Tag: nevin manimala

Eur J Cancer. 2024 Feb 10;201:113914. doi: 10.1016/j.ejca.2024.113914. Online ahead of print.

ABSTRACT

BACKGROUND: CDC37 is a key determinant of client kinase recruitment to the HSP90 chaperoning system. We hypothesized that kinase-specific dependency on CDC37 alters the efficacy of targeted therapies for metastatic colorectal cancer (mCRC).

MATERIAL AND METHODS: Two independent mCRC cohorts were analyzed to compare the survival outcomes between CDC37-high and CDC37-low patients (stratified by the median cutoff values): the CALGB/SWOG 80405 trial (226 and 207 patients receiving first-line bevacizumab- and cetuximab-containing chemotherapies, respectively) and Japanese retrospective (50 refractory patients receiving regorafenib) cohorts. A dataset of specimens submitted to a commercial CLIA-certified laboratory was utilized to characterize molecular profiles of CDC37-high (top quartile, N = 5055) and CDC37-low (bottom quartile, N = 5055) CRCs.

RESULTS: In the bevacizumab-treated group, CDC37-high patients showed significantly better progression-free survival (PFS) (median 13.3 vs 9.6 months, hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.79, p < 0.01) than CDC37-low patients. In the cetuximab-treated group, CDC37-high and CDC37-low patients had similar outcomes. In the regorafenib-treated group, CDC37-high patients showed significantly better overall survival (median 11.3 vs 6.0 months, HR 0.24, 95% CI 0.11-0.54, p < 0.01) and PFS (median 3.5 vs 1.9 months, HR 0.51, 95% CI 0.28-0.94, p = 0.03). Comprehensive molecular profiling revealed that CDC37-high CRCs were associated with higher VEGFA, FLT1, and KDR expressions and activated hypoxia signature.

CONCLUSIONS: CDC37-high mCRC patients derived more benefit from anti-VEGF therapies, including bevacizumab and regorafenib, but not from cetuximab. Molecular profiles suggested that such tumors were dependent on angiogenesis-relating pathways.

PMID:38359495 | DOI:10.1016/j.ejca.2024.113914

Addict Behav. 2024 Feb 10;152:107982. doi: 10.1016/j.addbeh.2024.107982. Online ahead of print.

ABSTRACT

BACKGROUND: Flavored novel oral nicotine products (ONP), such as pouches, gum, lozenges, tablets, and gummies, have recently entered the US market but have not been authorized for smoking cessation. This study assessed the prevalence and correlates of ONPs in a national sample of youth who smoked little filtered cigars or cigarillos (LCCs) or were susceptible to LCCs.

METHODS: We conducted a national online survey from September-October 2022, as part of a study to develop cigar warnings among youth. Those aged 15-20 years old who reported using (ever or current) or susceptibility to little filtered cigars or cigarillos (LCCs) were eligible. Descriptive statistics and chi-square analyses assessed the prevalence of flavored ONP use and associations with other past 30-day tobacco product use and participant characteristics.

RESULTS: Approximately one-fifth (17.1 %) of the sample (n = 680) reported past month flavored ONP use. Any past month tobacco use was correlated with past month flavored ONP use (ps < 0.001), increasing from 17.1 % in the overall sample to 26.8 % among those reporting e-cigarette use, 41.4 % (LCCs), 47.8 % (waterpipe tobacco), 61.8 % (large cigars), and 69.1 % (smokeless tobacco). The number of products used in the past month was significantly associated with higher odds of ONPs in the past month in a multivariable logistic regression model (aOR2.26; 95 % CI: 1.92, 2.65).

DISCUSSION: Almost one-fifth of participants who use or are susceptible to cigar use in our national sample of youth use ONPs. Dual/poly use of other tobacco products and ONPs among youth suggests that many of these youth may be addicted to nicotine. Additional surveillance and regulation of ONPs that exhibit enticing characteristics, such as flavors, kid-friendly formulations, and targeted marketing/branding may be needed.

