Tag: pubmed

Prostate. 2022 Jun 8. doi: 10.1002/pros.24396. Online ahead of print.

ABSTRACT

BACKGROUND: Enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival versus ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in ARCHES (NCT02677896). While health-related quality of life (HRQoL) was generally maintained in the intent-to-treat population, we further analyzed patient-reported outcomes (PROs) in defined subgroups.

METHODS: ARCHES was a randomized, double-blind, placebo-controlled, phase 3 study. Patients with mHSPC received enzalutamide (160 mg/day) plus ADT (n = 574) or placebo plus ADT (n = 576). Questionnaires, including the Functional Assessment of Cancer Therapy-Prostate, Brief Pain Inventory-Short Form, and EuroQol 5-Dimension, 5-Level (EQ-5D-5L), were completed at baseline, Week 13, and every 12 weeks until disease progression. PRO endpoints were time to first confirmed clinically meaningful deterioration (TTFCD) in HRQoL or pain. Subgroups included prognostic risk, pain/HRQoL, prior docetaxel, and local therapy (radical prostatectomy [RP] and/or radiotherapy [RT]).

RESULTS: There were several between-treatment differences in TTFCD for pain and functioning/HRQoL PROs. Enzalutamide plus ADT delayed TTFCD for worst pain in the prior RT group (not reached vs. 14.06 months; hazard ratio [HR]: 0.56 [95% confidence interval: 0.34-0.94]) and pain interference in low-baseline-HRQoL group (19.32 vs. 11.20 months; HR: 0.64 [0.44-0.94]) versus placebo plus ADT. In prior/no prior RP, prior RT, prior local therapy, no prior docetaxel, mild baseline pain, and low-risk subgroups, TTFCD was delayed for the EQ-5D-5L visual analog scale.

CONCLUSION: Enzalutamide plus ADT provides clinical benefits in defined patient subgroups versus ADT alone, while maintaining lack of pain and high HRQoL, with delayed deterioration in several HRQoL measures.

PMID:35675470 | DOI:10.1002/pros.24396

Braz J Cardiovasc Surg. 2022 Jun 8. doi: 10.21470/1678-9741-2021-0027. Online ahead of print.

ABSTRACT

INTRODUCTION: A clear assessment of the bleeding risk score in patients presenting with myocardial infarction (MI) is crucial because of its impact on prognosis. The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA score is a validated risk score to predict bleeding risk in atrial fibrillation (AF), but its predictive value in predicting bleeding after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) patients receiving antithrombotic therapy is unknown. Our aim was to investigate the predictive performance of the ATRIA bleeding score in STEMI and NSTEMI patients in comparison to the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) and ACUITY-HORIZONS (Acute Catheterization and Urgent Intervention Triage strategY-Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) bleeding scores.

METHODS: A total of 830 consecutive STEMI and NSTEMI patients who underwent PCI were evaluated retrospectively. The ATRIA, CRUSADE, and ACUITY-HORIZONS risk scores of the patients were calculated. Discrimination of the three risk models was evaluated using C-statistics.

RESULTS: Major bleeding occurred in 52 (6.3%) of 830 patients during hospitalization. Bleeding scores were significantly higher in the bleeding patients than in non-bleeding patients (all P<0.001). The discriminatory ability of the ATRIA, CRUSADE, and ACUITY-HORIZONS bleeding scores for bleeding events was similar (C-statistics 0.810, 0.832, and 0.909, respectively). The good predictive value of all three scores for predicting the risk of bleeding was observed in NSTEMI and STEMI patients as well (C-statistics: 0.820, 0.793, and 0.921 and 0.809, 0.854, and 0.905, respectively).

CONCLUSION: This study demonstrated that the ATRIA bleeding score is a useful risk score for predicting major in-hospital bleeding in MI patients. This good predictive value was also present in STEMI and NSTEMI patient subgroups.

PMID:35675497 | DOI:10.21470/1678-9741-2021-0027

Fam Med. 2022 Jun;54(6):471-476. doi: 10.22454/FamMed.2022.319716.

ABSTRACT

BACKGROUND AND OBJECTIVES: Medical educators and researchers have increasingly sought to embed online educational modalities into graduate medical education, albeit with limited empirical evidence of how trainees perceive the value and experience of online learning in this context. The purpose of this study was to explore the experiences of hybrid learning in a graduate research methods course in a family medicine and primary care research graduate program.

METHODS: This qualitative description study recruited 28 graduate students during the fall 2016 academic term. Data sources included qualitative group discussions and a 76-item online survey collected between March and September 2017. We used thematic analysis and descriptive statistics to analyze each data set.

RESULTS: Nine students took part in three group discussions, and completed an online survey. While students reported positive learning experiences overall, those attending virtually struggled with the synchronous elements of the hybrid model. Virtual students reported developing research skills not offered through courses at their home institution, and students attending the course in person benefited from the diverse perspectives of distance learners. All stressed the need to foster a sense of community.

