Nevin Manimala

Math Biosci. 2024 Mar 9:109170. doi: 10.1016/j.mbs.2024.109170. Online ahead of print.

ABSTRACT

Drug resistance is one of the most intractable issues to the targeted therapy for cancer diseases. To explore effective combination therapy schemes, we propose a mathematical model to study the effects of different treatment schemes on the dynamics of cancer cells. Then we characterize the dynamical behavior of the model by finding the equilibrium points and exploring their local stability. Lyapunov functions are constructed to investigate the global asymptotic stability of the model equilibria. Numerical simulations are carried out to verify the stability of equilibria and treatment outcomes using a set of collected model parameters and experimental data on murine colon carcinoma. Simulation results suggest that immunotherapy combined with chemotherapy contributes significantly to the control of tumor growth compared to monotherapy. Sensitivity analysis is performed to identify the importance of model parameters on the variations of model outcomes.

PMID:38467302 | DOI:10.1016/j.mbs.2024.109170

Food Chem Toxicol. 2024 Mar 9:114550. doi: 10.1016/j.fct.2024.114550. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of human 8-Oxoguanine DNA Glycosylase (hOGG1) on exogenous chemicals in esophageal squamous cell carcinoma (ESCC) remain unclear. The study plans to determine hOGG1 expression levels in ESCC and possible interactions with known environmental risk factors in ESCC.

MATERIAL AND METHODS: We analyzed levels of exposure to urinary nitrosamines in volunteers from high and low prevalence areas by GC-MS. And we performed the interaction between hOGG1 gene and nitrosamine disinfection by-products by analyzing hOGG1 gene expression in esophageal tissues.

RESULTS: In ESCC, nitrosamine levels were significantly increased and hOGG1 mRNA expression levels were significantly decreased. There was a statistically significant interaction between reduced hOGG1 mRNA levels and non-tap drinking water sources in ESCC. The apparent indirect association between ESCC and NMEA indicated that 33.4% of the association between ESCC and NMEA was mediated by hOGG1.

CONCLUSION: In populations which exposed to high levels of environmental pollutants NDMA, low expression of hOGG1 may promote the high incidence of esophageal cancer in Huai’an. hOGG1 may be a novel mediator in nitrosamine-induced esophageal tumorigenesis.

PMID:38467300 | DOI:10.1016/j.fct.2024.114550

Urology. 2024 Mar 9:S0090-4295(24)00141-9. doi: 10.1016/j.urology.2023.11.043. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of the recent changes to the urology residency application process on the criteria utilized by residency program directors (PDs) for interview invitations and their perspectives concerning these changes.

METHODS: One hundred thirty-seven urology residency PDs were invited to participate in an anonymous survey to explore interview selection criteria and the impact of the increase in preference signals (PS) per applicant.

RESULTS: Fifty-eight PDs (42.8%) completed the survey. The highest-ranked criteria were letters of recommendation (LoR) and successful sub-internship (sub-I) at the PD’s institution, without statistically significant differences between these two. Gender, ethnicity and medical school prestige were the lowest rated criteria, without significant differences between these three. Compared to before the increase in the number of PS per applicant, 80.7% of PDs reported that not receiving a PS from an applicant this cycle would more negatively impact the chances of offering an interview to that applicant. Moreover, 12.2% stated they would not interview any applicants who did not send a PS. Finally, 62.1% of PDs believed recent changes worsened the process.

CONCLUSION: Recent changes impacted PDs applicant evaluation, with the highest ranked criteria being LoRs and sub-I. Paradoxically, the increase in the number of PS per applicant has increased their importance as applicants are much less likely to receive interview offers from programs they have not signaled. Lastly, most PDs believe changes have worsened the evaluation process.

PMID:38467286 | DOI:10.1016/j.urology.2023.11.043

Clin Res Hepatol Gastroenterol. 2024 Mar 9:102315. doi: 10.1016/j.clinre.2024.102315. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the goal of offering comprehensive clinical evidence.

METHODS: Following predefined inclusion criteria, five databases were systematically searched, with a focus on identifying randomized controlled trials (RCTs) that compared the administration of dexmedetomidine and midazolam during complex digestive endoscopy procedures. The statistical software Stata 15.1 was employed for meticulous data analysis.

