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Nevin Manimala Statistics

Time-series clustering analysis reveals distinct patterns of cytomegalovirus viremia in critically ill adults

Intensive Care Med Exp. 2026 Feb 12;14(1):16. doi: 10.1186/s40635-026-00866-9.

ABSTRACT

BACKGROUND: Critically ill patients are at increased risk for cytomegalovirus (CMV) reactivation, which is associated with poorer clinical outcomes. However, little is known about the longitudinal viremia trajectories in this population.

METHODS: This retrospective single-center study was conducted in a medical ICU and included patients with CMV viremia ≥ 1000 International Units CMV-DNA per milliliter whole blood (IU/mL) treated between March 2014 and April 2021. Time-series clustering was applied to identify subgroups of patients with similar longitudinal viremia trajectories.

RESULTS: 82 patients were included in the final analysis. Time-series clustering identified three distinct clusters: (1) patients with initial high viremia (median 46,700 IU/mL), 94% receiving treatment and showing subsequent steep reduction of viremia; (2) patients with moderate viremia (median 2720 IU/mL) and subsequent increase in viral load, treated in 52%; and (3) patients with moderate viremia (median 3120 IU/mL), 63% receiving treatment and showing stable viral load in follow-up measurements. No significant differences were identified between the clusters with respect to patient characteristics, including underlying immunosuppression. With respect to disease severity, the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score was highest in cluster 3 and among patients without follow-up CMV-DNA measurements (P = 0.029), while the Sequential Organ Failure Assessment (SOFA) score demonstrated a similar directional trend without reaching statistical significance. Survival differed significantly between the clusters in the Kaplan-Meier estimate (p = 0.008); however, absolute 1-year survival was low across all clusters (cluster 1: 0%, cluster 2: 33%, cluster 3: 32%, patients without follow-up CMV measurement: 14%; p = 0.062). Probable CMV pneumonia with respiratory symptoms and CMV-DNA detection in bronchoalveolar lavage fluid was the most common disease manifestation (cluster 1: 35%; cluster 2: 28%; cluster 3: 7.5%; patients without follow-up CMV measurement: 23%; p = 0.040).

CONCLUSIONS: In this hypothesis-generating study, time-series clustering analysis identified three subgroups with distinct longitudinal viremia trajectories which significantly differed in viral load, treatment decisions and survival over time. The diagnostic and therapeutic relevance of longitudinal CMV viremia trajectories and the optimal CMV-DNA threshold for treatment initiation in ICU patients remain undefined and might differ from other cohorts.

PMID:41678036 | DOI:10.1186/s40635-026-00866-9

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Evaluating the Return on Investment of U.S. Army Holistic Health and Fitness Performance Teams: A Matched Difference-in-Differences Study of Readiness and Economic Outcomes

Sports Med. 2026 Feb 12. doi: 10.1007/s40279-026-02399-3. Online ahead of print.

ABSTRACT

PURPOSE: Holistic Health and Fitness (H2F) is the United States Army’s largest force modernization initiative aimed at preserving combat power by optimizing soldier readiness across five domains: physical, mental, nutritional, sleep, and spiritual. At the core of this effort are H2F Performance Teams (HPTs): embedded, interdisciplinary subject matter experts, composed of strength and conditioning coaches, athletic trainers, physical and occupational therapists, registered dietitians, and mental readiness professionals. These teams operate within brigades to deliver proactive, preventive, and performance-enhancing interventions that reduce injury risk, accelerate rehabilitation, improve fitness and cognitive performance, and sustain deployability. This evaluation quantified the return on investment (ROI) of embedded HPTs across 56 matched active-duty brigades (28 HPT-resourced, 28 controls), encompassing over 1,000,000 soldiers from fiscal year (FY) 2019 through FY2023.

METHODS: A quasi-experimental, presence-based difference-in-differences framework estimated multiyear treatment effects for musculoskeletal injury (MSKI) referrals and profiles, behavioral health (BH) and substance abuse (SA) profiles, Army Combat Fitness Test (ACFT) pass/failure rates, Army Body Composition Program (BCP) noncompliance, and Rifle Marksmanship Qualification (RMQ). Outcome deltas were monetized using validated cost-per-case benchmarks from military/government reports and peer-reviewed studies. A 10,000-draw Monte Carlo simulation, incorporating triangular distributions and a ρ = 0.15 Gaussian copula, modeled fiscal uncertainty, interdomain dependency, and force-wide extrapolation.

