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Heart Rate Reduction Is Associated With Reverse Left Ventricular Remodeling and Mechanism-Specific Molecular Phenotypes in Dilated Cardiomyopathy

Circ Heart Fail. 2025 Mar 7:e012484. doi: 10.1161/CIRCHEARTFAILURE.124.012484. Online ahead of print.

ABSTRACT

BACKGROUND: Heart rate (HR) affects heart failure outcomes, via uncertain mechanisms that may include left ventricular remodeling. However, in human ventricular myocardium, HR change has not been associated with a particular remodeling molecular phenotype.

METHODS: Patients with nonischemic dilated cardiomyopathy (N=22) in sinus rhythm and refractory to β-blockade for both HR lowering and reverse remodeling were randomized 2:1 double-blind to the HCN4 (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4) channel inhibitor ivabradine or placebo for 24 weeks treatment while maintaining target doses of β-blockers. Reverse remodeling was measured by left ventricular ejection fraction (LVEF), and myocardial gene expression by sequencing RNA extracted from endomyocardial biopsies. The primary statistical analysis was between HR change categories divided at the median, which resulted in Decreased HR (N=90) and Unchanged HR (N=8) groups.

RESULTS: Respective HRs at baseline and 24 weeks were as follows: Decreased HR, 82.9±6.8 and 69.7±8.0 beats per minute (P=0.0005) and Unchanged HR, 80.8±5.7 and 79.2±11.6 beats per minute (P=0.58). All completing Decreased HR subjects were treated with ivabradine, whereas in the Unchanged HR group, 3 received ivabradine and 5 placebo. In Decreased HR, LVEF increased from 29.4±8.8% at baseline to 44.2±9.4% at 24 weeks (P=0.0003), compared with respective values of 26.6±11.4% and 29.2±12.0% (P=0.28) in Unchanged HR. HR and LVEF changes were not different from a previously conducted β-blocker nonischemic dilated cardiomyopathy study subdivided into LVEF responders and nonresponders. However, differentially expressed genes (N=151) in the Decreased versus Unchanged HR groups were >99% nonconcordant and therefore individually unique compared with β-blocker HR/LVEF responders versus nonresponders (2 shared differentially expressed genes). Multiple unique differentially expressed genes in Decreased HR including NRG1 upregulation are considered cardioprotective or involved in cardiac development.

CONCLUSIONS: In patients with nonischemic dilated cardiomyopathy in sinus rhythm, HR lowering per se (1) is associated with substantial left ventricular reverse remodeling; (2) its absence can cause β-blocker reverse remodeling nonresponse; and (3) when from HCN4 channel inhibition, results in a unique molecular phenotype.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02973594.

PMID:40052260 | DOI:10.1161/CIRCHEARTFAILURE.124.012484

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Musculoskeletal characteristics in older adults with overweight or obesity: INVEST in Bone Health trial baseline analysis

Obesity (Silver Spring). 2025 Mar 6. doi: 10.1002/oby.24243. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to examine associations of computed tomography (CT)-derived musculoskeletal measures with demographics and traditional musculoskeletal characteristics.

METHODS: The Incorporating Nutrition, Vests, Education, and Strength Training (INVEST) in Bone Health trial (NCT04076618) acquired a battery of musculoskeletal measures in 150 older-aged adults living with overweight or obesity. At baseline, CT (i.e., volumetric bone mineral density, cortical thickness, muscle radiomics, and muscle/intermuscular adipose tissue [IMAT] area and density), dual-energy x-ray absorptiometry (DXA; i.e., areal bone mineral density, total body fat mass, appendicular lean mass, and lean body mass), and strength assessments (i.e., grip and knee extensor strength) were collected, along with demographic and clinical characteristics. Analyses employed linear regression and mixed-effects models along with factor analysis for dimensionality reduction of the radiomics data.

RESULTS: Participants were older-aged (mean [SD] age: 66 [5] years), mostly female (75%), and were living with overweight or obesity (mean [SD] BMI: 33.6 [3.3] kg/m2). Age was not significantly associated with most CT-derived bone, IMAT, or muscle measures. BMI was significantly associated with DXA and CT-derived muscle and IMAT measures, which were higher in male than female individuals (all p < 0.01). For the midthigh, muscle size was significantly related to grip and knee extensor strength (both p < 0.01).

CONCLUSIONS: Machine learning-derived CT metrics correlated strongly with DXA and muscle strength, with higher BMI linked to greater IMAT and poorer muscle quality.

