Tag: statistics

Adv Clin Exp Med. 2023 Oct 19. doi: 10.17219/acem/171537. Online ahead of print.

ABSTRACT

BACKGROUND: Sepsis is a life-threatening organ dysfunction without effective therapeutic options. Lipopolysaccharide (LPS), a bacterial endotoxin, is known to induce sepsis. It is associated with oxidative stress, inflammation and multiple organ failure. Gedunin (GN) is a tetranortriterpenoid isolated from the Meliaceae family. Gedunin possesses numerous pharmacological properties, including antibacterial, anti-inflammatory, antiallergic, and anticancer activities. However, the molecular anti-inflammatory mechanism of GN in sepsis has not been established.

OBJECTIVES: The aim of the study was to explore the antioxidant and anti-inflammatory molecular actions underlying the antiseptic activity of GN in an LPS-induced rat model.

MATERIAL AND METHODS: Rats were randomized into 4 sets: group 1 (control) was given 1 mL of dimethyl sulfoxide (DMSO) by gavage, group 2 rats were treated with LPS (100 μg/kg body weight (BW), intraperitoneally (ip.)), group 3 rats were given LPS (100 μg/kg BW, ip.)+GN (50 mg/kg BW in DMSO), and rats in the group 4 were given GN (50 mg/kg BW in DMSO) alone. We studied hepatic markers, inflammatory cytokines and antioxidants using specific biochemical kits and analyzed their statistical significance. Histopathology of liver, lungs and kidney tissues was also explored. The mRNA levels and conducted protein investigations were performed using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot, respectively.

RESULTS: Our findings revealed that GN significantly (p < 0.05) inhibited oxidative stress, lipid peroxides, toxic markers, pro-inflammatory cytokines, and histological changes, thereby preventing multi-organ impairment. Additionally, GN attenuated the HMGβ1/NLRP3/NF-κB signaling pathway and prevented the degradation of Iκβα.

CONCLUSIONS: Gedunin is a promising natural antiseptic agent for LPS-induced sepsis in rats.

PMID:37855061 | DOI:10.17219/acem/171537

J Med Screen. 2023 Oct 19:9691413231208160. doi: 10.1177/09691413231208160. Online ahead of print.

ABSTRACT

BACKGROUND: The lung cancer screening program at St Elizabeth Healthcare (Kentucky, USA) began in 2013. Over 33,000 low-dose computed tomography lung cancer screens have been performed. From 2015 through 2021, 2595 lung cancers were diagnosed systemwide. A Screening Program with Impactful Results from Early Detection, reviews that experience; 342 (13.2%) were diagnosed by screening and 2253 (86.8%) were non-screened. As a secondary objective, the non-screened cohort was queried to determine how many additional individuals could have been screened, identifying barriers and failures to meet eligibility.

METHODS: Our QlikSense database extracted the lung cancer patients from the Cancer Patient Data and Management System, and identified and categorized them separately as screened or non-screened populations. Stage distribution was compared in screened and non-screened groups. Those meeting age criteria, with any smoking history, were further queried for screening eligibility, accessing the electronic medical record smoking history and audit trail, and determining if enough information was available to substantiate screening eligibility. The same methodology was applied to CMS 2015 and USPSTF 2021 criteria.

RESULTS: The screened and non-screened patients were accounted for in a stage migration chart demonstrating clear shift to early stage among screened lung cancer patients. Additionally, analysis of non-screened individuals is presented.

CONCLUSION: Of the St Elizabeth Healthcare eligible patients attributed to primary care providers, 49.6% were screened in 2021. Despite this level of success, this study highlighted a sizeable pool of additional individuals that could have been screened. We are shifting focus to the non-screened pool of patients that meet eligibility, further enhancing the impact on our community.

PMID:37855047 | DOI:10.1177/09691413231208160

EClinicalMedicine. 2023 Oct 6;65:102250. doi: 10.1016/j.eclinm.2023.102250. eCollection 2023 Nov.

ABSTRACT

BACKGROUND: With the emergence of SARS-CoV-2 variants resistant to monoclonal antibody therapies and limited global access to therapeutics, the evaluation of novel therapeutics to prevent progression to severe COVID-19 remains a critical need.