RESULTS: Despite significantly worse baseline odds pre-resourcing, HPT brigades reversed all major readiness disadvantages by FY2023. MSKI referral odds declined 61% (odds ratio [OR] 1.16 → 0.45), SA profile odds dropped 79% (OR 1.92 → 0.41), and BH > 90-day profile odds fell 44% (OR 1.51 → 0.84). ACFT failure odds decreased 22% (OR 1.05 → 0.82), RMQ expert qualification odds increased 33% (OR 1.21 → 1.60), BCP failure odds decreased 12%, and RMQ failure odds declined 28%. Annually, per brigade, these effects translated to 1363 adverse events avoided and 37,484 duty days restored. Using domain-specific cost estimates, a 10,000-draw Monte Carlo simulation estimated mean annual cost avoidance of $14.06 M per brigade (95% CI $12.25-16.19 million), with 99.05% of draws exceeding a 4:1 ROI. Duty day restoration and expert RMQ gains added $10.38 million (95% CI $8.15-13.00 million) in readiness value. Combined, annual total economic value reached $24.44 million per brigade (ROI = 8.15:1; 95% CI 7.17-9.27), with force-wide extrapolation yielding $5.28 billion in annual total Army returns. Every $1 invested in HPTs returns $8.15 in value ($4.69 in cost avoidances and $3.46 in readiness improvements).

CONCLUSIONS: Embedded HPTs produce robust, statistically significant, multidomain improvements in readiness, performance, and cost efficiency. These estimates exclude long-horizon returns such as retention, disability deferral, or downstream system savings-suggesting total ROI is significantly underestimated. This study indicates HPTs are core readiness infrastructure. Their full-scale implementation is a strategic imperative for modernizing force sustainment and preserving the Army’s most critical asset: the soldier.

PMID:41678032 | DOI:10.1007/s40279-026-02399-3

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Spiritual Intelligence and its Association with the Coping Strategies of Jordanian Patients with Chronic Diseases

J Relig Health. 2026 Feb 12. doi: 10.1007/s10943-026-02578-6. Online ahead of print.

ABSTRACT

Chronic diseases impose substantial suffering that often exceeds individuals’ capacity to maintain effective coping. Spiritual intelligence (SI) may play an integral role in shaping patients’ responses to chronic diseases and in their ability to adopt adaptive coping strategies. This study assessed the association between SI and coping strategies among a convenience sample of 185 adult patients with chronic diseases. A descriptive design was used, and participants completed the Spiritual Intelligence Self-Report Inventory (SISRI-24) and the Brief-COPE. The overall level of SI was moderate. A statistically significant positive correlation was found between SI and both problem-focused and emotion-focused coping strategies. Sociodemographic factors explained approximately 11.2% of the variance in SI. Patients with higher SI appear more capable of selecting adaptive coping strategies when dealing with chronic conditions.

PMID:41678020 | DOI:10.1007/s10943-026-02578-6

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Effectiveness of Cranberry Supplementation for Prevention and Treatment of Infectious Urinary Tract Disease in Dogs and Cats: A Systematic Review

J Vet Pharmacol Ther. 2026 Feb 12. doi: 10.1111/jvp.70050. Online ahead of print.

ABSTRACT

Cranberry and cranberry extracts are available for treatment or prevention of urinary tract disease in dogs and cats, but guidance regarding their use is lacking. The objectives were to identify and assess literature pertaining to the efficacy of cranberry and cranberry extract supplementation for prevention and treatment of bacterial cystitis and subclinical bacteriuria in dogs and cats. A systematic review was performed, and three studies involving a total of 122 animals (106 dogs and 16 cats) were identified. No studies reported statistically significant or numerical impacts of treatment. Two studies were deemed at high risk of bias, and one was deemed at low risk. Certainty of evidence was low to very low. The small number of studies, small sample sizes, data from those studies, and low certainty of evidence preclude confident assessment of the role of cranberry for the prevention or treatment of infectious urinary tract disease in dogs and cats.