RESULTS: Sixteen RCTs were encompassed, involving a total of 1,218 patients. In comparison to the midazolam group, dexmedetomidine administration was associated with a reduced risk of respiratory depression (RR=0.25, 95%CI: 0.11-0.56) and hypoxemia (RR=0.22, 95%CI: 0.12-0.39). Additionally, the dexmedetomidine group exhibited lower incidence rates of choking (RR=0.27, 95%CI: 0.16-0.47), physical movement (RR=0.16, 95%CI: 0.09-0.27), and postoperative nausea and vomiting (RR=0.56,95%CI: 0.34-0.92). Patients and endoscopists in the dexmedetomidine group reported higher levels of satisfaction (patient satisfaction: SMD=0.73, 95%CI: 0.26-1.21; endoscopist satisfaction: SMD=0.84, 95%CI: 0.24-1.44). The incidence of hypotension and anesthesia recovery time did not significantly differ between the two groups (hypotension: RR=1.73,95%CI:0.94-3.20; anesthesia recovery time: SMD=0.02, 95%Cl: 0.44-0.49). It is noteworthy that the administration of dexmedetomidine was associated with a significant increase in the incidence of bradycardia in patients.

CONCLUSION: Compared to midazolam, dexmedetomidine exhibits a favorable safety profile for use in complex gastrointestinal endoscopy by significantly reducing the risk of respiratory depression and hypoxemia. Despite this, dexmedetomidine is associated with a higher incidence of bradycardia. These findings underscore the need for further research through larger, multi-center studies to thoroughly investigate dexmedetomidine’s safety and efficacy.

PMID:38467278 | DOI:10.1016/j.clinre.2024.102315

Magn Reson Imaging. 2024 Mar 9:S0730-725X(24)00064-X. doi: 10.1016/j.mri.2024.03.008. Online ahead of print.

ABSTRACT

OBJECTIVE: This study intended to investigate the feasibility and effectiveness of using clinical magnetic resonance imaging (MRI) radiomics features to predict lymphovascular invasion (LVI) status in breast cancer (BC) patients.

METHODS: A total of 182 BCE patients were retrospectively collected and randomly divided into a training set (n = 127) and a validation set (n = 55) in a 7:3 ratio. Based on pathological examination results, the training set was further divided into LVI group (n = 60) and non-LVI group (n = 67), and the validation set was divided into LVI group (n = 24) and non-LVI group (n = 31). General data and MRI examination indicators were compared. Multivariate logistic regression was utilized to analyze MRI radiomics features and clinically relevant indicators that were significant in the baseline information of patients in training set, independent risk factors were identified, and a logistic regression model was built. The accuracy of logistic model was validated using ROC curves in training and validation sets.

RESULTS: Age, pathohistological classification, tumor length, tumor width, presence or absence of Magnetic Resonance Spectroscopy (MRS) cho peak, presence or absence of spicule sign, peritumoral enhancement, and peritumoral edema were statistically significant (P < 0.05) between the two groups. Multivariate logistic regression analysis presented that spicule and peritumoral edema were independent risk factors for LVI in BC patients (P < 0.05). The ROC curve illustrated that AUC of the logistic regression model in the training set was 0.807 (95%CI: 0.730-0.885) and that in the validation set was 0.837 (95%CI: 0.731-0.944).

CONCLUSION: Radiomics features of spicule sign and peritumoral edema were independent risk factors for LVI in BC patients. A logistic regression model based on these factors, along with age, could accurately predict LVI occurrence in BC patients, providing data support for diagnosis and modeling of LVI in BC patients.

PMID:38467265 | DOI:10.1016/j.mri.2024.03.008

Acta Trop. 2024 Mar 9:107170. doi: 10.1016/j.actatropica.2024.107170. Online ahead of print.

ABSTRACT

Spatial analysis of infectious diseases can play an important role in mapping the spread of diseases and can support policy making at local level. Moreover, identification of disease clusters based on local geography and landscape forms the basis for disease control and prevention. Therefore, this study aimed to examine the spatial-temporal variations, hotspot areas, and potential risk factors of infectious diseases (including Viral Hepatitis, Typhoid and Diarrhea) in Ahmedabad city of India. We used Moran’s I and Local Indicators of Spatial Association (LISA) mapping to detect spatial clustering of diseases. Spatial and temporal regression analysis was used to identify the association between disease incidence and spatial risk factors. The Moran’s I statistics identified presence of positive spatial autocorrelation within the considered diseases, with Moran’s I from 0.09 for typhoid to 0.21 for diarrhea (p<0.001). This indicates a clustering of affected wards for each disease, suggesting that cases were not randomly distributed across the city. LISA mapping demonstrated the clustering of hotspots in central regions of the city, especially towards the east of the river Sabarmati, highlighting key geographical areas with elevated disease risk. The spatial clusters of infectious diseases were consistently associated with slum population density and illiteracy. Furthermore, temporal analysis suggested illiteracy rates could increase risk of viral hepatitis by 13% (95% Confidence Interval (CI): 1.01-1.26) and of diarrhea by 18% (95% CI: 1.07-1.31). Significant inverse association was also seen between viral hepatitis incidence and the distance of wards from rivers. Conclusively, the study highlight the impact of socio-economic gradients, such as slum population density (indicative of poverty) and illiteracy, on the localized transmission of water and foodborne infections. The evident social stratification between impoverished and affluent households emerges as a notable contributing factor and a potential source of differences in the dynamics of infectious diseases in Ahmedabad.

