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Nevin Manimala Statistics

Methodological Approaches for the Estimation of Confidence Intervals on Partial Youden Index Under Verification Bias

Pharm Stat. 2026 Mar-Apr;25(2):e70079. doi: 10.1002/pst.70079.

ABSTRACT

The advancement of precision medicine hinges on accurately tailored diagnostic strategies yet estimating reliable confidence intervals (CIs) for the maximal partial Youden Index under verification bias presents considerable challenges, especially within critical false positive rate (FPR) ranges (e.g., (0, 0.1), (0.05, 0.2)) vital for specific clinical applications. While previous work established the partial Youden Index framework, and methods like full imputation (FI), mean score imputation (MSI), inverse probability weighting (IPW), and semiparametric efficient (SPE) address verification bias, robustly integrating these for the partial index across demanding FPRs has needed further development. This paper significantly advances this area by adapting and applying these four bias-correction techniques to estimate the partial Youden Index and its confidence interval (CIs) under verification bias. We systematically evaluate their performance with the proposed (bootstrap-based, MOVER) CI construction approaches. Extensive simulations demonstrate distinct method-specific patterns across verification proportions and FPR ranges, revealing the complexities in achieving reliable estimates. Bootstrap-based CIs exhibit greater robustness to model misspecification, a common clinical uncertainty, while analytical CIs often face undercoverage issues. A cardiovascular disease biomarker analysis corroborates these findings, showing Blood Pressure’s superior discriminatory capability compared to Pulse Rate. Operating under the Missing at Random (MAR) assumption, these results offer crucial, updated guidance for CI estimation in diagnostic studies with incomplete verification, providing significant value where precise evaluation in specific FPR regions is paramount and complete verification is unfeasible. Our findings enhance the statistical foundation for diagnostic test evaluation, extending beyond previous work by comprehensively addressing the partial Youden Index with these updated verification bias correction and CI formula applications.

PMID:41710981 | DOI:10.1002/pst.70079

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Nevin Manimala Statistics

The impact of body mass index on the treatment response to neoadjuvant chemotherapy in patients with breast cancer: A systematic review and meta-analysis

Tumori. 2026 Feb 19:3008916251410090. doi: 10.1177/03008916251410090. Online ahead of print.

ABSTRACT

OBJECTIVE: Many studies have highlighted that elevated body mass index (BMI) not only correlates with an elevated likelihood of developing breast cancer (BC) but may also influence patients’ responsiveness to therapeutic regimens and long-term survival outcomes. The impact of BMI on therapeutic response to neoadjuvant chemotherapy (NAC) in patients with BC remains inconclusive. This study seeks to evaluate the effect of BMI on treatment response in the BC population undergoing NAC via a meta-analysis, thereby providing evidence-based support for clinical decision-making.

METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were thoroughly searched until July 29, 2024. Eligible studies were selected as per predefined eligibility criteria. Data extraction and quality assessment were executed via the Newcastle-Ottawa Scale (NOS). Statistical analyses were enabled by R 4.4.1 and Stata 17.

RESULTS: Fifteen studies encompassing 15,235 patients were incorporated. The meta-analysis revealed that in contrast to patients with a normal or low BMI, those who were overweight or obese had a significantly reduced pathlological complete response (pCR) rate (OR: 0.79, p = 0.040). The underweight cohort demonstrated a higher pCR rate in comparison to those with normal BMI (OR: 1.56, p=0.015). Moreover, overweight and obese cohorts displayed a lower pCR rate in contrast to those having normal BMI (OR: 0.83, p < 0.0001).

CONCLUSION: This study indicates that overweight and obese patients tend to exhibit a reduced pCR, highlighting the need for standardized BMI definitions. Future well-designed prospective studies are necessitated to validate these observations.

PMID:41710980 | DOI:10.1177/03008916251410090

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Nevin Manimala Statistics

Decline of phosphatidylethanol (B-PEth) during abstinence in patients with alcohol use disorder undergoing withdrawal treatment, and the correlation of B-PEth with self-reported alcohol intake

Addiction. 2026 Feb 19. doi: 10.1111/add.70359. Online ahead of print.

ABSTRACT

BACKGROUND AND AIM: Accurately estimating alcohol consumption is crucial for clinical decision-making and monitoring treatment outcomes. Phosphatidylethanol in blood (B-PEth), a direct alcohol biomarker, is currently the most reliable indicator of alcohol intake, with a detection window of several weeks; however, the factors influencing the decline of B-PEth levels remain largely unknown. This study aimed to investigate the decline of B-PEth levels during abstinence in patients with alcohol use disorder (AUD) undergoing withdrawal treatment.

