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Nevin Manimala Statistics

The Association of Long-Acting Insulin Analogue Use Versus Neutral Protamine Hagedorn Insulin Use With Major Adverse Cardiovascular Events Among Individuals With Type 2 Diabetes: A Population-Based Cohort Study

Diabetes Obes Metab. 2022 Jun 21. doi: 10.1111/dom.14802. Online ahead of print.

ABSTRACT

AIMS: To compare the risk of cardiovascular outcomes with long-acting insulin analogues versus Neutral Protamine Hagedorn (NPH) insulin among patients with type 2 diabetes.

MATERIALS AND METHODS: We conducted a population-based retrospective cohort study, using the United Kingdom Clinical Practice Research Datalink Aurum, linked with hospitalization and vital statistics data. Patients with type 2 diabetes who initiated basal insulin treatment between 2002-2018 were included in the study. Exposure was defined as current use of long-acting insulin analogues or NPH insulin, defined using a time-varying approach. The primary outcome was major adverse cardiovascular events (MACE, composite endpoint of myocardial infarction [MI], ischemic stroke, and cardiovascular death). We used a marginal structural Cox proportional hazards model to estimate the hazard ratio (HR) and 95% confidence interval (CI) for MACE with current use of long-acting insulin analogues versus NPH insulin, and by long-acting insulin molecule in secondary analyses.

RESULTS: Our cohort included 57 334 patients. A total of 3494 MACE events occurred over a mean follow-up of 1.6 years (incidence rate: 37.4, 95% CI: 36.2 to 38.7 per 1000 person-years). Long-acting insulin analogues were associated with a decreased risk of MACE compared to NPH insulin (HR: 0.89, 95% CI: 0.83 to 0.96).

CONCLUSIONS: Current use of long-acting insulin analogues is associated with a modestly reduced risk of MACE compared to current use of NPH insulin among patients with type 2 diabetes. This study can have important implications for drug plan managers and guideline writing committees for recommendations of insulin treatment for type 2 diabetes. This article is protected by copyright. All rights reserved.

PMID:35726454 | DOI:10.1111/dom.14802

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Nevin Manimala Statistics

The correlation between tumor thickness and aggressive histopathological pattern in Basal cell carcinoma

J Cosmet Dermatol. 2022 Jun;21(6):2577-2580. doi: 10.1111/jocd.14475. Epub 2021 Sep 28.

ABSTRACT

BACKGROUND: The significance of tumor thickness is not clear in the prognosis of basal cell carcinoma. We aimed to identify the relationship between the tumor thickness and aggressive histopathological growth pattern in BCC.

METHODS: We retrospectively reviewed 85 primary BCCs of 82 patients. A total of 78 (91.7%) tumor slides were available for review, 7 (8.2%) missing slides in archive could not to be re-evaluated. We recorded the histological subtype, ulceration, perineural invasion, and the tumor thickness. Tumors with infiltrative, micronodular, morpheaform and basosquamous features were classified as having an aggressive growth pattern.

RESULTS: The aggressive growth pattern was determined in 21 (26.9%) tumors with a mean tumor thickness of 2.19 ± 0.71 mm (range, 0.9-3.40). The non-aggressive growth pattern was detected in 57 (73%) tumors and the mean tumor thickness was 1.76 ± 0.87 mm (range 0.50-4.40 mm). There was a statistically significant difference in the mean tumor thickness between the tumors with aggressive growth pattern and non-aggressive growth pattern (p = 0.033).

CONCLUSION: Tumor thickness might have positive correlation with aggressive histological pattern. Measuring and reporting tumor thickness may be a more practical way to determine the pathological risk for BCC.

PMID:35726442 | DOI:10.1111/jocd.14475

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Nevin Manimala Statistics

Marker-dependent observation and carry-forward of internal covariates in Cox regression

Lifetime Data Anal. 2022 Jun 20. doi: 10.1007/s10985-022-09561-9. Online ahead of print.

ABSTRACT

Studies of chronic disease often involve modeling the relationship between marker processes and disease onset or progression. The Cox regression model is perhaps the most common and convenient approach to analysis in this setting. In most cohort studies, however, biospecimens and biomarker values are only measured intermittently (e.g. at clinic visits) so Cox models often treat biomarker values as fixed at their most recently observed values, until they are updated at the next visit. We consider the implications of this convention on the limiting values of regression coefficient estimators when the marker values themselves impact the intensity for clinic visits. A joint multistate model is described for the marker-failure-visit process which can be fitted to mitigate this bias and an expectation-maximization algorithm is developed. An application to data from a registry of patients with psoriatic arthritis is given for illustration.

