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Nevin Manimala Statistics

Hematological Inflammation Markers in the Prediction of Clinically Significant Prostate Cancer and the Individualization of Biopsy Decisions for PI-RADS 3 Lesions: A Two-Center Retrospective Study

Prostate. 2026 Jun 18. doi: 10.1002/pros.70210. Online ahead of print.

ABSTRACT

BACKGROUND: PI-RADS 3 lesions represent a diagnostic “gray zone” in which biopsy decision-making is particularly challenging, with reported clinically significant prostate cancer (csPCa) detection rates ranging from 13% to 50%. This study evaluated the predictive value of the systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR)-alone and in combination with PSA density (PSAD) and PI-RADS score-for the detection of prostate cancer (PCa) and csPCa, with a specific focus on the PI-RADS 3 subgroup.

METHODS: In this two-center retrospective observational study, 982 patients who underwent prostate biopsy between 2020 and 2025 were included. csPCa was defined as ISUP Grade Group ≥ 2. Univariable and multivariable logistic regression analyzes were performed to identify independent predictors of PCa and csPCa. In the PI-RADS 3 subgroup (n = 251), two predictive models were compared using receiver operating characteristic analysis and the DeLong test: Model 1 (age, free/total PSA ratio, PSAD) and Model 2 (Model 1 + SII + NLR).

RESULTS: Of the 982 patients, 188 (19.1%) were diagnosed with PCa and 150 (15.3%) with csPCa. In the overall cohort, NLR ≥ 2.11 was independently associated with csPCa (OR, 15.924; 95% CI, 2.472-102.567; p = 0.004), whereas SII did not retain independent significance. PLR showed an inverse association with PCa, possibly reflecting tumor-related platelet dynamics. In the PI-RADS 3 subgroup, SII ≥ 661.37 (OR, 2.317; p = 0.039) remained an independent predictor of PCa alongside age, free/total PSA ratio, and PSAD ≥ 0.20 (OR, 6.111; p = 0.013), while NLR showed borderline significance. The addition of SII and NLR to the clinical model increased the AUC from 0.795 to 0.816 in the PI-RADS 3 subgroup, although this improvement did not reach statistical significance (p = 0.134).

CONCLUSIONS: Systemic inflammatory markers-particularly SII and NLR-provide complementary predictive information in the pre-biopsy risk stratification of prostate cancer. SII emerged as an independent predictor of PCa specifically within the PI-RADS 3 gray zone, while NLR independently predicted csPCa in the overall cohort. These routinely available, low-cost parameters may serve as practical adjuncts to PSA derivatives and mpMRI in the individualization of biopsy decisions, particularly for PI-RADS 3 patients.

PMID:42314010 | DOI:10.1002/pros.70210

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Nevin Manimala Statistics

Understanding Motor Adaptation in the Transition to Sustained Pain: Protocol for a Longitudinal Experimental Study

JMIR Res Protoc. 2026 Jun 18;15:e99833. doi: 10.2196/99833.

ABSTRACT

BACKGROUND: Chronic pain affects over 30% of the global population and remains a major public health issue due to limited treatment efficacy and the need for mechanism-based, personalized approaches. Motor behavior is theorized to play a role in pain persistence through altered movement patterns, muscle recruitment, and proprioception. While motor behavior is linked to chronic pain, empirical evidence on underlying mechanisms, particularly cortical dynamics, remains scarce.

OBJECTIVE: This study aimed to investigate longitudinal changes in cortical sensorimotor excitability and their relationship with maladaptive motor behaviors.