METHOD: A total of 100 patients were recruited in withdrawal treatment and followed during three to four weeks of abstinence. Blood samples were collected at baseline and weekly during abstinence to measure B-PEth levels of two homologues (16:0/18:1 and 16:0/18:2). Self-reported alcohol consumption was documented using the Timeline Followback (TLFB) method for 30 days before abstinence and throughout the study period.

RESULTS: B-PEth elimination followed first-order kinetics. The mean half-life was 7.24 days [95% confidence interval (CI) = 6.98-7.53] for 16:0/18:1 and 4.55 days (95% CI = 4.44-4.67) for 16:0/18:2. The rate of decline varied by week, with a longer half-life observed in week three compared with week one. No statistically significant sex differences were detected. The strongest correlation between B-PEth levels and self-reported alcohol consumption was found for data from two weeks prior to abstinence.

CONCLUSION: Elimination of phosphatidylethanol in blood (B-Peth) follows first-order kinetics, with homologue 16:0/18:1 exhibiting a longer half-life than 16:0/18:2. The rate of decline is influenced by the week of alcohol abstinence and B-PEth levels are detectable even in the fourth week of abstinence. The strongest correlation between B-PEth and self-reported alcohol consumption is at two weeks prior to abstinence.

PMID:41710972 | DOI:10.1111/add.70359

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Nevin Manimala Statistics

Enhancement of Calcium Ion Permeation via Resonant Coupling of Ion and Terahertz Waves in Voltage Gated Calcium Channels

Adv Sci (Weinh). 2026 Feb 19:e20475. doi: 10.1002/advs.202520475. Online ahead of print.

ABSTRACT

Dysregulated calcium ion (Ca2+) influx is implicated in diverse channelopathies. Terahertz (THz) waves have been explored as a promising approach to modulate the influx, which primarily target resonant interactions with chemical groups in channels. Here, we demonstrate a strategy that directly regulates the motion of confined Ca2+ ions within the selectivity filter via resonant THz waves. We characterize the ions’ axial oscillations, identifying a distinct intrinsic frequency of 1.65 THz and two coherent modes. By tuning a THz electric field to this frequency, we induce a remarkable resonance excitation that lowers the energy barrier between binding sites, achieving a statistically significant enhancement of Ca2+ permeation in our model. Meanwhile, we show that the degree of coherence is precisely tunable by the resonant THz field and temperature. Furthermore, quantum mechanics analyses reveal transition frequencies and wavefunctions that validate the observed oscillation modes, confirming that the collective motion exhibits discrete quantum eigenstates. Our results introduce a proof-of-concept, ion-targeted strategy for manipulating Ca2+ permeation and propose a theoretical coherence mechanism for high-flux ions transport. This work advances the understanding of ion channel physics via a mechanism-oriented framework that lays the groundwork for exploring novel bio-electromagnetic modulation.

PMID:41710970 | DOI:10.1002/advs.202520475

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Nevin Manimala Statistics

Determination of Genital Hygiene Behaviors and Risk Factors of Women of Reproductive Age After the Earthquake

Disaster Med Public Health Prep. 2026 Feb 19;20:e47. doi: 10.1017/dmp.2026.10319.

ABSTRACT

OBJECTIVE: This research aims to determine the genital hygiene behaviors and risk factors of women of reproductive age after the earthquake.

METHODS: The descriptive and relationship-seeking research was conducted with 296 women reached online in the Malatya province, where the earthquake in Turkey caused heavy damage. Research data was collected using an online survey form created via Google Forms. Data were obtained using the Personal Information Form and Genital Hygiene Behavior Scale.

RESULTS: In the study, genital hygiene behaviors of women with low education level (p = .004), not working (p = .003), sharing underwear (p = .002), having vaginal itching (p = .006), bathing frequency once a week or less (p = .001), bathing while sitting on a stool (p = .001) and having no knowledge about genital infection (p = .001) were found to be inadequate.

CONCLUSIONS: In the study, it was determined that the genital hygiene behaviors of women of reproductive age were negative after the earthquake. It is recommended that health professionals should not ignore the adverse effects that may occur on women’s genital hygiene behaviors after disasters such as earthquakes and take the necessary initiatives.

PMID:41710966 | DOI:10.1017/dmp.2026.10319

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Nevin Manimala Statistics

Multicentre evaluation of teicoplanin prescribing and monitoring in the UK and Ireland: the TUcK-SHOP study

J Antimicrob Chemother. 2026 Feb 2;81(3):dkag038. doi: 10.1093/jac/dkag038.

ABSTRACT

BACKGROUND: Teicoplanin exhibits complex pharmacokinetics with substantial inter-patient variability. Therapeutic drug monitoring (TDM) is recommended to ensure adequate exposure, yet contemporary data on real-world prescribing practices are scarce. We evaluated current teicoplanin dosing and monitoring practices across UK and Irish hospitals.

