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Nevin Manimala Statistics

Why Women Appear To Have Better Outcomes When Undergoing Screening For Lung Cancer

Ann Am Thorac Soc. 2025 Feb 18. doi: 10.1513/AnnalsATS.202408-863OC. Online ahead of print.

ABSTRACT

RATIONALE: Randomized controlled trials (RCT) of lung cancer screening (LCS) using computed tomography (CT) documented lung cancer mortality reductions between 7.2%-29.2% compared to chest radiograph (CXR). Women appear to have a greater reduction than men.

OBJECTIVE: To determine why women appear to have better outcomes from LCS compared to Men.

METHODS: Secondary analysis of the National Lung Screening Trial (NLST), a RCT comparing CXR with CT among screen eligible individuals aged 55-74 years. Descriptive statistics and a competing risk proportional hazards model that included an interaction between sex and screening arm were used to examine differences in screening outcomes by sex.

RESULTS: Of 31,530 men and 21,922 women, 648 (2. 1%) and 373 (1.7%) died of lung cancer during the study, respectively. Overall mortality was higher in men: 2771 (8.8%) vs 1198 (5.5%). In an adjusted competing cause of death analysis, the LC mortality subdistribution hazard ratio (sHR) favoring CT was significant in women (sHR=0.74, 95% CI: 0.6, 0.9, p=0.003) but not men (sHR=0.91, 95% CI: 0.78, 1.06, p=0.24). The interaction between screening arm and sex was not significant (p=0.1). COPD and heart disease, more prevalent in men, were independently associated with LC death. LC deaths were consistently greater in the CT arm (vs CXR), for pre-existing COPD and DM in men but not women. Of those with lung cancer, women in the CT arm had 53.7% prevalence of adenocarcinoma (AD) histology, while women in the CXR arm and men in both arms had approximately 36-41% AD prevalence. However, there was no overall difference between sexes in the screening difference for AD lethality.

CONCLUSION: Women in the NLST had a greater reduction in LC mortality, that while not statistically significant, could be the result of more prevalent comorbid disease in men which contributed to greater all-cause and LC mortality. .

PMID:39965131 | DOI:10.1513/AnnalsATS.202408-863OC

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Nevin Manimala Statistics

Use of positive predictive value to evaluate the Armed Forces Health Surveillance Division brain cancer incidence rules, active component department of the Air Force pediatric dependent population, January 1, 2010-December 31, 2020

MSMR. 2025 Jan 20;32(1):7-10.

ABSTRACT

The Armed Forces Health Surveillance Division (AFHSD) uses a surveillance case definition to identify malignant brain tumors among U.S. active service members. This case definition was applied to the dependent pediatric population of the active component of the Department of the Air Force, which identified 179 malignant brain cancer cases. Those identified pediatric cases were reviewed using multiple data sources. The positive predictive value (PPV) of the AFHSD case definition was found to be 64.5% (95% confidence interval [CI], 55.9-72.5%). In 2019, Webber et al. reported a PPV of 84.3% for brain and other nervous system cancers among U.S. active component officers. The current pediatric study’s lower PPV suggests the case definition may be less effective for pediatric populations, indicating a need for refining surveillance methods for dependent populations. The AFHSD case definition was less effective at identifying malignant brain tumors in the active component Air Force pediatric dependent population, with a lower PPV compared to previous studies of the active component Air Force adult population. In addition, several cases were missed by the AFHSD rules. The PPV of the AFHSD case definition was lower when applied to the Air Force pediatric dependent population (64.5%; 95% CI, 55.9-72.5%) compared to the previously published PPV in the adult population (84.3%). There were an additional 16 cases of malignant brain tumors missed by initial screening utilizing AFHSD incidence rules.

PMID:39965130

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Nevin Manimala Statistics

The association of deployment-related probable traumatic brain injury with subsequent medical readiness status

MSMR. 2025 Jan 20;32(1):2-6.

