Tag: nevin manimala

J Neurovirol. 2023 Nov 10. doi: 10.1007/s13365-023-01184-6. Online ahead of print.

ABSTRACT

Hepatitis C virus (HCV) infection is a progressive, systemic disease which leads to the development of end-stage liver disease. In 70% of patients, HCV infection is followed by the development of extrahepatic manifestations (EHM). A common EHM is HCV associated neurocognitive disorder (HCV-AND), characterized by neuropsychological changes in attention, working memory, psychomotor speed, executive function, verbal learning, and recall. The aim of this study is to examine the correlation between the neurocognitive profile and routine, available laboratory parameters of inflammation, liver function tests, grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia in treatment naïve non-cirrhotic HCV patients. This is a single-center exploratory study in which we examined 38 HCV + treatment naïve patients. The complete blood count and hematological parameters of systemic inflammation, liver function tests, biopsy confirmed grade of liver fibrosis, and clinical and laboratory parameters of mixed cryoglobulinemia caused by chronic HCV infection were observed. In the study, we used a battery of neuropsychological tests assessing multiple cognitive domains: executive functions, verbal fluency, delayed memory, working memory and learning, and one measure for visuo-constructive performance. Before the Bonferroni correction for multiple comparisons, the results show significant correlations between the scores in the neurocognitive variables and the single measures of inflammation, liver function parameters, and mixed cryoglobulinemia. It has not found a statistically significant correlation between systemic inflammation and neurocognitive variables. After the Bonferroni adjustment, no correlations remained significant. Certainly, the obtained results can be a recommendation for additional validation through future research.

PMID:37948037 | DOI:10.1007/s13365-023-01184-6

Aging Clin Exp Res. 2023 Nov 10. doi: 10.1007/s40520-023-02617-2. Online ahead of print.

ABSTRACT

BACKGROUND: Aging and frailty pose significant challenges globally, placing a substantial burden on healthcare and social services due to their adverse consequences.

AIM: The primary objective of this study was to investigate the relationship between social participation and development of frailty transition and trajectory.

METHODS: This study utilized data from the CLHLS Cohort, a 10-year follow-up study involving 6713 participants, to investigate the association between social participation and development of frailty. Frailty reflects a comprehensive decline in various body functions. The study employed a group-based trajectory model to analyze the development trajectory of the frailty index and used logistic regression to assess the odds ratio (OR) of frailty risk.

RESULTS: We identified two distinct groups of frailty progression trajectories: the “stable development group” and the “rapid growth group.” Individuals who engaged in social activities at least once a month, but not daily, exhibited a significant association with an increased risk of transitioning into the “rapid growth group” (OR 1.305, 95% CI 1.032-1.649). Those with social participation less than once a month had an even greater risk (OR 1.872, 95% CI 1.423-2.463). Moreover, low social participation frequency (occasionally/never) has a more pronounced impact on frailty progression in males.

CONCLUSION: A higher frequency of social participation is associated with a lower risk of being classified into the “rapid growth group” and a slower rate of frailty index progression. Preventing the progression of frailty can contribute to enhanced support for healthy aging among older adults.

PMID:37948011 | DOI:10.1007/s40520-023-02617-2

Neurol Ther. 2023 Nov 10. doi: 10.1007/s40120-023-00562-w. Online ahead of print.

ABSTRACT

INTRODUCTION: There have been no prior trials directly comparing the efficacy of different calcitonin gene-related peptide (CGRP) antagonists for migraine prevention. Reported are the results from the first head-to-head study of two CGRP antagonists, galcanezumab (monoclonal antibody) versus rimegepant (gepant), for the prevention of episodic migraine.

METHODS: In this 3-month, double-blind, double-dummy study, participants were randomized (1:1) to subcutaneous (SC) galcanezumab 120 mg per month (after a 240 mg loading dose) and a placebo oral disintegrating tablet (ODT) every other day (q.o.d.) or to rimegepant 75 mg ODT q.o.d. and a monthly SC placebo. The primary endpoint was the proportion of participants with a ≥ 50% reduction in migraine headache days per month from baseline across the 3-month double-blind treatment period. Key secondary endpoints were overall mean change from baseline in: migraine headache days per month across 3 months and at month 3, 2, and 1; migraine headache days per month with acute migraine medication use; Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at month 3; and a ≥ 75% and 100% reduction from baseline in migraine headache days per month across 3 months.

