Gender Disparities in Mentorship and Career Outcomes in Ophthalmology.

Background: Gender disparities in the field of ophthalmology have been increasingly recognized. Although mentorship has been proposed as a contributing factor, there are limited data on the differences in mentorship experiences by gender among ophthalmologists. Objective: The purpose of this study was to evaluate gender disparities in mentorship experiences among ophthalmologists, and the impact of mentorship disparities on career outcomes. Design: Prospective, cross-sectional study. Setting: Web-based survey distributed through ophthalmology listservs. Participants: Ophthalmologists and ophthalmologists-in-training who completed the survey. Exposure: Training and practicing in the field of ophthalmology. Main Outcome Measures: Mentorship score based on 10 items from a previously published scale of mentorship quality and self-reported career outcomes (income, job satisfaction, achievement of career goals, and support to achieve future career goals). Results: We received survey responses from 202 male and 245 female ophthalmologists. Female ophthalmologists reported significantly lower mentorship satisfaction and worse quality of mentorship (p < 0.03). Female ophthalmologists also reported significantly lower income, worse job satisfaction, and lower rates of goal achievement and support to achieve future goals; all of these career outcomes, except income level, were partly mediated by mentorship score (mediation effect ranged from 29% to 68%, p < 0.014). Conclusions and Relevance: Gender-based inequities in achievement of career goals and job satisfaction are partly mediated by disparities in mentorship. Therefore, focused mentorship of women in ophthalmology at all career stages is imperative to reduce these inequities.

Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor.

INTRODUCTION: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) often require multiple lines of treatment and have a poor prognosis, particularly after failing covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. Newer treatments such as brexucabtagene autoleucel (brexu-cel, chimeric antigen receptor T cell therapy) and pirtobrutinib (non-covalent BTKi) show promise in improving outcomes. METHODS: Without direct comparative evidence, an unanchored matching-adjusted indirect comparison was conducted to estimate the relative treatment effects of brexu-cel and pirtobrutinib for post-cBTKi R/R MCL. Using logistic propensity score models, individual patient-level data from ZUMA-2 brexu-cel-infused population (N = 68) were weighted to match pre-specified clinically relevant prognostic factors based on study-level data from the BRUIN cBTKi pre-treated cohort (N = 90). The base-case model incorporated the five most pertinent factors reported in ≥ 50% of both trial populations: morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplant. A sensitivity analysis additionally incorporated TP53 mutation and Ki-67 proliferation. Relative treatment effects were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: In the base-case model, brexu-cel was associated with higher rates of objective response (OR 10.39 [95% CI 2.81-38.46]) and complete response (OR 10.11 [95% CI 4.26-24.00]), and improved progression-free survival (HR 0.44 [95% CI 0.25-0.75]), compared to pirtobrutinib. Overall survival and duration of response favored brexu-cel over pirtobrutinib but the differences crossed the bounds for statistical significance. Findings were consistent across the adjusted and unadjusted analyses. CONCLUSIONS: Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

Stakeholder perspectives on electronic prescribing in primary care: A scoping review.

BACKGROUND: Electronic prescribing (e-prescribing) provides a convenient, efficient, paperless mechanism for the legal transfer of prescriptions between service users, prescribers, and dispensers. There have been advances in e-prescribing processes and increased uptake of e-prescribing globally, in recent years. OBJECTIVE: To explore stakeholder perspectives on e-prescribing in primary care settings. METHODS: A scoping review was conducted by systematically searching Medline, EMBASE, Scopus, and International Pharmaceutical Abstracts databases, using the key concepts "primary care", "e-prescribing", and "perspectives". Publications were selected by screening for eligibility against inclusion and exclusion criteria, whereby any publication written in English exploring e-prescribing in primary care settings from the perspective(s) of at least one type of stakeholder was eligible for inclusion. Following a systematic screening process, relevant data were extracted, collated, and synthesized. RESULTS: Two thousand publications were identified and systematically screened, rendering 44 publications (e.g., primary research articles, abstracts) eligible for inclusion in this review. Most publications reported on studies conducted in the USA, the UK, and Europe and explored the views of pharmacists, pharmacy technicians, and pharmacy staff. Barriers to e-prescribing included system design and technical issues, lack of adequate training and communication issues between stakeholders. Enablers for e-prescribing included time savings, convenience, and increased legibility of prescriptions. CONCLUSIONS: This review highlights many benefits of e-prescribing such as time efficiency, convenience, increased legibility, and less mishandling. Despite this, key barriers to e-prescribing within primary care settings were also recognized, including system design, technical issues, and lack of adequate training. As such, forcing functions, prescription tracking technologies, and better training have been identified as potential ways to address these barriers. While some negative experiences were reported, stakeholders were generally satisfied and had positive experiences with e-prescribing.

