Tag: nevin manimala

Am J Epidemiol. 2023 Jun 30:kwad140. doi: 10.1093/aje/kwad140. Online ahead of print.

ABSTRACT

We examined the associations between lung function and incident dementia and cognitive decline in 12,688 participants of the ARIC study who provided lung function measurements in 1990-1992. Cognitive tests were administered up to seven times, and dementia was ascertained through 2019. We used shared parameter models to jointly model proportional hazard models and linear mixed-effect models to estimate lung function-associated dementia rate and cognitive change, respectively. Higher forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were associated with reduced dementia rate (n=2452 developed dementia); hazard ratios per 1L higher FEV1 and FVC were 0.79 (95%CI: 0.71-0.89) and 0.81 (95%CI: 0.74-0.89), respectively. Each 1L higher FEV1 and FVC was associated with 0.08 (95%CI: 0.05-0.12) SD and 0.05 (95%CI: 0.02-0.07) SD attenuation of 30-year cognitive decline, respectively. One percent higher FEV1/FVC was associated with 0.008 (95% CI: 0.004-0.012) SD less cognitive decline. We observed statistical interaction between FEV1 and FVC, suggesting that cognitive declines depended on values of specific FEV1 and FVC (as compared to FEV1, FVC, or FEV1/FVC% models that suggested linear incremental associations). Our findings may have important implications for reducing burden of cognitive decline that is attributable to environmental exposures and associated lung function impairment.

PMID:37392093 | DOI:10.1093/aje/kwad140

Eur J Clin Invest. 2023 Jul 1:e14055. doi: 10.1111/eci.14055. Online ahead of print.

ABSTRACT

BACKGROUND: Little is currently known about epigenetic alterations associated with body composition in obesity. Thus, we aimed to explore epigenetic relationships between genome-wide DNA methylation levels and three common traits of body composition as measured by body fat percentage (BF%), fat mass (FM) and lean body mass (LBM) among Chinese monozygotic twins.

METHODS: Generalized estimated equation model was used to regress the methylation level of CpG sites on body composition. Inference about Causation Through Examination Of Familial Confounding was used to explore the evidence of a causal relationship. Gene expression analysis was further performed to validate the results of differentially methylated genes.

RESULTS: We identified 32, 22 and 28 differentially methylated CpG sites (p < 10^-5 ) as well as 20, 17 and eight differentially methylated regions (slk-corrected p < 0.05) significantly associated with BF%, FM and LBM which were annotated to 65 genes, showing partially overlapping. Causal inference demonstrated bidirectional causality between DNA methylation and body composition (p < 0.05). Gene expression analysis revealed significant correlations between expression levels of five differentially methylated genes and body composition (p < 0.05).

CONCLUSIONS: These DNA methylation signatures will contribute to increased knowledge about the epigenetic basis of body composition and provide new strategies for early prevention and treatment of obesity and its related diseases.

PMID:37392072 | DOI:10.1111/eci.14055

Eur J Clin Invest. 2023 Jul 1:e14059. doi: 10.1111/eci.14059. Online ahead of print.

ABSTRACT

BACKGROUND: Macitentan has demonstrated its effectiveness in patients with pulmonary hypertension (PH), but its safety, especially for long-term use, needs to be further explored. This systematic review and meta-analysis aimed to determine the safety of long-term use of macitentan in patients with PH.

METHODS: A systematic search was made of PubMed, Embase, Cochrane Library and clinicaltrials.gov, without language restrictions. Randomised controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo, were reviewed. Estimated effects of included studies were pooled as risk ratios (RRs), with 95% confidence intervals (CIs).

RESULTS: Six RCTs (enrolling 1003 participants) met the inclusion criteria. Anaemia (RR 3.86, 95% CI 2.05-7.30), headache (RR 1.52, 95% CI 1.02-2.26) and bronchitis (RR 2.24, 95% CI 1.30-3.87) were more frequent in the macitentan groups. There was no statistically significant difference in the proportion of patients with at least one adverse event (AE) or serious adverse event (SAE), AEs leading to discontinuation of study treatment, all-cause death, right ventricular failure (RVF) and peripheral oedema between the two groups.

