Tag: statistics

Circ J. 2021 Mar 25. doi: 10.1253/circj.CJ-20-1075. Online ahead of print.

ABSTRACT

BACKGROUND: Recently, identification of independent risk factors for ischemic stroke in Japanese non-valvular atrial fibrillation (NVAF) patients was made by analyzing the 5 major Japanese registries: J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and the Hokuriku-Plus AF Registry.Methods and Results:The predictive value of the risk scheme in Japanese NVAF patients was assessed. Of 16,918 patients, 12,289 NVAF patients were analyzed (mean follow up, 649±181 days). Hazard ratios (HRs) of each significant, independent risk factor were determined by using adjusted Cox-hazard proportional analysis. Scoring system for ischemic stroke was created by transforming HR logarithmically and was estimated by c-statistic. During the 21,820 person-years follow up, 241 ischemic stroke events occurred. Significant risk factors were: being elderly (aged 75-84 years [E], HR=1.74), extreme elderly (≥85 years [EE], HR=2.41), having hypertension (H, HR=1.60), previous stroke (S, HR=2.75), type of AF (persistent/permanent) (T, HR=1.59), and low body mass index <18.5 kg/m²(L, HR=1.55) after adjusting for oral anticoagulant treatment. The score was assigned as follows: 1 point to H, E, L, and T, and 2 points to EE and S (HELT-E₂S₂score). The C-statistic, using this score, was 0.681 (95% confidence interval [CI]=0.647-0.714), which was significantly higher than those using CHADS₂(0.647; 95% CI=0.614-0.681, P=0.027 for comparison) and CHA₂DS₂-VASc scores (0.641; 95% CI=0.608-0.673, P=0.008).

CONCLUSIONS: The HELT-E₂S₂score may be useful for identifying Japanese NVAF patients at risk of ischemic stroke.

PMID:33762526 | DOI:10.1253/circj.CJ-20-1075

Eur Endod J. 2021 Mar 12. doi: 10.14744/eej.2020.29292. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study is to compare the cytotoxicity of triple antibiotic paste (TAP) with an antiinflammatory drug (TAP+Catafast-TAPC) in nano and regular formulations versus calcium hydroxide as intracanal medicaments.

METHODS: The TAPC drugs extraction were made in cell culture media MEM-E (Eagle’s minimal essential medium) using concentration of 10 mg/mL of each sample for seven days. Inhibitory concentrations (IC50 values) were determined for each extract. A human fibroblasts cell line was used to evaluate the cytotoxicity of different concentrations (10, 0.625 and 0.07 mg/mL) using MTT essay. The cell viability was measured after 24 h, 48 h and 7 days for all concentrations of the drugs. Flow cytometry analysis was carried out to identify the effect of materials on apoptosis/necrosis. Statistical analysis for the obtained results was done by one-way ANOVA.

RESULTS: The results revealed that cell viability was inversely proportional to the duration of treatment in all of the groups. Calcium hydroxide (Control group) demonstrated a significantly greater cytotoxic effect, followed by Nano Triple Antibiotic Paste with Catafast as an anti-inflamatory drug (Nano TAPC), while Triple Antibiotic Paste with Catafast (TAPC) had the least cytotoxic effect. Nano TAPC has the greatest apoptotic value, while TAPC had the least when compared with the reference group, with no significant difference between groups (P<0.05).

CONCLUSION: The cytotoxic effect of Nano TAPC was lower than that of calcium hydroxide and higher than that of TAPC. Although Nano TAPC has the highest apoptotic value when compared to TAPC and calcium hydroxide but still there is no statistically significant difference between them.

PMID:33762529 | DOI:10.14744/eej.2020.29292

Endocr J. 2021 Mar 24. doi: 10.1507/endocrj.EJ20-0622. Online ahead of print.