PMID:38467234 | DOI:10.1016/j.actatropica.2024.107170

Fam Med. 2024 Mar;56(3):190-194. doi: 10.22454/FamMed.2024.683797. Epub 2024 Jan 29.

ABSTRACT

BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) requires education on health care disparities (HCD), but research assessing formal curricula is limited. To improve knowledge and confidence in HCD, the family medicine residency program at Darnall Army Medical Center implemented a formal HCD curriculum.

METHODS: During the 2021-2022 academic year, starting July 2021, a formal HCD curriculum was implemented for family medicine residents and faculty. Ten lectures on HCDs and implicit bias were given over the course of the year. Residents and faculty were asked to incorporate HCD into their regular continuing medical education lectures. ACGME survey data as well as a pre- and postcurriculum survey were used to assess HCD knowledge and confidence. Descriptive statistics and a paired-sample t tests were calculated to compare pre- to postcurriculum changes.

RESULTS: The percentage of residents who reported that they had received HCD education increased from 72% on the 2021 ACGME survey to 100% in 2022 (N=18). We found a significant (P&lt;.05) improvement in knowledge and confidence across 11 of 12 questions on the pre- and postcurriculum survey.

CONCLUSIONS: A formal curriculum in a military family medicine residency setting was effective for improving self-reported HCD knowledge and confidence.

PMID:38467036 | DOI:10.22454/FamMed.2024.683797

J Healthc Manag. 2024 Mar-Apr 01;69(2):140-155. doi: 10.1097/JHM-D-23-00031.

ABSTRACT

GOAL: To address healthcare spending growth, coordinate care, and improve primary care utilization, a majority of states in the United States have adopted value-based care coordination programs. The objective of this study was to identify changes in national healthcare utilization for children with developmental disabilities (DDs), a high-cost and high-need population, following the broad adoption of value-based care coordination policies.

METHODS: This retrospective study included 9,109 children with DDs and used data from 2002-2018 Medical Expenditure Panel Survey. We applied an interrupted time series design approach to compare pre- and post-Affordable Care Act (ACA) care coordination policies concerning healthcare utilization outcomes, including outpatient visits, home provider days, emergency department (ED) visits, inpatient discharge, and inpatient nights of stay.

PRINCIPAL FINDINGS: We found statistically significant increases in low-cost care post-ACA, including outpatient visits (5% higher, p < .001) and home provider days (11% higher, p < .001). The study findings also showed a statistically significant increase in inpatient nights of stay post-ACA (4% higher, p = .001). There were no changes in the number of ED and inpatient visits. Overall, broad implementation of care coordination programs was associated with increased utilization of low-cost care without increases in the number of high-cost ED and inpatient visits for children with DDs. Our study also found changes in population composition among children with DDs post-ACA, including increases in Hispanic (16.9% post-ACA vs. 13.4% pre-ACA, p = .006) and non-Hispanic multiracial children (9.1% post-ACA vs. 5.5% pre-ACA, p = .001), a decrease in non-Hispanic Whites (60.2% post-ACA vs. 68.6% pre-ACA, p = .001), more public-only insurance (44.3% post-ACA vs. 35.7% pre-ACA, p = .001), fewer children with DDs from middle-income families (27.4% post-ACA vs. 32.8% pre-ACA, p < .001), and more children with DDs from poor families (28.2% post-ACA vs. 25.1% pre-ACA, p = .043).

PRACTICAL APPLICATIONS: These findings highlight the importance of continued support for broad care coordination programs for U.S. children with DDs and potentially others with complex chronic conditions. Policymakers and healthcare leaders might consider improving care transitions from inpatient to community or home settings by overcoming barriers such as payment models and the lack of home care nurses who can manage complex chronic conditions. Healthcare leaders also need to understand and consider the changing population composition when implementing care coordination-related policies. This study provides data regarding trends in hospital and home care utilization and evidence of the effectiveness of care coordination policies before the COVID-19 interruption. These findings apply to current healthcare management because COVID-19 has incentivized home care, which may have a strong potential to minimize high-cost care for people with complex chronic conditions. More research is warranted to continue monitoring care coordination changes over a longer period.

PMID:38467027 | DOI:10.1097/JHM-D-23-00031

Ann Intern Med. 2024 Mar 12. doi: 10.7326/M23-2960. Online ahead of print.

ABSTRACT

BACKGROUND: There is increasing concern for the potential impact of health care algorithms on racial and ethnic disparities.

PURPOSE: To examine the evidence on how health care algorithms and associated mitigation strategies affect racial and ethnic disparities.

