Nevin Manimala

J Prim Care Community Health. 2023 Jan-Dec;14:21501319231158280. doi: 10.1177/21501319231158280.

ABSTRACT

INTRODUCTION/OBJECTIVES: Dysphagia is a widespread clinical condition among older adults. Although known as a risk factor for nutritional status and dehydration, dysphagia also affects meal patterns. This study aimed to determine the relationship between dysphagia and undernutrition, as well as dietary consumption patterns in older adults.

METHODS: 268 older adults (144 women, 124 men) were included in the study. Mini Nutritional Assessment (MNA), dysphagia assessment (EAT-10), oral examination, and Semi-quantitative Food Frequency Questionnaire (SFFQ) were used for collecting data. Odds ratio and Chi square were used to compare independent variables in subjects with and without undernutrition as well as those who intake texture modified and non-texture modified diet.

RESULTS: Mean age of the undernutrition and normal nutrition groups was 68.9 ± 6.1 and 68.8 ± 6.0 years, respectively. The undernutrition group’s activities of daily living (ADL) were 19.7 ± 0.9, and the normal nutrition group was 19.8 ± 0.7. Older adults with dysphagia were 4.8 times more likely to experience undernutrition than older adults without dysphagia (95% CI = 1.75-13.13, P = .002). There was a statistically difference between the meal patterns among the dysphagic older adult group and the normal-swallowing older adults’ group at the .05 level.

CONCLUSIONS: According to this study, dysphagia was associated with the nutritional status of older adults and dietary patterns. The study results suggested some recommendations for dental health personnel on oral care related to dietary consumption and dietary patterns in older adults.

PMID:36852733 | DOI:10.1177/21501319231158280

J Prim Care Community Health. 2023 Jan-Dec;14:21501319231156132. doi: 10.1177/21501319231156132.

ABSTRACT

Health literacy continues to be an issue among minority groups. Population surveys are one strategy used to help better understand health disparities. The Behavioral Risk Factor Surveillance System (BRFSS) in Kansas added health literacy questions to the survey in 2012. This study examined population health literacy levels and health trends from 2012 to 2018. The health status variables included health care coverage status, general health rating, presence of chronic conditions, and length of time since the last check-up. The percentage of individuals reporting low health literacy decreased from 67% in 2012 to 51% in 2018. The percentage of participants with income levels less than $15 000 was 9% in 2012 and 7% in 2018. Health literacy was lowest among the age group 18 to 24-year-olds, those who identified as multiracial, separated, not graduated from high school, out of work for more than 1 year, income less than $10 000, with other living arrangements, and living in a suburban county of metropolitan statistical area. Additionally, many health conditions improved, and those reporting health insurance increased slightly. The study demonstrates how health literacy continues to be an issue, and how education and primary prevention are necessary to improve limited health literacy and health outcomes. Findings from both state-level and national BRFSS population surveys can help educate the public health and clinical health services workforce to provide better care and address health disparities for highrisk populations.

PMID:36852725 | DOI:10.1177/21501319231156132

J Clin Pharmacol. 2023 Feb 28. doi: 10.1002/jcph.2220. Online ahead of print.

ABSTRACT

Monalizumab is a novel, first-in-class humanized immunoglobulin G (IgG)-4 monoclonal antibody (mAb) immune checkpoint inhibitor that targets the inhibitory CD94/NKG2A receptors. The objectives of this analysis were to develop a population pharmacokinetic (PK) model of monalizumab, evaluate the impact of clinically relevant covariates on monalizumab PK, and provide dose justification for clinical trials. We developed a monalizumab population PK model to characterize the PK properties of monalizumab in patients with advanced solid tumors or head and neck squamous cell carcinoma. Data from clinical studies D419NC00001 (NCT02671435) and IPH2201-203 (NCT02643550) were pooled for the analysis, resulting in a dataset of 3066 PK samples derived from 507 subjects. The PK of monalizumab were reasonably described by a 2-compartment model with first-order elimination. Monalizumab generally exhibited linear PK over a dose range of 22.5-750 mg or 10 mg/kg every 2 weeks. The estimate of clearance was approximately 0.255 L/day and apparent volume of distribution was 6.36 L for a typical individual, consistent with previous findings for endogenous IgGs and other therapeutic mAbs. Baseline albumin and body weight were identified as significant covariates of clearance; body weight, sex, and smoking status had a significant impact on volume of distribution; and none of these covariates had impact on peripheral volume of distribution. Although these covariates were identified as statistically significant, they are considered to be not clinically meaningful, as changes in monalizumab exposure were less than 30%. Therefore, no dose adjustments of monalizumab based on patient or disease characteristics is recommended. This article is protected by copyright. All rights reserved.

