An Emerging Strategy for Neuroinflammation Treatment: Combined Cannabidiol and Angiotensin Receptor Blockers Treatments Effectively Inhibit Glial Nitric Oxide Release.

Cannabidiol (CBD), the major non-psychoactive phytocannabinoid found in cannabis, has anti-neuroinflammatory properties. Despite the increasing use of CBD, little is known about its effect in combination with other substances. Combination therapy has been gaining attention recently, aiming to produce more efficient effects. Angiotensin II activates the angiotensin 1 receptor and regulates neuroinflammation and cognition. Angiotensin receptor 1 blockers (ARBs) were shown to be neuroprotective and prevent cognitive decline. The present study aimed to elucidate the combined role of CBD and ARBs in the modulation of lipopolysaccharide (LPS)-induced glial inflammation. While LPS significantly enhanced nitric oxide synthesis vs. the control, telmisartan and CBD, when administered alone, attenuated this effect by 60% and 36%, respectively. Exposure of LPS-stimulated cells to both compounds resulted in the 95% inhibition of glial nitric oxide release (additive effect). A synergistic inhibitory effect on nitric oxide release was observed when cells were co-treated with losartan (5 µM) and CBD (5 µM) (by 80%) compared to exposure to each compound alone (by 22% and 26%, respectively). Telmisartan and CBD given alone increased TNFα levels by 60% and 40%, respectively. CBD and telmisartan, when given together, attenuated the LPS-induced increase in TNFα levels without statistical significance. LPS-induced IL-17 release was attenuated by CBD with or without telmisartan (by 75%) or telmisartan alone (by 60%). LPS-induced Interferon-γ release was attenuated by 80% when telmisartan was administered in the absence or presence of CBD. Anti-inflammatory effects were recorded when CBD was combined with the known anti-inflammatory agent dimethyl fumarate (DMF)/monomethyl fumarate (MMF). A synergistic inhibitory effect of CBD and MMF on glial release of nitric oxide (by 77%) was observed compared to cells exposed to MMF (by 35%) or CBD (by 12%) alone. Overall, this study highlights the potential of new combinations of CBD (5 µM) with losartan (5 µM) or MMF (1 µM) to synergistically attenuate glial NO synthesis. Additive effects on NO production were observed when telmisartan (5 µM) and CBD (5 µM) were administered together to glial cells.

Triptans utilization in Italian population: A real-life study in community pharmacies.

The term Headache Disorders (HD) refers to a number of nervous system pathologies characterised by recurrent headaches. Despite the serious impact HD have on the health system, society, and the economy, these are an underestimated, underdiagnosed, and, hence, undertreated phenomenon. Triptans are the first-line therapy for the acute treatment of moderate to severe migraine but their utilization is still inadequate, perhaps also because in Italy no triptan can be bought without a medical prescription. In this article, the data from a 2016-2017 study has been further analysed with the aim of evaluating any associations between the use of triptans and the other series of variables identified in the questionnaire. This further analysis has been connected to the role that community pharmacies could play on this issue. The questionnaire was administered to 4,424 pharmacy users by 610 purposely trained pharmacists working in 514 pharmacies. The survey was carried out in 19 of the 20 Italian regions. The data shows that only 25% of patients suffering from HDs are prescribed triptans. Older patients, those with definite migraines, and those with a chronic disorder resort more frequently to this class of pharmaceuticals, as do those patients in care at a specialist headache centre. The multivariable analysis also confirmed these results. Our study, which performed a direct detection, in real life, on patients requesting pharmacological treatment for a migraine headache, therefore confirmed the need to investigate the reasons behind the low use and prescription of triptans in the Italian population. Moreover, any future studies should take advantage of community pharmacies, plan actions that would allow a series of evaluations over time of the requirements of migraineurs, and establish a process to put these patients under the care of the pharmacy to ensure adherence to therapy.

Patient Care in Community Pharmacies during the COVID-19 (SARS-CoV-2) Pandemic: Effectiveness of Post-Graduate Education and Further Training Courses on Revenues.

