Categories
Nevin Manimala Statistics

Solving the diagnostic dilemma in bone infections: metagenomic next generation sequencing enhances pathogen identification accuracy

Front Med (Lausanne). 2026 Jan 7;12:1699607. doi: 10.3389/fmed.2025.1699607. eCollection 2025.

ABSTRACT

OBJECTIVE: Metagenomic Next Generation Sequencing (mNGS) offers a rapid, unbiased, and culture-independent approach to pathogen identification by analyzing all nucleic acids present in clinical samples. Despite its growing use, the diagnostic utility of mNGS in bone infections remains inadequately characterized. This study aimed to assess the diagnostic accuracy of mNGS compared to conventional microbial cultures and to explore its associations with clinical severity and patient outcomes.

METHODS: We retrospectively enrolled 135 adult patients treated for suspected bone infections between October 2023 to January 2025 at Union Hospital, Tongji Medical College. Among these, 101 patients were classified as the infection group (IG) based on clinical and laboratory criteria, encompassing osteomyelitis, post-traumatic limb infections, and diabetic foot infections. mNGS results were compared to traditional cultures in terms of sensitivity, specificity, predictive values, and discordant cases. The IG was further stratified into mNGS-positive (n = 95) and mNGS-negative (n = 6) subgroups. Clinical parameters-including leukocyte differentials, C-reactive protein (CRP), procalcitonin (PCT), albumin, length of hospital stay, and mortality-were analyzed in relation to mNGS findings.

RESULTS: Among all patients, 74.81% were confirmed to have infections. mNGS demonstrated a markedly higher sensitivity than culture (94.06% vs. 47.52%, p = 0.000) while maintaining comparable specificity (85.29% vs. 76.47%, p = 0.549). Age showed a potential trend in influencing mNGS positivity (p = 0.092). Although not statistically significant, mNGS-positive patients tended to have longer hospitalizations (p = 0.098), suggesting possible associations with infection complexity or pathogen load.

CONCLUSION: mNGS substantially enhances the diagnostic yield for bone infections, particularly in polymicrobial, low-abundance, or culture-negative scenarios. mNGS-negative patients had significantly shorter hospital stays and a lower rehospitalization rate. Its rapid and comprehensive pathogen detection may enable more timely and targeted antimicrobial therapy, potentially improving patient outcomes and reducing healthcare burden. These findings support the integration of mNGS as a valuable adjunct to conventional diagnostic workflows in orthopedic infectious diseases.

PMID:41574363 | PMC:PMC12819182 | DOI:10.3389/fmed.2025.1699607

Categories
Nevin Manimala Statistics

Efficacy and safety of probiotics combined with bismuth-containing quadruple therapy for Helicobacter pylori eradication: a systematic review and meta-analysis

Front Microbiol. 2026 Jan 7;16:1704508. doi: 10.3389/fmicb.2025.1704508. eCollection 2025.

ABSTRACT

OBJECTIVE: Helicobacter pylori (H. pylori) infection represents a global health challenge. This study aimed to evaluate the effect of probiotic supplementation on the efficacy and safety of bismuth-containing quadruple therapy (BQT) for H. pylori eradication.

METHODS: Randomized controlled trials (RCTs) meeting the eligibility criteria were identified through systematic searches of five databases, including PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. Meta-analyses were conducted using Review Manager software with a random-effects model to calculate pooled relative risks (RR) and 95% confidence intervals (CI). The potential publication bias was evaluated qualitatively, and the certainty of the evidence was subsequently assessed.

RESULTS: In total, 10 RCTs involving 1,630 patients were included in the analysis. The results demonstrated that, compared with the BQT group, the H. pylori eradication rate was significantly higher in the probiotics combined with the BQT group (RR 1.06, 95% CI 1.01-1.11, p = 0.009, ARR = 7.5%, NNT ≈ 13). Additionally, the combined therapy significantly reduced the adverse event rate (RR 0.58, 95% CI 0.42-0.80, p = 0.001, ARR = 11.1%, NNT ≈ 9), diarrhea (RR 0.48, 95% CI 0.32-0.73, p = 0.0007, ARR = 0.7%, NNT ≈ 142), and constipation (RR 0.53, 95% CI 0.29-0.94, p = 0.04, ARR = 2.5%, NNT ≈ 40). However, no statistically significant differences were observed for other specific adverse events, including nausea, vomiting, anorexia, heartburn, belching, taste disturbance, abdominal pain, and abdominal bloating. Sensitivity analyses confirmed the robustness of the results for the H. pylori eradication rate and adverse event rate.