DATA SOURCES: Several databases were searched for relevant studies published from 1 January 2011 to 30 September 2023.

STUDY SELECTION: Using predefined criteria and dual review, studies were screened and selected to determine: 1) the effect of algorithms on racial and ethnic disparities in health and health care outcomes and 2) the effect of strategies or approaches to mitigate racial and ethnic bias in the development, validation, dissemination, and implementation of algorithms.

DATA EXTRACTION: Outcomes of interest (that is, access to health care, quality of care, and health outcomes) were extracted with risk-of-bias assessment using the ROBINS-I (Risk Of Bias In Non-randomised Studies – of Interventions) tool and adapted CARE-CPM (Critical Appraisal for Racial and Ethnic Equity in Clinical Prediction Models) equity extension.

DATA SYNTHESIS: Sixty-three studies (51 modeling, 4 retrospective, 2 prospective, 5 prepost studies, and 1 randomized controlled trial) were included. Heterogenous evidence on algorithms was found to: a) reduce disparities (for example, the revised kidney allocation system), b) perpetuate or exacerbate disparities (for example, severity-of-illness scores applied to critical care resource allocation), and/or c) have no statistically significant effect on select outcomes (for example, the HEART Pathway [history, electrocardiogram, age, risk factors, and troponin]). To mitigate disparities, 7 strategies were identified: removing an input variable, replacing a variable, adding race, adding a non-race-based variable, changing the racial and ethnic composition of the population used in model development, creating separate thresholds for subpopulations, and modifying algorithmic analytic techniques.

LIMITATION: Results are mostly based on modeling studies and may be highly context-specific.

CONCLUSION: Algorithms can mitigate, perpetuate, and exacerbate racial and ethnic disparities, regardless of the explicit use of race and ethnicity, but evidence is heterogeneous. Intentionality and implementation of the algorithm can impact the effect on disparities, and there may be tradeoffs in outcomes.

PRIMARY FUNDING SOURCE: Agency for Healthcare Quality and Research.

PMID:38467001 | DOI:10.7326/M23-2960

JMIR Dermatol. 2024 Mar 11;7:e49965. doi: 10.2196/49965.

ABSTRACT

BACKGROUND: Seborrheic dermatitis (SD) affects 18.6%-59% of persons with Parkinson disease (PD), and recent studies provide evidence that oral cannabidiol (CBD) therapy could reduce sebum production in addition to improving motor and psychiatric symptoms in PD. Therefore, oral CBD could be useful for improving symptoms of both commonly co-occurring conditions.

OBJECTIVE: This study investigates whether oral CBD therapy is associated with a decrease in SD severity in PD.

METHODS: Facial photographs were collected as a component of a randomized (1:1 CBD vs placebo), parallel, double-blind, placebo-controlled trial assessing the efficacy of a short-term 2.5 mg per kg per day oral sesame solution CBD-rich cannabis extract (formulated to 100 mg/mL CBD and 3.3 mg/mL THC) for reducing motor symptoms in PD. Participants took 1.25 mg per kg per day each morning for 4 ±1 days and then twice daily for 10 ±4 days. Reviewers analyzed the photographs independently and provided a severity ranking based on the Seborrheic Dermatitis Area and Severity Index (SEDASI) scale. Baseline demographic and disease characteristics, as well as posttreatment SEDASI averages and the presence of SD, were analyzed with 2-tailed t tests and Pearson χ² tests. SEDASI was analyzed with longitudinal regression, and SD was analyzed with generalized estimating equations.

RESULTS: A total of 27 participants received a placebo and 26 received CBD for 16 days. SD severity was low in both groups at baseline, and there was no treatment effect. The risk ratio for patients receiving CBD, post versus pre, was 0.69 (95% CI 0.41-1.18; P=.15), compared to 1.20 (95% CI 0.88-1.65; P=.26) for the patients receiving the placebo. The within-group pre-post change was not statistically significant for either group, but they differed from each other (P=.07) because there was an estimated improvement for the CBD group and an estimated worsening for the placebo group.

CONCLUSIONS: This study does not provide solid evidence that oral CBD therapy reduces the presence of SD among patients with PD. While this study was sufficiently powered to detect the primary outcome (efficacy of CBD on PD motor symptoms), it was underpowered for the secondary outcomes of detecting changes in the presence and severity of SD. Multiple mechanisms exist through which CBD can exert beneficial effects on SD pathogenesis. Larger studies, including participants with increased disease severity and longer treatment periods, may better elucidate treatment effects and are needed to determine CBD’s true efficacy for affecting SD severity.

TRIAL REGISTRATION: ClinicalTrials.gov NCT03582137; https://clinicaltrials.gov/ct2/show/NCT03582137.

PMID:38466972 | DOI:10.2196/49965