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Nevin Manimala Statistics

Comparison of highest and overall percentage Gleason pattern 4 in prostate cancer biopsies

Virchows Arch. 2025 Jun 6. doi: 10.1007/s00428-025-04117-2. Online ahead of print.

ABSTRACT

Current guidelines recommend pathologists to report percentage Gleason pattern 4 (GP4%) in Gleason score (GS) 7 prostate cancer (PCa) biopsies. However, it is unspecified whether the highest or overall GP4% should be reported. This study aims to clarify which quantification method correlates best with radical prostatectomy (RP) pathology. This study included 308 men with the highest GS 3 + 4 = 7, 4 + 3 = 7, or 4 + 4 = 8 on centrally revised systematic and/or targeted biopsies who underwent RP between 2018 and 2022. The highest and overall biopsy GP4% were compared with RP GP4% using Spearman’s rank correlation coefficient and adverse pathology (AP) (pT-stage ≥ T3, GS ≥ 4 + 3 = 7 and/or pN1) using multivariable logistic regression models adjusted for clinical tumor stage, prostate specific antigen (PSA), percentage of tumor positive biopsies, biopsy modality (systematic/targeted/both), and cribriform pattern. Both quantification methods correlated with RP GP4% (both rho = 0.59), and no significant difference was found between them (p = 0.78). On multivariable analyses, both GP4% quantification methods were significantly associated with AP (per 10% increase, highest GP4% odds ratio [OR] 1.26 [95% CI 1.14-1.39], overall GP4% OR 1.38 [95% CI 1.22-1.58], both p < 0.001). The area under the curve (AUC) was slightly better for overall (0.78 [95% CI 0.73-0.83]) than the highest GP4% (0.76 [95% CI 0.71-0.81], p = 0.041). This study found that the highest and overall biopsy GP4% both correlated with RP GP4%. Although the discriminative performance of the highest and overall GP4% was comparable with respect to AP at RP, the overall GP4% statistically slightly outperformed the highest GP4%. Including the overall GP4% may have added value in risk stratification and clinical decision-making in a subset of PCa patients.

PMID:40478475 | DOI:10.1007/s00428-025-04117-2

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Nevin Manimala Statistics

Cost‑effectiveness analysis of fracture liaison services in Iran

Arch Osteoporos. 2025 Jun 6;20(1):72. doi: 10.1007/s11657-025-01555-y.

ABSTRACT

This study evaluates the cost-effectiveness of a Fracture Liaison Service (FLS) compared to current practice for individuals aged 50 and older with fragility fractures in Iran. The FLS was associated with an additional cost of $50 and a gain of 0.03 QALYs, resulting in an incremental cost-effectiveness ratio of $1663 per QALY, demonstrating its cost-effectiveness.

PURPOSE: This study aimed to assess the cost-effectiveness of a FLS program compared to current practice in Iran, from a societal perspective.

METHODS: The target population was patients aged 50 years or older with recent sentinel fragility fractures. Data were collected using various resources, including previously published literature, treatment guidelines, and hospitals. A state-based microsimulation model with a lifetime horizon was designed to simulate costs and quality-adjusted life years (QALYs). Treatment pathways for patients under current practice and FLS were compared using incremental cost-effectiveness ratios (ICERs).

RESULTS: For patients aged 50 years and older with a sentinel fragility fracture, FLS was associated with an incremental cost of $50 and a gain of 0.03 QALYs compared to current practice. Consequently, the ICER was estimated at $1663 per QALY gained, which is below the willingness-to-pay (WTP) threshold of one GDP per capita ($4466 per QALY). Simulations showed that comparing the current practice, FLS could prevent 59 new fractures and 10 related deaths per 1000 patients. The one-way sensitivity analysis indicated that treatment efficacy and medication costs exert the greatest influence on the ICER.

CONCLUSION: The findings of this study demonstrate that FLS is cost-effective compared to current practice in Iran. Given the significant prevalence of osteoporosis and the increasing aging population in Iran, these results underscore the potential of FLS to enhance patient outcomes.

PMID:40478456 | DOI:10.1007/s11657-025-01555-y

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Nevin Manimala Statistics

The Effect of Elevated Blood Pressure on Rich-Club Organization: A Multicenter MR Diffusion Tensor Imaging Study From Prehypertension to Hypertension

J Magn Reson Imaging. 2025 Jun 6. doi: 10.1002/jmri.29835. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension-induced alterations in brain network topology remain poorly understood, and diffusion tensor imaging (DTI) offers a promising approach for detecting early structural changes.