ABSTRACT

An elevated serum alkaline phosphatase (ALP) level is one of the markers for the presence of rickets in children, but it is also associated with bone formation. However, its role in diagnosing genu varum in pediatric patients with vitamin D-deficient rickets is still unknown. To clarify the role of the serum ALP level in assessing the severity of genu varum, we retrospectively investigated this issue statistically using data on rickets such as serum intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, ALP, the level of creatinine as the percentage of the median according to age (%Cr), and the metaphyseal diaphyseal angle (MDA) in the lower extremities as an index of the severity of genu varum. A multiple regression analysis revealed that log ALP and %Cr values were negatively associated with MDA values. The former association was also confirmed by a linear mixed model, while iPTH was positively associated with MDA by path model analysis. To elucidate the association of ALP with MDA in the presence of iPTH, we investigated three-dimensional figures by neural network analysis. This indicated the presence of a biphasic association of ALP with MDA: the first phase increases while the second decreases MDA. The latter phenomenon is considered to be associated with the increase in bone formation due to the mechanical stress loaded on the lower extremities. These findings are important and informative for pediatricians to understand the significance of the serum ALP level in pediatric patients with genu varum caused by vitamin D deficiency.

PMID:33762518 | DOI:10.1507/endocrj.EJ20-0622

Clin Med (Lond). 2021 Mar;21(2):e192-e197. doi: 10.7861/clinmed.2020-0851.

ABSTRACT

BACKGROUND: Perioperative optimisation can improve outcomes for older people having surgery. Integration with primary care could improve quality and reduce variability in access to preoperative optimisation.

AIM: Our aim was to explore attitudes, beliefs and behaviours of general practitioners (GPs) regarding the perioperative pathway, and evaluate enablers and barriers to GP-led preoperative optimisation.

METHODS: Stakeholder interviews (n=38) informed survey development. A purposive sampling frame was used to target delivery of online and paper surveys. Results were analysed using descriptive statistics.

RESULTS: We had 231 responses (response rate 32.7%). Enablers included belief among GPs that optimisation improves postoperative outcomes (86%) and that they have a role discussing modifiable risk factors with patients (85%). Barriers included low frequency exposure to older surgical patients, minimal training in perioperative medicine and rare interaction with perioperative services.

CONCLUSION: This survey illustrates the importance of interprofessional education, cross-sector training opportunities and collaboration to deliver integrated preoperative optimisation for older people undergoing surgery.

PMID:33762386 | DOI:10.7861/clinmed.2020-0851

Sci Transl Med. 2021 Mar 24;13(586):eabe0357. doi: 10.1126/scitranslmed.abe0357.

ABSTRACT

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1), an extracellular matrix protein, is associated with risk of coronary disease in humans independent of plasma lipids. Despite a robust statistical association, if and how SVEP1 might contribute to atherosclerosis remained unclear. Here, using Mendelian randomization and complementary mouse models, we provide evidence that SVEP1 promotes atherosclerosis in humans and mice and is expressed by vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque. VSMCs also interact with SVEP1, causing proliferation and dysregulation of key differentiation pathways, including integrin and Notch signaling. Fibroblast growth factor receptor transcription increases in VSMCs interacting with SVEP1 and is further increased by the coronary disease-associated SVEP1 variant p.D2702G. These effects ultimately drive inflammation and promote atherosclerosis. Together, our results suggest that VSMC-derived SVEP1 is a proatherogenic factor and support the concept that pharmacological inhibition of SVEP1 should protect against atherosclerosis in humans.

PMID:33762433 | DOI:10.1126/scitranslmed.abe0357

J Prosthodont Res. 2021 Mar 25. doi: 10.2186/jpr.JPR_D_20_00030. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study was to compare the correlation between the learning effect of dental computer-aided design (CAD) software and computer literacy in the clinical and preclinical experience groups of computer-aided design and computer-aided manufacturing (CAD/CAM).

METHODS: A total of 28 participants were recruited, including 14 dental students and 14 dental technicians. Their working time was evaluated using a custom abutment design with two dental CAD software program (exocad GmbH and Deltanine). The working time of custom abutment design was measured 3 times. A survey was conducted to evaluate the computer literacy. For statistical analysis, Mann-Whitney U test was used to analyze the difference between the clinical and preclinical experience groups and the correlation between computer literacy and reduction in working time was confirmed by Spearman’s Rank correlation analysis (α=.05).

