bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Effectiveness and Safety of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Chronic Liver Disease: A Nationwide Cohort Study
Authors: Lawal Oluwadolapo D. , Aronow Herbert D. , Shobayo Fisayomi , Hume Anne L. , Taveira Tracey H. , Matson Kelly L. , Zhang Yichi , Wen Xuerong 
Published: February 2023

Background:
The benefit-risk profile of direct oral anticoagulants (DOACs) compared with warfarin, and between DOACs in patients with atrial fibrillation (AF) and chronic liver disease is unclear.

Methods:
We conducted a new-user, retrospective cohort study of patients with AF and chronic liver disease who were enrolled in a large, US-based administrative database between January 1, 2011, and December 31, 2017. We assessed the effectiveness and safety of DOACs (as a class and individually) compared with warfarin, and between DOACs in patients with AF and chronic liver disease. The primary outcomes were hospitalization for ischemic stroke/systemic embolism and hospitalization for major bleeding. Inverse probability treatment weights were used to balance the treatment groups on measured confounders.

Results:
Overall, 10 209 participants were included, with 4421 (43.2%) on warfarin, 2721 (26.7%) apixaban, 2211 (21.7%) rivaroxaban, and 851 (8.3%) dabigatran. The incidence rates per 100 person-years for ischemic stroke/systemic embolism were 2.2, 1.4, 2.6, and 4.4 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. The incidence rates per 100 person-years for major bleeding were 7.9, 6.5, 9.1, and 15.0 for DOACs as a class, apixaban, rivaroxaban, and warfarin, respectively. After inverse probability treatment weights, the risk of hospitalization for ischemic stroke/systemic embolism was significantly lower between DOACs as a class (hazard ratio [HR], 0.64 [95% CI, 0.46–0.90]) or apixaban (HR, 0.40 [95% CI, 0.19–0.82]) compared with warfarin, but not significantly different between rivaroxaban versus warfarin (HR, 0.76 [95% CI, 0.47–1.21]) or rivaroxaban versus apixaban (HR, 1.73 [95% CI, 0.91–3.29]). Compared with warfarin, the risk of hospitalization for major bleeding was lower with DOACs as a class (HR, 0.69 [95% CI, 0.58–0.82]), apixaban (HR, 0.60 [95% CI, 0.46–0.78]), and rivaroxaban (HR, 0.79 [95% CI, 0.62–1.0]). However, the risk of hospitalization for major bleeding was higher for rivaroxaban versus apixaban (HR, 1.59 [95% CI, 1.18–2.14]).

Conclusions:
Among patients with AF and chronic liver disease, DOACs as a class were associated with lower risks of hospitalization for ischemic stroke/systemic embolism and major bleeding versus warfarin. However, the incidence of clinical outcomes among patients with AF and chronic liver disease varied between individual DOACs and warfarin, and in head-to-head DOAC comparisons.
Whole-Exome Sequencing Analyses Support a Role of Vitamin D Metabolism in Ischemic Stroke
Authors: Xie Yuhan , Acosta Julián N. , Ye Yixuan , Demarais Zachariah S. , Conlon Carolyn J. , Chen Ming , Zhao Hongyu , Falcone Guido J. 
Published: February 2023

Background:
Ischemic stroke (IS) is a highly heritable trait, and genome-wide association studies have identified several commonly occurring susceptibility risk loci for this condition. However, there are limited data on the contribution of rare genetic variation to IS.

Methods:
We conducted an exome-wide study using whole-exome sequencing data from 152 058 UK Biobank participants, including 1777 IS cases. We performed single-variant analyses for rare variants and gene-based analyses for loss-of-function and deleterious missense rare variants. We validated these results through (1) gene-based testing using summary statistics from MEGASTROKE—a genome-wide association study of IS that included 67 162 IS cases and 454 450 controls, (2) gene-based testing using individual-level data from 1706 IS survivors, including 142 recurrent IS cases, enrolled in the VISP trial (Vitamin Intervention for Stroke Prevention); and (3) gene-based testing against neuroimaging phenotypes related to cerebrovascular disease using summary-level data from 42 310 UK Biobank participants with available magnetic resonance imaging data.