RESULTS: Of 580 randomized participants (galcanezumab: 287, rimegepant: 293; mean age: 42 years), 83% were female and 81% Caucasian. Galcanezumab was not superior to rimegepant in achieving a ≥ 50% reduction from baseline in migraine headache days per month (62% versus 61% respectively; P = 0.70). Given the pre-specified multiple testing procedure, key secondary endpoints cannot be considered statistically significant. Overall, treatment-emergent adverse events were reported by 21% of participants, with no significant differences between study intervention groups.

CONCLUSIONS: Galcanezumab was not superior to rimegepant for the primary endpoint; however, both interventions demonstrated efficacy as preventive treatments in participants with episodic migraine. The efficacy and safety profiles observed in galcanezumab-treated participants were consistent with previous studies.

TRIAL REGISTRATION: ClinTrials.gov-NCT05127486 (I5Q-MC-CGBD).

PMID:37948006 | DOI:10.1007/s40120-023-00562-w

Gen Thorac Cardiovasc Surg. 2023 Nov 10. doi: 10.1007/s11748-023-01984-x. Online ahead of print.

ABSTRACT

OBJECTIVE: We evaluated the blood flow within the downstream aortic false lumen after frozen elephant trunk repair for acute aortic dissection and identified hemodynamic predictors of false lumen expansion and negative false lumen remodeling using four-dimensional flow magnetic resonance imaging.

METHODS: Thirty-one patients (Stanford type A, n = 28; Stanford type B, n = 3) with patent false lumen who underwent frozen elephant trunk procedures for acute aortic dissection were included in this observational study. Each patient underwent computed tomography during the follow-up period and four-dimensional flow magnetic resonance imaging within 3 postoperative months. The false lumen volumetric expansion rate was calculated using computed tomography data. The direction and the rate of flow in the lower descending aortic false lumen were analyzed. Negative false lumen remodeling was defined as a volumetric increase of > 10% from the baseline volume.

RESULTS: Negative false lumen remodeling had developed in 6 of the 31 patients during the observation period. Most of the false lumen flows were biphasic during systole. The range between peak and nadir flow rates was associated with the false lumen volumetric expansion rate (β coefficient = 6.77; p < 0.01, R² = 0.43).

CONCLUSIONS: The range between peak and nadir flow rates may serve as a hemodynamic predictor of negative false lumen remodeling, enabling further treatment for patients at risk of expansion in the downstream aorta.

PMID:37948001 | DOI:10.1007/s11748-023-01984-x

J Urban Health. 2023 Nov 10. doi: 10.1007/s11524-023-00790-3. Online ahead of print.

ABSTRACT

Rising ambient temperatures due to climate change will impact both indoor temperatures and heating and cooling utility costs. In traditionally colder climates, there are potential tradeoffs in how to meet the reduced heating and increased cooling demands, and issues related to lack of air conditioning (AC) access in older homes and among lower-income populations to prevent extreme heat exposure. We modeled a typical multi-family home in Boston (MA) in the building simulation program EnergyPlus to assess indoor temperature and energy consumption in current (2020) and projected future (2050) weather conditions. Selected households were those without AC (no AC), those who ran AC sometimes (some AC), and those with sufficient resources to run AC always (full AC). We considered stylized cooling subsidy policies that allowed households to move between groups, both independently and in conjunction with energy efficiency retrofits. Results showed that future weather conditions without policy changes yielded an increase in indoor summer temperatures of 2.1 °C (no AC), increased cooling demand (range: 34-50%), but led to a decrease in net yearly total utility costs per apartment (range: – $21 to – $38). Policies that allowed households to move to greater AC utilization yielded average indoor summer temperature decreases (- 3.5 °C to – 6.2 °C) and net yearly total utility increases (range: + $2 to + $94) per apartment unit, with greater savings for retrofitted homes primarily due to large decreases in heating use. Our model results reinforce the importance of coordinated public policies addressing climate change that have an equity lens for both health and climate goals.

