Category: Nevin Manimala

Front Pharmacol. 2024 Feb 6;14:1338975. doi: 10.3389/fphar.2023.1338975. eCollection 2023.

ABSTRACT

Objective: This study aims to evaluate the clinical and preclinical efficacy of SMI in treating CHF, and to summarize the relevant mechanisms of action in order to provide evidence for its role in CHF treatment. Methods: A systematic computerized search of eight databases and three registry systems was performed, with the time frame spanning from the inception of the databases to 30 June 2023. Strict procedures were used for data extraction, quality assessment, and data analysis. The methodological quality of the included studies was assessed using RoB-2 and SYRCLE tools. Statistical analysis was performed using Rev Man 5.4 software, using either fixed-effects or random-effects models. Results: A total of 25 clinical trials (including test group 1,367 patients, control group 1,338 patients) and 11 animal studies (including 201 animals) were included in this review. The meta-analysis of clinical studies showed that SMI can improve cardiac function indicators (LVEF, LVFS, LVEDV, LVESV, LVEDD, LVESD) (p < 0.00001), reduce BNP/NT-proBNP levels (p < 0.01), and improve inflammatory markers (hs-CRP, TNF-α, IL-6) (p < 0.00001) and endothelin (ET) levels (p < 0.0001). In animal studies, SMI demonstrated improved cardiac function (LVEF, LVFS) (p < 0.05), and improved heart failure markers (NT-proBNP, p < 0.05) when compared to control groups. Conclusion: This study represents the first meta-analysis which includes both preclinical and clinical studies on SMI. Clinical and animal studies have shown that SMI can improve cardiac function in CHF patients through its anti-apoptotic effects, antioxidant activities, anti-inflammatory effects, and improvement of myocardial metabolism. This study has certain limitations in terms of literature quality, quantity, and follow-up time. Therefore, the conclusions drawn from this study may require further validation through larger-scale, high-quality RCT trials.

PMID:38385058 | PMC:PMC10880451 | DOI:10.3389/fphar.2023.1338975

Front Neurol. 2024 Feb 7;15:1367735. doi: 10.3389/fneur.2024.1367735. eCollection 2024.

ABSTRACT

INTRODUCTION: To date, no systematic review or meta-analysis has critically evaluated the relevance of using optokinetic after-nystagmus (OKAN) in diagnosis of vestibular disorders. To assess the role of OKAN in diagnosis of vestibular disorders, the OKAN time constant (TC) between patients with vestibular disorders and healthy participants will be compared.

METHODS: Automated search strategies were carried out in the Embase, Medline PubMed, Web of Science, and Scopus databases from inception to December 2023. The following inclusion criteria were applied: (1) evaluation of OKAN in individuals with vestibular disorders, (2) clinical trials, and (3) inclusion of healthy individuals as the control group. Exclusion criteria were: (1) animal studies, (2) non-clinical trial study designs, (3) assessment of non-vestibular disorders, (4) no examination of OKAN TC, (5) only examination of healthy participants, (6) studies published in a language other than English, (7) no healthy participants as control group, (8) case reports, and (9) only abstract available. The random-effects model was used to pool the data. The Joanna Briggs Institute (JBI) Critical Appraisal Tools was used to assess the risk of bias. The quality assessment was performed with the aid of the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies, provided by NHLBI. The PRISMA guidelines were used as reporting guidelines. The main outcome of this study was the between-group mean difference (MDbetween) in OKAN TC and its 95% confidence interval between patients with vestibular disorders and healthy participants.

RESULTS: Seven out of 244 screened articles were included that studied 289 participants. The overall mean difference (MD = -7.08) with a 95% CI of [-10.18; -3.97] was significant (p = 0.014). The heterogeneity was significant (p = 0.02). Quality assessment was generally good (76%). The risk of bias was low in five studies and moderate in two studies.

CONCLUSION: The results demonstrate that OKAN TC is significantly shorter in patients with vestibular disorders compared to healthy controls. This finding is important for future research, particularly with the emergence of novel clinical tools and diagnostic syndromes.

SYSTEMATIC REVIEW: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=442695.