PMID:35725841 | DOI:10.1007/s10985-022-09561-9

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Nevin Manimala Statistics

Metabolomics with multi-block modelling of mass spectrometry and nuclear magnetic resonance in order to discriminate Haplosclerida marine sponges

Anal Bioanal Chem. 2022 Jun 20. doi: 10.1007/s00216-022-04158-5. Online ahead of print.

ABSTRACT

A comprehensive metabolomic strategy, integrating 1H NMR and MS-based multi-block modelling in conjunction with multi-informational molecular networking, has been developed to discriminate sponges of the order Haplosclerida, well known for being taxonomically contentious. An in-house collection of 33 marine sponge samples belonging to three families (Callyspongiidae, Chalinidae, Petrosiidae) and four different genera (Callyspongia, Haliclona, Petrosia, Xestospongia) was investigated using LC-MS/MS, molecular networking, and the annotations processes combined with NMR data and multivariate statistical modelling. The combination of MS and NMR data into supervised multivariate models led to the discrimination of, out of the four genera, three groups based on the presence of metabolites, not necessarily previously described in the Haplosclerida order. Although these metabolomic methods have already been applied separately, it is the first time that a multi-block untargeted approach using MS and NMR has been combined with molecular networking and statistically analyzed, pointing out the pros and cons of this strategy.

PMID:35725831 | DOI:10.1007/s00216-022-04158-5

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Nevin Manimala Statistics

Plasma Profile of Immune Determinants Predicts Pathological Complete Response in Locally Advanced Breast Cancer Patients: A Pilot Study

Clin Breast Cancer. 2022 May 23:S1526-8209(22)00112-4. doi: 10.1016/j.clbc.2022.05.007. Online ahead of print.

ABSTRACT

BACKGROUND: Complex interactions between cancer and the immune system have an impact on disease progression and therapeutic response. Our objective was to evaluate whether circulating immune-related determinants are associated with pathological complete response (pCR) in patients with locally advanced breast cancer (LABC) subjected to neoadjuvant chemotherapy (NACT).

PATIENTS AND METHODS: Luminex technology was used to profile 22 cytokines, 10 chemokines, FGF2, PDGF-BB, VEGF, and Ca15-3/Ca125 glycoforms. Measurements were performed alongside standard hematological determinations on pretreatment plasma samples from 151 patients including 41 cases with pCR assessed following RECIST criteria.

RESULTS: Random Forest model analysis selected platelets, eotaxin, IFN-γ, IP10, and TGFβ2 as significant predictors of pCR. These immune-related features were combined into a quantitative score predictive of pCR. In patients who scored 0 or 1, none had pCR; the pCR frequency increased in relation to the score value (23.5%, 41.2%, and 78.6%, in score groups 2, 3, and 4, respectively). At multivariable logistic analysis, the pCR score was highly significant (odds ratio = 3.15 per unit increment; CI: 1.85-5.38; P < .0001); among clinical covariates (age, menopausal status, tumor stage, IHC subtype, Ki-67, CA15.3, and CA125), only Ki-67 was statistically significant (P = .013).

CONCLUSION: This explorative study aimed to lay the conceptual and practical foundation that a distinctive pattern of the immune determinant blood signature at diagnosis of LABC significantly correlates with the patient’s response to NACT and provides the groundwork for larger studies that could lead to a minimally invasive tool for personalized medicine.

PMID:35725806 | DOI:10.1016/j.clbc.2022.05.007

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Nevin Manimala Statistics

Differential Expression of the Genes Coding for Adipokines and Epithelial Cell Polarity Components in Women With Low and High Mammographic Density

Clin Breast Cancer. 2022 May 20:S1526-8209(22)00095-7. doi: 10.1016/j.clbc.2022.05.005. Online ahead of print.

ABSTRACT

BACKGROUND: Women with extensive mammographic density (MD) are more likely to develop breast cancer than women with low MD because of a high epithelial component associated with a high proportion of stromal cells. To elucidate the biological association between high MD and risk of breast cancer, we compared the expression of a panel of genes coding for leptin, adiponectin, and some component of cell polarity and adherens junction complexes in dense and non-dense breast tissue.