METHODS: Safety, clinical and antiviral efficacy of inhaled interferon-β1a (SNG001) were evaluated in a phase II randomized controlled trial on the ACTIV-2/A5401 platform (ClinicalTrials.govNCT04518410). Adult outpatients with confirmed SARS-CoV-2 infection within 10 days of symptom onset were randomized and initiated either orally inhaled nebulized SNG001 given once daily for 14 days (n = 110) or blinded pooled placebo (n = 110) between February 10 and August 18, 2021.

FINDINGS: The proportion of participants reporting premature treatment discontinuation was 9% among SNG001 and 13% among placebo participants. There were no differences between participants who received SNG001 or placebo in the primary outcomes of treatment emergent Grade 3 or higher adverse events (3.6% and 8.2%, respectively), time to symptom improvement (median 13 and 9 days, respectively), or proportion with unquantifiable nasopharyngeal SARS-CoV-2 RNA at days 3 (28% [26/93] vs. 39% [37/94], respectively), 7 (65% [60/93] vs. 66% [62/94]) and 14 (91% [86/95] vs. 91% [83/81]). There were fewer hospitalizations with SNG001 (n = 1; 1%) compared with placebo (n = 7; 6%), representing an 86% relative risk reduction (p = 0.07). There were no deaths in either arm.

INTERPRETATION: In this trial, SNG001 was safe and associated with a non-statistically significant decrease in hospitalization for COVID-19 pneumonia.

FUNDING: The ACTIV-2 platform study is funded by the NIH. Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number UM1 AI068634, UM1 AI068636 and UM1 AI106701. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

PMID:37855026 | PMC:PMC10579289 | DOI:10.1016/j.eclinm.2023.102250

Int J Prev Med. 2023 Jun 22;14:80. doi: 10.4103/ijpvm.ijpvm_130_22. eCollection 2023.

ABSTRACT

BACKGROUND: The basis of the overcorrecting minus lens is to induce compliance and consequently prevent constant exotropia. Some previous studies advocated early surgical therapy and others suggested over-minus treatment. Our purpose is to evaluate the success rate of the over-minus lens.

METHODS: This descriptive cross-sectional study was carried out on 106 patients under the age of 7 years with intermittent exotropia (IXT) who attended Amir-Al-Momenin Hospital at Guilan University of Medical Sciences, Iran. The data was gathered by a form including sex, age, level of cycloplegic refraction, the amount of deviation before and after using the over-minus glasses, visual acuity, the amount of the over-minus glasses, duration of treatment, recovery, and follow-up. The success rate was defined as decreasing exotropia to less than ten prism diopters or exophoria.

RESULTS: A total of 106 patients with a mean age of 2.25 ± 0.74 years were enrolled in this study. The mean exotropia before and after treatment was 20.96 ± 8.20 and 12.16 ± 11.04 prism diopters, respectively, and there was a statistically significant difference (P < 0.002). The mean refractive spherical and astigmatic errors (cycloplegic refraction) were +1.34 ± 1.07 and -0.32 ± 0.72 diopters, respectively. At the end of the follow-up, exotropia increased in 5.6% of patients, there was no change in 15% of patients with a mean deviation of 25.0 ± 6.06 prism diopters, and 79.24% of patients were treated successfully.

CONCLUSIONS: According to the results of this study, treatment of IXT by over-correcting lenses can be a safe procedure and effective in preventing exotropia.

PMID:37854980 | PMC:PMC10580209 | DOI:10.4103/ijpvm.ijpvm_130_22

Postepy Kardiol Interwencyjnej. 2023 Sep;19(3):251-256. doi: 10.5114/aic.2023.131478. Epub 2023 Sep 27.

ABSTRACT

INTRODUCTION: Data regarding patients with a previous medical record of immunosuppression treatment who have undergone transcatheter aortic valve implantation (TAVI) are limited and extremely inconclusive. Available studies are mostly short term observations; thus there is a lack of evidence on efficacy and safety of TAVI in this specific group of patients.

AIM: To compare the in-hospital and long-term outcomes between patients with or without a medical history of immunosuppressive treatment undergoing TAVI for aortic valve stenosis (AS).

MATERIAL AND METHODS: We conducted a retrospective registry-based analysis including patients undergoing TAVI for AS at 5 centres between January 2009 and August 2017. The primary endpoint was long-term all-cause mortality. Secondary endpoints comprised major vascular complications, life-threatening or disabling bleeding, stroke and new pacemaker implantation.