ABSTRACT

Traumatic brain injury (TBI) has been a major source of morbidity within military forces during the last 2 decades, but research on the relationship between TBI and medical readiness is limited. This study population included 41,442 service members from the U.S. Navy and Marine Corps who completed a Post-Deployment Health Assessment (PDHA) and a Periodic Health Assessment (PHA). Presence of TBI was ascertained from a screening instrument on the PDHA, and provider determination of medical readiness was abstracted from the PHA. Multivariable logistic regression assessed the association between probable TBI and ‘not medically ready’ (NMR) service member disposition while adjusting for covariates. Overall, 1.8% of the study population screened positive for TBI, and individuals with TBI had a significantly higher prevalence of NMR disposition (7.8%) than those without (3.7%). After adjusting for all covariates, TBI was associated with higher odds of post-deployment NMR disposition (odds ratio 1.5; 95% confidence interval, 1.2-2.0). Deployment-related TBI is associated with medical readiness. Future studies are needed to elucidate the TBI sequelae that may lead to NMR disposition as well as the impact of repeated TBIs. This study identified 54% increased odds of NMR disposition for military personnel with probable TBI following deployment, after adjusting for post-traumatic stress disorder and other covariates.

PMID:39965127

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Nevin Manimala Statistics

Surgical tricuspid edge-to-edge repair: double-orifice repair versus clover repair

Eur J Cardiothorac Surg. 2025 Feb 18:ezaf050. doi: 10.1093/ejcts/ezaf050. Online ahead of print.

ABSTRACT

OBJECTIVES: Surgical edge-to-edge repair has been proposed to treat tricuspid regurgitation with various etiologies. Two techniques can be used for this repair: the “double-orifice” and the “clover” repairs. This study compares the clinical outcomes of these two techniques.

METHODS: The study enrolled 258 patients who underwent tricuspid edge-to-edge repair out of 2,257 tricuspid valve repairs between January 2001 and December 2021. Patients were categorised into two groups (double-orifice and clover repairs) and analysed using propensity score matching.

RESULTS: The mean age of the 258 patients was 60.8 ± 12.4 years, with 190 females (73.6%) and a mean EuroScore II of 4.6 ± 5.5. Of these, 169 underwent double-orifice repair and 89 clover repair, adjusted to 118 and 66 after matching, respectively. Using the reverse Kaplan-Meier method to account for censored data, the median follow-up duration[Q1-Q3] was 169[76-229] months. Early mortality and morbidity did not differ significantly between the groups. Survival analysis did not show statistical differences in overall mortality and late severe tricuspid regurgitation recurrence between the groups. Similarly, freedoms from late significant tricuspid stenosis (trans-tricuspid pressure gradient ≥5 mmHg) and tricuspid reoperations (8[4.7%] in the double-orifice repair group and 2[2.2%] in the clover repair group) were not significantly different between the groups. The sensitivity analysis, which included the inverse probability of treatment weighting analysis, produced consistent results.

CONCLUSIONS: The surgical outcomes of tricuspid edge-to-edge repair were not statistically significantly different, regardless of the repair techniques. Both methods can be valuable options for tricuspid regurgitation repair.

PMID:39965096 | DOI:10.1093/ejcts/ezaf050

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Nevin Manimala Statistics

Integrating State-Space Modeling, Parameter Estimation, Deep Learning, and Docking Techniques in Drug Repurposing: A Case Study on COVID-19 Cytokine Storm

J Am Med Inform Assoc. 2025 Feb 18:ocaf035. doi: 10.1093/jamia/ocaf035. Online ahead of print.

ABSTRACT

OBJECTIVE: This study addresses the significant challenges posed by emerging SARS-CoV-2 variants, particularly in developing diagnostics and therapeutics. Drug repurposing is investigated by identifying critical regulatory proteins impacted by the virus, providing rapid and effective therapeutic solutions for better disease management.

