Nevin Manimala

J Theor Biol. 2023 Aug 7:111592. doi: 10.1016/j.jtbi.2023.111592. Online ahead of print.

ABSTRACT

There has been an increasing recognition of the utility of models of the spatial dynamics of viral spread within tissues. Multicellular models, where cells are represented as discrete regions of space coupled to a virus density surface, are a popular approach to capture these dynamics. Conventionally, such models are simulated by discretising the viral surface and depending on the rate of viral diffusion and other considerations, a finer or coarser discretisation may be used. The impact that this choice may have on the behaviour of the system has not been studied. Here we demonstrate that under realistic parameter regimes – where viral diffusion is small enough to support the formation of familiar ring-shaped infection plaques – the choice of spatial discretisation of the viral surface can qualitatively change key model outcomes including the time scale of infection. Importantly, we show that the choice between implementing viral spread as a cell-scale process, or as a high-resolution converged PDE can generate distinct model outcomes, which raises important conceptual questions about the strength of assumptions underpinning the spatial structure of the model. We investigate the mechanisms driving these discretisation artefacts, the impacts they may have on model predictions, and provide guidance on the design and implementation of spatial and especially multicellular models of viral dynamics. We obtain our results using the simplest TIV construct for the viral dynamics, and therefore anticipate that the important effects we describe will also influence model predictions in more complex models of virus-cell-immune system interactions. This analysis will aid in the construction of models for robust and biologically realistic modelling and inference.

PMID:37558160 | DOI:10.1016/j.jtbi.2023.111592

Swiss Med Wkly. 2023 Aug 9;153:40098. doi: 10.57187/smw.2023.40098.

ABSTRACT

BACKGROUND: Addressing the current demographic development, the efficacy and safety of kidney transplantations from very senior donors needs to be carefully evaluated. The aim of this study was to analyse patient and graft outcomes of kidney allograft recipients stratified by donor age.

METHODS: We retrospectively investigated n = 491 patients from a prospective, observational renal transplant cohort. Patients with kidneys from very old donors (n = 75, aged >70 years), elderly donors (n = 158, between 60-70 years), and regular donors (n = 258, aged <60 years) were investigated. The primary outcome was death-censored graft survival within the predefined donor age groups.

RESULTS: Overall, n = 57 death-censored graft losses occurred. Graft loss was proportionally highest in the very old donor group (n = 11/75), but this did not reach statistical significance when compared to the elderly (14/158) and regular donor groups (32/258); (p = 0.37). Kaplan-Meier analysis demonstrated that 3-year/5-year death-censored graft survival in the very old donor group was 96%/86% and did not differ from the other age groups (p = 0.44). Median estimated glomerular filtration rate (eGFR), calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula (in ml/min/1.73 m2 of body surface) 12 months post-transplant did not differ between the elderly donor and very old donor groups (p = 0.53). However, patients who received regular donor kidneys had higher median eGFR compared to recipients in both the elderly and very old donor groups (p <0.0001). During follow-up, 31% of patients developed at least one acute rejection episode. Time-to-event analysis demonstrated no difference in occurrence of any acute rejection event across all three groups (p = 0.11).

CONCLUSIONS: This study demonstrates that kidney transplantation from carefully selected very old donors seems a valid option with reasonable short- and mid-term outcomes.

PMID:37556837 | DOI:10.57187/smw.2023.40098

Aesthet Surg J. 2023 Aug 10:sjad251. doi: 10.1093/asj/sjad251. Online ahead of print.

ABSTRACT

BACKGROUND: People of color (POC) are often underrepresented in clinical studies evaluating the safety and effectiveness of aesthetic products, including hyaluronic acid (HA) fillers, which to date have limited clinical data in POC.

OBJECTIVE: To assess the safety and effectiveness of a new line of dynamic HA fillers (RHA®, Revance, Nashville TN) for treating moderate-to-severe nasolabial folds (NLF) in POC versus non-POC.

METHODS: Post hoc subgroup analyses compared the efficacy and safety of POC versus non-POC subjects treated with RHA2, RHA3, or RHA4 for correction of moderate-to-severe nasolabial folds in the pooled Per Protocol population (N=217) in two clinical trials. Evaluated population cohorts were classified by Fitzpatrick Skin Type (FST) [high FST (IV-VI) versus low FST (I-III)] and by subject-reported race (non-White versus White) relative to baseline at 6, 9, 12, and 15 months.

RESULTS: POC consistently showed greater improvement in wrinkle severity and higher responder rates compared to non-POC, which reached statistical significance at several measured time points. Global aesthetic improvement scores (GAIS) and subject satisfaction were similar for POC and non-POC and remained high throughout the course of the study. Treatment-related adverse event rates were generally lower for high FSTs versus low FSTs, with no reported cases of keloidal scarring.