CONCLUSIONS: Quality delivery of online graduate education in family medicine research requires optimizing social exchanges among virtual and in-person learners, ensuring equitable engagement among all students, and leveraging the unique tools afforded by online platforms to create a shared sense of a learning community.

PMID:35675463 | DOI:10.22454/FamMed.2022.319716

Proc Natl Acad Sci U S A. 2022 Jun 14;119(24):e2121405119. doi: 10.1073/pnas.2121405119. Epub 2022 Jun 8.

ABSTRACT

Nonequilibrium interfacial thermodynamics has important implications for crucial biological, physical, and industrial-scale transport processes. Here, we discuss a theory of local equilibrium for multiphase multicomponent interfaces that builds upon the “sharp” interface concept first introduced by Gibbs, allowing for a description of nonequilibrium interfacial processes such as those arising in evaporation, condensation, adsorption, etc. By requiring that the thermodynamics be insensitive to the precise location of the dividing surface, one can identify conditions for local equilibrium and develop methods for measuring the values of intensive variables at the interface. We then use extensive, high-precision nonequilibrium molecular dynamics (NEMD) simulations to verify the theory and establish the validity of the local equilibrium hypothesis. In particular, we demonstrate that equilibrium equations of state are also valid out of equilibrium, and can be used to determine interfacial temperature and chemical potential(s) that are consistent with nonequilibrium generalizations of the Clapeyron and Gibbs adsorption equations. We also show, for example, that, far from equilibrium, temperature or chemical potential differences need not be uniform across an interface and may instead exhibit pronounced discontinuities. However, even in these circumstances, we demonstrate that the local equilibrium hypothesis and its implications remain valid. These results provide a thermodynamic foundation and computational tools for studying or revisiting a wide variety of interfacial transport phenomena.

PMID:35675427 | DOI:10.1073/pnas.2121405119

J Biopharm Stat. 2022 Jun 8:1-18. doi: 10.1080/10543406.2022.2080696. Online ahead of print.

ABSTRACT

In clinical studies that utilize real-world data, time-to-event outcomes are often germane to scientific questions of interest. Two main obstacles are the presence of non-proportional hazards and confounding bias. Existing methods that could adjust for NPH or confounding bias, but no previous work delineated the complexity of simultaneous adjustments for both. In this paper, a propensity score stratified MaxCombo and weighted Cox model is proposed. This model can adjust for confounding bias and NPH and can be pre-specified when NPH pattern is unknown in advance. The method has robust performance as demonstrated in simulation studies and in a case study.

PMID:35675418 | DOI:10.1080/10543406.2022.2080696

Acta Anaesthesiol Scand. 2022 Jun 8. doi: 10.1111/aas.14101. Online ahead of print.

ABSTRACT

BACKGROUND: In colorectal cancer, surgical resection is fundamental for curative treatment. Epidural analgesia mitigates the perioperative physiologic stress response caused by surgery, and reduction in perioperative stress may reduce postoperative complications. Nevertheless, epidural analgesia also causes hypotension and lower limb motor weakness that can impair postoperative recovery. Here, we aimed to assess the association between epidural analgesia and postoperative complications after colorectal cancer surgery.

METHODS: We identified patients undergoing colorectal cancer surgery 2008-2018 in Denmark in the Danish Colorectal Cancer Group Database and obtained anaesthesia data from the Danish Anaesthesia Database. The Danish National Prescription Registry was used to obtain data on prescriptions filled preoperatively reflecting current comorbidities. Databases were linked using the Danish Central Person Registry number and the operation day. Patients were classified according to preoperative insertion of an epidural catheter for analgesia. Confounders were adjusted by propensity score matching. Logistic regression was used to compute effect estimates of epidural analgesia on postoperative complications.

RESULTS: We identified 19932 individuals undergoing colorectal cancer surgery with available anaesthesia data. Propensity score matching yielded 5691 individuals in each group with balanced preoperative covariates. In the epidural analgesia group 1400 (24.6%) experienced complications compared with 1453 (25.5%) without epidural analgesia. We found no statistically significant association between epidural use and postoperative complications (OR 0.95, 95% CI 0.87-1.04).

CONCLUSION: In total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery.

PMID:35675388 | DOI:10.1111/aas.14101

PLoS One. 2022 Jun 8;17(6):e0268534. doi: 10.1371/journal.pone.0268534. eCollection 2022.