PMID:38385042 | PMC:PMC10879310 | DOI:10.3389/fneur.2024.1367735

Front Neurol. 2024 Feb 7;15:1302298. doi: 10.3389/fneur.2024.1302298. eCollection 2024.

ABSTRACT

BACKGROUND: Posterior cerebral circulation ischemic stroke (PCS) comprises up to 25% of all strokes. It is characterized by variable presentation, leading to misdiagnosis and morbidity and mortality. We aim to describe PCS in large multiethnic cohorts.

METHODS: A retrospective review of a large national stroke database from its inception on the 1st of January 2014 till 31 December 2020. Incidence per 100,000 adult population/year, demographics, clinical features, stroke location, and outcomes were retrieved. We divided the cohort into patients from MENA (Middle East and North Africa) and others.

RESULTS: In total, 1,571 patients were identified. The incidence of PCS was observed to be rising and ranged from 6.3 to 13.2/100,000 adult population over the study period. Men were 82.4% of the total. The mean age was 54.9 ± 12.7 years (median 54 years, IQR 46, 63). MENA patients comprised 616 (39.2%) while others were 954 (60.7%); of these, the majority (80.5%) were from South Asia. Vascular risk factors were prevalent with 1,230 (78.3%) having hypertension, 970 (61.7%) with diabetes, and 872 (55.5%) having dyslipidemia. Weakness (944, 58.8%), dizziness (801, 50.5%), and slurred speech (584, 36.2%) were the most commonly presenting symptoms. The mean National Institute of Health Stroke Score (NIHSS) score was 3.8 ± 4.6 (median 3, IQR 1, 5). The overall most frequent stroke location was the distal location (568, 36.2%). The non-MENA cohort was younger, less vascularly burdened, and had more frequent proximal stroke location (p < 0.05). Dependency or death at discharge was seen in 39.5% and was associated with increasing age, and proximal and multilocation involvement; while at 90 days it was 27.4% and was associated with age, male sex, and having a MENA nationality (p < 0.05).

CONCLUSION: In a multiethnic cohort of posterior circulation stroke patients from the MENA region and South Asia, we noted a rising incidence over time, high prevalence of vascular risk factors, and poor outcomes in older men from the MENA region. We also uncovered considerable disparities between the MENA and non-MENA groups in stroke location and outcome. These disparities are crucial factors to consider when tailoring individualized patient care plans. Further research is needed to thoroughly investigate the underlying reasons for these variations.

PMID:38385041 | PMC:PMC10879388 | DOI:10.3389/fneur.2024.1302298

Front Neurol. 2024 Feb 7;15:1336760. doi: 10.3389/fneur.2024.1336760. eCollection 2024.

ABSTRACT

OBJECTIVE: This systematic review aims to investigate a potential correlation between the administration of antiplatelets (APs) or anticoagulants (ACs) and perioperative complications, with a particular focus on hemorrhagic events, in patients undergoing decompressive craniectomy (DC). Additionally, the secondary objective is to assess the neurological outcomes in patients undergoing DC while taking APs/ACs, comparing them to patients not on APs/ACs.

METHODS: The study utilized PubMed and Science Direct as primary online medical databases for the systematic review. Articles underwent screening based on title, abstract, and full-text review. Four studies meeting the inclusion criteria were selected for comprehensive analysis.

RESULTS: Our findings suggest that the administration of APs/ACs in patients undergoing DC does not significantly impact functional outcomes. Notably, the occurrence of rebleeding within 6 months and other complications, including infections, appears to be less frequent in patients taking APs compared to those not taking APs/ACs.

CONCLUSION: Literature-derived data on the association between APs/ACs and DC presented considerable heterogeneity and insufficient volume for robust statistical analysis. Consequently, a definitive conclusion regarding the influence of suspending or continuing these therapies on complications and clinical outcomes cannot be confidently reached at present. To address this, a large-scale prospective study is warranted to gather substantial and precise data, facilitating a nuanced understanding of how to balance the risks and benefits associated with antiplatelet and anticoagulant agents in the context of decompressive craniectomy.

PMID:38385039 | PMC:PMC10879343 | DOI:10.3389/fneur.2024.1336760

Front Neurol. 2024 Feb 7;15:1262057. doi: 10.3389/fneur.2024.1262057. eCollection 2024.

