Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Comparing the effectiveness of capture and replay against automatic input generation for Android graphical user interface testing

Exploratory testing and fully automated testing tools represent two viable and cheap alternatives to traditional test‐case‐based approaches for graphical user interface (GUI) testing of Android apps. The former can be executed by capture and replay tools that directly translate execution scenarios registered by testers in test cases, without requiring preliminary test‐case design and advanced programming/testing skills. The latter tools are able to test Android GUIs without tester intervention. Even if these two strategies are widely employed, to the best of our knowledge, no empirical investigation has been performed to compare their performance and obtain useful insights for a project manager to establish an effective testing strategy. In this paper, we present two experiments we carried out to compare the effectiveness of exploratory testing approaches using a capture and replay tool (Robotium Recorder) against three freely available automatic testing tools (AndroidRipper, Sapienz, and Google Robo). The first experiment involved 20 computer engineering students who were asked to record testing executions, under strict temporal limits and no access to the source code. Results were slightly better than those of fully automated tools, but not in a conclusive way. In the second experiment, the same students were asked to improve the achieved testing coverage by exploiting the source code and the coverage obtained in the previous tests, without strict temporal constraints. The results of this second experiment showed that students outperformed the automated tools especially for long/complex execution scenarios. The obtained findings provide useful indications for deciding testing strategies that combine manual exploratory testing and automated testing

In-Situ Synthesis and Characterization of Chitosan/Hydroxyapatite Nanocomposite Coatings to Improve the Bioactive Properties of Ti6Al4V Substrates

Ti6Al4V alloy is still attracting great interest because of its application as an implant material for hard tissue repair. This research aims to produce and investigate in-situ chitosan/hydroxyapatite (CS/HA) nanocomposite coatings based on different amounts of HA (10, 50 and 60 wt.%) on alkali-treated Ti6Al4V substrate through the sol-gel process to enhance in vitro bioactivity. The influence of different contents of HA on the morphology, contact angle, roughness, adhesion strength, and in vitro bioactivity of the CS/HA coatings was studied. Results confirmed that, with increasing the HA content, the surface morphology of crack-free CS/HA coatings changed for nucleation modification and HA nanocrystals growth, and consequently, the surface roughness of the coatings increased. Furthermore, the bioactivity of the CS/HA nanocomposite coatings enhanced bone-like apatite layer formation on the material surface with increasing HA content. Moreover, CS/HA nanocomposite coatings were biocompatible and, in particular, CS/10 wt.% HA composition significantly promoted human mesenchymal stem cells (hMSCs) proliferation. In particular, these results demonstrate that the treatment strategy used during the bioprocess was able to improve in vitro properties enough to meet the clinical performance. Indeed, it is predicted that the dense and crack-free CS/HA nanocomposite coatings suggest good potential application as dental implants

Chitosan/PEGDA based scaffolds as bioinspired materials to control in vitro angiogenesis

In the current work, our purpose was based on the assessment of bioactive chitosan (CS)/Poly(ethylene glycol) diacrylate (PEGDA) based scaffolds ability to stimulate in vitro angiogenesis process. The bioactivation of the scaffolds was accomplished by using organic (BMP-2 peptide) and inorganic (hydroxyapatite nanoparticles) cues. In particular, the properties of the materials in terms of biological response promotion on human umbilical vein endothelial cells (HUVECs) were studied by using in vitro angiogenesis tests based on cell growth and proliferation. Furthermore, our interest was to examine the scaffolds capability to modulate two important steps involved in angiogenesis process: migration and tube formation of cells. Our data underlined that bioactive signals on CS/PEGDA scaffolds surface induce a desirable effect on angiogenic response concerning angiogenic marker expression (CD-31) and endothelial tissue formation (tube formation). Taken together, the results emphasized the concept that bioactive CS/PEGDA scaffolds may be novel implants for stimulating neovascularization of tissue-engineered constructs in regenerative medicine field.Peer ReviewedPostprint (author's final draft

Effect of inorganic and organic bioactive signals decoration on the biological performance of chitosan scaffolds for bone tissue engineering