CONCLUSION: Combining probiotics with BQT significantly increases the H. pylori eradication rate and reduces adverse events, particularly diarrhea and constipation. These findings support the role of probiotics as a supplementary strategy to enhance both the efficacy and safety of H. pylori eradication therapy. However, the overall certainty of the evidence is low to very low, and the optimal probiotic protocol has yet to be determined, highlighting the need for further high-quality research.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251060806, Identifier CRD420251060806.

PMID:41574348 | PMC:PMC12819727 | DOI:10.3389/fmicb.2025.1704508

Categories
Nevin Manimala Statistics

Effect of Cannabigerol on Sleep and Quality of Life in Veterans: A Decentralized, Randomized, Placebo-Controlled Trial

Med Cannabis Cannabinoids. 2025 Dec 9;9(1):1-14. doi: 10.1159/000549902. eCollection 2026 Jan-Dec.

ABSTRACT

INTRODUCTION: This decentralized, randomized, triple-blind, placebo-controlled study evaluated efficacy and safety of oral cannabigerol (CBG) in Veterans with sleep issues.

METHODS: After a 2-week run-in phase, participants received CBG (25 mg daily for 2 weeks, then 50 mg daily for a further 2 weeks) or placebo. The primary endpoint was change in sleep quality via the Medical Outcomes Study Sleep Problems Index II questionnaire (MOS-SS SPI-II). Additional endpoints included change in quality of life measured via the World Health Organization Disability Assessment Schedule, version 2.0 instrument (WHODAS-2.0-12), post-traumatic stress disorder (PTSD) symptoms evaluated via the PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (PCL-5 (PCL-5), and sleep actigraphy data via Fitbit.

RESULTS: A total of 63 participants were randomized to receive CBG (n = 33) or placebo (n = 30). A total of 35 participants completed the study without major protocol deviations (CBG [n = 18]; placebo [n = 17]). MOS-SS SPI-II scores indicated improved sleep with no statistically significant difference between the CBG and placebo groups. Similar patterns were observed for WHODAS-2.0-12 and PCL-5 scores. CBG was well tolerated.

CONCLUSION: While no firm conclusion on the efficacy of CBG in improving sleep can be made, the favorable safety profile supports future studies with CBG. ClinicalTrials.gov ID: NCT05088018.

PMID:41574318 | PMC:PMC12823110 | DOI:10.1159/000549902

Categories
Nevin Manimala Statistics

Epidemiologic characteristics and clinical outcomes of respiratory syncytial virus in hospitalized care in Lebanon: a prospective observational study

Front Cell Infect Microbiol. 2026 Jan 7;15:1711410. doi: 10.3389/fcimb.2025.1711410. eCollection 2025.

ABSTRACT

INTRODUCTION: The aim of this study was to describe the epidemiology and clinical outcomes of respiratory syncytial virus (RSV) infection in hospitalized children and adults from a sentinel surveillance network in Lebanon, and to compare the RSV rates and seasonality before and during COVID-19 pandemic.

METHODS: This study was based on the data from the Lebanese component of the Global Influenza Hospital Surveillance Network (GIHSN) during three consecutive seasons between 2019-2021 at six hospitals, following a standardized protocol based on age-specific criteria. Specimens were tested for RSV. The epidemiologic, clinical, and severity characteristics were analyzed. Descriptive statistics were used to summarize demographics, RSV rate, and outcomes. Univariate analyses were performed using Pearson’s Chi-square or Fisher’s exact test, and associations were expressed as unadjusted odds ratios (95% CI). A p-value ≤0.05 was considered significant.