PMID:40051020 | DOI:10.1002/oby.24243

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The interplay of socio-demographic factors and disease prevalence: insights into malaria, Hepatitis B, and Hepatitis C in Lafia, Nasarawa State, Nigeria

J Health Popul Nutr. 2025 Mar 6;44(1):67. doi: 10.1186/s41043-025-00779-5.

ABSTRACT

BACKGROUND: Infectious diseases, including malaria, Hepatitis B surface antigen (HBsAg), and Hepatitis C virus (HCV), remain significant public health concerns in developing regions like Lafia, Nasarawa State, Nigeria. Socio-demographic factors, such as gender, age, income level, and access to healthcare resources, have been shown to influence the prevalence and outcomes of these diseases. Despite their importance, there is limited research exploring the interrelationship between these infections and socio-demographic factors within this region. The study aims to investigate the prevalence of malaria, HBsAg, and HCV among patients in Lafia, Nigeria, and to examine the relationship between these infections and socio-demographic factors. Specifically, it seeks to identify correlations between demographic variables, clinical manifestations, and health behaviors, such as mosquito net usage and vaccination status.

METHOD: A cross-sectional design was employed, involving 264 patients from Lafia, Nasarawa State, Nigeria. Data were collected using structured questionnaires which were pretested in a previous study to gather demographic information, vaccination status, and clinical symptoms. Laboratory assessments confirmed the presence of malaria, HBsAg, and HCV. Statistical analysis, including correlations between socio-demographic factors and disease prevalence were analyzed, and used to identify associations between socio-demographic factors, clinical manifestations, and disease prevalence.

RESULTS: Significant findings include a negative correlation between male sex and malaria infection (Pearson Correlation = -0.139, p = 0.024), a positive correlation between age and HCV prevalence (Pearson Correlation = 0.218, p < 0.001), and a negative correlation between the use of mosquito nets and malaria infection (Pearson Correlation = -0.231, p < 0.001). Additionally, HBsAg-positive individuals exhibited more pronounced clinical symptoms (Pearson Correlation = 0.173, p = 0.005), while higher income levels correlated with reduced mosquito net usage (Pearson Correlation = -0.144, p = 0.020). The study underscores the role of socio-demographic factors in shaping the prevalence of malaria, HBsAg, and HCV.

CONCLUSION: This study highlights the interplay between socio-demographic factors and the prevalence of malaria, HBsAg, and HCV in Lafia, Nigeria. It underscores the importance of comprehensive public health interventions tailored to the specific needs of the population to reduce disease burden and improve health outcomes, including health education, to address socio-economic vulnerabilities and promote preventive measures such as mosquito net usage. Addressing these factors could mitigate the burden of infectious diseases in Lafia and similar regions.

PMID:40051006 | DOI:10.1186/s41043-025-00779-5

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Combined use of the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework with other implementation frameworks: a systematic review

Implement Sci Commun. 2025 Mar 6;6(1):25. doi: 10.1186/s43058-025-00704-1.

ABSTRACT

BACKGROUND: Appropriately and comprehensive applying implementation frameworks is one of the key challenges in implementation science resulting in increased use of multiple implementation frameworks within projects. This is particularly true for frameworks such as PARIHS/i-PARIHS. Therefore, this systematic review aimed to examine if and why the PARIHS/i-PARIHS framework has been applied in research with other implementation frameworks.

METHODS: We searched six databases from 2016 (the year following i-PARIHS’ publication) to April 2024 and supplemented this with a citation search of the seminal i-PARIHS paper. We included studies that 1) were peer-reviewed with a protocol or empirical study design, 2) have applied the PARIHS or i-PARIHS framework for implementation planning, delivery, analysis, or evaluation and 3) also used at least one other implementation framework. Descriptive statistics were conducted to report on study characteristics and frequency for each implementation framework used with PARIHS/i-PARIHS. A qualitative, content analysis was used to analyse the answers to open-ended extraction questions.

RESULTS: Thirty-six articles met criteria for inclusion and included 16 protocols and 20 empirical articles (twelve intervention and eight cross-sectional studies). Thirty-four of the studies used one additional implementation framework and two studies used two additional implementation frameworks. In total, nine implementation frameworks were applied with PARIHS/i-PARIHS, including: 1) RE-AIM, 2) CFIR, 3) NPT, 4) REP, 5) TDF, 6), DSF, 7) KTA, 8) Stetler’s Model, and 9) SIF. Thirty-four reported a rationale for using PARIHS/i-PARIHS and 34 reported a rationale for using the other implementation framework. Only eleven reported a rationale for using more than one implementation framework. Only three reported strengths of combining implementation frameworks.

