Tag: nevin manimala

Interact Cardiovasc Thorac Surg. 2022 Mar 14:ivac068. doi: 10.1093/icvts/ivac068. Online ahead of print.

ABSTRACT

OBJECTIVES: Presentation, management and outcomes in the aortic dissection (AD) of ascending thoracic aortic aneurysm (ATAA) differ in gender and age. The purpose of this study is to investigate the dissection properties of male and female ATAAs.

METHODS: Peeling tests were performed to quantitatively determine the delamination strength and dissection energy of 41 fresh ATAA samples (22 males and 19 females) in relatively young (≤65 years) and elderly (>65 years) patients. The delamination strength of the ATAAs was further correlated with patient ages for males and females. The histological investigation was employed to characterize the dissected morphology.

RESULTS: For elderly patients, circumferential and longitudinal delamination strengths of the female ATAAs were statistically significantly lower than those of the males (circumferential: 31 ± 6 vs 42 ± 6 mN/mm, P < 0.01; longitudinal: 35 ± 7 vs 49 ± 10 mN/mm, P = 0.02). No significant differences were found in the delamination strength between males and females for relatively young patients. The circumferential and longitudinal delamination strengths were significantly decreased and strongly correlated with patient ages for females. However, these correlations were not present in males. Dissection routes propagated in the aortic media to create ruptured surfaces for all specimens. Peeling tests of the male ATAAs generate rougher surfaces than females.

CONCLUSIONS: There is a higher propensity of AD occurrence for the elderly females as compared to males with matched ages. Surgeons should be cognizant of the risk of AD onset later in life, especially in females.

PMID:35285896 | DOI:10.1093/icvts/ivac068

JAMA. 2022 Mar 14. doi: 10.1001/jama.2022.2832. Online ahead of print.

ABSTRACT

IMPORTANCE: Older patients and those with comorbidities who are infected with SARS-CoV-2 may be at increased risk of hospitalization and death. Sotrovimab is a neutralizing antibody for the treatment of high-risk patients to prevent COVID-19 progression.

OBJECTIVE: To evaluate the efficacy and adverse events of sotrovimab in preventing progression of mild to moderate COVID-19 to severe disease.

DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial including 1057 nonhospitalized patients with symptomatic, mild to moderate COVID-19 and at least 1 risk factor for progression conducted at 57 sites in Brazil, Canada, Peru, Spain, and the US from August 27, 2020, through March 11, 2021; follow-up data were collected through April 8, 2021.

INTERVENTIONS: Patients were randomized (1:1) to an intravenous infusion with 500 mg of sotrovimab (n = 528) or placebo (n = 529).

MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with COVID-19 progression through day 29 (all-cause hospitalization lasting >24 hours for acute illness management or death); 5 secondary outcomes were tested in hierarchal order, including a composite of all-cause emergency department (ED) visit, hospitalization of any duration for acute illness management, or death through day 29 and progression to severe or critical respiratory COVID-19 requiring supplemental oxygen or mechanical ventilation.

RESULTS: Enrollment was stopped early for efficacy at the prespecified interim analysis. Among 1057 patients randomized (median age, 53 years [IQR, 42-62], 20% were ≥65 years of age, and 65% Latinx), the median duration of follow-up was 103 days for sotrovimab and 102 days for placebo. All-cause hospitalization lasting longer than 24 hours or death was significantly reduced with sotrovimab (6/528 [1%]) vs placebo (30/529 [6%]) (adjusted relative risk [RR], 0.21 [95% CI, 0.09 to 0.50]; absolute difference, -4.53% [95% CI, -6.70% to -2.37%]; P < .001). Four of the 5 secondary outcomes were statistically significant in favor of sotrovimab, including reduced ED visit, hospitalization, or death (13/528 [2%] for sotrovimab vs 39/529 [7%] for placebo; adjusted RR, 0.34 [95% CI, 0.19 to 0.63]; absolute difference, -4.91% [95% CI, -7.50% to -2.32%]; P < .001) and progression to severe or critical respiratory COVID-19 (7/528 [1%] for sotrovimab vs 28/529 [5%] for placebo; adjusted RR, 0.26 [95% CI, 0.12 to 0.59]; absolute difference, -3.97% [95% CI, -6.11% to -1.82%]; P = .002). Adverse events were infrequent and similar between treatment groups (22% for sotrovimab vs 23% for placebo); the most common events were diarrhea with sotrovimab (n = 8; 2%) and COVID-19 pneumonia with placebo (n = 22; 4%).

CONCLUSIONS AND RELEVANCE: Among nonhospitalized patients with mild to moderate COVID-19 and at risk of disease progression, a single intravenous dose of sotrovimab, compared with placebo, significantly reduced the risk of a composite end point of all-cause hospitalization or death through day 29. The findings support sotrovimab as a treatment option for nonhospitalized, high-risk patients with mild to moderate COVID-19, although efficacy against SARS-CoV-2 variants that have emerged since the study was completed is unknown.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04545060.