RESULTS: The median working time showed the clinical experience group had faster than the preclinical experience group (P<.001). On the other hand, the reduction in working time was higher in the preclinical experience group (P=.002). Only preclinical experience group had a significant positive correlation between the computer literacy and reduction in working time (P<.001).

CONCLUSIONS: Basic computer skills are required for first-time users to achie ve an excellent learning effect of dental CAD software program.

PMID:33762504 | DOI:10.2186/jpr.JPR_D_20_00030

J Prosthodont Res. 2021 Mar 25. doi: 10.2186/jpr.JPR_D_20_00251. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to clarify the effects of different bonding systems (BSs) with various polymerization modes and root canal regions on the bond strength of core build-up resin composite to dentin.

METHODS: Post cavities were prepared in the roots of 54 bovine teeth. Three types of BS with various polymerization modes (light, chemical, and dual-cure) were applied to the walls of the cavities, which were subsequently filled with core build-up resin composite, and stored in 37ºC water for 7 days. Each tooth was then sectioned perpendicular to the long axis of the tooth into 9-disk from the coronal to the apical side. Bond strengths were measured on two-thirds of the disks, while dye penetration was examined in the remaining third.

RESULTS: Statistical analysis revealed significant differences between the bond strengths of BSs with different polymerization modes, indicating chemical-cured BS had higher bond strength than light-cured BS. The chemical-cured BS group showed cohesive failure in both resin composite and dentin regardless of the root canal region, while adhesive failure was observed in the coronal region for dual-cured BS and in the apical region for light-cured BS. Dye penetration was significantly more at the bonding interface at the apical region of the light-cured BS.

CONCLUSIONS: Chemical-cured BS displayed a greater bond strength than light-cured BS. Cohesive failure was observed in both core build-up resin and dentin, indicating that the integration of tooth structure with resin composite was effective for retaining the resin core and sealing the root canal.

PMID:33762506 | DOI:10.2186/jpr.JPR_D_20_00251

J Immunother Cancer. 2021 Mar;9(3):e001458. doi: 10.1136/jitc-2020-001458.

ABSTRACT

BACKGROUND: Some sarcomas respond to immune checkpoint inhibition, but predictive biomarkers are unknown. We analyzed tumor DNA methylation profiles in relation to immunological parameters and response to anti-programmed cell death 1 (anti-PD-1) immune checkpoint inhibitor (ICI) therapy in patients with sarcoma.

PATIENTS AND METHODS: We retrospectively identified adult patients who had received anti-PD-1 ICI therapy for recurrent sarcoma in two independent centers. We performed (1) blinded radiological response evaluation according to immune response evaluation criteria in solid tumors (iRECIST) ; (2) tumor DNA methylation profiling of >850,000 probes using Infinium MethylationEPIC microarrays; (3) analysis of tumor-infiltrating immune cell subsets (CD3, CD8, CD45RO, FOXP3) and intratumoral expression of immune checkpoint molecules (PD-L1, PD-1, LAG-3) using immunohistochemistry; and (4) evaluation of blood-based systemic inflammation scores (neutrophil-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio). Response to anti-PD-1 ICI therapy was bioinformatically and statistically correlated with DNA methylation profiles and immunological data.

RESULTS: 35 patients (median age of 50 (23-81) years; 18 females, 17 males; 27 soft tissue sarcomas; 8 osteosarcomas) were included in this study. The objective response rate to anti-PD-1 ICI therapy was 22.9% with complete responses in 3 out of 35 and partial responses in 5 out of 35 patients. Adjustment of DNA methylation data for tumor-infiltrating immune cells resulted in identification of methylation differences between responders and non-responders to anti-PD-1 ICI. 2453 differentially methylated CpG sites (DMPs; 2043 with decreased and 410 with increased methylation) were identified. Clustering of sarcoma samples based on these DMPs revealed two main clusters: methylation cluster 1 (MC1) consisted of 73% responders and methylation cluster 2 (MC2) contained only non-responders to anti-PD-1 ICI. Median progression-free survival from anti-PD-1 therapy start of MC1 and MC2 patients was 16.5 and 1.9 months, respectively (p=0.001). Median overall survival of these patients was 34.4 and 8.0 months, respectively (p=0.029). The most prominent DNA methylation differences were found in pathways implicated in Rap1 signaling, focal adhesion, adherens junction Phosphoinositide 3-kinase (PI3K)-Akt signaling and extracellular matrix (ECM)-receptor interaction.