Results:

In single-variant association analyses, none of the evaluated variants were associated with IS at genome-wide significance levels (
P
<5×10
−8
). In the gene-based analysis focused on loss-of-function and deleterious missense variants, rare genetic variation at
CYP2R1
was significantly associated with IS risk (
P
=2.6×10
−6
), exceeding the Bonferroni-corrected threshold for 16 074 tests (
P
<3.1×10
−6
). Validations analyses indicated that
CYP2R1
was associated with IS risk in MEGASTROKE (gene-based test,
P
=0.003), with IS recurrence in the VISP trial (gene-based test,
P
=0.001) and with neuroimaging traits (white matter hyperintensity, mean diffusivity, and fractional anisotropy) in the UK Biobank neuroimaging study (all gene-based tests,
P
<0.05).

Conclusions:

Because
CYP2R1
plays an important role in vitamin D metabolism and existing observational evidence suggests an association between vitamin D levels and cerebrovascular disease, our results support a role of this pathway in the occurrence of IS.
What Do I Know about Severe Weather? The Influence of Weather Knowledge on Protective Action Decisions
Authors: Casteel Mark A. 
Published: February 2023

Abstract
Research has found that people who know the least about a topic are often very overconfident of their knowledge, while those who know the most often underestimate their knowledge. This finding, known as the Dunning–Kruger effect (DKE) has recently been shown to occur in knowledge of severe weather as well. The current study investigated whether being overconfident in one’s knowledge might translate into a tendency to make poorer sheltering decisions when faced with severe weather. Participants took two severe weather quizzes, one of perceived knowledge and one of objective knowledge. Participants also predicted their performance on both quizzes. The participants then saw four wireless emergency tornado warning alerts on a simulated smartphone screen, along with a tornado scenario, and then made two protective action decisions: one about immediately sheltering in place and the other the likelihood they would drive away. The results revealed that the participants did exhibit the DKE: those with the lowest levels of knowledge exhibited the most overconfidence while those with the highest levels of knowledge underestimated their performance. Also, in comparison with individuals with the most knowledge, those with the least knowledge were the most likely to state that they would not shelter immediately and that they would get in their car and drive away. Although more education is needed, the findings suggest a conundrum: those who know the least about severe weather, thinking they know a lot, are probably those individuals least likely to seek out additional education on the topic.

Significance Statement
Tornadoes are common in many states, and the National Weather Service issues tornado warnings in the hopes that individuals will take protective action. Previous research has found that people with low levels of knowledge (such as knowledge of severe weather) are often overconfident of their knowledge. This study explores whether those with low (as compared with high) severe weather knowledge make poorer decisions to a tornado warning. The findings show that those with the lowest knowledge were indeed overconfident and that they were less likely to shelter and more likely to drive away than those with high knowledge. The findings highlight that more severe weather education, although a worthy goal, might be difficult to implement if knowledge confidence is already high.
US and Dutch Perspectives on the Use of COVID-19 Clinical Prediction Models: Findings from a Qualitative Analysis
Authors: Basile Melissa J. , Helmrich I. R. A. Retel , Park Jinny G. , Polo Jennifer , Rietjens Judith A.C. , van Klaveren David , Zanos Theodoros P. , Nelson Jason , Lingsma Hester F. , Kent David M. , Alsma Jelmer , Verdonschot R. J. C. G. , Hajizadeh Negin 
Published: February 2023

