New drugs for type 2 diabetes mellitus: The challenge of the health care sustainability combined with a better patient care access

The increased prescribing and dispensing of new drugs for type 2 diabetes mellitus due to less stringent prescription regulations has led both to bringing therapies closer to the patient, as required by post-Covid-19 European policies, and to an unpredictable increase in health care spending. In particular, in Italy, with the introduction of the National Plan for Reconstruction and Resilience, an attempt has been made to give more prescriptive freedom to the General Practitioner (GP). Through the introduction of prescriptive notes, patients can directly go to the primary care physician for the prescription of chronic therapies, without going to the specialist doctor anymore. Note 100, introduced at the beginning of 2022, defines the prescription of specific categories of medicines which are indicated for the treatment of type 2 diabetes mellitus and which are directly prescribed by the GP. This study aimed to analyze the prescribing trend of these medicines, by comparing the first half of the year 2021, without Note 100, with the first half of the year 2022, afterwards the introduction of the new regulations. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Ras and Sars-Cov-2 Interaction: Short Review of the Latest Evidence

Coronavirus SARS-CoV-2 is responsible for the coronavirus disease (COVID-19) cause of the recent global pandemic, which is causing thousands of deaths worldwide and represents a health challenge with few precedents in human history. The angiotensin 2 conversion enzyme (ACE-2) has been identified as the receptor that facilitates access to SARSCoV-2 in cells;evidence shows that its concentration varies during the various stages of viral infection. Therapeutic agents modifying the renin-angiotensin system (RAS) may be able to modulate the concentration of ACE-2 and the various components of the system. In this article we examine the latest evidence on the association between the use of RAS modifying agents and coronavirus 2019 (COVID-19) disease caused by SARS-CoV-2. Our investigation and critical literature research does not suggest discontinuation of ACEIs/ARBs treatment in clinical practice as there is a lack of robust evidence. However, we recommend further well-structured epidemiological studies investigating this sensitive issue that may provide important new suggestions for implementing guidelines.Copyright © Vitiello A., Ferrara F., 2023.

Sustainability and evolution of health care regarding treatments concerning type 2 diabetes mellitus

Background: In Italy, prescriptions of new drugs for type 2 diabetes mellitus increased gradually. New regulatory regulations have facilitated the prescription of these drugs, with the aim of bring patients closer to therapies with difficult access. This European policy has been adopted in the wake of the Covid-19 pandemic. However, a gradual undesirable increase in health care spending related to the consumption of these medicines has been noted. In Italy in 2022, the introduction of Note 100 allowed more prescribing to general practitioners (GPs) in the field of type 2 diabetes. Methods: At Asl Napoli 3 Sud, a computer system recording all dispensations of these drugs was queried, and a Defined Dose Die (DDD) analysis was conducted. Results: The study showed dispensing data for the first half of 2021, when Note 100 was not in effect, compared with the first six months of 2022, following the introduction of the new regulations. The results show an increase in prescriptions for drugs belonging to the GLP-1 class (+74.01%) and SGLT2 (+25.93%). The dispensations of DPP4 inhibitors (+0.22) and the gold standard therapeutic metformin (–0.16%) turn out to be constant. Conclusion: European policies highlighted the need to implement healthcare strategies closer to citizens, but nevertheless the prescription of higher-cost drugs should be contained, according to the good principles of therapeutic appropriateness. Facilitation of access to care is necessary, but always ensuring the sustainability of our health care system. © 2023 Elsevier Masson SAS

SARS-CoV-2 caused a surge in antibiotic consumption causing a silent pandemic inside the pandemic. A retrospective analysis of Italian data in the first half of 2022.

BACKGROUND: The phenomenon of antibiotic resistance shows no sign of stopping, despite global policies to combat it that have been in place for several years. The risk of forms of pathogenic microorganisms that are increasingly resistant to common antibiotics has led health authorities around the world to pay greater attention to the phenomenon. The worrying situation, has led to further recommendations from the World Health Organization (WHO) and national recommendations in Italy through the new National Plan against Antibiotic Resistance 2022-2025 (PNCAR 2022-2025). AIM: This manuscript aims to raise the awareness of all health professionals to follow what is suggested by regulatory agencies and scientific societies. METHOD: We conducted a retrospective study of antibiotic pharmacoutilization in Italy, in the Campania region at the Azienda Sanitaria Locale (ASL) Napoli 3 Sud, on consumption in the first half of 2022 in a population of more than 1 million people. RESULT: The results indicate that consumption, based on defined daily doses (DDDs), is above the national average. Probably the COVID-19 pandemic has influenced this growth in prescriptions. CONCLUSIONS: Our study suggests an informed and appropriate use of antibiotics, so as to embark on a virtuous path in the fight against antibiotic resistance.