PMID:36852723 | DOI:10.1002/jcph.2220

Am Surg. 2023 Feb 28:31348231161089. doi: 10.1177/00031348231161089. Online ahead of print.

ABSTRACT

BACKGROUND: Resuscitation of traumatic cardiac arrest (TCA) is variable, with approaches that overlap Advanced Trauma Life Support (ATLS) and Advanced Cardiac Life Support (ACLS) algorithms. There is no standard algorithm for TCA, with some withholding ACLS protocols given abysmal outcomes. This study aims to assess surgeon practices and attitudes toward resuscitation practices in TCA.

MATERIALS AND METHODS: A 16-question web-based survey was distributed to the membership of a national trauma association. Respondent demographics and management of TCA were analyzed. Chi-squared tests determined statistical significance. Open-ended responses were coded and analyzed inductively.

RESULTS: Two hundred and three surveys were completed. 73.4% of respondents reported utilizing ACLS, while 26.6% reported they never utilized ACLS. A statistically significant difference in the performance of ACLS was found based on number of years in practice (P = .025) and the state of practice (P = .006). There was no significant difference in self-reported survival rates or legal, ethical, or interpersonal conflicts. Qualitative data highlighted themes of interpersonal conflict and futility.

DISCUSSION: This study shows that one-quarter of respondents never utilize ACLS in TCA. Of those that utilize ACLS, there was variability in the technique, indication, and duration of resuscitation. Despite significant variability in technique, there appears to be similar survival rates and incidence of conflict. The association between years in practice and ACLS use suggests this may represent an emerging change in practice. The low response rate limits generalizability; however, there is significant variability in practice, highlighting a need for evidence-based guidelines.

PMID:36852712 | DOI:10.1177/00031348231161089

Stroke. 2023 Feb 28. doi: 10.1161/STROKEAHA.122.041650. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed.

METHODS: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan.

RESULTS: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0-2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to <6), the number predicted to be eligible for the trial increased to 4%. At the time of trial conclusion, 57% of the enrolled patients qualified only by the modified criteria, and the trial was stopped at an interim analysis that demonstrated efficacy. We estimated that the Wilcoxon rank-sum value for the unadjusted predicted enrollment would not have crossed the threshold for efficacy and the trial not stopped.

CONCLUSIONS: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

PMID:36852687 | DOI:10.1161/STROKEAHA.122.041650

J Biomol Struct Dyn. 2023 Feb 28:1-16. doi: 10.1080/07391102.2023.2179542. Online ahead of print.

ABSTRACT

Cervical cancer (CC) is a global threat to women and our knowledge is frighteningly little about its underlying genomic contributors. Our research aimed to understand the underlying molecular and genetic mechanisms of CC by integrating bioinformatics and network-based study. Transcriptomic analyses of three microarray datasets identified 218 common differentially expressed genes (DEGs) within control samples and CC specimens. KEGG pathway analysis revealed pathways in cell cycle, drug metabolism, DNA replication and the significant GO terms were cornification, proteolysis, cell division and DNA replication. Protein-protein interaction (PPI) network analysis identified 20 hub genes and survival analyses validated CDC45, MCM2, PCNA and TOP2A as CC biomarkers. Subsequently, 10 transcriptional factors (TFs) and 10 post-transcriptional regulators were detected through TFs-DEGs and miRNAs-DEGs regulatory network assessment. Finally, the CC biomarkers were subjected to a drug-gene relationship analysis to find the best target inhibitors. Standard cheminformatics method including in silico ADMET and molecular docking study substantiated PD0325901 and Selumetinib as the most potent candidate-drug for CC treatment. Overall, this meticulous study holds promises for further in vitro and in vivo research on CC diagnosis, prognosis and therapies.Communicated by Ramaswamy H. Sarma.