CONCLUSION: The RHA line of dynamic fillers is well tolerated and effective for the correction of moderate-to-severe nasolabial folds in POC and can be confidently used in this important and growing patient population.

PMID:37556827 | DOI:10.1093/asj/sjad251

Nurse Educ. 2023 Aug 9. doi: 10.1097/NNE.0000000000001486. Online ahead of print.

ABSTRACT

BACKGROUND: Although just culture is reportedly integrated across education and practice, little is known about how perceptions may change across time as students transition from prelicensure education to registered nurse in the practice setting.

PURPOSE: The purpose of this study was to describe and compare just culture perceptions of registered nurses at 2 time points: (1) as prelicensure students and (2) as new graduate nurses with a minimum of 6 months of experience.

METHODS: Utilizing the Just Culture Assessment Tool for Nursing Education (JCAT-NE) and the Just Culture Assessment Tool (JCAT), this within-subject, longitudinal study measured just culture perceptions across time.

RESULTS: Although there was no statistically significant change in total scores across time, 8 individual items demonstrated statistically significant change.

CONCLUSIONS: Students use the knowledge, skills, and attitudes about just culture taught in prelicensure education as new graduate nurses. However, findings reveal areas where the practice environment has altered perceptions of just culture.

PMID:37556826 | DOI:10.1097/NNE.0000000000001486

Acad Med. 2023 Aug 3. doi: 10.1097/ACM.0000000000005366. Online ahead of print.

ABSTRACT

PURPOSE: The developmental trajectory of learning during residency may be attributed to multiple factors, including variation in individual trainee performance, program-level factors, graduating medical school effects, and the learning environment. Understanding the relationship between medical school and learner performance during residency is important in prioritizing undergraduate curricular strategies and educational approaches for effective transition to residency and postgraduate training. This study explores factors contributing to longitudinal and developmental variability in resident milestones ratings, focusing on variability due to graduating medical school, training program, and learners using national cohort data from emergency medicine (EM) and family medicine (FM).

METHOD: Data from programs with residents entering training in July 2016 were used (EM: n = 1,645 residents, 178 residency programs; FM: n = 3,997 residents, 487 residency programs). Descriptive statistics were used to examine data trends. Cross-classified mixed-effects regression were used to decompose variance components in milestones ratings.

RESULTS: During postgraduate year (PGY)-1, graduating medical school accounted for 5% and 6% of the variability in milestones ratings, decreasing to 2% and 5% by PGY-3 for EM and FM, respectively. Residency program accounted for substantial variability during PGY-1 (EM=70%; FM=53%) but decreased during PGY-3 (EM=62%; FM=44%), with greater variability across training period in patient care (PC), medical knowledge (MK), and systems-based practice (SBP). Learner variance increased significantly between PGY-1 (EM=23%; FM=34%) and PGY-3 (EM=34%; FM=44%), with greater variability in practice-based learning and improvement (PBLI), professionalism (PROF), and interpersonal communication skills (ICS).

CONCLUSIONS: The greatest variance in milestone ratings can be attributed to the residency program, and to a lesser degree, learners and medical school. The dynamic impact of program-level factors on learners shift during the first-year and across the duration of residency training, highlighting the influence of curricular, instructional, and programmatic factors on resident performance throughout residency.

PMID:37556818 | DOI:10.1097/ACM.0000000000005366

Comput Inform Nurs. 2023 Aug 9. doi: 10.1097/CIN.0000000000001049. Online ahead of print.

ABSTRACT

The cross-sectional study enrolled 231 patients with heart failure (n = 115; 60.87% were men; mean age, 74.34 ± 12.70 years) and heart transplantation (n = 116; 72.41% were men; mean age, 56.85 ± 11.87 years) who self-reported their technology usage, physical activity, and source of motivation for exercise. Patients with heart failure were significantly older (P = .0001) than patients with heart transplantation. Physical activity levels in patients with heart failure decreased as the New York Heart Association classification increased. Patients with heart failure reported significantly lower physical activity than patients with heart transplantation (P = .0008). Smartphones were the most widely used electronic device to access the Internet in both groups. Patients with heart transplantation seemed to use more than one device to access the Internet. In both groups, patients reporting more technology usage also reported higher levels of physical activity. Patients who accessed the Internet daily reported lower levels of physical activity. Whereas patients with heart failure identified encouragement by family members as a source of motivation for exercise, patients with heart transplantation reported that they were likely to exercise if motivated by their healthcare provider. Patients with heart failure and heart transplantation have unique technological and motivational needs that need consideration for mobile health-driven interventions.