Association between microbiota and immune response to Sars-CoV-2 infection.

In recent times, the key role of the human microbiota in the body's response to infectious diseases has been increasingly demonstrated. The human microbiota is the set of symbiotic microorganisms which coexist with the human organism without harming it. However, diseases related to the microbiota occur and are being studied, and numerous publications suggest that altered microbiota composition is implicated in psychiatric diseases, chronic inflammatory diseases, and some viral infections. On the other hand, the role of the human microbiota in the host immune response to viral infections is not entirely clear. Metabolites or components produced by the microbiota are the main mediators of microbiota-host interactions that influence host immunity. It has been shown that in patients with COVID-19 and post-acute COVID-19 syndrome (PACS), the microbiota is significantly altered. In this brief review, we examine the associations between the role of the microbiota in response to COVID-19 infection in terms of molecular biology and clinical relevance. We finally discuss the mechanisms by which metabolites produced by the microbiota modulate host immune responses to SARS-CoV-2 infection.

The Role of Vitamin C in the Treatment of Sepsis

Severe viral or bacterial infections can lead to sepsis and multiorgan dysfunction, and these latter events can even cause death. Multiple lines of evidence in the literature associate vitamin C with antioxidant, anti-inflammatory, anticoagulant and immunomodulatory actions. All of these biological effects make vitamin C a potential treatment for the prevention and treatment of sepsis. In this article, we briefly summarize the data supporting the use of vitamin C as a treatment for sepsis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. SARS-CoV-2 is responsible for the current ongoing coronavirus disease 2019 (COVID-19) pandemic.

ACUTE Lymphoblastic Leukemia (ALL) and COVID-19 Infection. a Campus ALL Report

[Formula presented] Introduction. The recent spread of the COVID-19 infection has represented an important challenge in the management of acute lymphoblastic leukemia (ALL) patients. Aims and methods. To investigate the incidence, features, source of contagion and outcome of patients with ALL who developed a COVID-19 infection, a survey was conducted among 34 hematology centers throughout Italy within the Campus ALL network. The period covered by the survey spanned from February 2020 to April 2021 and included 756 adult ALL patients actively followed during this time period. Results. Sixty-three of the 756 ALL patients (8.3%) developed a COVID-19 infection, with an equal distribution among the various regions. The majority of cases (90.5%) was recorded during the second wave of the pandemic, between September 2020 and April 2021. The source of the infection was nosocomial in 26 cases (41.3%), familial in 23 (36.5%), unknown in 13 (20.6%) and work-related in 1 (1.6%). The infected patients were prevalently male (n=43, 68.2%) with a similar distribution among age groups: 21 patients aged 18-35 years, 17 35-50, 15 50-65 and 10 older than 65. Seventeen patients (27%) had a diagnosis of T-ALL, 28 (44.4%) of Ph- B-ALL and 18 (28.6%) of Ph+ ALL. Thirty-six (57.1%) of the infected patients had no concomitant comorbidities, whereas 27 (42.9%) had one or more comorbidities. The infection was documented at the onset of the disease in 4 patients (6.3%), during induction in 10 (15.9%), consolidation in 13 (20.6%), chemotherapy maintenance in 11 (17.5%), after allogenic transplant in 15 (23.8%), during maintenance with tyrosine kinase inhibitors (TKI) treatment or off-treatment in 8 (12.7%) and at relapse in 2 (3.2%). Of the infected patients, 9 were asymptomatic, 10 had only isolated fever, 36 had respiratory symptoms and 8 presented other symptoms, including - but not limited to - ageusia and anosmia. As a consequence, management of the infection was variable: 29 (46%) patients did not require hospitalization, 28 (44.4%) were hospitalized in a COVID ward and 13 of them required respiratory assistance;finally, 6 (9.5%) patients were transferred to an ICU. Importantly, in 54 patients (85.7%) there were no sequelae, in 1 patient a pulmonary fibrosis was documented and in 1 patient the delay in treatment led to a relapse of the disease, while 7 (11.1%) succumbed to the infection. Finally, in 6 cases (9.5%) the infection was still ongoing at the time of the survey, and at the last update (July 2021) it had resolved in all. Since a key aspect in the management of ALL is the adherence to the timing of treatment, we also investigated if COVID-19+ patients stopped treatment during the infection. Out of the 42 evaluable patients (patients who had undergone an allogeneic transplant or were off-treatment were excluded from this analysis), ALL treatment was suspended in 28 (66.6%). Importantly, while in Ph+ ALL only very few patients stopped treatment (3/12), in Ph- B-ALL the majority did interrupt it (18/22, p<0.001);likewise, also in T-ALL most patients suspended treatment (7/8). Conclusions. The incidence of SARS-CoV-2 infection in adult ALL patients in Italy over a 15 month period has been similar to that observed in the general population and has been recorded mostly during the second wave of the pandemic. The contagion was mainly nosocomial, suggesting that outward care should be pursued as much as possible in ALL. The infection was manageable, with 46% of patients not requiring any medical intervention and an overall death rate of 11%. Strikingly, in line with previous reports 1, it appears that Ph+ ALL patients were more manageable, with less treatment interruptions. These findings underline the advantage of the TKI-based induction/consolidation strategy without systemic chemotherapy in Ph+ ALL used in the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) protocols and further point to a possible protective role of TKIs in COVID-19-infected patients. 1. Foà R et al, Br J Haematol. 2020;190(1):e3-e5 Disclosures: Chiarett : Incyte: Consultancy;novartis: Consultancy;pfizer: Consultancy;amgen: Consultancy. Bonifacio: Bristol Myers Squibb: Honoraria;Pfizer: Honoraria;Novartis: Honoraria;Amgen: Honoraria. Marco: Jazz: Consultancy;Insight,: Consultancy;Janssen: Consultancy. Curti: Novartis: Membership on an entity's Board of Directors or advisory committees;Abbvie: Membership on an entity's Board of Directors or advisory committees;Pfizer: Membership on an entity's Board of Directors or advisory committees;Jazz Pharma: Membership on an entity's Board of Directors or advisory committees. Delia: Gilead: Consultancy;Amgen: Consultancy;abbvie: Consultancy;Jazz pharmaceuticals: Consultancy. Forghieri: Jannsen: Membership on an entity's Board of Directors or advisory committees;Novartis: Speakers Bureau;Jazz: Honoraria. Lussana: Amgen: Honoraria;Astellas Pharma: Honoraria;Pfizer: Honoraria;Incyte: Honoraria.