MATERIALS AND METHODS: We employed a comprehensive approach combining mathematical modeling and efficient parameter estimation to study the transient responses of regulatory proteins in both normal and virus-infected cells. Proportional-integral-derivative (PID) controllers were used to pinpoint specific protein targets for therapeutic intervention. Additionally, advanced deep learning models and molecular docking techniques were applied to analyze drug-target and drug-drug interactions, ensuring both efficacy and safety of the proposed treatments. This approach was applied to a case study focused on the cytokine storm in COVID-19, centering on Angiotensin-converting enzyme 2 (ACE2), which plays a key role in SARS-CoV-2 infection.

RESULTS: Our findings suggest that activating ACE2 presents a promising therapeutic strategy, whereas inhibiting AT1R seems less effective. Deep learning models, combined with molecular docking, identified Lomefloxacin and Fostamatinib as stable drugs with no significant thermodynamic interactions, suggesting their safe concurrent use in managing COVID-19-induced cytokine storms.

DISCUSSION: The results highlight the potential of ACE2 activation in mitigating lung injury and severe inflammation caused by SARS-CoV-2. This integrated approach accelerates the identification of safe and effective treatment options for emerging viral variants.

CONCLUSION: This framework provides an efficient method for identifying critical regulatory proteins and advancing drug repurposing, contributing to the rapid development of therapeutic strategies for COVID-19 and future global pandemics.

PMID:39965087 | DOI:10.1093/jamia/ocaf035

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Patient adherence to surveillance colonoscopy after endoscopic resection of colorectal polyps and factors associated with loss to follow-up

Endosc Int Open. 2025 Jan 29;13:a24094916. doi: 10.1055/a-2409-4916. eCollection 2025.

ABSTRACT

BACKGROUND AND STUDY AIMS: Post-polypectomy surveillance colonoscopy (SC) plays an integral role in efforts to reduce colorectal cancer risk, but its effectiveness is invariably dependent on patient compliance. This study aimed to evaluate patient adherence to SC after endoscopic resection (ER) of polyps ≥ 20 mm and identify potential barriers associated with loss to follow-up.

PATIENTS AND METHODS: This was a single-center retrospective study evaluating adherence to SC after ER of polyps ≥ 20 mm between April 2018 to December 2021. Adherence to SC was defined as the proportion of patients who underwent follow-up colonoscopy. Multivariate logistic regression was performed to identify factors associated with loss to follow-up.

RESULTS: A total of 959 patients (mean age 67 years; 47.9% women) underwent endoscopic resection of colorectal polyps ≥ 20 mm (mean size 33.2 ± 13.7 mm). Nearly half of the patients (n = 478; 49.8%) were lost to follow-up. On multivariate analysis, factors associated with a higher likelihood of SC non-adherence were: lack of a primary care physician (odds ratio [OR] 1.7;95% confidence interval [CI] 1.3- 2.3; P < 0.05), American Society of Anesthesiologists grade 3 or 4 (OR 1.4; 95% CI 1.1-1.9; P < 0.05), residence > 60 miles from the endoscopy suite (OR 1.6; 95% CI 1.2-2.3; P = 0.02), being referred by a physician outside of our healthcare system (OR 1.4; 95% CI 1.1-1.8; P = 0.01), and lack of written follow-up recommendations on the colonoscopy report (OR 3.6; 95% CI 1.4-10.2; P = 0.01).

CONCLUSIONS: Nearly half of patients undergoing ER of colorectal polyps ≥ 20 mm are lost to follow-up. We identified several patient- and healthcare-related factors as barriers to SC adherence. Strategies to address these issues and targeting of high-risk populations are urgently needed to enhance SC programs.

PMID:39965041 | PMC:PMC11827743 | DOI:10.1055/a-2409-4916

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Nevin Manimala Statistics

Nowcasting reported covid-19 hospitalizations using de-identified, aggregated medical insurance claims data

PLoS Comput Biol. 2025 Feb 18;21(2):e1012717. doi: 10.1371/journal.pcbi.1012717. Online ahead of print.