HYPOTHESIS: Rich-club organization undergoes progressive disruption from prehypertension to hypertension, and these alterations may serve as potential imaging biomarkers for hypertension.

STUDY TYPE: Cross-sectional.

SUBJECTS: Five hundred thirteen participants (150 healthy controls, 175 prehypertensive individuals, and 188 hypertensive patients).

SEQUENCE: DTI with an echo planar imaging sequence at 3.0 T.

ASSESSMENT: Whole-brain structural networks were constructed using deterministic fiber tracking. Modularity, rich-club organization (rich-club, feeder and local connections), small-world property, global efficiency, local efficiency, clustering coefficient, and nodal efficiency were quantified using graph-theoretical analysis. Network-based statistics (NBS) were applied to identify significant group differences in white matter connectivity.

STATISTICAL TESTS: Analysis of variance for group comparisons, with post hoc least significant difference t-testing. Logistic regression assessed the predictive power of network features, while Pearson correlation evaluated relationships between blood pressure and network disruptions. Area under the receiver operating characteristic (ROC) curve (AUC) was used to assess diagnostic performance. A significance threshold of p < 0.05 was applied.

RESULTS: Prehypertensive individuals exhibited significant early reductions in feeder connections, whereas hypertensive patients demonstrated widespread significant deterioration in rich-club connections. A statistically significant compensatory increase in local connection strength was observed in prehypertension but declined in hypertension. Logistic regression confirmed that rich-club connection strength and density effectively differentiated hypertensive individuals, with ROC analysis showing good discriminatory power (AUC: 0.803 and 0.816, respectively).

DATA CONCLUSION: This study showed progressive disruption of rich-club organization in prehypertension and hypertension. This disruption has the potential to be an early neuroimaging biomarker for identifying individuals at risk of hypertension-related brain dysfunction.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.

PMID:40476333 | DOI:10.1002/jmri.29835

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Nevin Manimala Statistics

Peripherin: A Novel Early Diagnostic and Prognostic Plasmatic Biomarker in Amyotrophic Lateral Sclerosis

Eur J Neurol. 2025 Jun;32(6):e70241. doi: 10.1111/ene.70241.

ABSTRACT

BACKGROUND: Motor neuron diseases (MND) are heterogeneous and complex neurodegenerative disorders. Biomarkers could facilitate early diagnosis, prognosis determination, and patient stratification. Among the most studied biomarkers are neurofilaments, with peripherin (PRPH), a specific type predominantly expressed in the peripheral nervous system, gaining attention. To date, no studies have evaluated PRPH in human plasma.

METHODS: Sandwich-ELISA was used to quantify plasma peripherin from 120 MND (100 ALS, 4 PMA, 15 PLS), 73 MND-mimics, and 38 healthy-controls (HCs). Plasma was collected at diagnosis or some months earlier. 41 ALS were evaluated longitudinally. ALSFRSr, MRC, spirometry, genetic tests, disease progression rate (PR), blood examinations, and neuropsychological tests were performed. Statistical analyses included Kruskal-Wallis, Mann-Whitney, Cox regression, and Kaplan-Meier curves.

RESULTS: Plasma PRPH levels differed significantly among groups (p < 0.0001), showing higher values in MND participants than MND mimics and HCs. Moreover, PRPH levels were elevated in PLS compared with HSP patients (p = 0.0001). Differences persisted after adjusting for age and sex. ROC curve demonstrated that PRPH discriminated MND from MND mimics (AUC = 0.85). Elevated PRPH correlated positively with ALSFRSr and lower motor neuron index, whereas inversely with disease progression rate. Higher PRPH levels at the beginning of the disease were associated with longer survival.

DISCUSSION: Plasma PRPH is raised in MND, particularly ALS, from the earliest stages, distinguishing MND from mimics and correlating with clinical parameters and survival. This suggests PRPH may reflect an endogenous response of lower motor neuron to injury. Further multicenter studies are required to refine the diagnostic and prognostic utility of PRPH in MND.

PMID:40476320 | DOI:10.1111/ene.70241

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Nevin Manimala Statistics

Keeping Elo alive: Evaluating and improving measurement properties of learning systems based on Elo ratings

Br J Math Stat Psychol. 2025 Jun 6. doi: 10.1111/bmsp.12395. Online ahead of print.