PMID:37947996 | DOI:10.1007/s11524-023-00790-3

Ir J Med Sci. 2023 Nov 10. doi: 10.1007/s11845-023-03562-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess the most common lower limb acute muscle injuries on MRI imaging in a national specialist centre for orthopaedics and sports medicine and to explore potential gender differences.

METHODS: Over a 3-year time period, all MRI lower limb studies with acute muscle injury (AMI) were reviewed. A British Athletics muscle injury classification (BAMIC) was given and a statistical analysis was performed.

RESULTS: A total of 195 AMIs were diagnosed: 177 (91%) male and 18 (9%) female injuries (M to F = 9.8:1). The most common lower limb AMIs were BAMIC grade 1a injuries (n = 48, 25%). The most commonly injured muscle was biceps femoris (n = 87, 45%), specifically grade 1b and grade 2b injuries. There was no significant difference in age between men and women with acute lower limb muscle injuries (p = 0.19). Females were 1.5 times more likely to have a lower grade AMI than males, although this did not reach statistical significance (p = 0.7) owing to a striking lower number of female patients. There was no significant difference between genders in the likelihood of sustaining a hamstring or quadricep AMI (hamstrings OR = 2.47, p = 0.14 and quadriceps OR = 0.926, p 0.99).

CONCLUSIONS: Grade 1a is the most common lower limb AMI grade in our institution, accounting for 25%. Biceps femoris is the most commonly injured muscle (45%) with grade 1b and grade 2b being the most frequently encountered grades of biceps femoris injuries. Lower-grade injuries are more common in females compared to males, although not significantly so. Further studies are required to explore possible reasons for this gender gap.

PMID:37947993 | DOI:10.1007/s11845-023-03562-9

Stat Med. 2023 Nov 10. doi: 10.1002/sim.9931. Online ahead of print.

ABSTRACT

Prediction models are increasingly developed and used in diagnostic and prognostic studies, where the use of machine learning (ML) methods is becoming more and more popular over traditional regression techniques. For survival outcomes the Cox proportional hazards model is generally used and it has been proven to achieve good prediction performances with few strong covariates. The possibility to improve the model performance by including nonlinearities, covariate interactions and time-varying effects while controlling for overfitting must be carefully considered during the model building phase. On the other hand, ML techniques are able to learn complexities from data at the cost of hyper-parameter tuning and interpretability. One aspect of special interest is the sample size needed for developing a survival prediction model. While there is guidance when using traditional statistical models, the same does not apply when using ML techniques. This work develops a time-to-event simulation framework to evaluate performances of Cox regression compared, among others, to tuned random survival forest, gradient boosting, and neural networks at varying sample sizes. Simulations were based on replications of subjects from publicly available databases, where event times were simulated according to a Cox model with nonlinearities on continuous variables and time-varying effects and on the SEER registry data.

PMID:37947168 | DOI:10.1002/sim.9931

Rev Esc Enferm USP. 2023 Nov 3;57:e20220475. doi: 10.1590/1980-220X-REEUSP-2022-0475en. eCollection 2023.

ABSTRACT

OBJECTIVE: To compare the social support as perceived by elderly persons in a context of social vulnerability according to family functionality.

METHOD: A cross-sectional study using a quantitative approach, carried out in São Carlos-SP, with 123 elderly people living in a context of high social vulnerability. The sample was divided into two groups: good family functionality and moderate/severe family dysfunction. Data was collected on sociodemographic characteristics, family functionality (Family APGAR) and social support (Medical Outcomes Study Social Support Scale). The Mann-Whitney, Chi-square and Fisher’s exact statistical tests were used.

RESULTS: There was a statistically significant difference between social support and family functionality (p < 0.05). The group with good family functionality obtained higher median social support scores: affective 100.00; material 95.00; information 90.00; emotional 90.00; positive social interaction 85.00; when compared to the group with moderate/severe family dysfunction: affective 86.67; material 87.50; information 70.00; emotional 65.00; positive social interaction 65.00.