METHODS: This prospective longitudinal study will follow 150 healthy participants, aged 18-65 years, recruited from the community, experiencing experimentally induced muscle pain across 4 visits (day 0, day +2, day +4, and 5 days after pain resolution). Pain will be induced using intramuscular injections of nerve growth factor into the extensor carpi radialis brevis muscle. The primary outcome is motor variability assessed during multidimensional wrist movement tasks, and quantified using root-mean-square deviation and muscle synergies (derived from electromyographic recordings of 4 forearm muscles). Secondary outcomes include cortical mechanisms (electroencephalographic peak alpha frequency, transcranial magnetic stimulation mapping, short-interval intracortical inhibition, and intracortical facilitation), sensorimotor integration (evoked potential), cognitive control (multisource interference task), and endogenous pain modulation (conditioned pain modulation). Self-report questionnaires will assess pain intensity and disability (Patient-Rated Tennis Elbow Evaluation, McGill Pain Questionnaire-Short Form, and Likert Muscle Soreness Scale) as well as psychological factors such as fear of movement, pain-related beliefs, and coping strategies (Tampa Scale for Kinesiophobia, Pain Beliefs Questionnaire, and Coping Strategies Questionnaire-Revised). This sample size provides 80% power at 5% significance to detect a medium effect size across 23 predictor variables, with Bonferroni correction and 10% loss-to-follow-up allowance. Data will be analyzed using 2-level growth curve modeling to characterize interindividual differences in motor behavior, cortical dynamics, and pain processing trajectories.

RESULTS: All study procedures have been approved by the Western University Health Science Research Ethics Board (review reference 2025-125757-103291). Funding was provided by the Canadian Institutes of Health Research under grant number 517783 for the period 2024-2029. Recruitment for the study began in April 2025, and all data collection is expected to be completed by 2028. As of April 2026, we have enrolled 26 participants. Results are expected to be published at the end of 2028.

CONCLUSIONS: The findings will advance understanding of motor behavior in pain and lay the foundation for personalized therapies, moving beyond current generic treatments that offer limited benefits.

PMID:42313885 | DOI:10.2196/99833

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Allergen Immunotherapy for the Treatment of Eosinophilic Esophagitis. An EAACI Task Force Systematic Review

Clin Transl Allergy. 2026 Jun;16(6):e70176. doi: 10.1002/clt2.70176.

ABSTRACT

BACKGROUND: Multiple routes of allergen immunotherapy (AIT) are approved for several IgE-mediated allergic diseases; however, the use of AIT in eosinophilic esophagitis (EoE) remains controversial and is supported by limited evidence. This review, conducted within the frame of an EAACI Task Force, aims to systematically evaluate the use of AIT as a potential treatment for EoE.

METHODS: The protocol was registered and prepared in accordance with PRISMA guidelines. The literature search was conducted across three online databases (PubMed, Embase, and Scopus) and included studies published through January 31st, 2025. Risk of Bias was assessed for each eligible study.

RESULTS: Four articles met the inclusion criteria. Three articles evaluated EPIT for milk-induced EoE in pediatric patients, all from the SMILEE (Study of Efficacy and Safety of Viaskin Milk for milk-induced EoE) trial and its extensions. These included a randomized, placebo-controlled trial, its open-label extension, and a pilot immunological study. The SMILEE trial found no statistically significant difference in tissue eosinophilia between the active (EPIT) and control (placebo) arms in the intention-to-treat population, while 47% of treated EoE patients tolerated milk without recurrence of esophageal eosinophilia. This finding was further supported by a subsequent open-label study with a 2-year follow-up. In the third publication, the researchers found that EPIT was associated with decreased Th2-related transcripts and increased regulatory T-cell-associated transcripts. Only one eligible study evaluated the use of SCIT for treating EoE. It was a retrospective case-control study reporting that SCIT had a neutral effect and yielded inconclusive findings regarding the course of EoE.

CONCLUSION: There is insufficient high-quality evidence to support the effectiveness of alternative routes of AIT for the treatment of EoE, either as an add-on or a standalone treatment.

PMID:42313883 | DOI:10.1002/clt2.70176

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Public and patient involvement: exploring public partnership in pathogen whole-genome sequencing research and its data visualisation

Microb Genom. 2026 Jun;12(6). doi: 10.1099/mgen.0.001763.

NO ABSTRACT

PMID:42313461 | DOI:10.1099/mgen.0.001763

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Nevin Manimala Statistics

Handgrip and Acute Hemodynamic Responses During Cyclic Exercise: Randomized Clinical Trial

J Clin Hypertens (Greenwich). 2026 Jun;28(6):e70284. doi: 10.1111/jch.70284.