CONCLUSIONS: Overall, this review identified that implementation researchers are using PARIHS/i-PARIHS in combination with other implementation frameworks and providing little to no rationale for why. Use of multiple implementation frameworks without detailed rationales compromises our ability to evaluate mechanisms of effectiveness. Implementation researchers and practitioners need to be more explicit about their framework selection, detailing the complementary strengths of the frameworks that are being used in combination, including why using one is not sufficient.

TRIAL REGISTRATION: This systematic review was registered with PROSPERO: ID: 392147.

PMID:40051001 | DOI:10.1186/s43058-025-00704-1

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Predictive model for surgical intervention in pediatric acute hematogenous osteomyelitis

J Orthop Surg Res. 2025 Mar 7;20(1):249. doi: 10.1186/s13018-025-05641-2.

ABSTRACT

BACKGROUND: The emergence of multidrug-resistant bacteria has resulted in more complicated disease courses and worsening prognoses for patients with acute hematogenous osteomyelitis (AHO), increasing the necessity for surgical intervention. This research attempts to identify the risk variables related to surgical patients and build prediction models.

METHOD: From December 2015 to December 2022, children admitted to a single quaternary care pediatric hospital with AHO had their charts retrospectively reviewed. Based on the therapy methods, the patients were divided into 3 cohorts: multiple surgery, single surgery, and conservative care. Multivariate logistic regression analysis was used to identify independent risk factors related to single and recurrent surgery. A nomogram was created to visually represent the various risk factors, and a calibration curve was plotted to evaluate the model’s goodness of fit. The Hosmer-Lemeshow test and the area under the receiver operating characteristic (ROC) curve were used to assess how well the models matched.

RESULTS: A total of 218 patients were included in the analysis, out of which 150 patients underwent surgical procedures, with 21 individuals undergoing multiple surgeries. The multivariate binary logistic regression revealed that an increase in absolute neutrophil counts (ANC) (adjusted odds ratio [aOR], 1.14 [95% confidence interval {CI}, 1.05-1.24]) and the presence of Methicillin-resistant Staphylococcus aureus (MRSA) (aOR, 6.97 [95% CI, 1.94-25.06]) were strong predictors of surgical intervention. The prediction model demonstrated an area under the curve (AUC) value of 0.76, while the Hosmer-Lemeshow test showed χ2 = 7.3, P = 0.50. In another separated model, the C-reactive protein (CRP) level upon admission (aOR, 1.02 [95% CI, 1.00-1.03]) and the CRP level after the initial surgery (aOR, 1.04 [95% CI, 1.01-1.06]) strongly predict multiple surgeries, with the AUC value of 0.91 obtained and HosmerLemeshow test (χ2 = 8.7, P = 0.36) yielded. The calibration curves of the two models were drawn separately, and it was observed that the slopes of both models were close to one.

CONCLUSION: Two prediction models were developed by statistical analysis of clinical data. Their accuracy and discrimination were validated, indicating a promising potential for clinical application.

PMID:40050999 | DOI:10.1186/s13018-025-05641-2

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The impact of anterior cruciate ligament deficiency severity on the outcomes of fixed-bearing unicompartmental knee arthroplasty: a retrospective study

J Orthop Surg Res. 2025 Mar 6;20(1):244. doi: 10.1186/s13018-025-05635-0.

ABSTRACT

OBJECTIVE: Anterior cruciate ligament deficiency (ACLD) has traditionally been regarded as a contraindication for unicompartmental knee arthroplasty (UKA). However, advancements in surgical techniques and improvements in prosthetic manufacturing have challenged this notion. Controversy persists regarding whether the anterior cruciate ligament (ACL) influences the postoperative outcomes of fixed-bearing (FB) UKA. This study aimed to evaluate the impact of varying severities of ACLD on the clinical outcomes of FB-UKA.

METHODS: This retrospective analysis included 81 patients (87 knees) who underwent FB-UKA for anteromedial osteoarthritis (AMOA). Patients were categorised into three groups on the basis of preoperative MRI and intraoperative findings: the intact ACL group (31 knees), the partial ACLD group (39 knees), and the complete ACLD group (17 knees). Patient demographics (age, body mass index [BMI]), preoperative hip-knee-ankle angle (HKA), follow-up duration, and preoperative and last follow-up data, collected more than one year postoperatively, were recorded, including the Hospital for Special Surgery knee score (HSS), Lysholm score, visual analogue scale (VAS) for pain, range of motion (ROM), postoperative X-ray assessment of the position of the femoral component relative to the tibial component, as well as evaluation of radiolucent lines on the postoperative X-rays. Statistical analyses were conducted to determine differences in clinical outcomes, including pre-and postoperative changes, among the three groups. Postoperative complications, such as infection, aseptic loosening, prosthetic dislocation, or periprosthetic fractures requiring revision surgery, were recorded.