PMID:35285853 | DOI:10.1001/jama.2022.2832

J Vis Exp. 2022 Feb 22;(180). doi: 10.3791/62643.

ABSTRACT

Cardiac reprogramming has become a potentially promising therapy to repair a damaged heart. By introducing multiple transcription factors, including Mef2c, Gata4, Tbx5 (MGT), fibroblasts can be reprogrammed into induced cardiomyocytes (iCMs). These iCMs, when generated in situ in an infarcted heart, integrate electrically and mechanically with the surrounding myocardium, leading to a reduction in scar size and an improvement in heart function. Because of the relatively low reprogramming efficiency, purity, and quality of the iCMs, characterization of iCMs remains a challenge. The currently used methods in this field, including flow cytometry, immunocytochemistry, and qPCR, mainly focus on cardiac-specific gene and protein expression but not on the functional maturation of iCMs. Triggered by action potentials, the opening of voltage-gated calcium channels in cardiomyocytes leads to a rapid influx of calcium into the cell. Therefore, quantifying the rate of calcium influx is a promising method to evaluate cardiomyocyte function. Here, the protocol introduces a method to evaluate iCM function by calcium (Ca²⁺) flux. An αMHC-Cre/Rosa26A-Flox-Stop-Flox-GCaMP3 mouse strain was established by crossing Tg(Myh6-cre)1Jmk/J (referred to as Myh6-Cre below) with Gt(ROSA)26Sor^{tm38(CAG-GCaMP3)Hze}/J (referred to as Rosa26A-Flox-Stop-Flox-GCaMP3 below) mice. Neonatal cardiac fibroblasts (NCFs) from P0-P2 neonatal mice were isolated and cultured in vitro, and a polycistronic construction of MGT was introduced to NCFs, which led to their reprogramming to iCMs. Because only successfully reprogrammed iCMs will express GCaMP3 reporter, the functional maturation of iCMs can be visually assessed by Ca²⁺ flux with fluorescence microscopy. Compared with un-reprogrammed NCFs, NCF-iCMs showed significant calcium transient flux and spontaneous contraction, similar to CMs. This protocol describes in detail the mouse strain establishment, isolation and selection of neonatal mice hearts, NCF isolation, production of retrovirus for cardiac reprogramming, iCM induction, the evaluation of iCM Ca²⁺ flux using our reporter line, and related statistical analysis and data presentation. It is expected that the methods described here will provide a valuable platform to assess the functional maturation of iCMs for cardiac reprogramming studies.

PMID:35285824 | DOI:10.3791/62643

Aging Ment Health. 2022 Mar 14:1-9. doi: 10.1080/13607863.2022.2046692. Online ahead of print.

ABSTRACT

OBJECTIVES: In this article, we assess the feasibility and acceptability and the effect of the Plan Ahead for community dwelling older adults. In addition, we investigated the effects of the program. In addition, we aimed to examine whether the completion of the specific Future Care Planning depended on the participants’ competence level.

METHODS: In this single group feasibility study, trained facilitators delivered the program to a sample of 234 community-residing older adults. Participants completed both pre, post assessments about the acceptability of the program and their completion of the recommended future care planning activities.

RESULTS: Based on participant’s report on the usefulness and satisfaction of the program after the completion of the program, we found that participants reported high levels of acceptance of the program. Participation rates also confirmed the feasibility of the program. In terms of effects of program implementation, statistically significant changes were noted for several outcomes, such as resource building and FCP activities. In particular, we found that these gains were particularly robust for participants in the low competence group.

CONCLUSION: Pilot program results suggest the feasibility of a short community program enhancing proactive planning for future care needs among older adults residing in their community.

PMID:35285774 | DOI:10.1080/13607863.2022.2046692

Australas Psychiatry. 2022 Mar 14:10398562221077887. doi: 10.1177/10398562221077887. Online ahead of print.

ABSTRACT

OBJECTIVE: This longitudinal study examined changes in psychological outcomes of perioperative frontline healthcare workers at one of Australia’s most COVID-19 affected hospitals, following the surge and decline of a pandemic wave.

METHOD: A single-centred longitudinal online survey was conducted between 26 May and 17 November 2020. Recruitment was via poster advertisement and email invitation. The survey was sent out every 4 weeks, resulting in seven time-points.