PMID:36852684 | DOI:10.1080/07391102.2023.2179542

J Anim Sci. 2023 Feb 28:skad062. doi: 10.1093/jas/skad062. Online ahead of print.

ABSTRACT

Physiological and environmental stresses such as the transition into lactation and heat load contribute to gastrointestinal tract (GIT) dysfunction. The nonruminant gastrointestinal tract has mechanisms to cope with prooxidant and proinflammatory stressors arising from the gut lumen or within intestinal cells. One-carbon metabolism (OCM) contributes to antioxidant capacity via the production of glutathione (GSH) and taurine, and the synthesis of phospholipid, creatine, and the osmolyte glycinebetaine among others. A multipronged approach was used to assess the biological relevance of OCM and closely-related pathways on GIT function in dairy cows. Ruminal papillae (Rum) and scrapings from duodenum (Duo), jejunum (Jej), and ileum (Ile) were collected at slaughter from 8 multiparous Holstein cows averaging 128 ± 12 d in milk and producing 39 ± 5 kg·d -1. A MIXED model ANOVA with preplanned orthogonal contrasts was used for statistical analysis. Methionine adenosyl transferase 1 activity (MAT) was ~10-fold greater (P < 0.01) and cystathionine β-synthase activity doubled in Rum vs. small intestine. Total glutathione peroxidase (GPX) activity was greatest (P = 0.03) in Ile, but similar to Rum. Activity and mRNA abundance of betaine-homocysteine S-methyltransferase were undetectable. There was a 2.5-fold greater protein abundance of GPX1 (P < 0.01) and a ~2-fold greater abundance of GPX3 (P < 0.01) in Rum vs. small intestine. Among the various amino acids (AA) with roles in OCM or closely-related pathways (e.g. creatine synthesis), concentrations of arginine, aspartate, glutamine, methionine, and serine were lower (P < 0.01) in Rum vs. small intestine. Unlike AA, concentrations of OCM-related intermediates S-5′-adenosyl-homocysteine (SAH), glycinebetaine, carnitine, creatine (CRE), and cysteinesulfinic acid were greater (P < 0.01) while taurine was lower in Rum vs. small intestine. Intermediates of the folate cycle were undetectable. The fact that S-adenosylmethionine (SAM) was undetectable while MAT activity and SAH were greater in Rum suggested that availability of SAM (a methyl donor) is a key determinant of flux through the folate and methionine cycles in the GIT. Except for adenosine, concentrations of glutamate, glycine, α-ketoglutarate, hypotaurine, and GSH were lowest in Ile. Together, the data underscored unique differences in activity of one-carbon metabolism and related pathways across sections of the GIT.

PMID:36852676 | DOI:10.1093/jas/skad062

J Cachexia Sarcopenia Muscle. 2023 Feb 28. doi: 10.1002/jcsm.13199. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic inflammation, the most representative tumour-host interaction, plays a crucial role in disease progression and prognosis in patients with non-small cell lung cancer (NSCLC). Few studies have compared the performance of existing haematological systemic inflammation biomarkers in predicting the prognosis of NSCLC patients. The purpose of this study was to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with NSCLC through a multicentre prospective study.

METHODS: The predictive accuracy of systemic inflammation biomarkers for prognostic assessment in NSCLC was assessed using C-statistics. Inter-group differences in survival were assessed using the log-rank test and visualized using the Kaplan-Meier method. A restricted cubic spline (RCS) curve was used to explore the association between the biomarkers and survival. Independent prognostic biomarkers for overall survival were determined using multivariable Cox proportional hazards regression analysis. Logistic regression analysis was used to determine independent predictors of 90-day outcomes, length of hospitalization, hospitalization expenses and cachexia.