PMID:37556811 | DOI:10.1097/CIN.0000000000001049

Acad Med. 2023 Aug 1. doi: 10.1097/ACM.0000000000005368. Online ahead of print.

ABSTRACT

PURPOSE: Despite ongoing efforts to improve surgical education, surgical residents face gaps in their training. However, it is unknown if differences in the training of surgeons are reflected in the patient outcomes of those surgeons once they enter practice. This study aimed to compare the patient outcomes among new surgeons performing partial colectomy-a common procedure for which training is limited-and cholecystectomy-a common procedure for which training is robust.

METHOD: The authors retrospectively analyzed all adult Medicare claims data for patients undergoing inpatient partial colectomy and inpatient cholecystectomy between 2007-2018. Generalized additive mixed models were used to investigate the associations between surgeon years in practice and risk-adjusted rates of 30-day serious complications and death for patients undergoing partial colectomy and cholecystectomy.

RESULTS: A total of 14,449 surgeons at 4,011 hospitals performed 340,114 partial colectomy and 355,923 cholecystectomy inpatient operations during the study period. Patients undergoing a partial colectomy by a surgeon in their first vs fifteenth year of practice had higher rates of serious complications (5.22% [95% CI 4.85% to 5.60%] vs 4.37% [95% CI 4.22% to 4.52%]; P < 0.01) and death (3.05% [95% CI 2.92% to 3.17%] vs 2.83% [95% CI 2.75% to 2.91%]; P < 0.01). Patients undergoing a cholecystectomy by a surgeon in their first vs. fifteenth year of practice had similar rates of 30-day serious complications (4.11% vs. 3.89%; P = 0.11) and death (1.71% vs. 1.70%; P = 0.93).

CONCLUSIONS: Patients undergoing partial colectomy faced a higher risk of serious complications and death when the operation was performed by a new surgeon compared to an experienced surgeon. Conversely, patient outcomes following cholecystectomy were similar for new and experienced surgeons. More attention to partial colectomy during residency training may benefit patients.

PMID:37556799 | DOI:10.1097/ACM.0000000000005368

Am J Public Health. 2023 Sep;113(9):991-999. doi: 10.2105/AJPH.2023.307337.

ABSTRACT

Objectives. To examine the state-level history of US overdose deaths involving stimulants with and without opioids from 1999 to 2020. Methods. We used death certificate data from the National Center for Health Statistics to categorize deaths into 4 groups of interest: cocaine with and without opioids, and psychostimulants with and without opioids. We used a Bayesian multiple change point model to describe the timing and magnitude of changes in overdose death rates involving stimulants for each state and year. Results. There was little change in the death rates of cocaine without opioids. Death rates involving cocaine and opioids sharply increased around 2015, particularly in the Northeast and Mid-Atlantic. We also observed steady increases in deaths involving psychostimulants without opioids just before 2010, particularly in states in the West and South. Deaths involving psychostimulants with opioids increased around 2015 with largest increases concentrated in Appalachian states. Conclusions. There is significant geographic heterogeneity in the co-involvement of stimulants in the US overdose crisis. Results can inform public health efforts to inform state-level overdose efforts such as naloxone distribution. (Am J Public Health. 2023;113(9):991-999. https://doi.org/10.2105/AJPH.2023.307337).

PMID:37556789 | DOI:10.2105/AJPH.2023.307337

J Clin Oncol. 2023 Aug 9:JCO2300126. doi: 10.1200/JCO.23.00126. Online ahead of print.

ABSTRACT

PURPOSE: BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib.

METHODS: Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived.

RESULTS: Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months).

CONCLUSION: This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.

PMID:37556775 | DOI:10.1200/JCO.23.00126

J Biophotonics. 2023 Aug 9:e202300235. doi: 10.1002/jbio.202300235. Online ahead of print.

ABSTRACT

Ischemic stroke occurs when a blood vessel supplying the brain is blocked, leading to decreased blood flow. Early diagnosis and treatment are crucial. However, existing clinical imaging methods have limitations, such as safety issues and low time resolution. To address these challenges, we propose using photoacoustic tomography (PAT) with a contrast agent, known for its high resolution and contrast capabilities. Our study involved imaging brain vasculature in three groups: normal, unilateral common carotid artery ligation (UCAL), and middle cerebral artery occlusion (MCAO). On the ischemic stroke side, we observed reduced blood vessel density, and hemodynamic changes were evident after injecting indocyanine green (ICG) for PAT. The photoacoustic intensity was notably lower in the ligated sides of the UCAL and MCAO groups, with statistically significant differences between the three groups. This work highlights PAT’s potential as a powerful tool for early diagnosis and guidance in ischemic stroke cases. This article is protected by copyright. All rights reserved.

PMID:37556758 | DOI:10.1002/jbio.202300235