PMID:38359494 | DOI:10.1016/j.addbeh.2024.107982

Phys Med Biol. 2024 Feb 15. doi: 10.1088/1361-6560/ad29ba. Online ahead of print.

ABSTRACT

OBJECTIVE: Self-supervised learning methods have been successfully applied for low-dose Computed Tomography (LDCT) denoising, with the advantage of not requiring labeled data. Conventional self-supervised methods operate only in the image domain, ignoring valuable priors in the sinogram domain. Recently proposed dual-domain methods address this limitation but encounter issues with blurring artifacts in the reconstructed image due to the inhomogeneous distribution of noise levels in low-dose sinograms.

APPROACH: To tackle this challenge, this paper proposes SDBDNet, an end-to-end dual-domain self-supervised method for LDCT denoising. With the network designed based on the properties of inhomogeneous noise in low-dose sinograms and the principle of moderate sinogram-domain denoising, SDBDNet achieves effective denoising in dual domains without introducing blurring artifacts. Specifically, we split the sinogram into two subsets based on the positions of detector cells to generate paired training data with high similarity and independent noise. These sub-sinograms are then restored to their original size using 1-D interpolation and learning-based correction. To achieve adaptive and moderate smoothing in the sinogram domain, we integrate Dropblock, a type of convolution layer with regularization, into SDBDNet, and set a weighted average between the denoised sinograms and their noisy counterparts, leading to a well-balanced dual-domain approach.

MAIN RESULTS: Numerical experiments show that our method outperforms popular non-learning and self-supervised learning methods, demonstrating its effectiveness and superior performance.

SIGNIFICANCE: While introducing a novel high-performance dual-domain self-supervised LDCT denoising method, this paper also emphasizes and verifies the importance of appropriate sinogram-domain denoising in dual-domain methods, which might inspire future work.

PMID:38359449 | DOI:10.1088/1361-6560/ad29ba

Arch Cardiol Mex. 2024 Feb 15. doi: 10.24875/ACM.23000126. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: To communicate the experience in an Andean country with the OcclutechTM Duct Occluder device for the closure of patent ductus arteriosus.

METHOD: observational, retrospective, cross-sectional study with basic statistical analysis. Period: December/2014 to December/2022. Data: medical chart, reports of catheterization.

RESULTS: Forty-six patients, female 71.3%, male 28.7%; age: 0.6-38 years-old (median [Me]: 5.2); weight: 6.3-60 kg (Me: 16.5). Origin: Andean 91.3%, coast 8.7%. Types of patent ductus arteriosus: E 54.4%, A 32.6%, D 13%. Minimum ductal diameter: 1.8-11.8 mm (Me: 3.5). Mean pulmonary artery pressure prior to occlusion: 14-67 mmHg (Me: 27). Pulmonary vascular resistance index prior to occlusion: 0.28-4.9 WU/m2 (Me: 1.3). Six of them were classified as hypertensive patent ductus arteriosus. Occlusion rate: 47.8% immediate, 81% at 24 hours, 100% after six months. Fluoroscopy time: 2-13.8 minutes (Me: 4). Complications: a migrated device. Follow-up: 1-6.5 years.

CONCLUSIONS: Occlutech^TM Duct Occluder device was effective and safe for the closure of patent ductus arteriosus type E, A and D in low-altitude and high-altitude dwellers, whether they were children or adults, even when these ductus arteriosus were hypertensive.

PMID:38359430 | DOI:10.24875/ACM.23000126

Appl Neuropsychol Adult. 2024 Feb 15:1-15. doi: 10.1080/23279095.2024.2315555. Online ahead of print.

ABSTRACT

AIM: Given the ever-increasing evidence for the co-occurrence of attention impairments and language disorders in chronic aphasia, this study aimed to compare the effects of two naming treatment programs, one with and one without attention training components, on the naming performance of participants with aphasia.