CONCLUSIONS: Our data demonstrate that tumor DNA methylation profiles may serve as a predictive marker for response to anti-PD-1 ICI therapy in sarcoma.

PMID:33762319 | DOI:10.1136/jitc-2020-001458

J Immunother Cancer. 2021 Mar;9(3):e001813. doi: 10.1136/jitc-2020-001813.

ABSTRACT

BACKGROUND: Plasmacytoid dendritic cells (pDCs) play a key role in the induction and maintenance of antitumor immunity. Conversely, they can act as tolerogenic DCs by inhibiting tumor-directed immune responses. Therefore, pDCs may profoundly influence tumor progression. To gain novel insights into the role of pDCs in colon cancer, we investigated the frequency and clinical relevance of pDCs in primary tumor tissues from patients with colon cancer with different clinicopathological characteristics.

METHODS: Immunohistochemical stainings were performed to explore the frequency of tumor-infiltrating BDCA-2⁺ pDCs in patients with colon cancer. Statistical analyses were conducted to determine an association between the pDC density and clinicopathological characteristics of the patients. Furthermore, we used multiplex immunofluorescence stainings to evaluate the localization and phenotype of pDCs in stroma and tertiary lymphoid structures (TLS) of colon cancer tissues.

RESULTS: An increased density of infiltrating pDCs was associated with lower Union for International Cancer Control (UICC) stages. Furthermore, a higher pDC frequency was significantly correlated with increased progression-free and overall survival of patients with colon cancer. Moreover, a lower number of coloncancer-infiltrating pDCs was significantly and independently linked to worse prognosis. In addition, we found that a proportion of pDCs shows a nuclear expression of the transcription factor interferon regulatory factor 7 (IRF7), which is characteristic for an activated phenotype. In various tumor stroma regions, IRF7⁺ pDCs were located in the neighborhood of granzyme B-expressing CD8⁺ T cells. Moreover, pDCs were identified as a novel component of the T cell zone of colon cancer-associated TLS, which are major regulators of adaptive antitumor immunity. A proportion of TLS-associated pDCs displayed a nuclear IRF7 expression and was preferentially located close to CD4⁺ T cells.

CONCLUSIONS: These results indicate that higher densities of tumor-infiltrating pDCs are associated with prolonged survival of patients with colon cancer. Moreover, colon cancer-infiltrating pDCs may represent a novel prognostic factor. The colocalization of activated pDCs and T cells in tumor stroma and within TLS may contribute to the correlation between higher pDC densities and better prognosis. In addition, our findings may have implications for the design of novel immunotherapeutic strategies that are based on targeting colon cancer-infiltrating pDCs.

PMID:33762320 | DOI:10.1136/jitc-2020-001813

Clin Med (Lond). 2021 Mar;21(2):e171-e178. doi: 10.7861/clinmed.2020-0586.

ABSTRACT

Large reductions in emergency department attendances and hospitalisations with non-COVID acute medical illness early during the pandemic were attributed to reluctance to seek medical help and higher referral thresholds. Here, we compare acute medical admissions with a comparison cohort from 2017. Deaths in the same geographic area were examined, and Wales-wide deaths during these 4 weeks in 2020 were compared with a seasonally matched period in 2019. There were 528 patients admitted with non-COVID illness in 2020, versus 924 in 2017 (a reduction of 43%). Deaths from non-COVID causes increased by 10.9% compared with 2017, over half this rise being from neurological causes including stroke and dementia. While far fewer patients required hospitalisation as medical emergencies, rises in local non-COVID deaths proved small. Wales-wide non-COVID deaths rose by just 1% compared with 2019. The findings suggest that changes in population behaviour and lifestyle during lockdown brought about unforeseen health benefits.

PMID:33762383 | DOI:10.7861/clinmed.2020-0586