PMID:41676867 | DOI:10.1111/jvp.70050

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Electron-induced processes in ellagic acid molecules via gas-phase resonance electron attachment and electron transfer following photoexcitation in solution

Phys Chem Chem Phys. 2026 Feb 12. doi: 10.1039/d5cp04866d. Online ahead of print.

ABSTRACT

The low-energy (0-14 eV) resonance electron interaction with gas-phase ellagic acid (EA) molecules is studied using dissociative electron attachment (DEA) spectroscopy. Photoinduced electron transfer reactions with solvated EA are studied using the chemically induced dynamic nuclear polarization (CIDNP) technique. Molecular negative ions EA˙, the most abundant species generated by thermal electron attachment to EA, autodetach their extra electrons within 200 µs, allowing us to estimate the adiabatic electron affinity of EA as 1.3 eV-a value in excellent agreement with that predicted at B3LYP/6-31+G(d) level. In an intriguing observation, the slow (microsecond timescale) cleavage of a single O-H bond, resulting in [EA – H] fragments, can tentatively be explained by the H-atom roaming across the molecular framework or by the statistical accumulation of the energy required to overcome the potential barrier along the reaction coordinate. In contrast to a variety of polyphenolic molecules, [EA – 2H]˙ is not formed at thermal electron energies, despite this decay being energetically favorable, likely due to competition with single H-atom abstraction. Fully deprotonated EA (present in solution at pH > 10 as [EA – 4H+]4-) can attach solvated electrons to produce [EA – 4H+5- radicals, consistent with the high electron-accepting ability of isolated EA. However, deprotonated EA can also donate electrons to the model electron acceptor, 2,2′-dipyridyl, generating [EA – 4H+3- radicals, with no further decomposition observed in the present CIDNP experiments, in agreement with the limited fragmentation seen in gas-phase DEA applied to intact EA. The present findings could be important for understanding the biological effects produced by EA, namely, its synergism with radiotherapy and its antibacterial activity, both likely associated with electron-driven processes.

PMID:41676865 | DOI:10.1039/d5cp04866d

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Nevin Manimala Statistics

The Importance of Continuous Monitoring in Identifying Bradycardia during Propranolol Treatment for Infantile Hemangiomas

JMA J. 2026 Jan 15;9(1):302-308. doi: 10.31662/jmaj.2025-0213. Epub 2025 Nov 28.

ABSTRACT

INTRODUCTION: To clarify whether continuous-monitoring can detect bradycardia during propranolol treatment for infantile hemangioma (IH) and explore management practices for patients with bradycardia.

METHODS: This retrospective study with historic controls was conducted on children with IH aged 0-1 year admitted for propranolol treatment at the National Center for Child Health and Development between October 2016 and July 2023. Patients were divided into two groups based on the monitoring method, namely, the spot-measurement group (October 2016 to August 2018) and the continuous-monitoring group (September 2018 to July 2023). Bradycardia was defined as a heart rate of <90/min lasting for 20 minutes. Patient data included clinical characteristics, propranolol dosage, and adverse effects (bradycardia, hypotension, and hypoglycemia). Statistical analyses were performed using Fisher’s exact and Mann-Whitney U tests.

RESULTS: During the study period, 106 patients were admitted for propranolol therapy; 49 were in the spot-measurement group and 57 in the continuous-monitoring group. The frequency of bradycardia was significantly higher in the continuous-monitoring group than in the spot-measurement group (21% vs. 2%, p = 0.003). In the continuous-monitoring group, 2 of 12 patients with bradycardia were symptomatic. All patients experienced prompt resolution of symptoms with the reduction of propranolol dosage and had favorable outcomes for IH.

CONCLUSIONS: Continuous-monitoring can detect bradycardia more effectively during propranolol treatment for IH than spot-measurement, and reducing the dosage of propranolol can lead to favorable outcomes for IH while minimizing the risk of bradycardia.

