Small Molecules for the Treatment of Long-COVID-Related Vascular Damage and Abnormal Blood Clotting: A Patent-Based Appraisal.

People affected by COVID-19 are exposed to, among others, abnormal clotting and endothelial dysfunction, which may result in deep vein thrombosis, cerebrovascular disorders, and ischemic and non-ischemic heart diseases, to mention a few. Treatments for COVID-19 include antiplatelet (e.g., aspirin, clopidogrel) and anticoagulant agents, but their impact on morbidity and mortality has not been proven. In addition, due to viremia-associated interconnected prothrombotic and proinflammatory events, anti-inflammatory drugs have also been investigated for their ability to mitigate against immune dysregulation due to the cytokine storm. By retrieving patent literature published in the last two years, small molecules patented for long-COVID-related blood clotting and hematological complications are herein examined, along with supporting evidence from preclinical and clinical studies. An overview of the main features and therapeutic potentials of small molecules is provided for the thromboxane receptor antagonist ramatroban, the pan-caspase inhibitor emricasan, and the sodium-hydrogen antiporter 1 (NHE-1) inhibitor rimeporide, as well as natural polyphenolic compounds.

Where developmental toxicity meets explainable artificial intelligence: state-of-the-art and perspectives.

INTRODUCTION: The application of Artificial Intelligence (AI) to predictive toxicology is rapidly increasing, particularly aiming to develop non-testing methods that effectively address ethical concerns and reduce economic costs. In this context, Developmental Toxicity (Dev Tox) stands as a key human health endpoint, especially significant for safeguarding maternal and child well-being. AREAS COVERED: This review outlines the existing methods employed in Dev Tox predictions and underscores the benefits of utilizing New Approach Methodologies (NAMs), specifically focusing on eXplainable Artificial Intelligence (XAI), which proves highly efficient in constructing reliable and transparent models aligned with recommendations from international regulatory bodies. EXPERT OPINION: The limited availability of high-quality data and the absence of dependable Dev Tox methodologies render XAI an appealing avenue for systematically developing interpretable and transparent models, which hold immense potential for both scientific evaluations and regulatory decision-making.

Assessing the cost-effectiveness of waiting list reduction strategies for a breast radiology department: a real-life case study.

BACKGROUND: A timely diagnosis is essential for improving breast cancer patients' survival and designing targeted therapeutic plans. For this purpose, the screening timing, as well as the related waiting lists, are decisive. Nonetheless, even in economically advanced countries, breast cancer radiology centres fail in providing effective screening programs. Actually, a careful hospital governance should encourage waiting lists reduction programs, not only for improving patients care, but also for minimizing costs associated with the treatment of advanced cancers. Thus, in this work, we proposed a model to evaluate several scenarios for an optimal distribution of the resources invested in a Department of Breast Radiodiagnosis. MATERIALS AND METHODS: Particularly, we performed a cost-benefit analysis as a technology assessment method to estimate both costs and health effects of the screening program, to maximise both benefits related to the quality of care and resources employed by the Department of Breast Radiodiagnosis of Istituto Tumori "Giovanni Paolo II" of Bari in 2019. Specifically, we determined the Quality-Adjusted Life Year (QALY) for estimating health outcomes, in terms of usefulness of two hypothetical screening strategies with respect to the current one. While the first hypothetical strategy adds one team made up of a doctor, a technician and a nurse, along with an ultrasound and a mammograph, the second one adds two afternoon teams. RESULTS: This study showed that the most cost-effective incremental ratio could be achieved by reducing current waiting lists from 32 to 16 months. Finally, our analysis revealed that this strategy would also allow to include more people in the screening programs (60,000 patients in 3 years).

International good practices on central venous catheters' placement and daily management in adults and on educational interventions addressed to healthcare professionals or awake/outpatients. Results of a scoping review compared with the existent Italian good practices.

This scoping review aims to check the existing international literature related to the placement and management of central venous catheters (CVCs) in adults and compare them with the Good Practices published by the Italian Society of anesthesiology intensive care (hereafter "SIAARTI Good Practices") and the protocols written by the Italian Expert group on long-term central venous accesses (hereafter "GAVeCeLT Protocols") and verify the existence of experiences focused on the daily assessment of the implantation site and on educational interventions on awake patients or caregivers to enhance their empowerment. A systematic search approach has been applied. Our composite research question has been primarily defined by the PICO: only patients over 18 years of age with CVC for any clinical reason except for kidney replacement therapy; placement and management of CVCs with procedures recommended by the recent international guidelines/bundles and specific educational interventions are the interventions to be compared with standard CVC placement and management without any educational interventions. In total, two different types of outcomes have been taken into consideration: catheter-related complications rate (A) and patient/caregiver involvement (B). Eligible articles have been limited to Systematic Review OR Meta-analysis OR Guidelines in Human field, focusing on adults, English language only, from January 2015 to December 2020. Searched Medical Subject Headings (MeSHs) Terms were "venous" AND "catheters," and the correspondence with the designed PICO framework was then checked directly by the authors. A comprehensive search was conducted by two reviewers on 15 February 2021 in four databases, and 32 full-text articles were finally included and qualitatively assessed. The included articles appear to be in line with the indications provided by the available Italian Good Practices and explain the complexity of this procedure. The need to promote the use of bundles and checklists related to CVC placement and dressing procedures comes to light. These organizational technologies can be implemented following the creation of teams dedicated to venous access that are subjected to continuous training. As regards the impact of educational initiatives, implementing paths of health education and proper hospital discharge preparation for both healthcare workers and families increases safety for the patient with CVC.