METHODS: We interrogated a public dataset composed by 120 specimens of normal breast tissue with MD evaluation. The differential expression of the selected genes in the 2 MD subgroups was assessed by the Wilcoxon test, whereas Kruskal-Wallis test evaluated the differential expression of single genes in the fatty, epithelium, or nonfatty compartment. Spearman’s correlation measured the relationship among genes in the subset with the highest epithelium proportion.

RESULTS: In high MD, the expression level of PARD6B, CRB3, PATJ, LLGL2, CDH1, and MARVELD2 significantly lowered in tissues with the highest epithelium proportion, whereas, in low MD, the expression level of the genes increased with the increasing of the epithelium proportion. In the low MD subgroup, LEP correlated negatively with PRKCZ and DLG3, whereas, in high MD, such correlation was not observed.

CONCLUSIONS: The expression of the genes governing cell polarity establishment and cell-cell adhesion assembly differed significantly in the epithelial component of dense and non-dense breasts. The correlation pattern between LEP and PRKCZ or DLG3 agrees with the role of leptin in cell polarity disruption.

PMID:35725805 | DOI:10.1016/j.clbc.2022.05.005

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Nevin Manimala Statistics

How the COVID-19 pandemic influences the prevalence of pressure injuries in the Czech Republic: A nationwide analysis of a health registry in 2020

J Tissue Viability. 2022 Jun 15:S0965-206X(22)00060-2. doi: 10.1016/j.jtv.2022.06.003. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 significantly influences the overall patient status and, in severe symptomatology, the ability to move and the low oxygenation of the tissue for the ventilated patient in Intensive Care Units (ICU). There is a higher risk for Pressure injuries (PIs) development.

OBJECTIVES: The nationwide analyses of the National health register aimed to compare the prevalence of PIs reported before the pandemic COVID-19 started and during the pandemic in 2020.

METHOD: A retrospective, nationwide cross-sectional analysis of data regarding the STROBE checklist collected by the National Health Information System (NHIS), focusing on the PIs reporting based on the International Classification of Diseases (ICD-10) diagnoses L89.0-L89.9 for PIs in 2020. The data from the pandemic period of COVID-19 in 2020 were compared to the prevalence of PI cases in the period 2010-2019 in the Czech Republic in all hospitalized patients.

RESULTS: The total number of admissions for L89 in 2020 was 14,441, of which 1509 (10.4%) also had COVID-19. In the ICU were 4386 admissions, 12.1% of which also had COVID-19. A higher proportion of PIs is observed in patients hospitalized with COVID-19 than in patients without COVID-19 (2.62% vs 0.81%, respectively 1.05% vs 0.46% when standardized to the 2013 ESP = European Standard Population). In patients hospitalized in ICU, 3.68% with COVID-19 had PIs vs 1.42% without COVID-19 had PIs (1.97% vs 0.81% using the 2013 ESP).

CONCLUSION: The national health registers analyses have proven that the prevalence of PIs was higher among patients hospitalized with the SARS-CoV-2 infection.

PMID:35725785 | DOI:10.1016/j.jtv.2022.06.003

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Nevin Manimala Statistics

Diagnostic advantage of thin slice 2D MRI and multiplanar reconstruction of the knee joint using deep learning based denoising approach

Sci Rep. 2022 Jun 20;12(1):10362. doi: 10.1038/s41598-022-14190-1.

ABSTRACT

The purpose of this study is to evaluate whether thin-slice high-resolution 2D fat-suppressed proton density-weighted image of the knee joint using denoising approach with deep learning-based reconstruction (dDLR) with MPR is more useful than 3D FS-PD multi planar voxel image. Twelve patients who underwent MRI of the knee at 3T and 13 knees were enrolled. Denoising effect was quantitatively evaluated by comparing the coefficient of variation (CV) before and after dDLR. For the qualitative assessment, two radiologists evaluated image quality, artifacts, anatomical structures, and abnormal findings using a 5-point Likert scale between 2D and 3D. All of them were statistically analyzed. Gwet’s agreement coefficients were also calculated. For the scores of abnormal findings, we calculated the percentages of the cases with agreement with high confidence. The CV after dDLR was significantly lower than the one before dDLR (p < 0.05). As for image quality, artifacts and anatomical structure, no significant differences were found except for flow artifact (p < 0.05). The agreement was significantly higher in 2D than in 3D in abnormal findings (p < 0.05). In abnormal findings, the percentage with high confidence was higher in 2D than in 3D (p < 0.05). By applying dDLR to 2D, almost equivalent image quality to 3D could be obtained. Furthermore, abnormal findings could be depicted with greater confidence and consistency, indicating that 2D with dDLR can be a promising imaging method for the knee joint disease evaluation.