RESULTS: Of 1451 consecutive patients who underwent TAVI, two propensity-matched groups including 25 patients with a history of immunosuppression and 75 patients without it were analysed. No differences between groups in all-cause mortality were found in a median follow-up time of 2.7 years following TAVI (p = 0.465; HR = 0.73; 95% CI: 0.30-1.77). The rate of major vascular complications (4.0% vs. 5.3%) was similar in the two groups (p = 1.000). There were no statistically significant differences in the composite endpoint combining life-threatening or disabling bleeding, major vascular complications, stroke and new pacemaker implantation (40.0% vs. 20.0%, p = 0.218).

CONCLUSIONS: Patients who had undergone TAVI for AS had similar long-term mortality regardless of whether they had a previous medical record of immunosuppression. Procedural complication rates were comparable between the groups.

PMID:37854972 | PMC:PMC10580841 | DOI:10.5114/aic.2023.131478

Liver Res. 2023 Sep;7(3):256-262. doi: 10.1016/j.livres.2023.07.003. Epub 2023 Jul 16.

ABSTRACT

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is characterized by several clinically important prognostic parameters, including portal vein thrombosis (PVT), tumor multifocality, and serum alpha-fetoprotein (AFP) levels, in addition to maximum tumor diameter (MTD). However, associations among these parameters have not been thoroughly examined. Thus, the study aimed to investigate the correlations among these HCC characteristics in a prospectively collected database.

METHODS: An 8080 HCC patient database derived from our weekly HCC council meeting was examined with respect to the correlations at baseline patient presentation between increases in MTD and changes in the percentage of patients with PVT, multifocality, or AFP levels.

RESULTS: The percentage of patients with PVT and with multifocality (tumor nodule numbers ≥3) significantly increased with enlarging MTD, regardless of the serum AFP level, showing the independence of PVT and multifocality on AFP. The percentage of patients with multifocality increased with enlarging MTD, in the presence or absence of PVT, showing the independence of multifocality from PVT. Therefore, discordance was found between different tumor parameters.

CONCLUSIONS: A statistically significant association was found between PVT and MTD and between multifocality and MTD, all three of which are independent of AFP. PVT and multifocality appeared to be independent of each other. Although PVT and multifocality were independent of AFP, they were also augmented with high serum AFP levels. The results suggest the possibility of multiple pathways of tumor progression in the later stages of HCC development.

PMID:37854945 | PMC:PMC10583763 | DOI:10.1016/j.livres.2023.07.003

J R Stat Soc Series B Stat Methodol. 2017 Nov;79(5):1415-1437. doi: 10.1111/rssb.12224. Epub 2016 Dec 26.

ABSTRACT

This paper proposes a decorrelation-based approach to test hypotheses and construct confidence intervals for the low dimensional component of high dimensional proportional hazards models. Motivated by the geometric projection principle, we propose new decorrelated score, Wald and partial likelihood ratio statistics. Without assuming model selection consistency, we prove the asymptotic normality of these test statistics, establish their semiparametric optimality. We also develop new procedures for constructing pointwise confidence intervals for the baseline hazard function and baseline survival function. Thorough numerical results are provided to back up our theory.

PMID:37854943 | PMC:PMC10584375 | DOI:10.1111/rssb.12224

J Oral Maxillofac Pathol. 2023 Apr-Jun;27(2):307-314. doi: 10.4103/jomfp.jomfp_368_22. Epub 2023 Jul 13.

ABSTRACT

BACKGROUND: Inspite of having advanced treatment modalities the overall survival rate in oral squamous cell carcinoma (OSCC) remains poor. This is considered to be mainly due to local recurrence and distant metastasis. Various studies have concentrated on the role of oral cancer stem cells (OCSCs) in the progression and metastasis of OSCC. However, the role of tumor microenvironment components has been less delved into. Hence clarity on cell biology and metastatic potential OCSCs is essential for the development of more effective anti-cancer treatment.

AIM: To establish the role of OCSCs in different grades of OSCC and metastatic lymph nodes through the expression of cluster of differentiation 44 (CD44). To demonstrate and correlate the role of hypoxia and Epithelial mesenchymal transition (EMT) in the various grades and metastatic lymph nodes in the formation and maintenance of OCSCs by employing Hypoxia-inducible factor-1 Alpha (HIF 1α) and Snail respectively.