Thanks to their distribution throughout the territory and extended opening hours, community pharmacists are among the healthcare specialists most easily accessible to the public and often represent the first point of consultation both for the treatment of acute health conditions and, more generally, for health and therapy advice. The objective of the present study was to evaluate whether post-graduate courses/further training courses for pharmacists might influence the quality of patient management and care and, consequently, the satisfaction of the users who entered the pharmacy. We used the revenues of the pharmacies (Group A) in which these pharmacists are employed as a performance indicator. We compared the data for this group with the national averages for Italian pharmacies (Group B) and with those of a group (Group C) of selected pharmacies as similar as possible to the pharmacies in Group A based on a number of well-defined parameters. The comparison of revenues, year-on-year changes, and the average number of sales by the pharmacies in the three groups indicates that the pharmacies in Group A had the best performance, not only when compared with the national average but especially compared with the control group, specifically selected to make the comparison as significant as possible.

Community pharmacists as vaccinators in the Italian SARS-CoV-2 immunization campaign: implications beyond the pandemic.

Italy was one of the last European countries to introduce vaccination in pharmacies. The urgent need to extend the vaccination campaign against SARS-CoV-2 led to the approval of Law no. 178/2020. The Law allowed the administration of COVID-19 vaccines in Italian pharmacies by community pharmacists on an experimental basis for the years 2021-2022. Stakeholders took contrasting positions on the idea of enabling pharmacist to vaccinate after proper training. Sometimes, controversy existed even within the same associations representing pharmacists. As observed in other countries, the medical profession in Italy also expressed its opposition to the idea of pharmacists as vaccinators, while the general public and pharmacy customers were generally in favour of the policy. Over two million doses of SARS-CoV-vaccines were administered in Italian pharmacies in less than one year after the introduction of the policy. Criticism and concerns raised during the debate about the introduction of vaccination in pharmacies has subsided. It is yet unclear whether vaccination in pharmacies will be prolonged after the pandemic and whether it will, in fact, be expanded to other vaccines. Potentially, this could contribute towards increasing immunisation rates, not only for COVID-19, but also for other vaccines.

Cannabis-Based Oral Emulsion for Medical Purposes to Meet the Needs of Patients: Formulation, Quality and Stability.

Current Italian legislation provides that medical Cannabis can be administered orally as an extract if it has been titrated to determine the concentration of active molecules. In this context, there is a need to provide known and adequate quantities of active ingredients in order to guarantee uniform therapies that lead to the optimization of risks/benefits. This is fundamental considering that the limited availability on the market of registered Cannabis-based products for medical use means that prescribed therapies are usually prepared as galenic preparations. Consequently, the preparation procedures must be consistent with the instrumentation usually present in the laboratories of community pharmacies. In this context, the purpose of this work was to standardize the preparation procedure for oil-in-water (O/W) emulsions to exploit advantages in terms of ease of administration and dosage adjustment, but also to ensure the palatable organoleptic characteristics of the finished product. For the formulations being studied, in addition to the quality according to the directives set out in the European Pharmacopoeia, the stability was evaluated to assure adequate validity for therapeutic uses.

Oncological patient management on the territory: the results of a survey in the north-west of Italy.

Objective: To investigate the role of community pharmacists in the therapeutic process of oncological patients and to assess these patients' state of acceptance of their disease and their relationship with their therapies, we performed a survey in some oncological clinics in Turin (north-west of Italy). Methods: The survey was carried out in a three months' period by means of a questionnaire. The questionnaire was administered on paper to oncological patients that attended 5 oncological clinics in Turin. The questionnaire was self-administered. Results: 266 patients filled out the questionnaire. More than half of patients reported that their cancer diagnosis interfered with normal life very much or extremely and almost 70% of patients reported that they were accepting of what happened and were trying to fight back. 65% of patients answered that it is important or very important that pharmacists are aware of their health status. About 3 out of 4 patients thought that pharmacists giving information on medicines purchased and on how to use them is important or very important and that it is important to receive information concerning health and the effects of medication taken. Conclusion: Our study underlines the role of territorial health units in the management of oncological patients. It can be said that the community pharmacy is certainly a channel of election, not only in cancer prevention but also in the management of those patients who have already been diagnosed with cancer. More comprehensive and specific pharmacist training is necessary for the management of this type of patient. Furthermore, it is necessary to improve the awareness of this issue in community pharmacists at the local and national levels by creating a network of qualified pharmacies developed in collaboration with oncologists, GPs, dermatologists, psychologists and cosmetics companies.

Developing Actively Targeted Nanoparticles to Fight Cancer: Focus on Italian Research.