RESULTS: From January 2019 to September 2021, 2,626 of 7,081 eligible inpatients were enrolled in the study, with 188 tested positives for RSV (7.3%). The majority (74.5%) of RSV-positive subjects were children under 5 years of age, and 9.6% of patients were ≥ 65 years of age. The positivity rate varied across seasons (2.1%-11.1%) (p-value <0.001); the 2020-2021 season -was disrupted by COVID-19 pandemic – recording the lowest rate of 1.1% (p-value <0.001) during the typical winter months followed by an off-season RSV resurgence. Fever, cough, nasal congestion, wheezing, neurological symptoms, diarrhea and decreased oral intake were significantly associated with RSV infection (p < 0.05). Cough and wheezing were predominant in RSV-positive children <5 and adults aged ≥ 65 years. Among RSV-positive subjects, 8% required ICU admission, 5.3% received mechanical ventilation, and 2.7% died. Severe outcomes were more common in those ≥65 years, and the presence of ≥2 comorbidities and underlying cardiovascular disease significantly increased the risks of mechanical ventilation (OR = 7.44 [1.13-48.99], p-value 0.037 and OR = 8.32 [2.20-31.37], p-value 0.004, respectively) and in-hospital death (OR = 22.67 [1.91-268.50], p-value 0.013 and OR = 11.50 [1.82-72.85], p-value 0.016, respectively).

CONCLUSIONS: This study demonstrates the significant burden of RSV, especially in young infants with or without co-morbidities and in older adults with co-morbidities. Given the recent rollout of RSV vaccines and monoclonal antibodies, continued surveillance is needed to monitor changes in epidemiology, seasonality, and disease burden, especially in low- and middle-income countries.

PMID:41574300 | PMC:PMC12819600 | DOI:10.3389/fcimb.2025.1711410

Categories
Nevin Manimala Statistics

Determination of canine ROTEM Sigma reference ranges and comparative analysis with ROTEM Delta

Front Vet Sci. 2026 Jan 7;12:1737842. doi: 10.3389/fvets.2025.1737842. eCollection 2025.

ABSTRACT

INTRODUCTION: Hemostatic dysfunctions are frequent in critically ill dogs and can markedly affect clinical outcomes. Conventional plasma-based coagulation testing provides limited insight into the complex in vivo interactions among platelets, red blood cells, and coagulation factors. Viscoelastic testing has emerged to overcome these limitations by assessing the dynamics of clot formation and breakdown in whole blood. Among these, ROtational ThromboElastoMetry (ROTEM) provides a real-time evaluation of the coagulation process, reflecting clot initiation, propagation, and lysis. The recently developed ROTEM Sigma analyzer automates reagent handling and measurement minimizing operator variability and pre-analytical errors. Despite its growing use in human medicine, canine reference intervals for the ROTEM Sigma platform have not yet been established.

OBJECTIVE: To determine the reference intervals for ROTEM Sigma parameters in healthy dogs, to compare these values with published ROTEM Delta data, and to assess the influence of physiological variables such as age, sex, body weight, and neuter status.

METHODS: A prospective observational study was conducted in 42 clinically healthy dogs. Whole blood samples were analyzed using ROTEM Sigma EXTEM, INTEM, FIBTEM, and HEPTEM assays. Reference intervals were generated using both conventional parametric and robust median-MAD statistical methods. Comparisons were made with previously reported canine ROTEM Delta data. Multivariate regression explored associations between ROTEM parameters and demographic or hematologic variables.

RESULTS: Reference intervals were successfully defined for all ROTEM Sigma parameters (CT, CFT, A10, MCF, LI60, and G). EXTEM values agreed most closely with previously published ROTEM Delta data, whereas INTEM and FIBTEM exhibited greater variability. Regression analysis identified maximum clot firmness (MCF) as the only parameter significantly affected by biological variables. MCF decreased with higher body weight, increased with platelet count and showed minor sex-related differences.

CONCLUSION: This study establishes canine-specific ROTEM Sigma reference intervals. The close concordance with Delta data more (particularly EXTEM) suggests cross platform consistency while highlighting the necessity of dedicated Sigma-specific reference ranges. Body weight, sex, and platelet count were the primary determinants of MCF. These validated reference intervals enhance the clinical applicability of ROTEM Sigma for assessing hemostatic function in dogs.

PMID:41574258 | PMC:PMC12819721 | DOI:10.3389/fvets.2025.1737842

Categories
Nevin Manimala Statistics

SAIGE-GPU – Accelerating Genome- and Phenome-Wide Association Studies using GPUs

Bioinformatics. 2026 Jan 22:btag032. doi: 10.1093/bioinformatics/btag032. Online ahead of print.

ABSTRACT

MOTIVATION: Genome-wide association studies (GWAS) at biobank scale are computationally intensive, especially for admixed populations requiring robust statistical models. SAIGE is a widely used method for generalized linear mixed-model GWAS but is limited by its CPU-based implementation, making phenome-wide association studies impractical for many research groups.