ABSTRACT

The Elo Rating System which originates from competitive chess has been widely utilised in large-scale online educational applications where it is used for on-the-fly estimation of ability, item calibration, and adaptivity. In this paper, we aim to critically analyse the shortcomings of the Elo rating system in an educational context, shedding light on its measurement properties and when these may fall short in accurately capturing student abilities and item difficulties. In a simulation study, we look at the asymptotic properties of the Elo rating system. Our results show that the Elo ratings are generally not unbiased and their variances are context-dependent. Furthermore, in scenarios where items are selected adaptively based on the current ratings and the item difficulties are updated alongside the student abilities, the variance of the ratings across items and students artificially increases over time and as a result the ratings do not converge. We propose a solution to this problem which entails using two parallel chains of ratings which remove the dependence of item selection on the current errors in the ratings.

PMID:40476309 | DOI:10.1111/bmsp.12395

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Nevin Manimala Statistics

A Bayesian Approach to the G-Formula via Iterative Conditional Regression

Stat Med. 2025 Jun;44(13-14):e70123. doi: 10.1002/sim.70123.

ABSTRACT

In longitudinal observational studies with time-varying confounders, the generalized computation algorithm formula (g-formula) is a principled tool to estimate the average causal effect of a treatment regimen. However, the standard non-iterative g-formula implementation requires specifying both the conditional distribution of the outcomes and the joint distribution of all time-varying covariates. This process can be cumbersome to implement and is prone to model misspecification bias. As an alternative, the iterative conditional expectation (ICE) g-formula estimator solely depends on a series of nested outcome regressions and avoids the need for specifying the full distribution of all time-varying covariates. This simplicity lends itself to the natural integration of flexible machine learning techniques to develop more robust average causal effect estimators with time-varying treatments. In this work, we introduce a Bayesian approach that includes parametric regressions and Bayesian Additive Regression Trees to flexibly model a series of outcome surfaces. We fit the ICE g-formula and develop a sampling algorithm to obtain samples from the posterior distribution of the final causal effect estimator. We illustrate the performance characteristics of the Bayesian ICE estimator and the associated variations via simulation studies and applications to two real world data examples.

PMID:40476299 | DOI:10.1002/sim.70123

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Nevin Manimala Statistics

Molecular detection of Toxoplasma gondii in ready-to-eat salad mixes: multi-country survey using a validated and harmonised standard operating procedure, Europe, 2021 to 2022

Euro Surveill. 2025 Jun;30(22). doi: 10.2807/1560-7917.ES.2025.30.22.2400594.

ABSTRACT

BackgroundMost Toxoplasma gondii infections in humans are considered foodborne, but the relative importance of the various routes of infection is largely unknown. Consumption of green produce contaminated with T. gondii oocysts has been identified as a possible source.AimWe aimed to estimate the occurrence and prevalence of T. gondii oocysts in commercially available ready-to-eat (RTE) salad mixes in 10 European countries.MethodsA real-time PCR-based method for oocyst detection was developed and optimised by two laboratories and validated in an interlaboratory test. This detection method and a harmonised sampling strategy were applied in a multi-country study. Multivariable logistic regression was used to investigate risk factors for oocyst contamination of RTE salad.ResultsThe real-time PCR method had a detection limit of 10 oocysts per 30 g of salad. We collected 3,329 RTE salad samples (baby leaf and cut leaf mixes) from October 2021 to September 2022. The prevalence of T. gondii oocyst contamination was 4.1% (95% confidence interval (CI): 3.4-4.8%; n = 3,293). In multivariable regression analysis, winter season, sampling and packaging of salad in Northern Europe and production of salad in Western Europe were associated with detection of T. gondii, with no statistically significant differences between salad types.ConclusionWe estimated the prevalence of T. gondii oocysts in RTE leafy green salads using a validated and standardised procedure to assess the potential risk for human infection; highlighting the need to address this risk at each critical point of the salad production chain.

PMID:40476292 | DOI:10.2807/1560-7917.ES.2025.30.22.2400594

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Nevin Manimala Statistics

Use of cell phone data to correct Île-de-France population estimates and SARS-CoV-2 incidence, July to September, 2021: a proof-of-concept exercise

Euro Surveill. 2025 Jun;30(22). doi: 10.2807/1560-7917.ES.2025.30.22.2400530.