Gliptin evidence to fight SARS-CoV-2 infection

People with diabetes represent a population at greater risk of infection and complications from SARS-CoV-2. Diabetes represents one of the most important comorbidities related to the severity of viral infection causing an increased risk of serious complications such as severe acute respiratory syndrome and multiorgan dysfunction associated with a hyperinflammatory state. Glycaemic normalization in patients with diabetes must be managed in the best possible way even during SARS-CoV-2 infection to avoid serious complications. However, for some antidiabetic agents such as DPP-4 inhibitors (gliptins), there is evidence of efficacy against SARS-CoV-2 extrapancreatic glycaemic normalization. The objective of this article is to provide an overview of current evidence on the potential therapeutic benefits of gliptins to combat SARS-CoV-2 infection.

COVID-19 vaccines and decreased transmission of SARS-CoV-2.

A massive COVID-19 vaccination campaign is underway worldwide. Epidemiological data from studies indicate excellent efficacy and safety profile for COVID-19 vaccines. However, there are few data from studies on the effect of decreasing the probability of infection of vaccinated subjects compared to unvaccinated subjects. In this short communication, we describe some evidence on this important and current topic providing useful personal reflections.

Anti-diabetic therapy in covid-19

The COVID-19 virus is one of the most significant challenges of humanity and is causing thousands of deaths worldwide. Drugs active against the virus are being developed and tested, but it appears that lung lesions are the lethal ones that lead to the patient's death. The experimentation of new drugs has led to a few positive results, but an effective vaccine will soon become available, as the virus is further studied. People with chronic conditions, such as diabetes, are critically ill, and ongoing therapies can lead to management difficulties with many subsequent clinical complications in the pandemic period. Glycemic control and appropriate measures for a diabetic patient are key priorities, especially in patients that tested positive for COVID-19. This article describes the current evidence in the literature regarding the risks of the possible administration of antidiabetic drugs in the COVID-19 patient, as well as analyzing the blood glucose data and its homeostasis, which are fundamental data to combat a viral infection. © 2020 The Authors.

Potential pharmacological approach in the regulation of angiotensin-II conversion enzyme and dipeptidyl-peptidase 4 in diabetic COVID-19 patients

The global pandemic caused by coronavirus disease 2019 (COVID-19) has caused more than 1 million deaths worldwide. Some vaccines in clinical trials have reached stage 3. In the meantime, the understanding of biological and pathophysiological mechanisms of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection is still unclear, such as the role that angiotensin-II conversion enzyme (ACE-2) and dipeptidyl-peptidase 4 (DPP-IV) may play in patients with diabetes related to COVID-19. The individual with diabetes is a known COVID-19 risk patient. Probably, the pharmacological regulation of the angiotensin renin system and ACE-2 on the one hand, and of the incretin system and DPP-IV on the other hand, could represent a therapeutic route of fundamental importance to reduce the risk of SARS-CoV-2 infection or of severe complications caused by infection.