METHODS: We conducted a multicentre, retrospective cohort study (Teicoplanin in UK: Study of Hospital Practice; TUcK-SHOP) across 21 hospitals. Adults receiving ≥5 days of intravenous/intramuscular teicoplanin with at least one TDM sample were included. Primary outcome was adherence to local or national dosing guidelines. Secondary outcomes included initial trough level attainment (≥20 mg/L) and laboratory-confirmed toxicity. Multivariable linear regression identified predictors of first trough concentrations.

RESULTS: A total of 391 patients met inclusion criteria (median age 69 years; 57.5% male). Guideline adherence was 66% overall but varied widely between sites (5%-100%). Most patients received three-dose loading (61.3%) with median maintenance dosing of 10.6 mg/kg daily (IQR 7.3-12.1). Median first trough level was 24.6 mg/L (IQR 17.9-33.2); only 40.8% of patients on 6 mg/kg maintenance achieved ≥20 mg/L versus 86.6% on 12 mg/kg (P < 0.001). Independent predictors of higher trough levels included lower creatinine clearance, longer time to TDM sampling, higher loading and maintenance doses, and greater body weight (adjusted R2 = 0.26, P < 0.001). Dose adjustments were required in 30% of patients.

CONCLUSIONS: Teicoplanin prescribing demonstrates significant variation across UK and Irish hospitals. Higher maintenance dosing (10-12 mg/kg) predicts therapeutic target attainment. These real-world data support the need for standardized dosing protocols to optimize teicoplanin therapy.

PMID:41710963 | DOI:10.1093/jac/dkag038

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Nevin Manimala Statistics

Economic impact of a maternal Klebsiella pneumoniae vaccine: estimates for 107 low- and middle-income countries

Philos Trans R Soc Lond B Biol Sci. 2026 Feb 19;381(1944):20250002. doi: 10.1098/rstb.2025.0002.

ABSTRACT

Sepsis is a leading cause of morbidity and mortality among newborns in low- and middle-income countries, and its treatment is further complicated by high rates of antimicrobial resistance to current antibiotics. We assessed the economic impact of a proposed maternal vaccine to protect neonates against sepsis caused by Klebsiella pneumoniae in 107 low- and middle-income countries. We estimated vaccine-avertable medical expenditures, vaccine-avertable productivity losses owing to caregiver absenteeism from work, and vaccine-avertable monetized disability-adjusted life-years using a country-specific value of statistical life-year estimate. Implementing a maternal K. pneumoniae vaccine could avert US$6.9 billion (95% CI 5.6-8.3) in monetized disability-adjusted life-years annually across 107 countries. Countries in the African region displayed the highest median vaccine-avertable medical costs and productivity losses per capita associated with resistance to first- and second-line treatments compared with other regions. Low-income countries were disproportionately impacted by the increased medical expenditures associated with antimicrobial resistance, with the median price of third-line antibiotic treatment in these countries being 23.9 days of income. Our estimates indicate that a maternal K. pneumoniae vaccine could significantly reduce the societal economic burden and catastrophic health expenditures for families affected by neonatal sepsis and antimicrobial resistance in low- and middle-income countries. This article is part of the Royal Society Science+ meeting issue ‘Vaccines and antimicrobial resistance: from science to policy’.

PMID:41710952 | DOI:10.1098/rstb.2025.0002

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Nevin Manimala Statistics

Improving interprofessional communication skills among healthcare providers: a quasi-experimental design evaluating a clinical improvisation training program

J Interprof Care. 2026 Feb 19:1-8. doi: 10.1080/13561820.2026.2625075. Online ahead of print.

ABSTRACT

Effective interprofessional communication among healthcare teams is integral for the function of health systems. We sought to rigorously evaluate the effectiveness of clinical improvisation training in improving interprofessional communication skills among practicing providers, and to identify factors contributing to training success. We used a quasi-experimental wait-list design (intervention group n = 62; control group n = 66) to evaluate the effects of a clinical improvisational training program on interprofessional communication skills using validated baseline surveys and follow-up surveys several months later. Both groups included physicians and advanced practice nurses from various departments in a single academic medical institution. Statistical analysis was focused on examining changes in communication skills between groups and on contributors to communication change in the intervention group. Within-person changes indicated that communication skills significantly modestly improved from baseline to follow-up for the intervention group but not for the control group. Among the intervention group, we observed a significant interaction between excitement about the training and uncertainty tolerance in predicting improvement in communication skills. Clinical improvisation is likely to be effective in improving interprofessional communication skills among practicing healthcare workers. Increasing excitement about the clinical improvisation training programs and reducing uncertainty about it could bolster the success of these programs.