Introduction Clinical prediction models (CPMs) for coronavirus disease 2019 (COVID-19) may support clinical decision making, treatment, and communication. However, attitudes about using CPMs for COVID-19 decision making are unknown. Methods Online focus groups and interviews were conducted among health care providers, survivors of COVID-19, and surrogates (i.e., loved ones/surrogate decision makers) in the United States and the Netherlands. Semistructured questions explored experiences about clinical decision making in COVID-19 care and facilitators and barriers for implementing CPMs. Results In the United States, we conducted 4 online focus groups with 1) providers and 2) surrogates and survivors of COVID-19 between January 2021 and July 2021. In the Netherlands, we conducted 3 focus groups and 4 individual interviews with 1) providers and 2) surrogates and survivors of COVID-19 between May 2021 and July 2021. Providers expressed concern about CPM validity and the belief that patients may interpret CPM predictions as absolute. They described CPMs as potentially useful for resource allocation, triaging, education, and research. Several surrogates and people who had COVID-19 were not given prognostic estimates but believed this information would have supported and influenced their decision making. A limited number of participants felt the data would not have applied to them and that they or their loved ones may not have survived, as poor prognosis may have suggested withdrawal of treatment. Conclusions Many providers had reservations about using CPMs for people with COVID-19 due to concerns about CPM validity and patient-level interpretation of the outcome predictions. However, several people who survived COVID-19 and their surrogates indicated that they would have found this information useful for decision making. Therefore, information provision may be needed to improve provider-level comfort and patient and surrogate understanding of CPMs. Highlights While clinical prediction models (CPMs) may provide an objective means of assessing COVID-19 prognosis, provider concerns about CPM validity and the interpretation of CPM predictions may limit their clinical use. Providers felt that CPMs may be most useful for resource allocation, triage, research, or educational purposes for COVID-19. Several survivors of COVID-19 and their surrogates felt that CPMs would have been informative and may have aided them in making COVID-19 treatment decisions, while others felt the data would not have applied to them.
Palliative Medicine Referral and End-of-Life Interventions Among Racial and Ethnic Minority Patients With Advanced or Recurrent Gynecologic Cancer
Authors: Tabuyo-Martin Angel , Torres-Morales Angelica , Pitteloud Marie J. , Kshetry Alisha , Oltmann Carina , Pearson Joseph Matthew , Khawand Mariana , Schlumbrecht Matthew P. , Sanchez Julia C. 
Published: February 2023

Background Referral to palliative medicine (PM) has been shown to improve quality of life, reduce hospitalizations, and improve survival. Limited data exist about PM utilization among racial minorities with gynecologic malignancies. Our objective was to assess differences in palliative medicine referrals and end of life interventions (within the last 30 days of life) by race and ethnicity in a diverse population of gynecologic oncology patients. Methods A retrospective cohort study of patients receiving gynecologic oncologic care at a tertiary referral center between 2017 – 2019 was conducted. Patients had either metastatic disease at the time of diagnosis or recurrence. Demographic and clinical data were abstracted. Exploratory analyses were done using chi-square and rank sum tests. Tests were two-sided with significance set at P < .05. Results A total of 186 patients were included. Of those, 82 (44.1%) were referred to palliative medicine. Underrepresented minorities accounted for 47.3% of patients. English was identified as the primary language for 69.9% of the patients and Spanish in 24.2%. Over 90% of patients had insurance coverage. Ovarian cancer (37.6%) and uterine cancer (32.8%) were the most common sites of origin. Most patients (75%) had advanced stage at the time of diagnosis. Race and language spoken were not associated with referral to PM. Black patients were more likely to have been prescribed appetite stimulants compared to White patients (41% vs 24%, P = .038). Black patients also had a higher number of emergency department visits compared to White patients during the study timeframe. Chemotherapy in the last 30 days of life was also more likely to be given to Black patients compared to White ( P = .019). Conclusions Race was associated with variation in interventions and healthcare utilization near end-of-life. Understanding the etiologies of these differences is crucial to inform interventions for care optimization as it relates specifically to the health of minority patients.
Pharmacokinetics and Dosing Regimens of Direct Oral Anticoagulants in Morbidly Obese Patients: An Updated Literature Review
Authors: Zhao Ying , Guo Mingxing , Li Dandan , Xu Wanyi , Pan Chen , He Chaoran , Cui Xiangli 
Published: February 2023