Insulin treatment in patients with diabetes mellitus and heart failure in the era of new antidiabetic medications.

BACKGROUND: Coexistent heart failure (HF) and diabetes mellitus (DM) are associated with marked morbidity and mortality. Optimizing treatment strategies can reduce the number and severity of events. Insulin is frequently used in these patients, but its benefit/risk ratio is still not clear, particularly since new antidiabetic drugs that reduce major adverse cardiac events (MACEs) and renal failure have recently come into use. Our aim is to compare the clinical effects of insulin in a real-world setting of first-time users, with sodium-glucose cotransporter-2 inhibitor (SGLT-2i), glucagon-like peptide-1 receptor agonist (GLP-1RA) and the other antihyperglycemic agents (other-AHAs). METHODS: We used the administrative databases of two Italian regions, during the years 2010-2018. Outcomes in whole and propensity-matched cohorts were examined using Cox models. A meta-analysis was also conducted combining the data from both regions. RESULTS: We identified 34 376 individuals ≥50 years old with DM and HF; 42.0% were aged >80 years and 46.7% were women. SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin and particularly death from any cause (SGLT-2i, hazard ratio (95% CI) 0.29 (0.23 to 0.36); GLP-1RA, 0.482 (0.51 to 0.42)) and first hospitalization for HF (0.57 (0.40 to 0.81) and 0.67 (0.59 to 0.76)). CONCLUSIONS: In patients with DM and HF, SGLT-2i and GLP-1RA significantly reduced MACE compared with insulin, and particularly any cause of death and first hospitalization for HF. These groups of medications had high safety profiles compared with other-AHAs and particularly with insulin. The inadequate optimization of HF and DM cotreatment in the insulin cohort is noteworthy.

Impact Assessment of an Innovative Integrated Care Model for Older Complex Patients with Multimorbidity: The CareWell Project.

OBJECTIVES: To evaluate the impact in terms of use of health services, clinical outcomes, functional status, and patient's satisfaction of an integrated care program, the CareWell program, for complex patients with multimorbidity, supported by information and communication technology platforms in six European regions. DATA SOURCES: Primary data were used and the follow-up period ranged between 8 and 12 months. STUDY DESIGN: A quasi-experimental study, targeting chronic patients aged 65 or older, with 2 or more conditions - one of them necessarily being diabetes, congestive heart failure or congestive obstructive pulmonary disease. The intervention group received the integrated care program and the control group received usual care. Generalized mixed regression models were used. DATA COLLECTION: Data were obtained from individual interviews and electronic clinical records. PRINCIPAL FINDINGS: Overall, 856 patients were recruited (475 intervention and 381 control). In the intervention group, the number of visits to emergency rooms was significantly lower, and the number of visits to the general practitioners and primary care nurses was higher than in the control group. CONCLUSION: The CareWell program resulted in improvements in the use of health services, strengthening the role of PC as the cornerstone of care provision for complex patients with multimorbidity.

The effects of the introduction of a chronic care model-based program on utilization of healthcare resources: the results of the Puglia care program.

BACKGROUND: Ageing is continuously increasing the prevalence of patients with chronic conditions, putting pressure on the sustainability of Healthcare Systems. Chronic Care Models (CCM) have been used to address the needs of frail people in the continuum of care, testifying to an improvement in health outcomes and more efficient access to healthcare services. The impact of CCM deployment has already been experienced in a selected cohort of patients affected by specific chronic illnesses. We have investigated its effects in a heterogeneous frail cohort included in a regional CCM-based program. METHODS: a retrospective population-based cohort study was carried out involving a non-oncological cohort of adult subjects with chronic diseases included in the CCM-oriented program (Puglia Care). Individuals in usual care with comparable demographic and clinical characteristics were selected for matched pair analysis. Study cohorts were defined by using a record linkage analysis of administrative databases and electronic medical records, including data on the adult population in the 6 local area health authorities of Puglia in Italy (approximately 2 million people). The effects of Puglia Care on the utilizations of healthcare resources were evaluated both in a before-after and in a case-control analysis. RESULTS: There were 1074 subjects included in Puglia Care and 2126 matched controls. In before-after analysis of the Puglia Care cohort, 240 unplanned hospitalizations occurred in the pre-inclusion period, while 239 were registered during follow-up. The incidence of unplanned hospitalization was 10.3 per 100 person/year (95% CI, 9.1-11.7) during follow-up and 12.1 per 100 person/year (95% CI, 10.7-13.8) in the pre-inclusion period (IRR, 0.84; 95% CI, 0.80-0.99). During follow-up a significant reduction in costs related to unplanned hospitalizations (IRR, 0.92; 95% CI, 0.91-0.92) was registered, while costs related to drugs (IRR, 1.14; p < 0.01), out-patient specialist visits (IRR, 1.19; p < 0.01), and planned hospitalization (IRR 1.03; p < 0.01) increased significantly. These modifications can be related to the aging of the population and modifications to healthcare delivery; for this reason, a case-control analysis was performed. The results testify to a significantly lower number (IRR, 0.79; 95% CI, 0.68-0.91), length of hospital stay (IRR, 0.80; 95% CI, 0.76-0.84), and costs related to unplanned hospitalizations (IRR, 0.80; 95% CI, 0.80-0.80) during follow-up in the intervention group. However, there was a higher increase in costs of hospitalizations, drugs and out-patients specialist visits during follow-up in Puglia Care when compared with patients in usual care. CONCLUSION: In a population-based cohort, inclusion of chronic patients in a CCM-based program was significantly associated with a lower recourse to unplanned hospital admissions when compared with patients in usual care with comparable clinical and demographic characteristics.