ABSTRACT

During exercise, fine hemodynamic adjustments are essential to ensure adequate energy supply. Although cyclic treadmill exercise has been widely studied, isometric exercise with Handgrip (HG) has gained relevance in conditioning and rehabilitation contexts, yet data on the acute hemodynamic effects of combining these modalities remain scarce. In this context, the present study tested the hypothesis that isometric contraction with HG modifies the hemodynamic responses of Heart Rate (HR), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and Double Product (DP) during cyclic treadmill exercise. A clinical trial was conducted with 40 young, active or irregularly active men, using a crossover design in which three protocols were applied: protocol 1 without HG, protocol 2 with HG at 30% of handgrip strength (HGS), and protocol 3 with HG at 60% of HGS. The exercise sessions were performed on a treadmill and consisted of four blocks of 2 min at 50% of heart rate reserve, followed by 1 min at 30%. Statistical analysis was carried out using Kruskal-Wallis and Friedman tests with appropriate post hoc procedures. The results demonstrated that protocols 2 and 3 significantly increased SBP and DBP compared to protocol 1 (p < 0.05), while DP was significantly higher only in protocol 3 (p < 0.01). Heart rate increased throughout exercise in all protocols (p < 0.05), with no differences between them. Additionally, HG did not modify the hemodynamic response during recovery. Overall, HG promotes increases in SBP, DBP, and DP during treadmill exercise without altering HR.

PMID:42313450 | DOI:10.1111/jch.70284

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Nevin Manimala Statistics

Paediatric outpatient antibiotic utilization patterns and use of healthcare services before, during and after the COVID-19 pandemic: interrupted time series analysis using data from Norway and Japan

J Antimicrob Chemother. 2026 Jun 3;81(7):dkag217. doi: 10.1093/jac/dkag217.

ABSTRACT

OBJECTIVES: Quantification of prescription of antimicrobial agents and use of paediatric outpatient services before, during and after the COVID-19 pandemic.

METHODS: We conducted a population-based study using Norwegian linked health registries and Japanese claims (2018-2023). Paediatric antibiotic prescription rates, broad-spectrum use, and proportion of antibiotic prescriptions with prior presumed bacterial infection diagnoses were analysed monthly, overall and by age groups and sex. Interrupted time series analyses were performed to evaluate pandemic-related changes, expressed in rate ratio (RR) and its CI, using March 2020 as the interruption point and the pre-pandemic trend/level as reference.

RESULTS: Data on 5.5 million children and 19.5 million antibiotic prescriptions were analysed. Before the pandemic, antibiotic prescribing was higher in Japan (120-200/1000 children/month) than in Norway (10-20/1000). At pandemic onset, rates fell by 45% in Norway (RR = 0.55; 95% CI, 0.45-0.67) and by 53% in Japan (RR = 0.47; 95% CI, 0.41-0.55), then by 2023 had returned to expected levels. Broad-spectrum antibiotic use was much higher in Japan (70%) compared with Norway (10%) before the pandemic. However, Norway experienced a sharp 20% increase whereas Japan remained largely unchanged post-pandemic. The proportion of prescriptions with a prior presumed bacterial diagnosis was between 50% and 65% before the pandemic then decreased modestly by 5%-10% at pandemic onset, followed by gradual rebound in both countries.

CONCLUSIONS: The COVID-19 pandemic significantly altered paediatric antibiotic prescribing in both countries. Sustained antibiotic stewardship efforts are needed to ensure appropriate paediatric antibiotic use in the post-pandemic era.

PMID:42313421 | DOI:10.1093/jac/dkag217

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Nevin Manimala Statistics

Safety of antibiotic audit and feedback: secondary analysis of a randomized controlled trial

J Antimicrob Chemother. 2026 Jun 3;81(7):dkag216. doi: 10.1093/jac/dkag216.

ABSTRACT

BACKGROUND: We previously demonstrated in a randomized controlled trial that antibiotic prescribing feedback to family physicians reduced antibiotic use. However, that trial did not evaluate for patient harms from potential under-prescribing of antibiotics.

OBJECTIVES: To evaluate the safety of an antibiotic audit and feedback intervention.

METHODS: We performed a post hoc secondary analysis of a randomized controlled trial that compared an intervention group, who received a mailed antibiotic prescribing peer comparison feedback letter, compared with a control group who did not receive a letter. The initial trial was limited to patients aged 65 years or older due to availability of pharmacy claims data. The primary outcome was an emergency department visit or hospital admission for a bacterial infection. The outcome was assessed at 6 months post-intervention using administrative data claims data and multivariable linear regression models. The initial trial was registered (NCT04594200).