MATERIALS AND METHODS: This was a single-subject crossover study in which six people with chronic aphasia and different degrees of naming and attention impairments participated. Two treatment programs were implemented for each participant, with the sequence of the treatments with crossover design. Each program consisted of 12 treatment sessions plus pre- and post-treatment assessment sessions (15 weeks for each participant). The visual analysis and WEighted STatistics methods were employed for data analysis.

RESULTS: Based on visual analysis, both treatments improved in comparison to the baseline phase. Statistical analysis revealed that the number of participants with significant naming improvement following combined program (5 participants) was larger than the number of participants showing improvement following completion of the single, program.

CONCLUSION: Although integrating attention training into a conventional treatment for anomia can increase the effect of treatment on naming ability, more studies are required to clarify the role of attention in remediating naming impairments in aphasia.

PMID:38359428 | DOI:10.1080/23279095.2024.2315555

Appl Neuropsychol Child. 2024 Feb 15:1-8. doi: 10.1080/21622965.2024.2311096. Online ahead of print.

ABSTRACT

This study investigates the effectiveness of a computerized cognitive test battery embedded within a video game to assess executive functions (EF) in deaf and hearing children. We evaluated a diverse cohort of 290 elementary school students aged 5 to 13 years (mean age = 8.86, SD = 1.96), comprising 74 sign language users, 14 Spanish-speaking deaf participants, 23 children with mixed communication methods, and 179 typically hearing individuals. Our statistical analysis focused on item discrimination, reliability, and criterion validation of the game-based assessments. The results indicated high reliability and effective discrimination of EF across the game’s three primary stages. External validation was conducted using the Matrices Test, educational attainment, and age as variables. A significant positive correlation (r = 0.377, p < 0.001) was observed between the Matrices Test scores and game-based achievement scores. Furthermore, linear regression analysis revealed education (Standardized Beta = 0.339) and age (Standardized Beta = 0.179) as significant predictors of performance in these scores. This study underscores the value of integrating computerized cognitive assessments within a video game environment for comprehensive neuropsychological evaluations, highlighting its potential in diverse child populations.

PMID:38359416 | DOI:10.1080/21622965.2024.2311096

Prehosp Emerg Care. 2024 Feb 15:1-19. doi: 10.1080/10903127.2024.2319139. Online ahead of print.

ABSTRACT

Background: Emergency Medical Service (EMS) clinicians experience high levels of occupational stress due to long hours, short staffing, and patient deaths, among other factors. While gender has been partially examined, little is known regarding the role of empathy on occupational stress and mental health (MH) outcomes among EMS clinicians. Therefore, the current study examines the moderating role of empathy and, separately, gender on associations between occupational stress and mental health.Methods: A cross-sectional examination of EMS clinician occupational and personal wellbeing was conducted via an anonymous, electronic survey. Information on clinician demographics, and validated measures of occupational stress, burnout, and MH outcomes were collected. Empathy was assessed using the Toronto Empathy Scale (TEQ). Descriptive/bivariate statistics were conducted for variables of interest. Separate multivariable regression models evaluated associations between occupational stress and mental health outcomes. Empathy and gender were examined as potential moderators using interactions.Results: A total of 568 EMS clinicians completed the survey. High levels of mental health difficulties were reported (34.0% anxiety, 29.2% depression, 48.6% burnout). Increased occupational stress was associated with increased anxiety (OR =1.08, 95% CI 1.05-1.10), depression (OR = 1.09, 95% CI 1.06-1.10), and burnout (OR = 1.10, 95% CI 1.07-1.12). No moderation analyses were significant. Greater resilience was associated with lower depression, anxiety, and burnout.Conclusion: EMS clinicians, much like other first responders, experience considerable occupational stress, of which is associated with mental health difficulties and burnout. Findings underscore the need for intervention programs aimed at reducing the impact of occupational stress and the promotion of resilience. Continuing to understand the full scope of EMS mental health, including the role of resilience, is imperative, particularly in light of future public emergencies.

PMID:38359401 | DOI:10.1080/10903127.2024.2319139

J Clin Oncol. 2024 Feb 15:JCO2301291. doi: 10.1200/JCO.23.01291. Online ahead of print.