RESULTS: The inflammatory burden index (IBI) had the highest C-statistic for predicting the prognosis of patients with NSCLC, reaching 0.640 (0.617, 0.663). Patients with a high IBI had significantly worse outcomes than those with a low IBI (35.46% vs. 57.22%; log-rank P < 0.001). The IBI was also able to differentiate the prognosis of patients with NSCLC with the same pathological stage. The RCS curve showed an inverted L-shaped dose-response relationship between the IBI and survival of patients with NSCLC. Multivariable Cox proportional hazards regression analysis showed that a high IBI was an independent risk factor for death of patients with NSCLC (hazard ratio = 1.229, 95% confidence interval [CI]: 1.131-1.335, P < 0.001). A high IBI was an independent predictor of 90-day outcomes (odds ratio [OR] = 1.789, 95% CI: 1.489-2.151, P < 0.001), prolonged hospital stays (OR = 1.560, 95% CI: 1.256-1.938, P < 0.001), high hospitalization expenses (OR = 1.476, 95% CI: 1.195-1.822, P < 0.001) and cachexia (OR = 1.741, 95%CI = 1.374-2.207, P < 0.001) in patients with NSCLC.

CONCLUSIONS: The IBI was independently associated with overall survival, 90-day outcomes, length of hospitalization, hospitalization expenses and cachexia in NSCLC patients. As an optimal systemic inflammation biomarker, the IBI has broad clinical application prospects in predicting the prognosis of patients with NSCLC.

PMID:36852672 | DOI:10.1002/jcsm.13199

J Med Virol. 2023 Feb 28. doi: 10.1002/jmv.28625. Online ahead of print.

ABSTRACT

Recombination is the main contributor to RNA virus evolution, and SARS-CoV-2 during the pandemic produced several recombinants. The most recent SARS-CoV-2 recombinant is the lineage labeled XBB, also known as Gryphon, which arose from BJ.1 and BM.1.1.1. Here we performed a genome-based survey aimed to compare the new recombinant with its parental lineages that never became dominant. Genetic analyses indicated that the recombinant XBB and its first descendant XBB.1 show an evolutionary condition typical of an evolutionary blind background with no further epidemiologically relevant descendant. Genetic variability and expansion capabilities are slightly higher than parental lineages. Bayesian Skyline Plot indicates that XBB reached its plateau around October 6, 2022 and after an initial rapid growth the viral population size did not further expand, and around November 10, 2022 its levels of genetic variability decreased. Simultaneously with the reduction of the XBB population size, an increase of the genetic variability of its first sub-lineage XBB.1 occurred, that in turn reached the plateau around November 9, 2022 showing a kind of vicariance with its direct progenitors. Structure analysis indicates that the affinity for ACE2 surface in XBB/XBB.1 RBDs is weaker than for BA.2 RBD. In conclusion, at present XBB and XBB.1 do not show evidence about a particular danger or high expansion capability. Genome-based monitoring must continue uninterrupted in order to individuate if further mutations can make XBB more dangerous or generate new subvariants with different expansion capability. This article is protected by copyright. All rights reserved.

PMID:36852665 | DOI:10.1002/jmv.28625

Hum Brain Mapp. 2023 Feb 28. doi: 10.1002/hbm.26251. Online ahead of print.

ABSTRACT

Schizophrenia (SZ) is a severe mental disorder characterized by failure of functional integration (aka dysconnection) across the brain. Recent functional connectivity (FC) studies have adopted functional parcellations to define subnetworks of large-scale networks, and to characterize the (dys)connection between them, in normal and clinical populations. While FC examines statistical dependencies between observations, model-based effective connectivity (EC) can disclose the causal influences that underwrite the observed dependencies. In this study, we investigated resting state EC within seven large-scale networks, in 66 SZ and 74 healthy subjects from a public dataset. The results showed that a remarkable 33% of the effective connections (among subnetworks) of the cognitive control network had been pathologically modulated in SZ. Further dysconnection was identified within the visual, default mode and sensorimotor networks of SZ subjects, with 24%, 20%, and 11% aberrant couplings. Overall, the proportion of discriminative connections was remarkably larger in EC (24%) than FC (1%) analysis. Subsequently, to study the neural correlates of impaired cognition in SZ, we conducted a canonical correlation analysis between the EC parameters and the cognitive scores of the patients. As such, the self-inhibitions of supplementary motor area and paracentral lobule (in the sensorimotor network) and the excitatory connection from parahippocampal gyrus to inferior temporal gyrus (in the cognitive control network) were significantly correlated with the social cognition, reasoning/problem solving and working memory capabilities of the patients. Future research can investigate the potential of whole-brain EC as a biomarker for diagnosis of brain disorders and for neuroimaging-based cognitive assessment.

PMID:36852654 | DOI:10.1002/hbm.26251