CONCLUSION: Elderly persons living in dysfunctional families have less perceived social support when compared to those living in families with good family functionality.

PMID:37947163 | DOI:10.1590/1980-220X-REEUSP-2022-0475en

Cancer. 2023 Nov 10. doi: 10.1002/cncr.35103. Online ahead of print.

ABSTRACT

BACKGROUND: Recurrent/metastatic adenoid cystic carcinoma (ACC) is a rare, incurable disease. MYB is a putative oncogenic driver in ACC that is often overexpressed through an MYB-NFIB rearrangement. The authors hypothesized that AKT inhibition with the allosteric inhibitor MK-2206 could decrease MYB expression and induce tumor regression in patients with incurable ACC (ClinicalTrials.gov identifier NCT01604772).

METHODS: Patients with progressive, incurable ACC were enrolled and received MK-2206 150 mg weekly; escalation to 200 mg was allowed. The primary end point was confirmed response. Secondary end points were progression-free survival, overall survival, and safety. An exploratory analysis evaluating the effect of MK-2206 on MYB expression was conducted in a subset of patients.

RESULTS: Sixteen patients were enrolled, and 14 were evaluable for efficacy. No confirmed responses were observed. Thirteen patients had stable disease, and one had disease progression as their best response. The median progression-free survival was 9.7 months (95% CI, 3.8-11.8 months), and the median overall survival was 18.0 months (95% CI, 11.8-29.9 months). Nine of 16 patients (56%) had at least one grade 3 treatment-related adverse event, and the most common were rash (38%), fatigue (19%), decreased lymphocyte count (13%), and hyperglycemia (13%). Twelve of 14 tumors (86%) had detectable MYB expression by immunohistochemistry, and seven of 14 tumors (50%) had an MYB-NFIB gene rearrangement. Serial biopsies revealed decreased MYB levels with MK-2206 in four of five patients.

CONCLUSIONS: MK-2206 failed to induce clinical responses in patients with incurable ACC. AKT inhibition may diminish MYB protein levels, although the effect was highly variable among patients. Novel approaches to target MYB in ACC are needed.

PMID:37947157 | DOI:10.1002/cncr.35103

J Prosthodont. 2023 Nov 10. doi: 10.1111/jopr.13792. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the effects of 1 vs. 2 glaze firings on the color and mechanical properties of an extrinsically characterized lithium disilicate ceramic after thermal-cycling, brushing, or both.

MATERIALS AND METHODS: Eighty specimens were divided into 2 groups: one glaze firing (GL1) and two glaze firings (GL2). Each group was subdivided into 4 groups (n = 10), according to the experimental conditions: thermal-cycling, brushing, thermal-cycling + brushing, and immersion in distilled water (control). Color variation, surface roughness, and Vickers microhardness were analyzed before each designated experiment and after the simulated periods of 2.5, 5, and 10 years. Three-way mixed ANOVA was used for all outcomes, followed by one-way ANOVA, repeated measures one-way ANOVA, Bonferroni post hoc test, and t-test to check for statistical differences (α = .05).

RESULTS: Thermal-cycling generated greater color changes in the GL1 group at 2.5- and 5 years (P<.001; P = .013). Brushing generated color changes in GL1 at 5 years (P = .003) and in GL2 at 10 years (P = .017). Regarding surface roughness, the GL1 group suffered alterations in thermal-cycling + brushing at 5 years. In the control group, the GL1 group exhibited higher roughness values than GL2 (P<.05). Most of the groups experienced an increase in microhardness at 2.5 years (P<.05). In the GL1 group, thermal-cycling increased the microhardness at 5 years (P = .006); at 5 and 10 years, the GL1 group had a higher microhardness than the GL2 in thermal-cycling + brushing (P<.05).

CONCLUSIONS: Ceramics with one glaze firing showed greater color, roughness, and microhardness changes compared to those submitted to two firings. This article is protected by copyright. All rights reserved.

PMID:37947149 | DOI:10.1111/jopr.13792