ABSTRACT

BackgroundDuring the COVID-19 pandemic, Santé publique France (SpF) published incidence (SpFi) rates based on census denominators. Denominators using cell phone connection (CPC) data can better reflect the population present and seasonal mobilities.AimGiven uncertainties regarding the actual number of Île-de-France (IdF) residents present in IdF during summer 2021, we aimed to better approximate true incidence rates from positive SARS-CoV-2 tests in IdF using CPC-derived population denominators.MethodThis longitudinal study used the daily number of positive tests (PCR and Ag) on IdF residents in IdF as the numerator and the estimated resident population present in IdF at midnight as the denominator. We computed the mean corrected incidence rate (MCIR) per moving week between 4 July and 9 September 2021.ResultsThe MCIR showed higher incidence rates than initially estimated, especially during August when residents had left IdF for the holidays. Incidence rates reached a peak on 16 August when the SpFi rate per moving week was 200.9 per 100,000 compared with 315.6 per 100,000 with the MCIR, representing a 57% increase.ConclusionUsing local SARS-CoV-2 testing data and real-time population denominators, we showed that indicators using non-geographically referenced test results and fixed population denominators that ignore seasonal mobility can significantly underestimate incidence rates in IdF. New data sources using CPC data provide the opportunity to calculate more accurate and dynamic incidence rates and to map epidemics more precisely and in real time.

PMID:40476291 | DOI:10.2807/1560-7917.ES.2025.30.22.2400530

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Nevin Manimala Statistics

Stereotactic body radiotherapy for unresectable or locally recurrent pancreatic cancer: A single centre experience

J Radiosurg SBRT. 2025;9(3):207-213.

ABSTRACT

PURPOSE: To refer our experience with stereotactic body radiotherapy (SBRT) in patients with pancreatic cancer.

MATERIALS AND METHODS: 45 Patients with unresectable or locally recurrent pancreatic cancer after primary surgery, were submitted to SBRT. Toxicities were graded according to CTCAE version 5. Statistical analysis was performed by the Kaplan-Meier method.

RESULTS: The characteristics of the patients were median age 70 years (range, 46-84 years), median KPS 90% (range, 80-90%). Six patients had recurrent cancer after surgery, the other 39 patients were unresectable. Median radiation dose was 35 Gy (range, 27-40 Gy) delivered in 5 fractions. Simultaneous integrated boost with median dose of 35 Gy (range, 30-45 Gy) was given in 7 patients.After median follow-up of 10 months (range, 3-61 months) median local control was 10 months (range,5-15 months) and 49% (±8%) at 1-year. Median overall survival (OS) was 10 months (range,7-14 months), 38 % (±7%) at 1 year. Type of radiological response statistically significant influenced LC and OS, stage only LC in non-significant way. Clinical response was obtained in 12 of 36 (33%) cases. Median Numeric Rating Scale (NRS) was 7 (range, 4-8) before radiotherapy and 1 (range, 0-5) post SBRT. Acute G1-2 gastrointestinal toxicities were registered in 15% of patients, no late toxicities were found.

CONCLUSION: In our series we obtained a good local palliation with SBRT that is a safe and effective treatment option. Higher doses could be administered in selected patients to obtain better response to treatment that is correlated with LC and OS.

PMID:40476277 | PMC:PMC12136683

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Nevin Manimala Statistics

What tool do undergraduate pharmacy students prefer when grading systematic review evidence: AMSTAR-2 or ROBIS?

Cochrane Evid Synth Methods. 2023 Aug 9;1(6):e12023. doi: 10.1002/cesm.12023. eCollection 2023 Aug.

ABSTRACT

INTRODUCTION: While systematic reviews (SRs) are considered the highest form of evidence in the hierarchy, the quality and standard of reviews varies. Two quality assessment tools have been developed to assess the variation in such standards. This study compared the preference, validity, reliability, and applicability of using A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) and the Risk of Bias in Systematic Reviews (ROBIS) for critically appraising evidence by pharmacy students.

MATERIALS AND METHODS: Students attended eight lectures on evidence-based medicine. Students independently assessed two SRs using AMSTAR-2 and ROBIS. The agreement between both tools were calculated using Spearman’s test while interrater reliability was calculated using Fleiss’ κ statistics.

RESULTS: Students reported a preference for the AMSTAR-2 tool due to its clear and distinct rating criteria as well as guidance provided by the tool’s developer. In comparison, students found the items on the ROBIS tool difficult to judge as it was subjective. A moderate agreement between both tools on the overall domain ratings was noted (Spearman r s = 0.60). There was slight agreement in the overall confidence using AMSTAR-2 (κ = 0.05; 95% confidence interval [CI]: 0.01-0.12) and the overall domain in ROBIS (κ = 0.09; 95% CI: 0.01-0.16).

CONCLUSION: The AMSTAR-2 tool had a low level of concordance in ratings of review among students. However, the AMSTAR-2 tool was preferred by students due to the clear guidance and ease of use.

PMID:40476276 | PMC:PMC11795889 | DOI:10.1002/cesm.12023