Research Progress on the Antitumor Molecular Mechanism of Ginsenoside Rh2.

Cancer has evolved into a substantial public health concern as the second-leading cause of mortality globally. Radiotherapy and chemotherapy have been the two most widely used cancer therapies in recent years; however, both have drawbacks. Therefore, the focus has shifted to the creation of herbal medicines, the extraction of active ingredients, replacement therapy, and the adverse effects of these medications. Ginsenoside Rh2, which is extracted from ginseng, has been identified in many cancer cells. The immune system of the body is strengthened by ginsenoside Rh2, which can also cause the proliferation, death, and differentiation of tumor cells through various pathways. For instance, it inhibits the expression of the NF-[Formula: see text]B signaling pathway and induces cell apoptosis, affects the expression levels of mitochondrial apoptosis proteins Bcl-2 and Bax, and cooperates with the PD-1 blockade to reactivate T cells to promote an antitumor immune response. Furthermore, ginsenosides Rh2 has the effect of reversing the toxic effect of chemotherapy drugs on normal cells, reducing myocardial damage, and relieving bone marrow function suppression. For clinical applications, it is mainly used as an adjuvant drug for preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and rescue treatment of advanced cancer. This paper summarizes the pharmacological action and mechanism of ginsenosides Rh2 in all kinds of cancer and looks forward to its future development and application.

Evolution of gene expression across brain regions in behaviourally divergent deer mice.

The evolution of innate behaviours is ultimately due to genetic variation likely acting in the nervous system. Gene regulation may be particularly important because it can evolve in a modular brain-region specific fashion through the concerted action of cis- and trans-regulatory changes. Here, to investigate transcriptional variation and its regulatory basis across the brain, we perform RNA sequencing (RNA-Seq) on ten brain subregions in two sister species of deer mice (Peromyscus maniculatus and P. polionotus)-which differ in a range of innate behaviours, including their social system-and their F1 hybrids. We find that most of the variation in gene expression distinguishes subregions, followed by species. Interspecific differential expression (DE) is pervasive (52-59% of expressed genes), whereas the number of DE genes between sexes is modest overall (~3%). Interestingly, the identity of DE genes varies considerably across brain regions. Much of this modularity is due to cis-regulatory divergence, and while 43% of genes were consistently assigned to the same gene regulatory class across subregions (e.g. conserved, cis- or trans-regulatory divergence), a similar number were assigned to two or more different gene regulatory classes. Together, these results highlight the modularity of gene expression differences and divergence in the brain, which may be key to explain how the evolution of brain gene expression can contribute to the astonishing diversity of animal behaviours.

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Diabetes, Hypertension, and Smoking Do Not Affect Outcomes of Iliofemoral Vein Stenting for Chronic Proximal Venous Outflow Obstruction.

BACKGROUND: Diabetes, hypertension, and smoking are well-recognized risk factors for peripheral artery disease (PAD), but little is known of their impact on chronic venous insufficiency (CVI). This study evaluates these factors in patients undergoing iliac vein stenting (IVS) for CVI. METHODS: A registry of 708 patients who underwent IVS from August 2011 to June 2021 was retrospectively analyzed. Symptoms were quantified using venous clinical severity score (VCSS) and CEAP classification. Both major and minor reinterventions were recorded. Logistic regression models were used to determine the unadjusted and adjusted odds ratio of any reintervention. Log-rank test was used to assess differences in reintervention-free survival. RESULTS: The prevalence of hypertension was 51.1% (N = 362), diabetes was 23.0% (N = 163), and smoking was 22.2% (N = 157). Patients with diabetes (3.6 vs. 3.4; P = 0.062), hypertension (3.6 vs. 3.3; P < 0.001), and smoking (3.7 vs. 3.4; P = 0.003) had higher CEAP scores than those without these comorbidities. Improvement in VCSS composite scores showed no differences postoperatively (diabetes: P = 0.513; hypertension: P = 0.053; smoking: P = 0.608), at 1-year follow-up (diabetes: P = 0.666; hypertension: P = 0.681; smoking: P = 0.745), or at 5-year follow-up (diabetes: P = 0.525; hypertension: P = 0.953; smoking: P = 0.146). Diabetes (P = 0.454), smoking (P = 0.355), and hypertension (P = 0.727) were not associated with increased odds of major reintervention. Log-rank test similarly showed no differences in reintervention-free survival for major or minor reoperations between those with and without diabetes (P = 0.79), hypertension (P = 0.14), and smoking (P = 0.80). CONCLUSIONS: Diabetes, hypertension, and smoking were prevalent among CVI patients, but unlike in PAD patients, they had little to no impact on long-term outcomes or reinterventions after IVS.