CONCLUSIONS: The long-term use of macitentan is safe for patients with PH, although with a higher risk of anaemia, headache and bronchitis.

PMID:37392063 | DOI:10.1111/eci.14059

J Magn Reson Imaging. 2023 Jul 1. doi: 10.1002/jmri.28882. Online ahead of print.

ABSTRACT

BACKGROUND: Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision.

PURPOSE: To develop a nomogram to identify DSI in cervical AC/ASC.

STUDY TYPE: Retrospective.

POPULATION: Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52).

FIELD STRENGTH/SEQUENCE: 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA).

ASSESSMENT: The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts.

STATISTICAL TESTS: Student’s t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram.

RESULTS: The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2.

DATA CONCLUSION: The nomogram achieved good performance for evaluating DSI in cervical AC/ASC.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

PMID:37392060 | DOI:10.1002/jmri.28882

Semin Dial. 2023 Jun 30. doi: 10.1111/sdi.13167. Online ahead of print.

ABSTRACT

INTRODUCTION: Vascular calcification is an intervenable factor in the pathophysiology of cardiovascular disease. Treatment-related factors might worsen the arterial stiffness in chronic hemodialysis patients. The aim of the study is to compare the effects of 1-year treatment with paricalcitol or calcitriol on pulse wave velocity (PWV), which is an indicator of arterial stiffness and osteocalcin and fetuin-A levels.

METHODS: Seventy-six hemodialysis patients who had similar PWV1 at the beginning were evaluated after a 1-year treatment of paricalcitol or calcitriol. PWV2, serum osteocalcin, and fetuin-A levels were measured at the end of the study.

RESULTS: At the end of the study, PWV2 of paricalcitol group was statistically lower than the calcitriol group. Osteocalcin levels were statistically lower and fetuin-A levels were statistically higher in the paricalcitol group than the calcitriol group at the end of the study. The number of patients with PWV2 > 7 m/s and using paricalcitol was 16 (39%) but 25 (41%) patients were using calcitriol; the differences were statistically significant.

CONCLUSIONS: The long-term benefits of paricalcitol were superior to the benefits of calcitriol. Paricalcitol has protective effects from vascular calcification in chronic hemodialysis patients.

PMID:37392044 | DOI:10.1111/sdi.13167

Pain Pract. 2023 Jul 1. doi: 10.1111/papr.13267. Online ahead of print.

ABSTRACT

BACKGROUND: Chronic low back pain (cLBP) is the most common cause of years lived with disability (YLD). Chronic overlapping pain conditions (COPCs) is a relatively new taxonomy for widespread pain. Researchers have postulated that patients with COPCs have more pain-related impact than those with isolated pain conditions. We know little about the combination of COPCs with cLBP. This study aims to characterize patients with isolated cLBP compared to those with cLBP and associated COPCs across multiple domains of physical, psychological, and social functioning.

METHODS: Using Stanford’s CHOIR registry-based learning health system, we performed a cross-sectional study on patients with localized cLBP (group L) versus cLBP with COPCs (group W). We used demographic, PROMIS (Patient-Reported Outcomes Measurement Information System), and legacy survey data to characterize the physical, psychological, social, and global health outcomes. We further subdivided the COPCs into intermediate and severe based on the number of body regions involved. We used descriptive statistics and generalized linear regression models to characterize and compare the pain groups.