Active targeting is a valuable and promising approach with which to enhance the therapeutic efficacy of nanodelivery systems, and the development of tumor-targeted nanoparticles has therefore attracted much research attention. In this field, the research carried out in Italian Pharmaceutical Technology academic groups has been focused on the development of actively targeted nanosystems using a multidisciplinary approach. To highlight these efforts, this review reports a thorough description of the last 10 years of Italian research results on the development of actively targeted nanoparticles to direct drugs towards different receptors that are overexpressed on cancer cells or in the tumor microenvironment. In particular, the review discusses polymeric nanocarriers, liposomes, lipoplexes, niosomes, solid lipid nanoparticles, squalene nanoassemblies and nanobubbles. For each nanocarrier, the main ligands, conjugation strategies and target receptors are described. The literature indicates that polymeric nanoparticles and liposomes stand out as key tools for improving specific drug delivery to the site of action. In addition, solid lipid nanoparticles, squalene nanoparticles and nanobubbles have also been successfully proposed. Taken together, these strategies all offer many platforms for the design of nanocarriers that are suitable for future clinical translation.

Monitoring adherence to pharmacological therapy and follow-up examinations among patients with type 2 diabetes in community pharmacies. Results from an experience in Italy.

INTRODUCTION: Type 2 diabetes is an important public health issue, yet adherence to drugs and regular clinical follow-up is still suboptimal. This study aims to evaluate a community pharmacy programme for monitoring and enhancing adherence to prescribed pharmacological therapies and recommended examinations among patients with confirmed diabetes. METHODS: The intervention was conducted in different Italian areas between April 2017 and January 2018. All adult patients who entered a pharmacy with a personal prescription for any antidiabetic drug and agreed to participate, were interviewed. Those found to be non-adherent received counselling from the pharmacists. All patients were invited for a follow-up interview after 3 months. RESULTS: Overall, 930 patients were enrolled and completed the baseline interview. We found low rates of non-adherence, ranging from 8% to 13% for prescribed pharmacological therapies, and 11-29% for the recommended clinical examinations. Non-adherence to oral therapies was higher among younger and recently diagnosed patients; that to clinical examinations was higher in men, those with an intermediate duration of diabetes and less educated patients. Large geographical differences persisted after the adjustment for individual factors. Only 306 patients (32.9%) returned for the follow-up interview, most of whom were already adherent at baseline. CONCLUSIONS: Poor adherence to drugs or clinical examinations is not easy to identify in the usual operating setting of community pharmacies. Furthermore, the majority of patients did not return for follow-up, making it impossible to evaluate the efficacy of the pharmacists' counselling. It might be more effective to plan interventions addressed to specific subgroups of patients or areas.

The Relationship between Customers and Community Pharmacies during the COVID-19 (SARS-CoV-2) Pandemic: A Survey from Italy.

Community pharmacies are among the most easily accessible health services. Considering the major impact of COVID-19 in social terms, the purpose was to analyse the evolution of the relationship between community pharmacies and customers during the pandemic in 2020 and to understand which strategies should be implemented in the future. The data have been collected from May to December 2020. Pharmacists administered a questionnaire, also available online, to all customers that agreed to participate. The total number of respondents was 502. The results obtained confirm a generally high level of satisfaction with pharmacies among customers and appreciation for the role of community pharmacies. For the future, the priority is to monitor the situation to break down social inequalities. A task that can be entrusted to the branch of the healthcare service ideally suited to this end: local medicine, of which the community pharmacy is an essential element. The post-pandemic pharmacy will need to have the skills to provide accurate and reliable information on issues, including broad topics such as prevention and lifestyle to fight "syndemic" (two or more factors that work together to make a disease worse) and "infodemic" (too much information including false or misleading information during a disease outbreak).

[The concrete contribution of the local pharmacy to improving adherence to therapies.] / Il contributo della farmacia territoriale al miglioramento dell'aderenza alle terapie.

The deontological duties of the pharmacist recommend advising customers on the correct use of medicines. In addition, they recommend giving the citizen up-to-date and complete information on drugs, understandable to the customer. These are the prerequisites for improving the effectiveness of doctor's prescriptions and counteract the inappropriate use of medicines. Recent scientific literature confirms the effectiveness of the pharmacist's interventions based on counseling for patients with chronic diseases. The article provides an account of some of the projects and studies on the role of the so-called "farmacia dei servizi" carried out in Italy in recent years.

Cannabis-Based Oral Formulations for Medical Purposes: Preparation, Quality and Stability.