Associations of neutral pH, low-GDP peritoneal dialysis solutions with patient survival, transfer to haemodialysis and peritonitis.

BACKGROUND: Peritoneal dialysis (PD) solutions containing low levels of glucose degradation products (GDPs) are associated with attenuation of peritoneal membrane injury and vascular complications. However, clinical benefits associated with neutral-pH, low-GDP (N-pH/L-GDP) solutions remain unclear. METHODS: Using data from the Australia and New Zealand Dialysis and Transplant Registry, we examined the associations between N-pH/L-GDP solutions and all-cause mortality, cause-specific mortality, transfer to haemodialysis (HD) for ≥30 days and PD peritonitis in adult incident PD patients in Australia and New Zealand between 1 January 2005 and 31 December 2020 using adjusted Cox regression analyses. RESULTS: Of 12 814 incident PD patients, 2282 (18%) were on N-pH/L-GDP solutions. The proportion of patients on N-pH/L-GDP solutions each year increased from 11% in 2005 to 33% in 2017. During the study period, 5330 (42%) patients died, 4977 (39%) experienced transfer to HD and 5502 (43%) experienced PD peritonitis. Compared with the use of conventional solutions only, the use of any form of N-pH/L-GDP solution was associated with reduced risks of all-cause mortality {adjusted hazard ratio [aHR] 0.67 [95% confidence interval (CI) 0.61-0.74]}, cardiovascular mortality [aHR 0.65 (95% CI 0.56-0.77)], infection-related mortality [aHR 0.62 (95% CI 0.47-0.83)] and transfer to HD [aHR 0.79 (95% CI 0.72-0.86)] but an increased risk of PD peritonitis [aHR 1.16 (95% CI 1.07-1.26)]. CONCLUSIONS: Patients who received N-pH/L-GDP solutions had decreased risks of all-cause and cause-specific mortality despite an increased risk of PD peritonitis. Studies assessing the causal relationships are warranted to determine the clinical benefits of N-pH/L-GDP solutions.

Association Between Hearing Difficulty and Mobility in Adults of All Ages: National Health Interview Survey.

OBJECTIVE: To investigate the relationship between hearing difficulty and measures of mobility for US adults. STUDY DESIGN: Cross-sectional study. SETTING: 2021 National Health Interview Survey. METHODS: The survey asked US adults about hearing difficulty and mobility measures, including difficulty walking 100 yards, difficulty climbing 12 steps, and injury from falling within the past 3 months. Multivariable logistic regressions examined the associations between hearing and mobility outcomes, controlling for visual difficulty, medical comorbidities, and various demographic characteristics (age [18-39, 40-64, 65+], race/ethnicity, sex, socioeconomic status). RESULTS: The 2021 NHIS surveyed 29,467 adults, representing 253 million people in weighted responses (52% female; mean age 48.3, standard deviation = 18.6). Controlling for covariates, hearing difficulty was associated with increased odds of difficulty walking 100 yards (odds ratio, OR = 1.47, P < .001), difficulty climbing stairs (OR = 1.62, P < .001), and injury from falling in the past 3 months (OR = 1.51, P < .001). There was a significant interaction between age and hearing difficulty for injurious falls; stratifying by age revealed that younger adults (ages 18-39) with hearing difficulty were more likely to report recent harmful falls than their normal hearing peers; this increased risk was greater in magnitude than that observed comparing older adults with and without hearing difficulty. CONCLUSION: The hearing difficulty is associated with worsened mobility for US adults and may be a stronger independent predictor of injury from falls for younger adults as compared to older adults. These findings can inform interventions to reduce the burden of declining mobility in adults with hearing difficulty.