ABSTRACT

We propose, implement, and evaluate a method for nowcasting the daily number of new COVID-19 hospitalizations, at the level of individual US states, based on de-identified, aggregated medical insurance claims data. Our analysis proceeds under a hypothetical scenario in which, during the Delta wave, states only report data on the first day of each month, and on this day, report COVID-19 hospitalization counts for each day in the previous month. In this hypothetical scenario (just as in reality), medical insurance claims data continues to be available daily. At the beginning of each month, we train a regression model, using all data available thus far, to predict hospitalization counts from medical insurance claims. We then use this model to nowcast the (unseen) values of COVID-19 hospitalization counts from medical insurance claims, at each day in the following month. Our analysis uses properly-versioned data, which would have been available in real-time at the time predictions are produced (instead of using data that would have only been available in hindsight). In spite of the difficulties inherent to real-time estimation (e.g., latency and backfill) and the complex dynamics behind COVID-19 hospitalizations themselves, we find altogether that medical insurance claims can be an accurate predictor of hospitalization reports, with mean absolute errors typically around 0.4 hospitalizations per 100,000 people, i.e., proportion of variance explained around 75%. Perhaps more importantly, we find that nowcasts made using medical insurance claims are able to qualitatively capture the dynamics (upswings and downswings) of hospitalization waves, which are key features that inform public health decision-making.

PMID:39965031 | DOI:10.1371/journal.pcbi.1012717

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Evaluation of a Game-Based Mechatronic Device for Rehabilitation of Hand-Arm Function in Children With Cerebral Palsy: Feasibility Randomized Controlled Trial

JMIR Rehabil Assist Technol. 2025 Feb 18;12:e65358. doi: 10.2196/65358.

ABSTRACT

BACKGROUND: Children with neurodevelopmental disorders, such as cerebral palsy (CP), often experience motor impairments in manual dexterity, which hinder daily tasks and social interactions. Traditional rehabilitation methods require repetitive task practice, which can be difficult for children to sustain due to low engagement. Game-based rehabilitation devices and robots offer a promising alternative by combining therapy with digital play, improving motivation and compliance. However, many systems fail to incorporate actual object manipulation, which is essential for motor learning through sensory feedback. To address this limitation, a low-cost, easy-to-use robotic manipulandum device (RMD) was developed. The RMD enables real-time object manipulation during gameplay while providing assistive force, allowing the practice of a wide range of manual dexterity skills beyond gross reaching. This system offers an engaging and effective rehabilitation approach to enhance hand function in children with CP.

OBJECTIVE: This study aimed to provide evidence for the feasibility and therapeutic value of the RMD game-based exercise program for children with CP.

METHODS: In total, 34 children with CP, aged 4 to 10 years, were randomly assigned to the experimental group (XG) or the control group (CG). The XG received a computer game-based exercise program using the RMD, focusing on object manipulation tasks, while the CG received task-specific training similar to constraint-induced movement therapy. Both groups received their respective therapy programs 3 times per week for 8 weeks. Semistructured interviews with parents and children, along with qualitative analysis, were conducted to evaluate their experiences with the exercise program. The following outcome measures were used: (1) the Peabody Developmental Motor Scale-2 (PDMS-2) grasping and visual-motor integration subtests and (2) the computer game-based upper extremity (CUE) assessment of manual dexterity.

RESULTS: No dropouts occurred during the 8-week program. Both groups showed significant improvements in the PDMS-2 subtests (P<.001) and the CUE assessment of manual dexterity, including success rates (tennis ball: P=.001; cone: P<.001; medicine ball: P=.001; and peanut ball: P<.001) and movement errors (tennis ball: P=.01; cone: P<.001; medicine ball: P=.04; and peanut ball: P<.001). The XG outperformed the CG, showing greater improvements in PDMS-2 grasping (P=.002) and visual-motor integration (P=.01). In the CUE assessment, the XG demonstrated higher success rates (medicine ball: P=.001 and peanut ball: P=.02) and fewer movement errors (cone: P<.001). Parents reported an increase in the children’s independence in daily tasks.