RESULTS: We developed SAIGE-GPU, a GPU-accelerated version of SAIGE that replaces CPU-intensive matrix operations with GPU-optimized kernels. The core innovation is distributing genetic relationship matrix calculations across GPUs and communication layers. Applied to 2,068 phenotypes from 635,969 participants in the Million Veteran Program (MVP), including diverse and admixed populations, SAIGE-GPU achieved a 5-fold speedup in mixed model fitting on supercomputing infrastructure and cloud platforms. We further optimized the variant association testing step through multi-core and multi-trait parallelization. Deployed on Google Cloud Platform and Azure, the method provided substantial cost and time savings.

AVAILABILITY: Source code and binaries are available for download at https://github.com/saigegit/SAIGE/tree/SAIGE-GPU-1.3.3. A code snapshot is archived at Zenodo for reproducibility (DOI: [10.5281/zenodo.17642591]). SAIGE-GPU is available in a containerized format for use across HPC and cloud environments and is implemented in R/C ++ and runs on Linux systems.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:41572430 | DOI:10.1093/bioinformatics/btag032

Categories
Nevin Manimala Statistics

Age and sex as risk factors for health-related quality of life outcomes in patients with glioma: a CODAGLIO 2.0 analysis

Oncologist. 2026 Jan 22:oyag005. doi: 10.1093/oncolo/oyag005. Online ahead of print.

ABSTRACT

BACKGROUND: We assessed the clinical relevance of age and sex as risk factors for health-related quality of life (HRQoL) in patients with adult-type diffuse glioma.

MATERIALS AND METHODS: The CODAGLIO 2.0 database contains 16 randomized trials from 5,369 patients with glioma. Patients’ HRQoL was assessed using EORTC QLQ-C30 and QLQ-BN20 questionnaires. In 8 HRQoL scales, we compared mean HRQoL at baseline with the general population and evaluated factors associated with HRQoL over time using linear mixed models (LMMs). We used anchor-based minimally important difference to interpret clinically relevant changes.

RESULTS: We included 4,301 patients with baseline HRQoL followed until 3 months. Compared to the general population, patients with glioma at baseline had statistically and clinically relevant worse HRQoL, which was still evident after stratifying by age and sex groups. In LMMs, compared to patients aged ≤60 years, those >60 years had statistically significant associations with worse physical functioning: -2.40 (95% confidence interval (CI) -4.14 to -0.71), better social: 4.88 (2.68 to 7.30) and role: 3.79 (1.39 to 6.16) functioning, and less fatigue: -3.43 (-5.44 to -1.33) and pain: -4.56 (-6.18 to -2.93). Compared to men, women had statistically significant associations with worse physical and social functioning and more fatigue and pain. Associations between age, sex, and HRQoL were not clinically relevant. Performance status had clinically relevant associations in 5/8 scales.

CONCLUSION: Patients with glioma have clinically relevant worse HRQoL compared to the general population. There are statistically but not clinically significant associations between age, sex, and certain HRQoL scales.

PMID:41572423 | DOI:10.1093/oncolo/oyag005

Categories
Nevin Manimala Statistics

What is a normal left ventricular ejection fraction in healthy adults? A meta-analysis of population-based echocardiographic studies

J Cardiovasc Imaging. 2026 Jan 22;34(1):2. doi: 10.1186/s44348-025-00063-4.

ABSTRACT

BACKGROUND: Transthoracic echocardiography derived left ventricular ejection fraction (LVEF) is a cornerstone in heart failure risk prevention. However, the lower limits of normal LVEF remains imprecisely defined. We aimed to define normal LVEF ranges by sex, age group, and self-reported race/ethnicity using data from population-based echocardiographic studies.

METHODS: We systematically searched MEDLINE for studies published between January 1, 2000, and January 3, 2025, that reported the mean and standard deviation of LVEF measured by 2D or 3D echocardiography in healthy, community-based adult populations.