The present work is focused on the design of a bioactive chitosan-based scaffold functionalized with organic and inorganic signals to provide the biochemical cues for promoting stem cell osteogenic commitment. The first approach is based on the use of a sequence of 20 amino acids corresponding to a 68–87 sequence in knuckle epitope of BMP-2 that was coupled covalently to the carboxyl group of chitosan scaffold. Meanwhile, the second approach is based on the biomimetic treatment, which allows the formation of hydroxyapatite nuclei on the scaffold surface. Both scaffolds bioactivated with organic and inorganic signals induce higher expression of an early marker of osteogenic differentiation (ALP) than the neat scaffolds after 3 days of cell culture. However, scaffolds decorated with BMP-mimicking peptide show higher values of ALP than the biomineralized one. Nevertheless, the biomineralized scaffolds showed better cellular behaviour than neat scaffolds, demonstrating the good effect of hydroxyapatite deposits on hMSC osteogenic differentiation. At long incubation time no significant difference among the biomineralized and BMP-activated scaffolds was observed. Furthermore, the highest level of Osteocalcin expression (OCN) was observed for scaffold with BMP2 mimic-peptide at day 21. The overall results showed that the presence of bioactive signals on the scaffold surface allows an osteoinductive effect on hMSC in a basal medium, making the modified chitosan scaffolds a promising candidate for bone tissue regeneration

ROS-Generating Hyaluronic Acid-Modified Zirconium Dioxide-Acetylacetonate Nanoparticles as a Theranostic Platform for the Treatment of Osteosarcoma

Materials that are able to produce free radicals have gained increasing attention for environmental and biomedical purposes. Free radicals, such as the superoxide anion (O2•−-), act as secondary messengers in many physiological pathways, such as cell survival. Therefore, the production of free radicals over physiological levels has been exploited in the treatment of different types of cancer, including osteosarcoma (OS). In most cases, the production of reactive oxygen species (ROS) by materials is light-induced and requires the use of chemical photosensitisers, making it difficult and expensive. Here, for the first time, we propose photoluminescent hybrid ZrO2-acetylacetonate nanoparticles (ZrO2-acac NPs) that are capable of generating O2•− without light activation as an adjuvant for the treatment of OS. To increase the uptake and ROS generation in cancer cells, we modify the surface of ZrO2-acac NPs with hyaluronic acid (HA), which recognizes and binds to the surface antigen CD44 overexpressed on OS cells. Since these nanoparticles emit in the visible range, their uptake into cancer cells can be followed by a label-free approach. Overall, we show that the generation of O2•− is toxic to OS cells and can be used as an adjuvant treatment to increase the efficacy of conventional drugs

Eumelanin‐Coated Aligned PLA Electrospun Microfibers to Guide SH‐SY5YCells Spreading, Alignment, And Maturation

Abstract During the development of the nervous system, neurons sense and respond to topographical and biochemical cues found in the brain's native environment. Such niche‐specific cues are pivotal for neural tissue formation and development and have been now widely exploited in neural tissue engineering to develop biologically‐inspired scaffolds able to trigger a desired neuronal behavior. In particular, anisotropic aligned fibers, recapitulating the design of extending axonal tracts or aligned fibers found in the extracellular environment, have emerged as ideal candidates to guide cell alignment and elongation along the substrate main axis as well as promote neuronal differentiation. Among natural polymers used for coatings, melanins, including eumelanin, have been shown to possess antioxidant, anti‐inflammatory, immunomodulatory, and photo‐protective properties. Here, aligned poly(lactic acid) (PLA) fibers are fabricated via electrospinning and then coated with eumelanin via spin coating. Eumelanin‐coated aligned PLA fibers are highly biocompatible and greatly influenced the adhesion, morphology, and spreading of SH‐SY5Y neuroblastoma cells. Furthermore, the eumelanin coating is crucial in promoting cell alignment at the cell‐material interface and SH‐SY5Y cell maturation towards a more mature neuronal phenotype