RESULTS: We included 4879 physicians-3909 intervention physicians and 970 control physicians. There were 37 345 severe infection events in the 6 month post-intervention period. The observed mean (SD) of all severe infection events per physician was 7.73 (12.42) for control and 7.64 (11.91) for intervention groups. The model-based adjusted mean difference was -0.23 (95% CI, -0.92 to 0.45; P = 0.505).

CONCLUSIONS: In this post hoc analysis of a randomized controlled trial comparing antibiotic prescribing feedback versus no feedback to physicians in primary care, there was no evidence of severe bacterial infection complications associated with reduced antibiotic prescribing. These findings support antibiotic peer comparison feedback as a safe and effective tool to reduce unnecessary antibiotic prescribing.

PMID:42313420 | DOI:10.1093/jac/dkag216

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Development, validity, and reliability of the pre-attendance conference evaluator (PACE) tool for identifying predatory conferences

Account Res. 2026 Jun 18:2691602. doi: 10.1080/08989621.2026.2691602. Online ahead of print.

ABSTRACT

BACKGROUND: Predatory conferences (PCs) scam researchers by compromising them financially and professionally. This study presents the empirical development of the Pre-Attendance Conference Evaluator (PACE) to help academics assess a conference’s legitimacy.

MATERIALS AND METHOD: An expert group of six academics validated a preliminary list of PC traits. After identifying latent constructs through pilot testing, the list underwent four iterations based on statistical factor loadings to assess reliability, predictive validity, and concurrent validity. Later, confirmatory factor analysis included a battery of model-fit indices to assess the scale’s dimensionality.

RESULTS: Content validity ratio and semi-structured interviews reduced the number of PC traits from 70 to 29. Cronbach’s alpha and the Kaiser-Meyer-Olkin test indicated 15 items suitable for factor analysis. Parallel analysis of pilot-testing data from 800 conference-level observations revealed the scale’s unidimensionality. Eventually, 11 items showed strong factor loadings and a high fit across model indices. Concurrent validity assessed by 616 conference-level observations showed high correlations (rs = 0.73-0.80) with existing tools. High predictive validity (>0.9) and test-retest reliability (ICC = 0.47-0.68) indicated moderate-to-good temporal stability. The ROC analysis yielded a cutoff score of < 14 to deem a conference predatory.

CONCLUSION: PACE demonstrated acceptable validity and reliability as a tool for diagnosing potentially predatory conferences.

PMID:42313396 | DOI:10.1080/08989621.2026.2691602

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Group Therapy for Posttraumatic Stress Disorder Symptoms Among Veterans With Military Sexual Trauma: A Randomized Clinical Trial

JAMA Netw Open. 2026 Jun 1;9(6):e2618896. doi: 10.1001/jamanetworkopen.2026.18896.

ABSTRACT

IMPORTANCE: Military sexual trauma (MST) is associated with substantial psychiatric sequelae, but treatment options lack evidence-based protocols tailored to this specific trauma.

OBJECTIVE: To evaluate the efficacy of a MST-focused treatment using an 8-week virtual delivery format compared with an active control treatment to reduce symptoms of posttraumatic stress disorder (PTSD).

DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial compared Warrior Renew (MST-focused group) with Health and Wellness (active control group) at baseline, week 8 (after treatment), and week 16 (follow-up). The study was conducted at 2 Veterans Affairs health care systems in the Pacific Northwest region of the US. Participant enrollment occurred from July 19, 2023, to March 24, 2025. Veterans aged 18 to 75 years with a history of MST-related PTSD symptoms were recruited via informational letters, self-referral, and clinician referral. Participants were randomized 1:1 to the MST-focused group or active control group. Analysis of participants with baseline data was based on the intention-to-treat principle.

INTERVENTION: The MST-focused treatment targets themes of MST using cognitive and experiential strategies, including imagery reprocessing. The active control targets health and well-being, including behavioral engagement with weekly goals. Both treatments consisted of 8 weekly, 90-minute sessions delivered via telehealth in groups separated by sex.