RESULTS: In total, 385 survey results were analysed from 193 staff (about 64% response rate), 72 (37%) of whom completed the survey more than once. The prevalence of moderate-to-severe anxiety and depressive symptoms peaked at 27% and 25%, respectively, during the pandemic surge. Up to 35% displayed post-traumatic stress disorder (PTSD) symptoms. Although not statistically significant, the trend of depressive and PTSD symptoms worsened over time, especially among females and anaesthetic/surgical trainees, despite subsidence of the pandemic curve. Technicians and anaesthetic/scrub nurses were the at-risk groups with worst psychological outcomes.

CONCLUSION: We found persistent mental health impacts on frontline perioperative HCWs despite subsidence of the pandemic wave. Further research is needed to determine the extent and trajectory of such impacts with larger sample sizes to determine generalisability to frontline HCWs in general.

PMID:35285740 | DOI:10.1177/10398562221077887

Zhongguo Zhong Yao Za Zhi. 2022 Feb;47(4):951-958. doi: 10.19540/j.cnki.cjcmm.20210901.301.

ABSTRACT

The present study established the spectrum-effect relationship model of flavonoids in Citri Reticulatae Pericarpium(CRP) from 15 batches of Liujunzi Decoction and statistically analyzed the correlation between chemical peaks and efficacy to identify the main effective components. HPLC fingerprints of flavonoids in CRP from 15 batches of Liujunzi Decoction were established. HPLC analysis was carried out on the Venusil XBP C_(18)(L) column(4.6 mm×250 mm, 5 μm) at 30 ℃ with acetonitrile-water(containing 0.1% formic acid) as mobile phase for gradient elution, a flow rate of 1.0 mL·min~(-1), and detection wavelength of 300 nm to obtain chemical fingerprints. Additionally, the effects of flavonoids from CRP in 15 batches of Liujunzi Decoction on the content of GAS, MTL, and VIP, TFF3 mRNA expression, and percentage of CD3~+ T-cells of model rats with spleen deficiency were determined. The spectrum-effect relationship model was established by gray correlation analysis. The results showed that the main characteristic peaks with great contribution to the regulation of gastrointestinal tract were peak 16(vicenin-2), peak 63(sinensetin), peak 64(isosinensetin), peak 65(nobiletin), peak 67(3,5,6,7,8,3′,4′-heptemthoxyflavone), peak 68(tangeretin), and peak 69(5-desmethylnobiletin). Therefore, there was a linear correlation between flavonoids from CRP in Liujunzi Decoction and the efficacy, and the medicinal effect was achieved by multi-component action. This study is expected to provide a new idea for exploring the material basis of the effect, i.e., regulating qi prior to replenishing qi, of CRP in Liujunzi Decoction.

PMID:35285194 | DOI:10.19540/j.cnki.cjcmm.20210901.301

J Thromb Haemost. 2022 Mar 14. doi: 10.1111/jth.15698. Online ahead of print.

ABSTRACT

BACKGROUND: Multi-phenotype analysis of genetically correlated phenotypes can increase the statistical power to detect loci associated with multiple traits, leading to the discovery of novel loci. This is the first study to date to comprehensively analyze the shared genetic effects within different hemostatic traits, and between these and their associated disease outcomes.

OBJECTIVES: To discover novel genetic associations by combining summary data of correlated hemostatic traits and disease events.

METHODS: Summary statistics from genome wide-association studies (GWAS) from 7 hemostatic traits (factor VII [FVII], factor VIII [FVIII], von Willebrand factor [VWF] factor XI [FXI], fibrinogen, tissue plasminogen activator [tPA], plasminogen activator inhibitor 1 [PAI-1]) and 3 major cardiovascular (CV) events (venous thromboembolism [VTE], coronary artery disease [CAD], ischemic stroke [IS]), were combined in 27 multi-trait combinations using metaUSAT. Genetic correlations between phenotypes were calculated using Linkage Disequilibrium Score Regression (LDSC). Newly associated loci were investigated for colocalization. We considered a significance threshold of 1.85 x 10^-9 obtained after applying Bonferroni correction for the number of multi-trait combinations performed (n = 27).

RESULTS: Across the 27 multi-trait analyses, we found 4 novel pleiotropic loci (XXYLT1, KNG1, SUGP1/MAU2, TBL2/MLXIPL) that were not significant in the original individual datasets, were not described in previous GWAS for the individual traits, and that presented a common associated variant between the studied phenotypes.

CONCLUSIONS: The discovery of 4 novel loci contributes to the understanding of the relationship between hemostasis and CV events and elucidate common genetic factors between these traits.

PMID:35285134 | DOI:10.1111/jth.15698

Int J Nurs Pract. 2022 Mar 13:e13049. doi: 10.1111/ijn.13049. Online ahead of print.

ABSTRACT

AIM: To determine the effectiveness of auscultatory, colorimetric capnometry and pH measurement methods for confirmation of correct nasogastric tube placement in critically ill patients.

BACKGROUND: Incorrect nasogastric tube placement causes serious complications.