PMID:35725760 | DOI:10.1038/s41598-022-14190-1

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Nevin Manimala Statistics

Peritumoral radiomics features on preoperative thin-slice CT images can predict the spread through air spaces of lung adenocarcinoma

Sci Rep. 2022 Jun 20;12(1):10323. doi: 10.1038/s41598-022-14400-w.

ABSTRACT

The spread through air spaces (STAS) is recognized as a negative prognostic factor in patients with early-stage lung adenocarcinoma. The present study aimed to develop a machine learning model for the prediction of STAS using peritumoral radiomics features extracted from preoperative CT imaging. A total of 339 patients who underwent lobectomy or limited resection for lung adenocarcinoma were included. The patients were randomly divided (3:2) into training and test cohorts. Two prediction models were created using the training cohort: a conventional model based on the tumor consolidation/tumor (C/T) ratio and a machine learning model based on peritumoral radiomics features. The areas under the curve for the two models in the testing cohort were 0.70 and 0.76, respectively (P = 0.045). The cumulative incidence of recurrence (CIR) was significantly higher in the STAS high-risk group when using the radiomics model than that in the low-risk group (44% vs. 4% at 5 years; P = 0.002) in patients who underwent limited resection in the testing cohort. In contrast, the 5-year CIR was not significantly different among patients who underwent lobectomy (17% vs. 11%; P = 0.469). In conclusion, the machine learning model for STAS prediction based on peritumoral radiomics features performed better than the C/T ratio model.

PMID:35725754 | DOI:10.1038/s41598-022-14400-w

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Nevin Manimala Statistics

Childhood ‘bronchitis’ and respiratory outcomes in middle-age: a prospective cohort study from age 7 to 53 years

BMJ Open Respir Res. 2022 Jun;9(1):e001212. doi: 10.1136/bmjresp-2022-001212.

ABSTRACT

BACKGROUND: Chronic bronchitis in childhood is associated with a diagnosis of asthma and/or bronchiectasis a few years later, however, consequences into middle-age are unknown.

OBJECTIVE: To investigate the relationship between childhood bronchitis and respiratory-related health outcomes in middle-age.

DESIGN: Cohort study from age 7 to 53 years.

SETTING: General population of European descent from Tasmania, Australia.

PARTICIPANTS: 3202 participants of the age 53-year follow-up (mean age 53, range 51-55) of the Tasmanian Longitudinal Health Study cohort who were born in 1961 and first investigated at age 7 were included in our analysis.

STATISTICAL METHODS: Multivariable linear and logistic regression. The association between parent reported childhood bronchitis up to age 7 and age 53-year lung conditions (n=3202) and lung function (n=2379) were investigated.

RESULTS: Among 3202 participants, 47.5% had one or more episodes of childhood bronchitis, classified according to severity based on the number of episodes and duration as: ‘non-recurrent bronchitis’ (28.1%); ‘recurrent non-protracted bronchitis’ (18.1%) and ‘recurrent-protracted bronchitis’ (1.3%). Age 53 prevalence of doctor-diagnosed asthma and pneumonia (p-trend <0.001) and chronic bronchitis (p-trend=0.07) increased in accordance with childhood bronchitis severities. At age 53, ‘recurrent-protracted bronchitis’ (the most severe subgroup in childhood) was associated with doctor-diagnosed current asthma (OR 4.54, 95% CI 2.31 to 8.91) doctor-diagnosed pneumonia (OR=2.18 (95% CI 1.00 to 4.74)) and, paradoxically, increased transfer factor for carbon monoxide (z-score +0.51 SD (0.15-0.88)), when compared with no childhood bronchitis.

CONCLUSION: In this cohort born in 1961, one or more episodes of childhood bronchitis was a frequent occurrence. ‘Recurrent-protracted bronchitis’, while uncommon, was especially linked to multiple respiratory outcomes almost five decades later, including asthma, pneumonia and raised lung gas transfer. These findings provide insights into the natural history of childhood ‘bronchitis’ into middle-age.

PMID:35725733 | DOI:10.1136/bmjresp-2022-001212