MAIN OUTCOMES AND MEASURES: The primary outcome was change in PTSD symptom severity from baseline to week 8, which was measured by the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (PCL-5) and the Posttraumatic Cognitions Inventory (PTCI). A linear mixed model was used to compare outcomes of the treatments at weeks 8 and 16.

RESULTS: Of the 191 veterans who consented, 140 (mean [SD] age, 50.6 [14.7] years; 71 males [50%]) completed baseline assessments and were included in the intent-to-treat analyses. Participants in the MST-focused group showed significant score improvements from baseline to week 8 on the PCL-5 (-7.97; 95% CI, -11.01 to -4.92; P < .001) and the PTCI (-19.99; 95% CI, -26.86 to -13.12; P < .001), which were maintained at week 16. Active control group participants also showed significant score improvements on the PCL-5 and PTCI; however, the MST-focused group demonstrated greater score improvements on the PTCI (-9.61; 95% CI, -18.98 to -0.25; P = .04) and the PTCI self-blame subscale (-3.10; 95% CI, -5.30 to -0.90; P = .006) compared with the active control group. Additionally, only participants in the MST-focused group exceeded a 10-point score threshold indicating meaningful change on the PCL-5 at week 16. Women in the MST-focused group demonstrated greater results on the PCL-5 over the control group (-5.90; 95% CI, -11.58 to -0.22; P = .04) at week 8. Both treatments had low dropout rates (around 11%).

CONCLUSIONS AND RELEVANCE: This randomized clinical trial showed that both treatments demonstrated efficacy in reducing PTSD symptoms, but the MST-focused treatment compared with the active control demonstrated greater improvements in posttraumatic cognitions. The results support the use of the MST-focused group treatment for PTSD symptoms associated with MST.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05776719.

PMID:42313385 | DOI:10.1001/jamanetworkopen.2026.18896

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A Community-Level Digital Health Readiness Index for the US

JAMA Netw Open. 2026 Jun 1;9(6):e2619372. doi: 10.1001/jamanetworkopen.2026.19372.

ABSTRACT

IMPORTANCE: Digital health services are expanding, yet community readiness for digital care varies widely. Without a validated, granular measure of readiness, health systems and policymakers cannot reliably enable targeted support or monitor equitable deployment.

OBJECTIVE: To develop and validate a reproducible census tract-level index of community digital health readiness integrating socioeconomic conditions, access to care, and digital connectivity.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional index development and validation study analyzed public data from 2018 to 2022. The Digital Health Index (DHI) was constructed from 21 indicators with equal weighting representing 3 domains: socioeconomic, health access, and connectivity. Content validity was assessed using a 2-round Delphi panel including 37 experts. Structural validity was assessed with exploratory and confirmatory factor analyses. Convergent validity was assessed against the Social Vulnerability Index (SVI), Area Deprivation Index (ADI), and Digital Divide Index (DDI). External validity was assessed using health care spending. Robustness was assessed using leave-one-out, weight-perturbation, and group-based cross-validation analysis. Data were analyzed between June 2023 and April 2026.

MAIN OUTCOMES AND MEASURES: Primary outcomes were validation metrics, including factor structure fit indices, correlations with established indices, association with health care spending per capita, and Delphi consensus rates for each indicator. Robustness outcomes included stability of tract rankings under indicator removal or weight changes.

RESULTS: The DHI was computed for 85 396 US census tracts across all 50 states. DHI scores correlated with SVI, ADI, and DDI scores (Spearman ρ = 0.61-0.84) but prioritized different low-readiness communities, with only 33% to 44% overlap between tracts in the highest DHI decile and those in the highest SVI, ADI, or DDI deciles. Health care spending showed similar inverse associations across indices. DHI rankings remained stable in sensitivity analyses. All 21 indicators met Delphi consensus criteria after 1 or 2 rounds.

CONCLUSIONS AND RELEVANCE: In this cross-sectional index development and validation study, a reproducible measure of community digital health readiness was constructed at the census tract level, integrating socioeconomic, access, and connectivity factors. The DHI may help health systems, public agencies, and researchers identify communities requiring support and track readiness over time as digital health and artificial intelligence initiatives expand.

PMID:42313384 | DOI:10.1001/jamanetworkopen.2026.19372