METHOD AND MATERIAL: A total of 36 cases of OSCC, 12 from each grade and 12 normal oral mucosal tissues were included in the study. Immunohistochemical staining was performed for the demonstration of CD44, HIF1α, and Snail.

STATISTICS: Descriptive analysis, Chi-square, and Spearman’s rank correlation were used to analyze frequency and proportion, to compare expression and correlate between lesion proper and lymph node in each group respectively.

RESULTS: Significant expression of CD44, HIF1 α, and Snail among advancing grades of OSCC and their metastatic lymph node were observed. A positive correlation was seen between them.

CONCLUSIONS: The prognosis of OSCC can be improved by better understanding and targeting the molecules involved in the formation and maintenance of OCSCs.

PMID:37854934 | PMC:PMC10581292 | DOI:10.4103/jomfp.jomfp_368_22

J Oral Maxillofac Pathol. 2023 Apr-Jun;27(2):295-301. doi: 10.4103/jomfp.jomfp_301_22. Epub 2023 Jul 13.

ABSTRACT

BACKGROUND: The purpose of this experimental study was to evaluate and compare the degree of expression of Wilm’s Tumor Gene-1 (WT-1), Syndecan (CD 138) and Snail in Ameloblastoma and odontogenic keratocyst (OKC) and to analyse their potential role in pathogenesis.

METHODS AND MATERIAL: Immunohistochemical analysis was performed to evaluate WT-1, Syndecan and Snail expression in Ameloblastoma (n = 20) and OKC (n = 20). Topographical immunoexpression pattern of Ameloblast-like cells, Stellate Reticulum-like cells in Ameloblastoma and basal layer as well as suprabasal layer of cells of OKC were also compared. The results obtained were subjected to ANOVA test and Tukey HSD test through SPSS software 20.0 for Microsoft Windows.

RESULTS: WT-1 and Snail overexpression was seen in both Ameloblastoma and OKCs. Syndecan, responsible for maintaining normal cellular morphology, cell-cell adhesion and differentiation was significantly downregulated in both the lesions. The Ameloblasts-like cells and the basal cells showed significantly higher immunopositivity for WT-1 and Syndecan as compared to that of basal cells. An inverse relation was noted for Snail protein. The ANOVA test predicted a statistically significant difference of expression across the lesions with a P value <0.0001 for Syndecan and Snail.

CONCLUSIONS: The under-expression of epithelial membrane protein Syndecan-1 and upregulation of EMT transcription factor Snail can promote local invasion and is indicative of poor prognosis of these lesions. The overexpression of WT-1 results in tumorigenesis, proliferation and localized aggressiveness of Ameloblastoma and intrabony growth of OKC. Further investigation on the biologic behaviour of OKC is still recommended to arrive at more specific conclusions regarding its nature.

PMID:37854929 | PMC:PMC10581317 | DOI:10.4103/jomfp.jomfp_301_22

J Oral Maxillofac Pathol. 2023 Apr-Jun;27(2):427. doi: 10.4103/jomfp.jomfp_198_22. Epub 2023 Jul 13.

ABSTRACT

AIM: This is a cross-sectional comparative study, aimed to quantify the expression of patched (PTCH) gene in ameloblastoma, odontogenic keratocyst (OKC) and also the comparison of both the expressions.

MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted and quantified, and the expression of the PTCH gene was done in 17 cases of ameloblastoma and 17 cases of OKC by quantitative real-time polymerase chain reaction (RT-qPCR).

RESULTS: It was observed that there was an overexpression of the PTCH gene in both ameloblastoma and OKC with a good mean cycle threshold (CT) value of 32.71 ± 2.432 and 34.69 ± 1.875, respectively. When comparing the PTCH expression between the two, ameloblastoma showed higher expression than the OKC and the difference is statistically significant with P value of 0.025.

CONCLUSIONS: Our findings suggest that there is overexpression of PTCH in ameloblastoma and OKC, but it is highly expressed in ameloblastoma when compared to OKC. Overexpression of PTCH may constitute the activation of the Sonic Hedgehog pathway and may suggest the mechanism for the development of ameloblastoma and OKC. Hence it can be used as a valuable marker for early diagnosis and in the identification of therapeutic targets.

PMID:37854928 | PMC:PMC10581290 | DOI:10.4103/jomfp.jomfp_198_22