CONCLUSIONS: This study demonstrates the feasibility, acceptability, and positive outcomes of the RMD game-based exercise program for improving hand function in children with CP. The findings support further research and development of computer game-assisted rehabilitation technologies.

TRIAL REGISTRATION: Clinical Trials Registry – India CTRI/2021/07/034903; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NTc4ODU.

PMID:39964707 | DOI:10.2196/65358

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Effect of adjuvant chemotherapy with toad venom injection in the treatment of intermediate and advanced colon cancer and its effect on cellular immunity, PTEN, and PI3k

Anticancer Drugs. 2025 Feb 18. doi: 10.1097/CAD.0000000000001706. Online ahead of print.

ABSTRACT

The objective of this study is to explore the effect of adjuvant chemotherapy with toad venom injection in patients with intermediate and advanced colon cancer, in order to provide new reference drugs for clinical treatment. Prospectively, 148 patients with mid-stage to late-stage colon cancer in our hospital from January 2021 to May 2023 were selected for the study and randomly divided into two groups of 74 cases each. The control group was treated with FOLFOX4 chemotherapy, and the observation group was treated with four consecutive chemotherapy cycles based on the control group combined with toad venom injection. The treatment effects, adverse reactions, quality of life improvement rate, prognosis and cellular immune indexes [natural killer (NK) cells, CD4+/CD8+, CD4+, CD3+], phosphatase tensin gene (PTEN), phosphatidylinositol-3-kinase (PI3k), and serine threonine protein kinase (pAKT) protein expression before and after treatment were counted in the two groups. The total effective rate of treatment in the observation group was 58.11% (43/74) after four cycles of chemotherapy, which was higher than that in the control group of 41.89% (31/74) (P < 0.05). After two cycles of chemotherapy and four cycles of chemotherapy, PTEN, CD4+/CD8+, CD4+, CD3+, and NK cells in peripheral blood were higher in the observation group than in the control group, and PI3k and pAKT were lower than in the control group (P < 0.05). There was no statistically significant difference in the rate of adverse reactions in the observation group compared with the control group (P > 0.05); the improvement rate of quality of life in the observation group was better than that in the control group after four chemotherapy cycles of treatment (P < 0.05); the survival rate was 75.00% (54/72) in the observation group compared with 54.29% (38/70) in the control group at 1-year follow-up. Toad venom injection adjuvant chemotherapy is effective in treating patients with intermediate and advanced colon cancer, which can upregulate PTEN level, inhibit PI3k and AKT expression, and improve immune function and quality of life of patients, thus improving prognosis.

PMID:39964699 | DOI:10.1097/CAD.0000000000001706

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Improving forecasts of imperfect models using piecewise stochastic processes

Chaos. 2025 Feb 1;35(2):023142. doi: 10.1063/5.0242061.

ABSTRACT

Forecasting complex systems is important for understanding and predicting phenomena. Due to the complexity and error sensitivity inherent in these predictive models, forecasting proves challenging. This paper presents a novel approach to assimilate system observations into predictive models. The approach makes use of a recursive partitioning algorithm to facilitate the computation of local sets of model corrections as well as provide a data structure to traverse the model space. These local sets of corrections act as a sample from a piecewise stochastic process. Appending these corrections to the predictive model incorporates hidden residual dynamics, resulting in improved forecasting performance. Numerical experiments demonstrate that this approach results in improved forecasting for the Lorenz 1963 model. In addition, comparisons are made between two types of corrections: Vector Difference and Gaussian. Vector Difference corrections provide the best computational efficiency and forecasting performance. To further justify the effectiveness of this approach it is successfully applied to more complex systems such as Lorenz for various chaotic parameterizations, coupled Lorenz, and cubic Lorenz.

PMID:39964695 | DOI:10.1063/5.0242061