ABSTRACT

OBJECTIVE: This research aims to investigate whether peripheral biomarkers might differentiate individuals with Tourette syndrome (TS) from those without the condition.

METHODS: A broad range of databases was searched through November 2022. This study employed a systematic literature review and subsequent meta-analysis of case-control studies that assessed the aberration of biomarkers of patients with TS and controls.

RESULTS: A total of 81 studies were identified, out of which 60 met the eligibility criteria for inclusion in the meta-analysis. Following a meticulous screening procedure to determine the feasibility of incorporating case-control studies into the meta-analysis, 13 comparisons were statistically significant [CD3+ T cell, CD4+ T cell, CD4+ T cell to CD8+ T cell ratio, NK-cell, anti-streptolysin O antibodies, anti-DNase antibodies, glutamic acid (Glu), aspartic acid (Asp), ferritin (Fe), zinc (Zn), lead (Pb), vitamin D, and brain-derived neurotrophic factor (BDNF)]. Publication bias was found for anti-streptolysin O antibodies. Suggestive associations were evidenced for norsalsolinol (NSAL), neuron-specific enolase (NSE), and S100B.

CONCLUSION: In this study, we present empirical evidence substantiating the link between several peripheral biomarkers and the early diagnosis of TS. Larger and more standardized studies are necessary to replicate the observed results, elucidate the specificity of the biomarkers for TS, and evaluate their precision for use in clinical settings.

PMID:38385037 | PMC:PMC10879287 | DOI:10.3389/fneur.2024.1262057

Ultrasound J. 2024 Feb 21;16(1):13. doi: 10.1186/s13089-023-00354-1.

ABSTRACT

BACKGROUNDS: Dehydration is among the most common causes of Pediatric Emergency Department admission; however, no clinical signs, symptoms, or biomarkers have demonstrated sufficient sensitivity, specificity, or reliability to predict dehydration.

METHODS: We conducted a prospective, monocentric, observational study at Giannina Gaslini Hospital, a tertiary care pediatric hospital. Our study aimed to compare inferior vena cava ultrasound measurement with volume depletion biomarkers to understand if point-of-care ultrasound could help grade, evaluate, and better manage dehydration in children presenting to the pediatric emergency department. We enrolled patients under the age of 14 who required blood tests in the suspect of dehydration; for each patient, we collected values of venous pH, natremia, bicarbonatemia, uric acid, chloremia, and blood urea nitrogen. For each patient, we performed two ultrasound scans to calculate the Inferior Vena Cava/Aorta area ratio and to assess the IVC collapsibility index; moreover, we described the presence of the “kiss sign” (100% IVC walls collapsing during the inspiratory phase).

RESULTS: Patients with the “kiss sign” (25/65 patients, 38.5% of the total) showed worse blood tests, in particular, uric acid levels (p = 0.0003), bicarbonatemia (p = 0.001) and natriemia (p = 0.0003). Moreover, patients with the “kiss sign” showed a high frequency of ≥ 2 pathological blood tests (p = 0.0002). We found no statistical significant difference when comparing the IVC/Ao ratio and IVC-CI with the considered blood tests.

CONCLUSIONS: The “kiss sign” seems to be related to worse hydration state, whereas IVC/Ao and IVC-CI are not. In an emergency setting, where physicians must take diagnostic-therapeutic decisions quickly, the presence of the “kiss sign” in patients suspected to be dehydrated can be a helpful tool in their management.

PMID:38383828 | DOI:10.1186/s13089-023-00354-1

Lab Anim (NY). 2024 Feb 21. doi: 10.1038/s41684-024-01334-1. Online ahead of print.

NO ABSTRACT

PMID:38383820 | DOI:10.1038/s41684-024-01334-1

Behav Res Methods. 2024 Feb 21. doi: 10.3758/s13428-024-02359-7. Online ahead of print.