RESULTS: In 10 studies (n = 10,427; female sex, 48%), the pooled mean LVEF was 62.8% (95% confidence interval, 61.0%-64.7%), with estimated lower and upper normal limits of 51.8% and 73.2%, respectively. Women had higher mean LVEF (63.7%) than men (61.9%), with corresponding lower normal limits of 52.7% and 51.7%, respectively. LVEF was similar across age groups. Individuals of Asian origin had 2 to 3 percentage points higher LVEF than Black or White individuals, with lower normal limits of 54% for women and 53% for men. Fewer than 1% of women and approximately 1% of men would be expected to have an LVEF below 50%. Across all demographic subgroups, the probability that an LVEF < 50% is within the normal range was < 5%. There was significant heterogeneity of the included studies (e.g., τ2 = 8.82, I2 = 99.7% for overall analysis) that appeared unexplained by sex, age, or echocardiography modality (2D vs. 3D).

CONCLUSIONS: In healthy adults, the lower limit of normal LVEF is approximately 53% for women and 52% for men, with slightly higher thresholds among individuals of Asian origin. An LVEF < 50% is highly unlikely to reflect normal function, regardless of sex, age, or self-reported race/ethnicity. Given the high statistical heterogeneity, the results should be interpreted with caution.

PMID:41572417 | DOI:10.1186/s44348-025-00063-4

Categories
Nevin Manimala Statistics

Clinical outcomes in newly diagnosed patients with Waldenström’s macroglobulinaemia treated in a tertiary academic centre

Br J Haematol. 2026 Jan 22. doi: 10.1111/bjh.70342. Online ahead of print.

ABSTRACT

Waldenström’s macroglobulinaemia (WM) is a rare B-cell lymphoproliferative disorder with multiple effective front-line treatment options. However, real-world comparative data on commonly used regimens are limited. We conducted a retrospective cohort study of 348 consecutive, newly diagnosed WM patients treated between 2002 and 2024. Patients received first-line therapy with either bortezomib-dexamethasone-rituximab (BDR, n = 35), Bruton’s tyrosine kinase inhibitors (BTKis, n = 57) or dexamethasone-rituximab-cyclophosphamide (DRC, n = 256). BTKi demonstrated the highest MRR (major response rate, ≥PR) (80.7%), followed by DRC (68.4%) and BDR (40.0%) (p < 0.001). The median PFS and OS did not differ significantly among regimens. TTNT seemed to be longer in the BTKi group (log-rank p = 0.025), with a 74% reduced risk of salvage therapy compared to DRC (aHR = 0.26, p = 0.016). Cumulative WM-related mortality at 5 years was lowest in BTKi-treated patients (4.1% vs. 13.0% DRC vs. 17.1% BDR), though differences were not statistically significant. In this single-centre analysis, both BTKi and DRC led to prolonged disease control in the upfront treatment of patients with WM. Extended follow-up and prospective validation are needed to reveal potential long-term survival differences.

PMID:41572416 | DOI:10.1111/bjh.70342

Categories
Nevin Manimala Statistics

A latent profile transition analysis of internet addiction for rural adolescents and its associations with emotional and interpersonal problems

BMC Psychol. 2026 Jan 22. doi: 10.1186/s40359-026-03992-x. Online ahead of print.

ABSTRACT

BACKGROUND: Improved internet access has exposed rural adolescents in China to a greater risk of internet addiction. However, existing studies seldom examine the relationship between dynamic changes in internet addiction and psychosocial maladjustment. This study aims to explore the transition patterns of internet addiction and its associations with emotional and interpersonal problems over time.

METHODS: A one-year longitudinal survey was conducted among 782 middle school students in rural China. Latent Profile Analysis (LPA) was conducted to identify internet addiction profiles at two time points. Latent Profile Transition Analysis (LPTA) was then used to examine the transition patterns between profiles over time. Subsequently, statistical analyses were conducted to explore how these transitions were associated with emotional and interpersonal problems.

RESULTS: Three profiles of internet addiction were identified: minimal-internet addiction, low-internet addiction, and high-internet addiction. Based on LPTA, most adolescents with higher internet addiction at T1 shifted to lower-severity profiles over time (high → minimal: 35.3%; low → minimal: 39.8%; high → low: 33.3%), while some with initially lower levels transitioned to more severe profiles (minimal → high: 6.9%; low → high: 12.2%; minimal → low: 25.7%). Transition into higher addiction profiles predicted increased depression, anxiety, and poorer relationships with parents, peers, and teachers. Conversely, reductions in addiction were linked to improved depressive symptoms.

CONCLUSIONS: Changes in internet addiction have an impact on adolescent psychosocial maladjustment. Early detection and flexible interventions are essential in rural settings.

PMID:41572413 | DOI:10.1186/s40359-026-03992-x