PMID:41676847 | PMC:PMC12889071 | DOI:10.31662/jmaj.2025-0213

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Nevin Manimala Statistics

Geriatric Assessment with Geriatric-8, Body Weight Loss, and Bioelectrical Impedance Analysis in Older Patients with Lung Cancer: A Single-Center Retrospective Study

JMA J. 2026 Jan 15;9(1):309-320. doi: 10.31662/jmaj.2025-0395. Epub 2025 Dec 19.

ABSTRACT

INTRODUCTION: There is no standard geriatric assessment (GA) for patients aged ≥65 years with lung cancer (hereafter referred to as patients). This retrospective study evaluated whether GA could be achieved by combining Geriatric-8 (G8) score (G8s), body weight loss (BWL) of more than 5% (5%BWL), and bioelectrical impedance analysis (BIA).

METHODS: This study included patients who underwent G8 screening, BIA (measuring skeletal muscle mass index [SMI] and extracellular water-to-total body water ratio [ECW/TBW]), and physical function tests before treatment at our hospital between March 1, 2023, and December 31, 2024. Patient clinical records were reviewed to collect baseline data. Statistical analyses were conducted using R (version 4.1.1).

RESULTS: A total of 120 patients were analyzed. We found the following significant associations: G8s ≤14.0 and 5%BWL were associated with advanced-stage disease; G8s >14.0 and SMI ≥cut-off value (CV) with higher body mass index; ECW/TBW ≥0.4 (0.4 ECW/TBW) with aging and poor performance status; 5%BWL with lower maximum lower leg calf circumference (MLLCC); SMI ≥CV with higher maximum handgrip strength (MHGS) and MLLCC; 0.4 ECW/TBW with lower MHGS, gait speed, and five-time sit-to-stand performance. The multivariate analysis confirmed significant associations: G8s ≤14.0 was associated with cancer cachexia; SMI < CV and 0.4 ECW/TBW were associated with sarcopenia, and 0.4 ECW/TBW was associated with physical function decrease, as indicated by a Short Physical Performance Battery score of ≤9. Patients with G8s ≤14.0, 5%BWL, or 0.4 ECW/TBW had shorter survival durations than their respective counterparts. Patients were classified into three frailty categories (none, mild combined with moderate, severe) based on a combination of four factors (G8, BWL, SMI, and ECW/TBW) and had distinct survival curves.

CONCLUSIONS: The combination of these four factors offers a simple and objective approach for GA in patients.

PMID:41676841 | PMC:PMC12889063 | DOI:10.31662/jmaj.2025-0395

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Predictive Value of EGFR Expression for the Efficacy of Near-Infrared Photoimmunotherapy in Head and Neck Cancer

JMA J. 2026 Jan 15;9(1):180-188. doi: 10.31662/jmaj.2025-0174. Epub 2025 Nov 21.

ABSTRACT

INTRODUCTION: Near-infrared photoimmunotherapy (NIR-PIT) has emerged as a promising treatment for unresectable locally advanced or recurrent head and neck cancer. This study aimed to identify potential predictors of NIR-PIT efficacy before treatment by focusing on blood biomarkers in addition to pathological findings, including epidermal growth factor receptor (EGFR) expression in tumors.

METHODS: A retrospective analysis of the medical records of 10 patients with head and neck cancer, who exhibited confirmed EGFR expression and underwent NIR-PIT treatment at Akita University Hospital from December 2021 to April 2024, was conducted (13 cycles of NIR-PIT). EGFR expression, cluster of differentiation (CD)4/CD8 ratio, regulatory T cell (Treg) frequency, serum albumin, neutrophil-to-lymphocyte ratio (NLR), and neutrophil-to-eosinophil ratio (NER) were calculated from the tumor tissue and blood collected immediately before treatment. Correlations of these factors with tumor response to NIR-PIT were determined.

RESULTS: The objective response rate (ORR) was 61.5% and the disease control rate (DCR) was 100%. A statistically significant association was observed between the EGFR index and tumor response. No statistically significant correlation was found between other biomarkers (CD4/CD8 ratio, Treg frequency, serum albumin, NLR, NER) and tumor response.