Scientific Hypothesis for Treatment of COVID-19's Lung Lesions by Adjusting ACE/ACE2 Imbalance.

In March 2019 began the global pandemic COVID-19 caused by the new Coronavirus SARS-CoV-2. The first cases of SARS-CoV-2 infection occurred in November-19 in Wuhan, China. The preventive measures taken did not prevent the rapid spread of the virus to all countries around the world. To date, there are about 2.54 million deaths, effective vaccines are in clinical trials. SARS-CoV-2 uses the ACE-2 protein as an intracellular gateway. ACE-2 is a key component of the Renin Angiotensin (RAS) system, a key regulator of cardiovascular function. Considering the key role of ACE-2 in COVID-19 infection, both as an entry receptor and as a protective role, especially for the respiratory tract, and considering the variations of ACE-2 and ACE during the stages of viral infection, it is clear the important role that the pharmacological regulation of RAS and ACE-2 can assume. This biological knowledge suggests different pharmacological approaches to treat COVID-19 by modulating RAS, ACE-2 and the ACE/ACE2 balance that we describe in this article.

Support oncologic patient care during covid 19: Experience with telemedicine

Background: After the first weeks in which all efforts were concentrated to prevent contagion and treat Covid-19 patients, it is now increasingly important to secure assistance to ordinary patients suspended from outpatient activity until today and still struggling with the quota policy and precautions required by 'phase 2'. As established by recent regional resolutions (cf. Tuscany, Veneto, Lombardy), telemedicine is 'the strategy' to meet and fulfill the needs. It permits remote assistance to particularly fragile, chronic patients with long term pathologies giving a rapid, practical and economical response through the use of common, free instruments, readily available and already known to patients. These instruments must be structured within a legislative and regulatory organic framework that permits: a) the integration in existing clinical welfare processes without requesting organizational variations;b) the use of existing IT systems already in use, without determining additional fragmentation of necessary data for the treatment of the patient, between archives and distinct clouds, owners and those not connected;c) personal data protection according to that required by GDPR both under a technological profile and an organizational one;d) the registration and the traceability of carried-out activity, both in the perspective of safety of the patient and in the administrative reports. Material and methods: From April 2020, our center started a telemedicine project in partnership with ALTEMS. The manual is available for downloading at www.dati-sanita.it . Through this project we were able to continue to assist oncologic patients in follow-up or in therapy with oral drugs. Results: Between 28th April 2020 and 5th June 2020 thirty patients were enrolled with the median age 59.6 years (range 42-85), 20 women and 10 men with residence throughout the whole province of Foggia. Fifteen of 30 patients used a mobile phone, fifteen pc. The average length of the visit was 17.5 minutes (range 10-30 minutes). A customer satisfaction survey was collected at the end of each visit: 100% of patients expressed maximum value of approval. Conclusions: A virtual surgery will never be able to substitute a clinical exam of the patient, although in certain circumstances like Covid-19 emergency, difficulty in reaching hospital or in situations that require frequent patient monitoring, technology certainly represents a valid arm in the healthcare setting.

Pharmacological approach for the reduction of inflammatory and prothrombotic hyperactive state in COVID-19 positive patients by acting on complement cascade.

The novel Coronavirus SARS-CoV-2 is the viral pathogen responsible for the ongoing global pandemic, COVID-19 (Coronavirus disease 2019). To date, the data recorded indicate 1.62 Mln deaths and 72.8 Mln people infected (WHO situation report Dec 2020). On December 27, the first anti-COVID-19 vaccinations started in Europe. There are no direct antivirals against SARS-CoV-2. Understanding the pathophysiological and inflammatory/immunological processes of SARS-CoV-2 infection is essential to identify new drug therapies. In the most severe COVID-19 cases, an unregulated immunological/inflammatory system results in organ injury that can be fatal to the host in some cases. Pharmacologic approaches to normalize the unregulated inflammatory/immunologic response is an important therapeutic solution. Evidence associates a non-regulation of the "complement system" as one of the causes of generalized inflammation causing multi-organ dysfunction. Serum levels of a complement cascade mediator, factor "C5a", have been found in high concentrations in the blood of COVID-19 patients with severe disease. In this article we discuss the correlation between complement system and COVID-19 infection and pharmacological solutions directed to regulate.