Categories
Nevin Manimala Statistics

Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy

Diabetes Obes Metab. 2022 Jan 10. doi: 10.1111/dom.14648. Online ahead of print.

ABSTRACT

AIMS: We compared the association of metformin use and COVID-19 outcomes in a cohort of 31 966 patients with diabetes in Lombardy.

METHODS: We used a COVID-19 linkable administrative regional database to select diabetic patients over 40 years old. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for SARS-CoV-2 between February 15, 2020 and March 15, 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching. Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19 and admission to an intensive care unit (ICU).

RESULTS: In multivariable models metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91) and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar in propensity score analysis; metformin was associated with significantly lower risk of total mortality (OR 0.79; 95% CI, 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI, 0.67-0.81) and ICU admission (OR 0.77; 95% CI, 0.63-0.95).

CONCLUSIONS: In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized clinical trials (RCT) are needed to confirm this. While awaiting the results of RCT, we suggest continuing prescribing metformin to diabetic patients with COVID-19. This article is protected by copyright. All rights reserved.

PMID:35014746 | DOI:10.1111/dom.14648

Categories
Nevin Manimala Statistics

Combined prick and patch tests for diagnosis of food hypersensitivity in dogs with chronic pruritus

Vet Dermatol. 2022 Jan 11. doi: 10.1111/vde.13055. Online ahead of print.

ABSTRACT

BACKGROUND: Previous studies have shown that patch testing with food extracts can assist formulation of elimination diets (ED) in human patients with suspected adverse food reactions (AFR). Little is known about the use of these tests in dogs.

OBJECTIVES: To evaluate the effectiveness of a combination of prick and patch testing in current protocols, and food challenge (FC) tests in dogs with AFR.

METHODS AND MATERIALS: Prick and patch tests were performed on 21 dogs with chronic, nonseasonal pruritus. Dogs then were fed an ED formulated on the basis of the results. All dogs with improved clinical signs then were challenged with a food to which there had been a positive reaction in the tests. Six dogs subsequently were challenged with a food to which they had been negative on testing. Pruritus Visual Analog Scale (pVAS) and Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) were evaluated on Day (D)0, D30 and D60 of the ED. Sensitivity (SE), specificity (SP), positive (PPV) and negative (NPV) predictive values, and the Kappa (κ)value were calculated.

RESULTS: Of the 21 dogs, there was a significant mean improvement in pVAS and CADESI-04 scores in 16 (76%) dogs after D30 (P < 0.01) and D60 (P < 0.01) of the ED. There were no statistical differences between D30 and D60. The combination of tests had SE, SP, PPV, NPV and κ values of 80%, 66.7%, 66.7%, 80% and -0.17, respectively.

CONCLUSIONS AND CLINICAL RELEVANCE: The combination of prick and patch testing reached high values of SE and NPV. A diagnosis of AFR was made in 76% of the dogs, and test results were useful for the selection of an ED.

PMID:35014738 | DOI:10.1111/vde.13055

Categories
Nevin Manimala Statistics

Prolonged twice-daily administration of oclacitinib for the control of canine atopic dermatitis: a retrospective study of 53 client-owned atopic dogs

Vet Dermatol. 2022 Jan 11. doi: 10.1111/vde.13053. Online ahead of print.

ABSTRACT

BACKGROUND: Oclacitinib administered at the licensed dose twice daily for two weeks and then once daily as required is recommended for the treatment of atopic dogs. In some cases, the once-daily regimen is insufficient to control the clinical signs.

OBJECTIVES: To provide preliminary safety and efficacy data on the prolonged twice-daily administration of oclacitinib in atopic dogs.

ANIMALS: Fifty-three client-owned atopic dogs.

METHODS AND MATERIALS: The medical records of dogs with atopic dermatitis treated with oclacitinib twice daily for more than two weeks were reviewed retrospectively. Animal details, treatment dose and duration, concurrent diseases, adjunctive medications and possible adverse events were recorded. Treatment efficacy was assessed retrospectively and, when available, the selected blood parameters before and during the treatment were compared. Statistical analyses of the collected data were performed.