CONCLUSIONS: These findings underscore the important role of EGFR expression in predicting the efficacy of NIR-PIT in the management of head and neck cancer, and highlight the significance of incorporating EGFR assessment in patient selection and optimized treatment strategies. Further studies are needed to elucidate the role that these other potential predictors, including tumor immune response markers, play in NIR-PIT outcomes.

PMID:41676833 | PMC:PMC12888994 | DOI:10.31662/jmaj.2025-0174

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Genetic and Genomic Analysis of Systemic Sclerosis: A Narrative Review of the Recent Advancement

JMA J. 2026 Jan 15;9(1):1-9. doi: 10.31662/jmaj.2025-0167. Epub 2025 Nov 14.

ABSTRACT

Systemic sclerosis (SSc) is one of the systemic autoimmune diseases characterized by disease-specific autoantibodies and generalized fibrosis in connective tissues and internal organs, resulting from microvascular and immune dysfunctions, which lead to premature death in affected individuals. The etiology of SSc is complex and poorly understood; however, as with most autoimmune conditions, it is widely accepted that both environmental and genetic factors interact and contribute to disease development. Over the last decade, genome-wide association studies (GWAS) have identified multiple genetic markers associated with SSc, and a number of causal variants have also been fine-mapped using state-of-the-art statistical techniques. Furthermore, the latest East Asian GWAS identified novel risk variants that were not as strongly represented in Europeans as in East Asians, and also provided additional novel risk variants, highlighting the importance of enrolling a diverse population for the analysis of complex traits. The association of human leukocyte antigen regions has been clarified mainly in individuals of European descent, with the identification of clinical subtype-specific associations of certain alleles. The associations in East Asian SSc are currently being analyzed by our team. Recent advances in single-cell ribonucleic acid (RNA) sequence technology have enabled the identification of transcriptomic changes at the single-cell level in a cell type or tissue-specific manner, allowing for the identification of disease-relevant cells or transcriptomes. To date, multiple single-cell RNA sequence studies have been conducted, primarily focusing on cells and transcriptomes in peripheral blood, skin, or lung. Despite the remarkable advances in state-of-the-art technology for both genetics and transcriptomics, gene expression regulations, especially by enhancers, enriched for disease heritability and thus critical for SSc development, remain unresolved. Integrative analysis using multi-omics approaches, combined with deep phenotyping of study cohorts, is imperative to fully characterize the genetic component of this disease and to identify causal variants, which may lead to more targeted and effective treatment of SSc.

PMID:41676820 | PMC:PMC12889322 | DOI:10.31662/jmaj.2025-0167

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A Review of Japan’s Medical Care Reimbursement Programs in Primary Care from the Perspective of Social Determinants of Health

JMA J. 2026 Jan 15;9(1):355-359. doi: 10.31662/jmaj.2024-0313. Epub 2025 Dec 26.

ABSTRACT

There is increasing awareness of the need to incorporate social determinants of health (SDH) into medical practice. However, the extent to which the reimbursement system addresses SDH remains unclear. This narrative policy review aimed to evaluate the Japanese medical reimbursement system to determine whether and to what degree it incorporates assessments and actions related to SDH, with a special focus on primary care settings. We also explored the potential impacts and challenges of these programs in addressing patients’ SDH issues. A team consisting of physicians experienced in clinics, hospitals, home care, social epidemiological research, and a community care nurse reviewed the current reimbursement system. They identified eight medical reimbursement programs for evaluation. Two programs directly included SDH elements (“Hospitalization and Discharge Support Fee” and “Guidance in Cooperation with Mental Health Care Fee”). The two programs were introduced in 2022. It was found that SDH assessments are often optional and need more clarity in their items; few programs offer SDH assessments in outpatient and home care settings, and there is no mandate for collaboration with community supporters. We found the Japanese reimbursement system has provisions for some programs involving SDH. However, significant challenges remain that require revision. This study offers insights and recommendations for addressing health disparities related to SDH in the future.

PMID:41676803 | PMC:PMC12889345 | DOI:10.31662/jmaj.2024-0313