Noninvasive cardiac radioablation for ventricular tachycardia: dosimetric comparison between linear accelerator- and robotic CyberKnife-based radiosurgery systems.

BACKGROUND: Few dosimetric comparisons have been published between linear accelerator (LA)-based systems and CyberKnife (CK)-based robotic radiosurgery systems for cardiac radio-ablation in ventricular tachycardia. This study aimed to compare the dosimetry of noninvasive cardiac radio-ablation deliverable on LA with that on CK. METHODS: Thirteen patients who underwent noninvasive cardiac radio-ablation by LA were included. The prescribed dose was 25 Gy in 1 fraction, and the average planning target volume was 49.8 ± 31.0 cm3 (range, 14.4-93.7 cm3). CK plans were generated for comparison. RESULTS: Both the CK and LA plans accomplished appropriate dose coverage and normal tissue sparing. Compared with the LA plans, the CK plans achieved significantly lower gradient indices (3.12 ± 0.71 vs. 3.48 ± 0.55, p = 0.031) and gradient measures (1.00 ± 0.29 cm vs. 1.17 ± 0.29 cm, p < 0.001). They had similar equivalent conformity indices (CK vs. LA: 0.84 ± 0.08 vs. 0.87 ± 0.07, p = 0.093) and maximum doses 2 cm from the planning target volume (PTV) in any direction (CK vs. LA: 50.8 ± 9.9% vs. 53.1 ± 5.3%, p = 0.423). The dosimetric advantages of CK were more prominent in patients with a PTV of ≤ 50 cm3 or a spherical PTV. In patients with a PTV of > 50 cm3 or a non-spherical PTV, the LA and CK plans were similar regarding dosimetric parameters. CK plans involved more beams (232.2 ± 110.8 beams vs. 10.0 ± 1.7 arcs) and longer treatment times (119.2 ± 43.3 min vs. 22.4 ± 1.6 min, p = 0.007). CONCLUSIONS: Both CK and LA are ideal modalities for noninvasive cardiac radio-ablation. Upfront treatment should be considered based on clinical intent.

Prognostic nutritional index and neutrophil-lymphocyte ratio predict toxicities and prognosis in patients with cervical cancer treated with curative radiochemotherapy.

BACKGROUND: This study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. METHODS: Patients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. RESULTS: Among the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (<49.5) or high NLR (>2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. CONCLUSIONS: Pretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Matching-Adjusted Indirect Comparisons of Brexucabtagene Autoleucel with Alternative Standard Therapies for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients.

INTRODUCTION: Brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, is approved for relapsed/refractory B-cell precursor acute lymphoblastic leukemia in adults aged 18+/26+ years in the US/European Union (EU), based on efficacy results from the single-arm ZUMA-3 trial. This study aimed to estimate the relative treatment effects of brexu-cel versus inotuzumab ozogamicin (InO), blinatumomab (blina), and chemotherapies using unanchored matching-adjusted indirect comparison (MAIC) methods. METHODS: Individual patient data from ZUMA-3 and published aggregate level data from two randomized controlled trials, INO-VATE (InO versus chemotherapy) and TOWER (blina versus chemotherapy), were used. Patient-level data from ZUMA-3 were weighted to match the mean of the following prognostic variables at baseline, which were pre-specified based on clinical input, for each comparator population: primary refractory disease, duration of first remission < 12 months, prior stem-cell transplantation, age, performance status, salvage status, bone marrow blast, complex karyotype, and Philadelphia chromosome status. The base case analysis was conducted using the modified intention-to-treat population (i.e., received brexu-cel) from ZUMA-3. Relative treatment effects for overall survival (OS) and event-free survival (EFS) were expressed as hazard ratios (HR) and differences in restricted mean survival time (RMST) with 95% confidence intervals (CI). RESULTS: The base case MAIC results suggested brexu-cel improved OS and EFS compared to blina (OS HR 0.46 [95% CI 0.28, 0.75]; EFS HR 0.37 [95% CI 0.25, 0.56]) and pooled INO-VATE/TOWER chemotherapy (OS HR 0.32 [95% CI 0.18, 0.56]; EFS HR 0.27 [0.18, 0.40]). Brexu-cel also improved OS compared to InO (HR 0.45 [95% CI 0.24, 0.85]). The point estimate for EFS favored brexu-cel over Ino but the difference was not statistically significant (HR 0.67 [95% CI 0.41, 1.10]). Findings were consistent between the HR and RMST analyses. CONCLUSION: Despite limitations, these MAIC results suggest that brexu-cel may improve OS and EFS versus currently used therapies in this population.

PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.

RATIONALE AND OBJECTIVES: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer. MATERIALS AND METHODS: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [18F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival. RESULTS: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin, ADCmean, and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033). CONCLUSION: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS.

Healthcare professionals' knowledge, confidence and attitudes in relation to psychosis care: A systematic review.

BACKGROUND: Psychosis is a mental disorder that, despite its low prevalence, causes high disease and economic burden. Inadequate knowledge, lack of confidence and stigmatising attitudes of healthcare professionals (HCPs) may lead to suboptimal care. AIM: To review the literature exploring HCPs' knowledge, confidence and attitudes in relation to psychosis care. METHOD: A systematic search was undertaken across three databases (MEDLINE, Embase, PsycINFO) using a search strategy encompassing the concepts: 'healthcare professionals', 'knowledge, attitude, and confidence in care' and 'psychotic illnesses and symptoms' to identify relevant records published from 1st January 2002 to 18th March 2022. Results were screened against predetermined inclusion and exclusion criteria by title and abstract, followed by full text. Data were extracted into tables and synthesised narratively. RESULTS: Initially, 7,397 studies were identified. Following two-stage screening, 24 studies were eligible for inclusion. Of these studies, 16 explored attitudes, four explored knowledge and attitudes, one explored knowledge, one explored confidence, one explored attitudes and confidence in care and one explored all three constructs. Most HCPs in the included studies demonstrated stigmatising attitudes towards people with psychosis. Furthermore, certain HCPs, including nurses and general practitioners, demonstrated low levels of knowledge, while psychiatrists, occupational therapists, psychologists and nurses had low levels of confidence in caring for people with psychosis. Conversely, positive attitudes were also observed in some HCPs resulting from having acquaintances with lived experience of psychosis. The need for additional education and training to improve HCPs' knowledge and confidence in relation to caring for people living with psychosis was identified. CONCLUSIONS: Most attitudes identified were negative and stemmed from stigma, while some were positive due to HCPs' compassion and familiarity with psychosis. The level of knowledge and confidence identified were mostly suboptimal, and so further research is required to develop and evaluate tailored interventions to address this gap.

Mapping tissue microstructure of brain white matter in vivo in health and disease using diffusion MRI.

Diffusion magnetic resonance imaging offers unique in vivo sensitivity to tissue microstructure in brain white matter, which undergoes significant changes during development and is compromised in virtually every neurological disorder. Yet, the challenge is to develop biomarkers that are specific to micrometer-scale cellular features in a human MRI scan of a few minutes. Here we quantify the sensitivity and specificity of a multicompartment diffusion modeling framework to the density, orientation and integrity of axons. We demonstrate that using a machine learning based estimator, our biophysical model captures the morphological changes of axons in early development, acute ischemia and multiple sclerosis (total N=821). The methodology of microstructure mapping is widely applicable in clinical settings and in large imaging consortium data to study development, aging and pathology.

Competency-based medical education in the United States: What the otolaryngologist needs to know.

Competency-based medical education (CBME) is an outcomes-focused approach to educating medical professionals that will be central to future efforts to improve resident training in otolaryngology. The transition to CBME for otolaryngology in the United States will require the development of specialty-specific assessments and benchmarks, the financial and administrative support for implementation, the professional development of faculty and learners, and the cooperation of all major stakeholders in graduate medical education. In this article, we describe the need for evidence-based innovation in surgical training, the history of CBME in the United States, and the progress towards defining "entrustable professional activities" as the building blocks of assessments for CBME. We explore what such a paradigm shift in surgical education could mean for academic otolaryngologists by examining innovative educational practices in other surgical specialties and discussing foreseeable challenges in implementation for the American healthcare system.

A Pilot Randomized Trial of a Purposeful and Stimulating Volunteer Opportunity: Program Satisfaction and Potential Impacts on Perceived Cognitive Change in a Neurologically Mixed Sample of Older Adults.