RESULTS: There were no significant differences among the three groups in terms of age, BMI, follow-up duration, preoperative HKA, baseline Lysholm score, HSS knee score, VAS score, or ROM (P > 0.05). Postoperatively, all three groups showed significant improvements in the Lysholm score, HSS knee score, VAS score, and ROM (P < 0.001), with no significant differences in the extent of improvement among the groups (P > 0.05). The position of the femoral component relative to the tibial component did not differ significantly among the groups (P > 0.05), and no radiolucent lines were observed in any of the patients. No patients experienced complications such as infection, aseptic loosening, periprosthetic fractures, or prosthetic dislocations that required revision surgery at the latest follow-up.

CONCLUSION: FB-UKA is a viable surgical option for the treatment of AMOA. For patients with AMOA and stable anteroposterior knee alignment, ACLD does not adversely affect short- to midterm outcomes following FB-UKA. Even in cases of partial or complete ACLD, careful patient selection and optimised surgical techniques can yield outcomes comparable to those in patients with intact ACLs.

PMID:40050997 | DOI:10.1186/s13018-025-05635-0

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Relationship between anterior or posterior femoral head necrosis and collapse based on MRI-defined key necrotic layer sets

J Orthop Surg Res. 2025 Mar 7;20(1):251. doi: 10.1186/s13018-025-05633-2.

ABSTRACT

BACKGROUND: Current clinical studies on femoral head necrotic lesions primarily focus on the medial and lateral regions, while detailed MRI-based methods to evaluate the relationship between anterior or posterior necrosis and collapse remain lacking.

OBJECTIVE: By defining the anterior and posterior positions of the femoral head in MRI, a method was proposed for rapid clinical prognosis assessment of femoral head necrosis based on necrotic location.

METOHD: A retrospective analysis was conducted on TSE sequence T1W1 coronal plane images from 200 cases of femoral head necrosis. The frequency of necrotic lesions appearing on each MRI layer was statistically analyzed to construct a high-frequency necrotic layer set. Among these cases, 100 hips were randomly selected, and the relationship between femoral head collapse at one-year follow-up and different high-frequency necrotic layer sets was analyzed to identify the key necrotic layer set. Based on this, the anterior and posterior regions of the femoral head were defined on MRI. The remaining 100 hips were used as a validation set to assess the impact of anterior or posterior necrosis of the femoral head, as defined by this method, on collapse.

RESULTS: In this study, a total of eight high-frequency necrotic lesion layer sets (S1-S8) were constructed based on MRI data. Among them, S3 (L1 + L2 + L0 + L3) showed the strongest correlation with femoral head collapse, with an AUC of 0.662. Therefore, S3 was defined as the anterior side of the femoral head. Analysis of the validation set revealed that, using this method, the probability of femoral head collapse was 11.4 times higher when necrotic lesions appeared on the anterior side compared to the absence of necrosis on the anterior side.

CONCLUSION: In MRI, the anterior side of the femoral head corresponds to the S3 region, where necrosis increases the risk of collapse by 11.4 times.

PMID:40050989 | DOI:10.1186/s13018-025-05633-2

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Alternative stable states of microbiome structure and soil ecosystem functions

Environ Microbiome. 2025 Mar 6;20(1):28. doi: 10.1186/s40793-025-00688-4.

ABSTRACT

BACKGROUND: Theory predicts that biological communities can have multiple stable states in terms of their species/taxonomic compositions. The presence of such alternative stable states has been examined in classic ecological studies on the communities of macro-organisms (e.g., distinction between forest and savanna vegetation types). Nonetheless, it remains an essential challenge to extend the target of the discussion on multistability from macro-organismal systems to highly species-rich microbial systems. Identifying alternative stable states of taxonomically diverse microbial communities is a crucial step for predicting and controlling microbiome processes in light of classic ecological studies on community stability.