DESIGN: This was a methodological and comparative study.

METHODS: The study sample consisted of 88 new insertions of nasogastric feeding tubes between April 2018-2019. Results from the ‘auscultatory’, ‘pH’ and ‘colorimetric capnometry’ methods were compared with the location of the nasogastric tube as determined through radiography. Descriptive statistics, Eta analysis and the Cohen kappa compliance test as well as sensitivity and specificity were conducted.

RESULTS: There was a weak agreement (26.3%) between the auscultation and radiological evaluation for confirming nasogastric tube placement. The pH measurement and colorimetric capnometry methods were not correlated with radiological evaluation. Stomach pH increased as patient age increased and use of the colorimetric capnometry method failed to confirm the oesophageal and duodenal location. The specificity of the auscultation was low, and both the specificity and sensitivity pH methods were low.

CONCLUSION: It was determined that auscultation, measuring pH and colorimetric capnometry were unreliable methods for confirming placement of nasogastric tubes. It is recommended to confirm initial placement of the nasogastric tube with radiography and to develop effective and reliable non-radiological measurement methods that can be performed at the bedside.

PMID:35285146 | DOI:10.1111/ijn.13049

Pharmacoepidemiol Drug Saf. 2022 Mar 14. doi: 10.1002/pds.5427. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to examine trends in valproate use among women of childbearing potential aged 16-44 years (WCBP) in Ireland following two European-directed regulatory interventions in December 2014 and April 2018.

METHODS: This was a repeated cross-sectional study using monthly national pharmacy claims data, to examine trend changes in the prevalence of valproate use among WCBP pre and post two separate regulatory events in December 2014 and April 2018. Annual population estimates from the Central Statistics Office were used to calculate the prevalence rate per 1000 eligible women. Segmented regression analysis of interrupted time series with negative binomial regression was used to examine rates for WCBP aged 16-44 years, and by 10-year age groups. Prevalence ratios (PR) are presented with 95% confidence intervals (CIs).

RESULTS: Among WCBP aged 16-44 years, there was no statistically significant change in the month-to-month prevalence ratio in the post- compared to pre-December 2014 intervention period. A significant decline was, however, observed in the post-, compared to pre-April 2018 intervention period (PR = 0.998, [95%CIs: 0.996, 1.000]; p = 0.029). Among those aged 16-24 years, a significant decreasing trend in the month-to-month prevalence ratio was found in the post- compared to pre-December 2014 intervention period (PR = 0.991, [95%CIs: 0.984, 0.998], p <0.01). A marginal effect was observed in the post- compared to pre-April 2018 intervention period for those aged 25-34 years (PR = 0.996, [95%CIs: 0.992, 1.000]; p = 0.048).

CONCLUSION: Although no evidence of change was observed following the December 2014 intervention period, a significant decline in the prevalence ratio of valproate use was observed after the 2018 intervention, which may reflect the introduction of the most recent contraindication measures. This article is protected by copyright. All rights reserved.

PMID:35285110 | DOI:10.1002/pds.5427

J Clin Lab Anal. 2022 Mar 13:e24334. doi: 10.1002/jcla.24334. Online ahead of print.

ABSTRACT

BACKGROUND: Among patients with diabetic retinopathy (DR), no proof was available to confirm the prognostic significance of the neutrophil percentage-to-albumin ratio (NPAR). We hypothesized that NPAR plays a role in the incidence of DR in diabetic patients.

METHODS: We extracted all diabetes mellitus (DM) data from the National Health and Nutrition Examination Survey (NHANES) database between 1999 and 2018, NPAR was expressed as neutrophil percentage/albumin. Multivariable logistic regression and generalized additive model were utilized for the purpose of examining the correction between NPAR levels and DR. Subgroup analysis of the associations between NPAR and DR was carried out to investigate if the impact of the NPAR varied among different subgroups.

RESULTS: An aggregate of 5850 eligible participants were included in the present research. The relationship between NPAR levels and DR was positive linear. In the multivariate analysis, following the adjustment for confounders (gender, white blood cell, age, monocyte percent, red cell distribution width, eosinophils percent, bicarbonate, body mass index, iron, glucose, basophils percent, total bilirubin, creatinine, and chloride), higher NPAR was an independent risk factor for DR compared to lower NPAR (OR, 95% CI: 1.18, 1.00-1.39; 1.24, 1.04-1.48). For the purpose of sensitivity analysis, we found a trend of consistency (p for trend: 0.0190). The results of the subgroup analysis revealed that NPAR did not exert any statistically significant interactions with any of the other DR risk variables.

CONCLUSIONS: Elevated NPAR is associated with an elevated risk of occurrence of DR in diabetic patients.

PMID:35285099 | DOI:10.1002/jcla.24334