RESULTS: The median treatment duration was 113 days. Excellent-to-good efficacy was observed in 38 dogs (72%), including 24 of 33 dogs that failed to respond to the once-daily regimen. Eight dogs showed a poor response despite the addition of systemic glucocorticoids. Pyoderma, gastrointestinal signs and otitis externa were the most frequent adverse events recorded whilst on treatment. Blood tests performed in 35 dogs showed slightly decreased leucocyte, neutrophil, eosinophil and monocyte counts that remained within the reference ranges in most cases. Three dogs developed hypercholesterolemia.

CONCLUSIONS AND CLINICAL RELEVANCE: Prolonged twice-daily administration of oclacitinib generally was well-tolerated and was effective in most of the treated dogs. Regular clinical evaluation and blood tests are advisable for this treatment regimen.

PMID:35014745 | DOI:10.1111/vde.13053

Categories
Nevin Manimala Statistics

Scalable algorithms for semiparametric accelerated failure time models in high dimensions

Stat Med. 2022 Jan 11. doi: 10.1002/sim.9264. Online ahead of print.

ABSTRACT

Semiparametric accelerated failure time (AFT) models are a useful alternative to Cox proportional hazards models, especially when the assumption of constant hazard ratios is untenable. However, rank-based criteria for fitting AFT models are often nondifferentiable, which poses a computational challenge in high-dimensional settings. In this article, we propose a new alternating direction method of multipliers algorithm for fitting semiparametric AFT models by minimizing a penalized rank-based loss function. Our algorithm scales well in both the number of subjects and number of predictors, and can easily accommodate a wide range of popular penalties. To improve the selection of tuning parameters, we propose a new criterion which avoids some common problems in cross-validation with censored responses. Through extensive simulation studies, we show that our algorithm and software is much faster than existing methods (which can only be applied to special cases), and we show that estimators which minimize a penalized rank-based criterion often outperform alternative estimators which minimize penalized weighted least squares criteria. Application to nine cancer datasets further demonstrates that rank-based estimators of semiparametric AFT models are competitive with estimators assuming proportional hazards in high-dimensional settings, whereas weighted least squares estimators are often not. A software package implementing the algorithm, along with a set of auxiliary functions, is available for download at github.com/ajmolstad/penAFT.

PMID:35014701 | DOI:10.1002/sim.9264

Categories
Nevin Manimala Statistics

Does secondhand smoke exposure increase the risk of acute respiratory infections among children aged 0-59 months in households that use clean cooking fuel? A cross-sectional study based on 601 509 households in India

Indoor Air. 2022 Jan 11. doi: 10.1111/ina.12980. Online ahead of print.

ABSTRACT

This study examines whether exposure to secondhand smoke (SHS) increases the risk of acute respiratory infections (ARI) among children aged 0-59 months. Study utilized nationally representative data from National Family Health Survey (2015-2016), which adopted two-stage stratified random sampling. Four mutually exclusive groups based on the type of cooking fuel usage and SHS exposure were created. Descriptive statistics and multivariate logistics regression analysis were applied. At the national level, 10.5% prevalence of ARI was reported during 2015-2016. About 47.9% (95%CI 47.7-48.2) of households was exposed to SHS and used solid biomass fuel for cooking. Nearly, 20.7% of households with clean fuel usage was exposed to SHS. Regression analysis suggests that the likelihood of ARI among children who were living in households with solid biomass fuel usage and exposed to SHS was 11% (95%CI 1.06-1.17) greater than children living in households with clean fuel usage with no SHS exposure. Moreover, our results further revealed that the odds of ARI among children living in households with clean fuel but exposed to SHS were 19% (95%CI 1.13-1.25) higher than the children living in the household with no SHS exposure and clean fuel use. Children living in households exposed to SHS are at higher risk of ARI.

PMID:35014716 | DOI:10.1111/ina.12980

Categories
Nevin Manimala Statistics

Hindi Translation and Validation of Childhood Asthma Control Test (C-ACT)

Indian Pediatr. 2022 Jan 9:S097475591600400. Online ahead of print.

ABSTRACT

OBJECTIVE: Hindi translation and validation of the Childhood Asthma Control Test (C-ACT).

METHODS: Children from 5-11 years with newly diagnosed asthma were enrolled and followed every 4-weeks for 12 weeks. Asthma control was assessed with C-ACT and Global Initiative for Asthma (GINA) criteria.