RESULTS: Among 8783 patients with cLBP, 485 (5.5%) had localized cLBP (Group L) without widespread pain. Compared to Group L, patients in Group W were more likely to be females, younger, and reported longer duration of pain. Although the mean pain scores were significantly higher in group W, this difference did not appear clinically significant (average pain scores MD -0.73, 95% CI [-0.91 to -0.55]). Group W had significantly worse outcomes in all PROMIS outcomes. However, outcomes with large clinical differences (Cohen’s d > 0.5) were fatigue (MD = -7.0, 95% CI [-8.0 to -6.1]); sleep impairment (MD = -6.2, 95% CI [-7.1 to -5.3]); sleep disturbance (MD = -5.3, 95% CI [-6.2 to -4.5]); pain behavior (MD = -2.2, 95% CI [-2.5 to -1.8]); physical function (MD = 4.0, 95% CI [3.2-5.0]); pain interference (MD = -3.4, 95% CI [-4.0 to -2.8]); and anxiety (MD = -4.9, 95% CI [-5.7 to -4.0]). Adjusted analysis controlling for age, gender, BMI category, and duration of pain confirmed worsening of all outcomes with more widespread pain.

CONCLUSION: COPCs are a common presentation with cLBP. The combination of COPCs with cLBP is associated with significantly worse physical, psychological, social, and global health outcomes. This information may identify patients with COPCs and cLBP to optimally risk and treatment stratify their care and individualize their management.

PMID:37392043 | DOI:10.1111/papr.13267

CNS Neurosci Ther. 2023 Jun 30. doi: 10.1111/cns.14332. Online ahead of print.

ABSTRACT

BACKGROUND: Accumulating evidences indicate regional gray matter (GM) morphology atrophy in spinocerebellar ataxia type 3 (SCA3); however, whether large-scale morphological brain networks (MBNs) undergo widespread reorganization in these patients remains unclear.

OBJECTIVE: To investigate the topological organization of large-scale individual-based MBNs in SCA3 patients.

METHODS: The individual-based MBNs were constructed based on the inter-regional morphological similarity of GM regions. Graph theoretical analysis was taken to assess GM structural connectivity in 76 symptomatic SCA3, 24 pre-symptomatic SCA3, and 54 healthy normal controls (NCs). Topological parameters of the resulting graphs and network-based statistics analysis were compared among symptomatic SCA3, pre-symptomatic SCA3, and NCs groups. The inner association between network properties and clinical variables was further analyzed.

RESULTS: Compared to NCs and pre-symptomatic SCA3 patients, symptomatic SCA3 indicated significantly decreased integration and segregation, a shift to “weaker small-worldness”, characterized by decreased C_p , lower E_loc, and E_glob (all p < 0.005). Regarding nodal properties, symptomatic SCA3 exhibited significantly decreased nodal profiles in the central executive network (CEN)-related left inferior frontal gyrus, limbic regions involving the bilateral amygdala, left hippocampus, and bilateral pallidum, thalamus; and increased nodal degree, efficiency in bilateral caudate (all p_FDR <0.05). Meanwhile, clinical variables were correlated with altered nodal profiles (p_FDR ≤0.029). SCA3-related subnetwork was closely interrelated with dorsolateral cortico-striatal circuitry extending to orbitofrontal-striatal circuits and dorsal visual systems (lingual gyrus-striatal).

CONCLUSION: Symptomatic SCA3 patients undergo an extensive and significant reorganization in large-scale individual-based MBNs, probably due to disrupted prefrontal cortico-striato-thalamo-cortical loops, limbic-striatum circuitry, and enhanced connectivity in the neostriatum. This study highlights the crucial role of abnormal morphological connectivity alterations beyond the pattern of brain atrophy, which might pave the way for therapeutic development in the future.

PMID:37392035 | DOI:10.1111/cns.14332

Eur J Clin Invest. 2023 Jul 1:e14056. doi: 10.1111/eci.14056. Online ahead of print.

ABSTRACT

BACKGROUND: Evidence of a clear causal relationship between telomere length and aortic aneurysms is limited by the potential for confounding or reverse causation effects. In this study, we used a Mendelian randomisation (MR) approach to investigate this putative causal association.