Current legislation in Italy provides that medical Cannabis may be administered orally or by inhalation. One of the fundamental criteria for the administration of oral formulations is that they deliver a known consistent quantity of the active ingredients to ensure uniform therapies leading to the optimisation of the risks/benefits. In 2018, our group developed an improved Cannabis oil extraction technique. The objective of the present work was to carry out a stability study for the oil extracts obtained by this method. Furthermore, in order to facilitate the consumption of the prescribed medical Cannabis therapy by patients, a standard procedure was defined for the preparation of a single-dose preparation for oral use (hard capsules) containing the oil extract; thereafter, the quality and stability were evaluated. The hard capsules loaded with the oil extract were analysed and found to be uniform in content. The encapsulation process did not alter the quantity of the active molecule present in the oil. The stability tests yielded excellent results. Since the capsule dosage form is easily transported and administered, has pleasant organoleptic properties and is stable at room temperature for extended periods of time, this would facilitate the adherence to therapy by patients in treatment.

Community Pharmacy Practice in Italy during the COVID-19 (SARS-CoV-2) Pandemic: Regulatory Changes and a Cross-Sectional Analysis of Seroprevalence.

Pharmacists in the community and the essential requirement to safeguard their own health have become fundamental since the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aims of this paper were (I) to analyze the directives provided to pharmacists in 2020 regarding preventative safety measures to be adopted; (II) to determine the number of pharmacists who came into contact with SARS-CoV-2 in North-West Italy and relate this to the adopted preventative measures. The first aim was pursued by conducting a bibliographic research, consulting the principal regulatory sources. The second one was achieved with an observational study by administering a questionnaire and performing a serological test. The various protection measures imposed by national and regional legislation were analyzed. Two hundred and eighty-six pharmacists (about 8% of the invited ones) responded to the survey. Ten pharmacists reported a positive result to the serological test. Of the subjects who presented a positive result, three declared that they had not used a hand sanitizer, while two stated that they had not scheduled the cleaning and decontamination of surfaces. Two interviewees had not set up a system of quota restrictions on admissions. In four cases, a certified cleaning company had decontaminated the premises. The results of our study show that during the coronavirus disease 2019 (COVID-19) pandemic, the most pressing challenge for community pharmacists has been the protection of staff and clients inside the pharmacy; the challenge to be faced in the near future will probably be the management of new responsibilities.

Knowledge on arterial hypertension in general population: Results from a community pharmacy screening program.

BACKGROUNDS AND AIMS: Hypertension is a risk factor for renal, cardiovascular and cerebrovascular diseases. It is responsible for a large proportion of overall morbidity and mortality every year. Hypertension-mediated organ damage is largely not reversible. For these reasons, prevention has primary importance: sensibilization of population on hypertension-related consequences is essential for therapeutic adherence and reduction of unhealthy lifestyle behaviour. This study aimed to evaluate awareness about hypertension among community pharmacies customers. METHODS AND RESULTS: A questionnaire about hypertension was collected by 2731 customers from 94 community pharmacies in North West Italy, during a hypertension screening program. Hypertension awareness was unsatisfactory in a large proportion of the sample, with only 15% of subjects having an overall good level of knowledge. Furthermore, lower awareness was associated to higher blood pressure values (132/79 ± 19/11 mmHg vs 128/78 ± 18/10 mmHg, p < 0.001) and subjects resulted hypertensive or uncontrolled despite antihypertensive therapy, presented worse questionnaire scores (4.7 ± 1.9 vs 4.9 ± 2.0, p = 0.03). CONCLUSION: Knowledge about hypertension is largely unsatisfactory among population. Community pharmacies may play as a setting for health education and hypertension screening.

Adherence to oral chemotherapy: Evidence from a randomised clinical trial.

OBJECTIVE: To evaluate the efficacy of a reinforcement message (RM) administered by a hospital pharmacist on adherence, through a randomised study involving patients undergoing oral chemotherapy from which an objective outcome measure and patients' subjective opinions were collected. A secondary aim was to detect which psychological or clinical factors influence adherence. METHODS: Forty patients were enrolled and randomised to an experimental group (EG) or a control group (CG). The EG received a 10-minute RM provided by a hospital pharmacist with a doctor and a nurse. The CG received the standard of care. To measure adherence, plasma drug concentration and subjective evaluation were taken during the visits, in addition to a psychological assessment (coping strategies, psychological distress and personality traits). RESULTS: The EG reported higher drug levels and a statistically significant higher mean score on the subjective evaluation. A linear regression model highlighted statistically significant differences in the plasma drug concentration, after considering toxicity and dose reduction and controlling for the Reward Dependence Scale of the Temperament and Character Inventory between the EG and the CG. CONCLUSION: Adequate information and education on the therapy, using an RM strategy provided by a hospital pharmacist, seems to positively influence adherence to the treatment.