ABSTRACT

BACKGROUND: The clinical implementation of pharmacogenomics (PGx) could be one of the first milestones towards realizing personalized medicine in routine care. However, its widespread adoption requires the availability of suitable clinical decision support (CDS) systems, which is often impeded by the fragmentation or absence of adequate health IT infrastructures. We report results of CDS implementation in the large-scale European research project Ubiquitous Pharmacogenomics (U-PGx), in which PGx CDS was rolled out and evaluated across more than 15 clinical sites in the Netherlands, Spain, Slovenia, Italy, Greece, United Kingdom and Austria, covering a wide variety of healthcare settings.

METHODS: We evaluated the CDS implementation process through qualitative and quantitative process indicators. Quantitative indicators included statistics on generated PGx reports, median time from sampled upload until report delivery and statistics on report retrievals via the mobile-based CDS tool. Adoption of different CDS tools, uptake and usability were further investigated through a user survey among healthcare providers. Results of a risk assessment conducted prior to the implementation process were retrospectively analyzed and compared to actual encountered difficulties and their impact.

RESULTS: As of March 2021, personalized PGx reports were produced from 6884 genotyped samples with a median delivery time of twenty minutes. Out of 131 invited healthcare providers, 65 completed the questionnaire (response rate: 49.6%). Overall satisfaction rates with the different CDS tools varied between 63.6% and 85.2% per tool. Delays in implementation were caused by challenges including institutional factors and complexities in the development of required tools and reference data resources, such as genotype-phenotype mappings.

CONCLUSIONS: We demonstrated the feasibility of implementing a standardized PGx decision support solution in a multinational, multi-language and multi-center setting. Remaining challenges for future wide-scale roll-out include the harmonization of existing PGx information in guidelines and drug labels, the need for strategies to lower the barrier of PGx CDS adoption for healthcare institutions and providers, and easier compliance with regulatory and legal frameworks.

PMID:35675343 | DOI:10.1371/journal.pone.0268534

Genome Biol Evol. 2022 Jun 8:evac088. doi: 10.1093/gbe/evac088. Online ahead of print.

ABSTRACT

As both natural selection and population history can affect genome-wide patterns of variation, disentangling the contributions of each has remained as a major challenge in population genetics. We here discuss historical and recent progress towards this goal – highlighting theoretical and computational challenges that remain to be addressed, as well as inherent difficulties in dealing with model complexity and model violations – and offer thoughts on potentially fruitful next steps.

PMID:35675379 | DOI:10.1093/gbe/evac088

Vet Surg. 2022 Jun 8. doi: 10.1111/vsu.13837. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the mechanical characteristics of a novel angle-stable interlocking nail (NAS-ILN) and compare them to those of a locking compression plate (LCP) by using a gap-fracture model.

STUDY DESIGN: Experimental study.

SAMPLE POPULATION: Synthetic bone models.

METHODS: Synthetic bone models simulating a 50 mm diaphyseal comminuted canine tibial fracture were treated with either a novel angle-stable interlocking nail (NAS-ILN) or a locking compression plate (LCP). Maximal axial deformation and load to failure in compression and 4-point bending, as well as maximal angular deformation, slack, and torque to failure in torsion, were statistically compared (P < .05).

RESULTS: In compression, the maximal axial deformation was lower for NAS-ILN (0.11 mm ± 0.03) than for LCP (1.10 mm ± 0.22) (P < .0001). The ultimate load to failure was higher for NAS-ILN (803.58 N ± 29.52) than for LCP (328.40 N ± 11.01) (P < .0001). In torsion, the maximal angular deformation did not differ between NAS-ILN (22.79° ± 1.48) and LCP (24.36° ± 1.45) (P = .09). The ultimate torque to failure was higher for NAS-ILN (22.45 Nm ± 0.24) than for LCP (19.10 Nm ± 1.36) (P = .001). No slack was observed with NAS-ILN. In 4-point bending, the maximal axial deformation was lower for NAS-ILN (3.19 mm ± 0.49) than for LCP (4.17 mm ± 0.34) (P = .003). The ultimate bending moment was higher for NAS-ILN (25.73 Nm, IQR [23.54-26.86] Nm) than for LCP (16.29 Nm, IQR [15.66-16.47] Nm) (P = .002).

CONCLUSION: The NAS-ILN showed greater stiffness in compression and 4-point bending, and a greater resistance to failure in compression, torsion, and 4-point bending, than LCP.

CLINICAL IMPACT: Based on these results, NAS-ILNs could be considered as alternative implants for the stabilization of comminuted fractures.

PMID:35675144 | DOI:10.1111/vsu.13837

Clin Nucl Med. 2022 Jul 1;47(7):575-582. doi: 10.1097/RLU.0000000000004190. Epub 2022 Apr 27.

ABSTRACT

PURPOSE: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG.

PATIENTS AND METHODS: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs.

RESULTS: Of the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10-4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10-5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area.

CONCLUSIONS: Detecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

PMID:35675134 | DOI:10.1097/RLU.0000000000004190