RESULTS: A total of 60 children (34 boys, 56%) were enrolled. C-ACT showed a statistically significant correlation with GINA criteria at all visits. Cronbach’s alpha to assess the internal consistency was 0.74, and the intraclass correlation coefficient to measure test-retest reliability was 0.83. The maximum area under the curve (AUC) for C-ACT was 0.95 (95% CI: 0.89-1.0; P<0.001). At a cutoff score of ≥ 20, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of C-ACT were 97.9%, 25%, 88.7%, and 87.5%, respectively.

CONCLUSIONS: Hindi version of the C-ACT score is valid, reliable, and correlates well with the GINA criteria for asthma control in children. It has a high sensitivity at a cutoff score of ≥20, but the specificity was poor in differentiating asthma control.

PMID:35014617

Categories
Nevin Manimala Statistics

Three-Dimensional Melt-Electrowritten Polycaprolactone/Chitosan Scaffolds Enhance Mesenchymal Stem Cell Behavior

ACS Appl Bio Mater. 2021 Feb 15;4(2):1319-1329. doi: 10.1021/acsabm.0c01213. Epub 2021 Jan 13.

ABSTRACT

Melt electrowriting (MEW) is an emerging technique that precisely fabricates microfibrous scaffolds, ideal for tissue engineering, where biomimetic microarchitectural detail is required. Polycaprolactone (PCL), a synthetic polymer, was selected as the scaffold material due to its biocompatibility, biodegradability, mechanical strength, and melt processability. To increase PCL bioactivity, a natural polymer, chitosan, was added to construct MEW fibrous composite scaffolds. To date, this is the first study of its kind detailing the effects of stem cell behavior on PCL containing chitosan MEW scaffolds. The aim of this study was to melt electrowrite a range of PCL/chitosan tissue-engineered constructs (TECs) and assess their suitability to promote the growth of human bone-marrow-derived mesenchymal stem cells (hBMSCs). In vitro physical and biological characterizations of melt-electrowritten TECs were performed. Physical characterization showed that reproducible, layered micron-range scaffolds could be successfully fabricated. As well, cell migration and proliferation were assessed via an assay to monitor cell infiltration throughout the three-dimensional (3D) melt-electrowritten scaffold structure. A statistically significant increase (∼140%) in hBMSC proliferation in 1 wt % chitosan PCL blends in comparison to PCL-only scaffolds was found when monitored over two weeks. Overall, our study demonstrates the fabrication of melt-electrowritten PCL/chitosan composite scaffolds with controlled microarchitecture and their potential use for regenerative, tissue engineering applications.

PMID:35014483 | DOI:10.1021/acsabm.0c01213

Categories
Nevin Manimala Statistics

The Awareness and Empowerment Aspects of the Needlesticks and Other Sharps Injuries and Reporting in Nursing Education: A Cross-Sectional Survey

Workplace Health Saf. 2022 Jan 11:21650799211049810. doi: 10.1177/21650799211049810. Online ahead of print.

ABSTRACT

BACKGROUND: Occurrence and underreporting of needlesticks and other sharps injuries (NSIs) are still immediate concerns among nursing students. This study examined the relationship between occupational health and safety (OHS) awareness and empowerment levels of nursing students and the occurrence and reporting of NSIs.

METHODS: This cross-sectional study was conducted among purposively selected 840 students in a nursing school in 2018-2019. A self-report questionnaire was used to collect data about students’ sociodemographic characteristics, OHS awareness and empowerment levels, and NSIs characteristics. After bivariate analyses, multivariate logistic regression was used.

RESULTS: The number of evaluated questionnaires was 469, for a response rate of 55.8%. Participants, 21.2% (n = 99), had suffered NSIs, and 47.8% had reported their injuries. The NSIs were statistically related to age, academic year, working night shift, OHS awareness level of students, and the number of clinical placements completed by students. The odds of experiencing NSIs was 2.3 (95% confidence interval [CI] = [1.0, 5.3]) times higher in male students, 4.3 (95% CI = [2.4, 7.4]) times higher in those beyond the second academic year, and 2.5 (95% CI = [1.4, 4.4]) times higher in those who had received OHS training for a shorter period than the average duration.