METHODS: In total, 118 telomere length-associated single-nucleotide polymorphisms, identified in 472,174 individuals of European ancestry, were used as the instrumental variables. Summary statistics for genome-wide association studies of aortic aneurysms were obtained from the FinnGen consortium. For the primary MR analyses, the inverse-variance weighted random-effects method was used and was supplemented with multivariable MR, weighted median and MR-Egger approaches. The MR-Egger intercept test, Cochran’s Q test and ‘leave-one-out’ sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneity and stability of the genetic variants. Forward and reverse MR analyses were performed.

RESULTS: All forward univariable MR analyses showed that longer telomere lengths decreased aortic aneurysm risks (total aortic aneurysms: OR = 0.80, 95% CI 0.67-0.96, p = .015; thoracic aortic aneurysms: OR = 0.82, 95% CI 0.68-0.98, p = .026; abdominal aortic aneurysms: OR = 0.525, 95% CI 0.398-0.69, p < .001), whereas all reverse MR analyses suggested the absence of aortic aneurysm liability on telomere length. The sensitivity analysis results were robust, and no evidence of horizontal pleiotropy was observed.

CONCLUSIONS: Our results support a possible causal association between telomere length and aortic aneurysms, providing new insights into the involvement of telomere biology in this condition and offering a potential avenue for targeted therapeutic interventions.

PMID:37392033 | DOI:10.1111/eci.14056

AIDS Res Hum Retroviruses. 2023 Jun 30. doi: 10.1089/AID.2022.0186. Online ahead of print.

ABSTRACT

With the advancement of effective antiretroviral therapy (ART), people with HIV live longer, and many are developing non-AIDS comorbidities. It is important to assess how comorbidities are associated with HIV-related health outcomes, such as viral suppression (VS). The aim of this study was to analyze the association between comorbidity burden, measured using a modified Quan-Charlson Comorbidity Index (QCCI), and VS (viral load result of <200 copies/mL). We hypothesized that an increase in QCCI score, indicating a higher risk for mortality, would correlate with lower likelihood of VS because of the burden of comorbidity treatment, possibly leading to worse antiretroviral adherence. Our analysis included participants from the DC Cohort Longitudinal HIV Study in Washington, D.C. Eligible participants were aged ≥18 years and enrolled in the cohort as of January 1, 2018 (n=2,471). A modified QCCI score, which weighs selected comorbidities (not including HIV/AIDS) and predicts mortality, was calculated using ICD-9/10 codes from electronic health records. Multivariable logistic regressions were used to characterize the association between QCCI composite scores and VS. Participants were predominantly virally suppressed (89.6%), male (73.9%), Non-Hispanic Black (74.7%) and between 18-55 years old (59.3%). The median QCCI score was 1 (range= 1-12, IQR= 0-2), demonstrating predominately low mortality risk. We did not establish a statistically significant association between QCCI score and VS (adjusted odds ratio=1.06, 95% CI 0.96-1.17). Our findings suggest that a higher QCCI score was not associated with lower VS in this population, which may be partly due to the high retention in care among Cohort participants.

PMID:37392022 | DOI:10.1089/AID.2022.0186

AIDS Res Hum Retroviruses. 2023 Jun 30. doi: 10.1089/AID.2022.0150. Online ahead of print.

ABSTRACT

The challenge of designing future HIV prevention efficacy trials in a rapidly evolving HIV prevention landscape was explored through a series of virtual stakeholder’s engagement meetings convened online between October 2020 and April 2021. A broad array of stakeholders from the HIV prevention research community reviewed current trial designs and lessons learned, explored issues specific to unique product classes, and concluded with specialist-focused examinations of statistical design concepts and the importance of community engagement in research. The aim was to reflect on current approaches and evaluate new trial design approaches for evaluating efficacy of a candidate prevention strategy in the context of an active-controlled trial, which does not include a placebo arm. Here, we provide a summary of the discussion points that included gaps in understanding and logical next steps in the prevention research pathway. The technical challenges involved in the statistical design approaches are described in a companion paper.

PMID:37392020 | DOI:10.1089/AID.2022.0150