The 2017 deregulation of pharmacies in Italy: Introducing non-pharmacist ownership.

Italy is the last European country to adopt policies on the liberalization of pharmacy ownership. In August 2017, the Italian government approved the law n. 124 (annual market and competition law), despite the opposition of some stakeholders. This law extended the ownership of pharmacies to non-pharmacist business partners. Law n. 124 is an important turning point for pharmacists in Italy and could lead to a general reorganization of the Italian pharmaceutical system. As has already happened in several European countries, the removal of barriers to pharmacy ownership incentivizes finance companies and pharmaceutical wholesalers to make significant investments in this sector, leading to the emergence of commercial pharmacy chains. The future of community pharmacies is uncertain and is closely linked to the fate of the current government. However, progressive polarization between independent pharmacies and pharmacies that are part of chains can already be observed.

Opportunistic screening for type 2 diabetes in community pharmacies. Results from a region-wide experience in Italy.

BACKGROUND AND AIMS: Given the paucity of symptoms in the early stages of type 2 diabetes, its diagnosis is often made when complications have already arisen. Although systematic population-based screening is not recommended, there is room to experience new strategies for improving early diagnosis of the disease in high risk subjects. We report the results of an opportunistic screening for diabetes, implemented in the setting of community pharmacies. METHODS AND RESULTS: To identify people at high risk to develop diabetes, pharmacists were trained to administer FINDRISC questionnaire to overweight, diabetes-free customers aged 45 or more. Each interviewee was followed for 365 days, searching in the administrative database whether he/she had a glycaemic or HbA1c test, or a diabetologists consultation, and to detect any new diagnosis of diabetes defined by either a prescription of any anti-hyperglycaemic drug, or the enrolment in the register of patients, or a hospital discharge with a diagnosis of diabetes. Out of 5977 interviewees, 53% were at risk of developing diabetes. An elevated FINDRISC score was associated with higher age, lower education, and living alone. Excluding the number of cases expected, based on the incidence rate of diabetes in the population, 51 new cases were identified, one every 117 interviews. FINDRISC score, being a male and living alone were significantly associated with the diagnosis. CONCLUSIONS: The implementation of a community pharmacy-based screening programme can contribute to reduce the burden of the disease, particularly focusing on people at higher risk, such as the elderly and the socially vulnerable.

Assessment of Non-Adherence to Oral Metformin and Atorvastatin Therapies: A Cross-Sectional Survey in Piedmont (Italy).

INTRODUCTION: It is not possible to recover from chronic diseases; however, a healthy lifestyle and correct adherence to therapy can avoid complications and co-morbidities. The aim of this study was the cross-sectional evaluation, by means of a questionnaire, of real-world data on the prevalence of non-adherence to metformin and atorvastatin oral therapies in a sample of patients that attend community pharmacies in the Piedmont Region. The secondary aim was to evaluate the presence of correlations between non-adherence and a number of variables detected by the questionnaire. MATERIALS AND METHODS: Data were gathered from face-to-face interviews in six community pharmacies in Piedmont. The questionnaire was divided into two sections: the first included the Morisky, Green and Levine Medication Adherence Questionnaire (MAQ) (to assess therapy adherence); the second included questions on gender, age, level of education and the pharmacy in which the questionnaire was administered. Comparisons between proportions and mean values were performed using the χ2 test. Modified Poisson regression with robust standard errors was used for multivariate analysis. The level of significance was fixed at 0.05, CI at 95%. RESULTS: The sample analysed was composed of 408 subjects (receiving either metformin or atorvastatin). According to MAQ, 62 patients were non-adherent (15% of the total cohort). Crude and multivariate analysis did not show any statistically significant correlation between gender, age, level of education and non-adherence. It emerged that there was a correlation between non-adherence and being a customer of two of the pharmacies involved [PR = 3.31 (p=0.028) and PR = 3.11 (p=0.027)]. CONCLUSIONS: Community pharmacies can be an appropriate setting to identify non-adherent patients. Therefore, healthcare professionals could realize an integrated and structured intervention to improve adherence. However, MAQ could underestimate the number of non-adherent patients. Further studies to test the association between non-adherence prevalence and being the customer of a specific pharmacy should be performed.