Data on the impact of morbid obesity (body mass index [BMI] ≥ 40 kg/m2) on the pharmacokinetics (PK), pharmacodynamics (PD) of direct oral anticoagulants (DOACs) are relatively limited, making it difficult to design optimal dosing regimens in morbidly obese patients. To review literature on PK/PD profile, efficacy, and safety of DOACs in venous thromboembolism (VTE) and nonvalvular atrial fibrillation (AF) patients with morbid obesity and make recommendations regarding optimal dosing regimens in these patient populations. A detailed literature search was conducted (from inception to June 22, 2022) for relevant articles involving PK/PD and clinical data on DOACs use in morbidly obese patients with VTE or AF, or healthy volunteers. A total of 28 studies were identified. DOAC-specific PK variations and clinical outcomes have been observed. Obesity may have a modest effect on PK/PD of dabigatran, apixaban, or rivaroxaban. Dabigatran was effective in AF patients with morbid obesity but might increase the risk of gastrointestinal bleeding. Standard dosing of apixaban or rivaroxaban is effective and safe for VTE and AF patients with morbid obesity. Trough edoxaban concentration and anti-Xa activity were similar in different BMI groups (18.5 to >40 kg/m2), and standard dosing of edoxaban may be effective and safe for AF patients. Current evidence suggests dabigatran should be used with caution in patients with AF as it might increase the risk of gastrointestinal bleeding; Standard dosing of apixaban or rivaroxaban can be used in VTE or AF patients; Standard dosing of edoxaban may be considered in AF patients.
Ribociclib-induced hepatotoxicity
Authors: Er Muhammed Muhiddin , Araz Murat , Hendem Engin , Eryılmaz Melek Karakurt , Artaç Mehmet 
Published: February 2023

Introduction Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown a different adverse effect. In this case, persistent grade 3 hepatoxicity was observed after ribociclib. Therefore, ribociclib therapy was stopped, and then palbociclib was introduced. Transaminase levels returned to normal by switching to palbociclib therapy. Case report 71-year-old postmenopausal female patient with luminal subtypes of metastatic breast cancer treated with ribociclib. Management & outcome Grade 3 hepatotoxicity secondary to ribociclib developed. She was successfully treated with palbociclib 125 mg. Discussion In our case, palbociclib was started with a full dose, to increase treatment success. Starting with a 125 mg dose was not cause any toxicity. Nevertheless, laboratory follow-up is required in terms of neutropenia and increased transaminases.
Anterior versus posterior retractor reinsertion with a lateral tarsal strip for involutional entropion repair: A multicentric experience
Authors: Mateos-Olivares Milagros , Belani-Raju Minal , Sánchez-Tocino Hortensia , Ye-Zhu Cristina , Sales-Sanz Marco , Bragante André , Fernandes de Sousa Meneghim Roberta Lilian , Schellini Silvana A. , Galindo Ferreiro Alicia 
Published: February 2023

Purpose The aim was the comparison of two different approaches to re-insert the inferior eyelid retractors within addition to lateral tarsal strip at lower eyelid involutional entropion (LEIE) surgical correction. Method This multicentric retrospective case series involved 233 consecutive patients (195 eyelids) who underwent LEIE repair. All the lids had a lateral tarsal strip (LTS) in addition to the reinsertion of retractors onto the tarsal plate via the anterior approach (group 1) or the posterior approach (group 2). The desired normal position of the eyelids at 6-month follow-up was considered ‘surgical successes, while entropion recurrence and overcorrection (ectropion) were considered ‘surgical failures’. Results One-hundred ninety-one (82%) surgeries were included in group 1 and 42 (18%) in group 2. The success rate was 92.1% (176 lids) in group 1 and 85.7% (36 lids) in group 2 (p = 0.188). The recurrence rate was statistically higher for group 2 (14.3%) than for group 1 (3.7%) (p = 0.016). Overcorrection only described in group 1 (3.1%). Both groups had a similar complication rate (p = 0.268), with trichiasis being the most frequent (14, 6%). Ten eyelids (47.6%) from the 21 overall failures were satisfactorily reoperated, and the remaining ones were treated conservatively. Conclusion The anterior or posterior approach to reinsert lower eyelid retractors to tarsal plate in addition to LTS to correct LEIE can provide a similar outcome. However, the anterior approach achieves a slightly higher success rate with fewer recurrences but with a higher overcorrection rate.
Sociodemographic Aspects and Healthy Behaviors Associated With Perceived Life Satisfaction in Health Professionals
Authors: Durand-Sanchez Esther , Ruiz-Alvarado Carlos , Contreras-Valderrama Ricardo , Morales-García Wilter C. , Mamani-Benito Oscar , Huancahuire-Vega Salomón , Saintila Jacksaint , Morales-García Mardel , Ruiz Mamani Percy G. 
Published: February 2023