CONCLUSION/APPLICATION TO PRACTICE: The levels of awareness and empowerment were higher in students who received OHS and NSIs prevention training and those who received OHS training for the above-average duration. Increasing awareness and empowerment levels of nursing students through training can reduce the occurrence and the underreporting of NSIs.

PMID:35014570 | DOI:10.1177/21650799211049810

Categories
Nevin Manimala Statistics

Tunable Crosslinking, Reversible Phase Transition, and 3D Printing of Hyaluronic Acid Hydrogels via Dynamic Coordination of Innate Carboxyl Groups and Metallic Ions

ACS Appl Bio Mater. 2021 Mar 15;4(3):2408-2428. doi: 10.1021/acsabm.0c01300. Epub 2021 Feb 15.

ABSTRACT

This article reports tunable crosslinking, reversible phase transition, and three-dimensional printing (3DP) of hyaluronic acid (HyA) hydrogels via dynamic coordination of Fe3+ ions with their innate carboxyl groups for the first time. The concentrations of Fe3+ and H+ ions and the reaction time determine the tunable ratios of mono-, bi-, and tridentate coordination, leading to the low-to-high crosslinking densities and reversible solid-liquid phase transition of HyA hydrogels. At the monodentate-dominant coordination, the liquid hydrogels have low crosslinking densities (HyA_L). At the mixed coordination of mono-, bi-, and tridentate bonding, the solid hydrogels have medium crosslinking densities (HyA_M). At the tridentate-dominant coordination, the solid hydrogels have high crosslinking densities (HyA_H). The reversible solid-liquid phase transitions among HyA_L, HyA_M, and HyA_H were achieved via controlling the concentrations of Fe3+ and H+ ions and reaction time. When the crosslinking densities are between HyA_L and HyA_M, the hydrogels become 3D printable (HyA_P). HyA_P hydrogels were 3D-printed successfully using cold-stage or direct writing methods, and the 3D constructs achieved better structural stability using the latter method. In the direct exposure culture with bone marrow-derived mesenchymal stem cells, the 3D-printed HyA_H (HyA_H_3D) and HyA_H hydrogels showed higher average cell adhesion densities than the HyA_M, HyA_P, and HyA_L hydrogel groups under both direct and indirect contact conditions. For all hydrogel groups, cell adhesion densities under direct contact conditions were statistically lower than the same groups under indirect contact conditions. In this article, we elucidated the mechanisms of dynamic coordination and the relationships among the key parameters in controlling the tunable crosslinking, reversible phase transition, and 3DP of HyA hydrogels without blending with other polymers or adding functional groups. This approach can be potentially adapted to crosslink and 3D print other polymeric hydrogels with carboxyl groups, which is promising for a wide range of applications.

PMID:35014361 | DOI:10.1021/acsabm.0c01300

Categories
Nevin Manimala Statistics

Amphiphilic Graft Copolymers Capable of Mixed-Mode Interaction as Alternative Nonviral Transfection Agents

ACS Appl Bio Mater. 2021 Feb 15;4(2):1268-1282. doi: 10.1021/acsabm.0c01123. Epub 2021 Jan 12.

ABSTRACT

Nonviral gene delivery vectors are attractive candidates compared to viral ones due to their lower cytotoxicity and immunogenicity. However, their efficacy still requires improvement. Major challenges are the effective complexation and protection of the DNA cargo and the intracellular dissociation of the polyplexes at the site of action. It is commonly accepted that polymer architecture and chemistry influence polyplex characteristics and have an impact on the transfection mechanism. We developed a library of biocompatible copolymers based on methoxy poly(ethylene glycol) and a hydrophobic block of poly(ε-caprolactone-co-propargyl carbonate) grafted with a predetermined number of poly(2-(dimethylamino)ethyl methacrylate) segments. Such copolymers could efficiently deliver their cargo even in the presence of serum proteins and to various “difficult to transfect” cells, thereby outperforming the current gold standard 25 kDa linear poly(ethylenimine). Statistical correlation analysis shows that an optimization of the transfection in the case of copolymers combining several interactive functions benefits from treatment as a multiparameter problem.

PMID:35014479 | DOI:10.1021/acsabm.0c01123