ABSTRACT

Count outcomes are frequently encountered in single-case experimental designs (SCEDs). Generalized linear mixed models (GLMMs) have shown promise in handling overdispersed count data. However, the presence of excessive zeros in the baseline phase of SCEDs introduces a more complex issue known as zero-inflation, often overlooked by researchers. This study aimed to deal with zero-inflated and overdispersed count data within a multiple-baseline design (MBD) in single-case studies. It examined the performance of various GLMMs (Poisson, negative binomial [NB], zero-inflated Poisson [ZIP], and zero-inflated negative binomial [ZINB] models) in estimating treatment effects and generating inferential statistics. Additionally, a real example was used to demonstrate the analysis of zero-inflated and overdispersed count data. The simulation results indicated that the ZINB model provided accurate estimates for treatment effects, while the other three models yielded biased estimates. The inferential statistics obtained from the ZINB model were reliable when the baseline rate was low. However, when the data were overdispersed but not zero-inflated, both the ZINB and ZIP models exhibited poor performance in accurately estimating treatment effects. These findings contribute to our understanding of using GLMMs to handle zero-inflated and overdispersed count data in SCEDs. The implications, limitations, and future research directions are also discussed.

PMID:38383801 | DOI:10.3758/s13428-024-02359-7

Nature. 2024 Feb 21. doi: 10.1038/s41586-024-07029-4. Online ahead of print.

ABSTRACT

Persistent SARS-CoV-2 infections may act as viral reservoirs that could seed future outbreaks^1-5, give rise to highly divergent lineages^6-8 and contribute to cases with post-acute COVID-19 sequelae (long COVID)^9,10. However, the population prevalence of persistent infections, their viral load kinetics and evolutionary dynamics over the course of infections remain largely unknown. Here, using viral sequence data collected as part of a national infection survey, we identified 381 individuals with SARS-CoV-2 RNA at high titre persisting for at least 30 days, of which 54 had viral RNA persisting at least 60 days. We refer to these as ‘persistent infections’ as available evidence suggests that they represent ongoing viral replication, although the persistence of non-replicating RNA cannot be ruled out in all. Individuals with persistent infection had more than 50% higher odds of self-reporting long COVID than individuals with non-persistent infection. We estimate that 0.1-0.5% of infections may become persistent with typically rebounding high viral loads and last for at least 60 days. In some individuals, we identified many viral amino acid substitutions, indicating periods of strong positive selection, whereas others had no consensus change in the sequences for prolonged periods, consistent with weak selection. Substitutions included mutations that are lineage defining for SARS-CoV-2 variants, at target sites for monoclonal antibodies and/or are commonly found in immunocompromised people^11-14. This work has profound implications for understanding and characterizing SARS-CoV-2 infection, epidemiology and evolution.

PMID:38383783 | DOI:10.1038/s41586-024-07029-4

Commun Med (Lond). 2024 Feb 21;4(1):26. doi: 10.1038/s43856-024-00441-x.

ABSTRACT

BACKGROUND: Geographical variations in mood and psychotic disorders have been found in upper-income countries. We looked for geographic variation in these disorders in Colombia, a middle-income country. We analyzed electronic health records from the Clínica San Juan de Dios Manizales (CSJDM), which provides comprehensive mental healthcare for the one million inhabitants of Caldas.

METHODS: We constructed a friction surface map of Caldas and used it to calculate the travel-time to the CSJDM for 16,295 patients who had received an initial diagnosis of mood or psychotic disorder. Using a zero-inflated negative binomial regression model, we determined the relationship between travel-time and incidence, stratified by disease severity. We employed spatial scan statistics to look for patient clusters.

RESULTS: We show that travel-times (for driving) to the CSJDM are less than 1 h for ~50% of the population and more than 4 h for ~10%. We find a distance-decay relationship for outpatients, but not for inpatients: for every hour increase in travel-time, the number of expected outpatient cases decreases by 20% (RR = 0.80, 95% confidence interval [0.71, 0.89], p = 5.67E-05). We find nine clusters/hotspots of inpatients.

CONCLUSIONS: Our results reveal inequities in access to healthcare: many individuals requiring only outpatient treatment may live too far from the CSJDM to access healthcare. Targeting of resources to comprehensively identify severely ill individuals living in the observed hotspots could further address treatment inequities and enable investigations to determine factors generating these hotspots.

PMID:38383761 | DOI:10.1038/s43856-024-00441-x