BACKGROUND: Purposeful social interactions are important for healthy aging. We conducted a pilot trial of SPEAK! (Seniors Promoting English Acquisition and Knowledge), an intervention providing older volunteers with a safe, accessible opportunity to converse via webcam with English-language learners. METHODS: A neurologically mixed sample of older adults was randomized to 8 weekly, webcam conversations with English-language learners or a waitlist control. Outcomes included the Cognitive Change Index (CCI) and surveys of program satisfaction. Here, we report on session completion, intervention satisfaction, and follow-up CCI scores. Exploratory analyses of CCI intervention effects controlled for baseline CCI scores and the interaction between group and baseline CCI. RESULTS: Participants (N=38) were on average 70.8 years of age, 28/38 were White, and 16/38 demonstrated possible cognitive impairment on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Pairs completed 115/136 sessions (85%) and all volunteers said they would recommend the program. Controlling for the interaction between baseline CCI and randomization group, SPEAK! volunteers had better follow-up CCI scores than controls (P=0.018). Improvements in CCI were greater among participants with fewer baseline memory problems. CONCLUSIONS: SPEAK! was feasible and appreciated by older adults with and without cognitive impairment. Larger studies should confirm benefits for memory and other determinants of quality of life.

Identifying venous clinical severity score thresholds for Clinical-Etiology-Anatomy-Pathophysiology classifications of venous edema and higher.

OBJECTIVE: Venous Clinical Severity Score (VCSS) is a widely used standard for assessing and grading the severity of chronic venous disease (CVD). Prior research highlighted its high validity in detecting and quantifying venous disease. However, there is little, if any, known about the precise thresholds at which VCSS discriminates important stages of deep venous disease. This study sought to elucidate the diagnostic accuracy, thresholds, and correlation at which VCSS detects salient CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classes in deep venous disease progression. METHODS: A registry of 840 patients who presented with chronic proximal venous outflow obstruction (PVOO) secondary to non-thrombotic iliac vein lesions from August 2011 to June 2021 was retrospectively analyzed. VCSS and CEAP classifications were used to evaluate preoperative symptoms. VCSS was compared to CEAP classes to determine the precise VCSS composite values at which the instrument was able to detect CEAP C3 and higher, C4 and higher, and C5 and higher. Receiver operative characteristic (ROC) curve and area under the curve (AUC) were used to evaluate VCSS for its ability to discriminate disease at these stages of CEAP classification. Spearman's rank coefficient was used to determine the correlation between CEAP VCSS composite as well as individual VCSS components (pain, varicose vein, edema, pigmentation, inflammation, induration, ulcer number, ulcer size, ulcer duration, compression). RESULTS: VCSS composite was able to detect venous edema (C3) and higher at a sensitivity of 68.9% and a specificity of 54.8% at an optimized threshold of 8.5 (AUC = 0.648; 95% C.I. = 0.575-0.721). To detect changes in skin and subcutaneous tissue from CVD (C4) and higher, an optimal threshold of 11.5 was found with a sensitivity of 51.7% and specificity of 76.5% (AUC = 0.694; 95% C.I. = 0.656-0.731). Healed venous ulcer (C4) and higher was detectable at an optimized threshold of 13.5 at a sensitivity of 67.7% and a specificity of 88.9% (AUC = 0.819; 95% C.I. = 0.766-0.873). The correlation between VCSS composites and CEAP was weak (ρ = 0.372; p < .001). Attributes of VCSS that reflect more severe venous disease correlated more closely with CEAP classes, namely pigmentation (ρ = 0.444; p < .001), inflammation (ρ = 0.348; p < .001), induration (ρ = 0.352; p < .001), number of active ulcers (ρ = 0.497; p < .001), active ulcer size (ρ = 0.485; p < .001), and ulcer duration (ρ = 0.497; p < .001). The correlation between CEAP class and the other four components of VCSS were not statistically significant. CONCLUSION: VCSS composite thresholds of 8.5, 11.5, and 13.5 are threshold values for detecting CEAP classification C3 and higher, C4 and higher, and C5 and higher, respectively. Consistent with prior work, VCSS appears to have a better ability to discriminate CVD at more severe CEAP classifications. In this registry, the correlation between VCSS and CEAP was found to be weak while components of VCSS that suggest more advanced disease exhibited the strongest correlation with CEAP.