RESULTS: By targeting soil microbiomes, we inferred the stability landscapes of community structure based on a mathematical framework of statistical physics. We compiled a dataset involving 11 archaeal, 332 bacterial, and 240 fungal families detected from > 1,500 agroecosystem soil samples and applied the energy landscape analysis to estimate the stability/instability of observed taxonomic compositions. The statistical analysis suggested that both prokaryotic and fungal community structure could be classified into several stable states. We also found that the inferred alternative stable states differed greatly in their associations with crop disease prevalence in agroecosystems. We further inferred “tipping points”, through which transitions between alternative stable states could occur.

CONCLUSION: Our results suggest that the structure of complex soil microbiomes can be categorized into alternative stable states, which potentially differ in ecosystem-level functioning. Such insights into the relationship between structure, stability, and functions of ecological communities will provide a basis for ecosystem restoration and the sustainable management of agroecosystems.

PMID:40050988 | DOI:10.1186/s40793-025-00688-4

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Biomarker identification for Alzheimer’s disease through integration of comprehensive Mendelian randomization and proteomics data

J Transl Med. 2025 Mar 6;23(1):278. doi: 10.1186/s12967-025-06317-5.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) is the main cause of dementia with few effective therapies. We aimed to identify potential plasma biomarkers or drug targets for AD by investigating the causal association between plasma proteins and AD by integrating comprehensive Mendelian randomization (MR) and multi-omics data.

METHODS: Using two-sample MR, cis protein quantitative trait loci (cis-pQTLs) for 1,916 plasma proteins were used as an exposure to infer their causal effect on AD liability in individuals of European ancestry, with two large-scale AD genome-wide association study (GWAS) datasets as the outcome for discovery and replication. Significant causal relationships were validated by sensitivity analyses, reverse MR analysis, and Bayesian colocalization analysis. Additionally, we investigated the causal associations at the transcriptional level with cis gene expression quantitative trait loci (cis-eQTLs) data across brain tissues and blood in European ancestry populations, as well as causal plasma proteins in African ancestry populations.

RESULTS: In those of European ancestry, the genetically predicted levels of five plasma proteins (BLNK, CD2AP, GRN, PILRA, and PILRB) were causally associated with AD. Among these five proteins, GRN was protective against AD, while the rest were risk factors. Consistent causal effects were found in the brain for cis-eQTLs of GRN, BLNK, and CD2AP, while the same was true for PILRA in the blood. None of the plasma proteins were significantly associated with AD in persons of African ancestry.

CONCLUSIONS: Comprehensive MR analyses with multi-omics data identified five plasma proteins that had causal effects on AD, highlighting potential biomarkers or drug targets for better diagnosis and treatment for AD.

PMID:40050982 | DOI:10.1186/s12967-025-06317-5

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Impact of gastrointestinal and psychological symptoms on disease activity and functional impairment in patients with spondyloarthritis: a cross-sectional study

BMC Rheumatol. 2025 Mar 6;9(1):28. doi: 10.1186/s41927-025-00478-y.

ABSTRACT

INTRODUCTION: Spondyloarthritis (SpA) exhibits predominantly musculoskeletal symptoms but also significant gastrointestinal (GI) and psychological manifestations. Subclinical gut inflammation is common in SpA, with frequent symptoms such as abdominal pain and diarrhea. Psychological issues like depression and anxiety are also prevalent, with a negative impact on quality of life. This study aimed to evaluate the presence of GI and psychiatric symptoms in SpA patients without inflammatory bowel disease (IBD) and their association with disease characteristics.

METHODS: Cross-sectional study, which included SpA patients from two rheumatology outpatient clinics. Patients were assessed for GI, and depressive symptoms (PHQ-9), perceived stress (PSS-10), disease activity (ASDAS, BASDAI) and functionality (BASFI). Laboratory tests included C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fecal calprotectin, and Secretory IgA. Statistical analysis involved Spearman correlation, linear regression, and multiple correspondence discriminant analysis (MCDA).

RESULTS: Among 98 SpA patients, 79.6% had axial SpA. High disease activity and functional impairment were common. 65.3% reported ≥ 2 GI symptoms, predominantly abdominal pain and diarrhea. Depression (PHQ-9 ≥ 10) was observed in 46.7% of patients, being moderate to severe in 25.0%. Depression, perceived helplessness, and lack of self-efficacy were associated with high disease activity and GI symptoms. MCDA identified strong correlations between depression, GI symptoms, and disease activity.

CONCLUSION: This study highlights the association between GI and psychological symptoms with disease activity and functionality in SpA patients. Depression and perceived helplessness are prevalent and closely associated with high disease activity and GI symptoms, suggesting the need for interdisciplinary management from early stages to improve patient outcomes.

PMID:40050979 | DOI:10.1186/s41927-025-00478-y