PMID:41710951 | DOI:10.1080/13561820.2026.2625075

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Nevin Manimala Statistics

Nanoscopic Imaging the Lithiation of Sulfur Nanoparticles under Electron Beam Irradiation

Adv Sci (Weinh). 2026 Feb 19:e19640. doi: 10.1002/advs.202519640. Online ahead of print.

ABSTRACT

In situ Transmission Electron Microscopy (TEM) provides powerful insights into the reaction mechanisms of Lithium-Sulfur (Li-S) batteries. However, distinguishing intrinsic electrochemical behaviors from artifacts induced by high-energy electron beam irradiation remains a critical challenge. Here, we systematically investigate the lithiation kinetics of sulfur nanoparticles triggered exclusively by electron beam irradiation, decoupling beam effects from electrochemical driving forces. We first conduct control experiments on pure lithium oxide (Li2O) and pure sulfur to assess their stability under electron irradiation, and then monitor lithiation behavior in a mixed system of sulfur and lithium oxide (Li2O), under varying irradiation times and temperatures. We report a striking “explosive” lithiation phenomenon, characterized by a massive volume expansion of up to 8300% and rapid kinetics (19312 nm2 s-1), which starkly contrasts with the ∼80% expansion observed in conventional electrochemical cycling. By conducting comparative experiments across a wide temperature range (25°C to -150°C), we identify the thermal effect of the electron beam as the dominant driving force; notably, the explosive reaction is completely suppressed at cryogenic temperatures (-150°C). Furthermore, we observe unique beam-induced artifacts, including directional cavity formation and rapid phase transitions from crystalline S to amorphous Li2S. This work establishes a critical baseline for distinguishing beam-induced damage from genuine electrochemical reactions in in situ TEM studies and provides nanoscopic insights into the thermal runaway mechanisms of sulfur cathodes under high-energy abuse conditions, underpinning accurate characterization of Li-S battery materials and development of advanced battery systems.

PMID:41710945 | DOI:10.1002/advs.202519640

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Nevin Manimala Statistics

Impact of chronic endometritis on assisted reproductive technology outcomes: a propensity score inverse probability weighting cohort study

Front Cell Dev Biol. 2026 Jan 28;14:1749173. doi: 10.3389/fcell.2026.1749173. eCollection 2026.

ABSTRACT

BACKGROUND: Chronic endometritis (CE), characterized by CD138+ plasma cell infiltration, has been proposed to impair reproductive outcomes in assisted reproductive technology (ART). However, current evidence remains inconsistent, and diagnostic criteria vary widely. This study aimed to evaluate whether CE diagnosis and antibiotic treatment influence clinical pregnancy, live birth, and miscarriage outcomes following in vitro fertilization with fresh embryo transfer (IVF-ET) and frozen embryo transfer (FET).

METHODS: We retrospectively analyzed 3,041 embryo transfer cycles (1,507 IVF-ET; 1,534 FET) from 1,401 infertile women treated at the Reproductive Medicine Center of Liuzhou Hospital, Guangzhou Women and Children’s Medical Center (2008-2023). Chronic endometritis (CE) was primarily defined as the presence of ≥1 CD138+ plasma cell per 10 high-power fields (HPFs, ×400). Standard therapy was doxycycline 100 mg twice daily for 14 days. Outcomes were analyzed per transfer cycle using Poisson regression with robust standard errors and propensity score weighting.

RESULTS: Untreated CE patients had comparable live birth and clinical pregnancy rates to non-CE patients in both IVF-ET (live birth 37.7% vs. 36.7%) and FET (39.0% vs. 37.9%), and were also associated with a lower observed miscarriage risk after IVF-ET (adjusted RR 0.67, 95% CI 0.46-0.97). Among CE patients, antibiotic treatment did not improve outcomes compared with no treatment (IVF-ET live birth 36.8% vs. 37.7%; FET 41.5% vs. 38.7%; all p > 0.05). Similarly, post-treatment “cured” and “persistent” CE groups showed no significant differences in live birth or miscarriage rates in either transfer type. Exploratory analyses revealed context-dependent trends, but most interactions were nonsignificant.

CONCLUSION: In this large single-center cohort, CE defined by CD138+ plasma cell infiltration was not associated with reduced clinical pregnancy or live birth rates, and no statistically significant benefit of antibiotic treatment was observed. The observed reduction in miscarriage risk among CE patients suggests complex immunological dynamics. Routine CE screening in all ART candidates may be unnecessary, and targeted evaluation for high-risk subgroups warrants further investigation.

PMID:41710942 | PMC:PMC12910471 | DOI:10.3389/fcell.2026.1749173