 RBPs with P < 0.005, stepwise multivariate COX regression analysis was used to construct an 8—RBP signature (TERT, PPARGC1A, BRCA1, CELF4, TDRD7, LUZP4, PNLDC1, ZC3H12C). Based on the model, systematic analysis illustrated that a high risk score was obviously connected to a poor prognosis. The prognostic value of the risk score was validated in GSE38832 dataset, indicating that the risk model was accurate and effective. The prognostic signature-based risk score was identified as an independent prognostic indicator for CRC. The expression results of qRT-PCR were consistent with the results of differential expression analysis. Conclusions: The eight-RBP signature can predict the survival of CRC patients and potentially act as CRC prognostic biomarker.