ABSTRACT

PURPOSE: For patients with advanced cancer, early consultations with palliative care (PC) specialists reduce costs, improve quality of life, and prolong survival. However, capacity limitations prevent all patients from receiving PC shortly after diagnosis. We evaluated whether a prognostic machine learning system could promote early PC, given existing capacity.

METHODS: Using population-level administrative data in Ontario, Canada, we assembled a cohort of patients with incurable cancer who received palliative-intent systemic therapy between July 1, 2014, and December 30, 2019. We developed a machine learning system that predicted death within 1 year of each treatment using demographics, cancer characteristics, treatments, symptoms, laboratory values, and history of acute care admissions. We trained the system in patients who started treatment before July 1, 2017, and evaluated the potential impact of the system on PC in subsequent patients.

RESULTS: Among 560,210 treatments received by 54,628 patients, death occurred within 1 year of 45.2% of treatments. The machine learning system recommended the same number of PC consultations observed with usual care at the 60.0% 1-year risk of death, with a first-alarm positive predictive value of 69.7% and an outcome-level sensitivity of 74.9%. Compared with usual care, system-guided care could increase early PC by 8.5% overall (95% CI, 7.5 to 9.5; P < .001) and by 15.3% (95% CI, 13.9 to 16.6; P < .001) among patients who live 6 months beyond their first treatment, without requiring more PC consultations in total or substantially increasing PC among patients with a prognosis exceeding 2 years.

CONCLUSION: Prognostic machine learning systems could increase early PC despite existing resource constraints. These results demonstrate an urgent need to deploy and evaluate prognostic systems in real-time clinical practice to increase access to early PC.

PMID:38359380 | DOI:10.1200/JCO.23.01291

JCO Glob Oncol. 2024 Feb;10:e2300311. doi: 10.1200/GO.23.00311.

ABSTRACT

PURPOSE: To achieve the WHO cervical cancer elimination targets, countries globally must achieve 70% cervical cancer screening (CCS) coverage. We evaluated CCS uptake and predictors of screening positive at two public HIV care programs in western Kenya.

METHODS: From October 2007 to February 2019, data from the Family AIDS Care and Education Services (FACES) and Academic Model Providing Access to Healthcare (AMPATH) programs in western Kenya were analyzed. The study population included women age 18-65 years enrolled in HIV care. Screening uptake was calculated annually and overall, determining the proportion of eligible women screened. Multivariate logistic regression assessed predictors of positive screening outcomes.

RESULTS: There were 57,298 women living with HIV (WLWHIV) eligible for CCS across both programs during the study period. The mean age was 31.4 years (IQR, 25.9-37.8), and 39% were on antiretroviral therapy (ART) at the first CCS-eligible visit. Of all eligible women, 29.4% (95% CI, 29.1 to 29.8) underwent CCS during the study period, 27.0% (95% CI, 26.5 to 27.4) in the AMPATH program, and 35.6% (95% CI, 34.9 to 36.4) in the FACES program. Annual screening uptake varied greatly in both programs, with coverage as low as 1% of eligible WLWHIV during specific years. Age at first screening, CD4 count within 90 days of screening, current use of ART, and program (AMPATH v FACES) were each statistically significant predictors of positive screening.

CONCLUSION: CCS uptake at two large HIV care programs in Kenya fell short of the WHO’s 70% screening target. Screening rates varied significantly on the basis of the availability of funding specific to CCS, reflecting the limitations of vertical funding programs.

PMID:38359369 | DOI:10.1200/GO.23.00311

Pediatr Infect Dis J. 2024 Feb 12. doi: 10.1097/INF.0000000000004278. Online ahead of print.

ABSTRACT

BACKGROUND: Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients.

METHODS: A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV.

RESULTS: Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort (P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m2 (P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%).

CONCLUSIONS: CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

PMID:38359358 | DOI:10.1097/INF.0000000000004278