Background: Life satisfaction is a determining factor for the improvement of mental and physical health. Health care workers are a vulnerable population to suffer alterations in the factors that affect life satisfaction. Determining the influence of these factors on quality of life is important for their proper management. Objective: To examine sociodemographic factors and healthy behaviors influencing life satisfaction in Peruvian professionals. Methods: A cross-sectional study was conducted with 506 health care workers, who had a mean age of 40.34 years (SD = 10.39). A sociodemographic questionnaire, sleep quality, physical activity, eating habits, and life satisfaction were used. A regression model was fitted with the life satisfaction variable as the dependent variable. Results: In multivariable analysis, age (β = −.938, P < .01) and perception of poor health status (β = −4.743, P < .001) were found to be associated with lower life satisfaction. On the other hand, higher university education level (β = 1.667, P < .001), absence of smoking (β = 3.202, P < .01), absence of depressive symptoms (β = 3.390, P < .001), interest in daily activities (β = 3.503, P < .05), good sleep quality (β = 1.027, P < .01), a high frequency of physical activity (β = 1.056, P < .01), and healthy eating are variables associated with higher life satisfaction. Conclusion: Sociodemographic aspects such as age and the perception of poor health are associated with lower life satisfaction. On the other hand, healthy behaviors such as absence of smoking, absence of depressive symptoms, interest in daily activities, good quality of sleep, high frequency of physical activity, and a healthy diet were associated with higher life satisfaction.
Opioid Sparing by ERAS Protocol in Cleft Lip and Palate Craniofacial Surgery
Authors: Thawanyarat Kometh , Waitt Taylor , Navarro Yelissa , Collar John , Doroodchi Atbin , Yu Jack 
Published: February 2023

Background: Enhanced Recovery After Surgery (ERAS) protocols have been shown to improve both clinical outcomes and cost savings in various perioperative settings. Our study focuses on the effects of ERAS protocol in craniomaxillofacial surgery in a single institution within 2 years leading up to and following implementation. The purpose of this research is to quantify the changes in effective pain management in pediatric patients undergoing craniomaxillofacial procedures before and after our ERAS protocol, which did not include IV acetaminophen. We hypothesize that ERAS protocol, even without IV acetaminophen, will provide effective pain management while decreasing the opioid use4 in the perioperative and postoperative period without associated complications from NSAID therapy. Methods: A retrospective chart review was conducted on 137 pediatric patients that underwent craniofacial surgery between July 1, 2014, and June 30, 2020. Patients were divided into 2 cohorts: Pre-ERAS and Post-ERAS with the implementation of ERAS on July 1, 2017. Results: Post-ERAS cohort showed increased NSAID use in the preoperative and postoperative period for both IV and PO ( P = .006 and P = .0064). Morphine use showed no immediate changes until a year after implementation with a statistically significant reduction ( P = .0051). When stratified by procedure type, IV NSAID (Ketorolac) use increased in Palatoplasty procedures ( P = .0154) while PO NSAID (Ibuprofen) use increased in Cleft Lip Repair ( P = .0224). Conclusion: ERAS protocol implementation can provide benefit for pediatric patients undergoing craniomaxillofacial surgery by decreasing opioid use, even in the absence of IV acetaminophen. Outcomes may potentially be delayed in the immediate post-implementation period. This study can add to the expanding literature for the use of ERAS protocol in craniomaxillofacial surgical settings. Further studies can include analyzing potential barriers to implementation and future complications related to ERAS long term outcomes.