Impact of the COVID-19 Pandemic on the Use of Antidepressants by Young Adults in the ASL TO4 Regione Piemonte (Italy).

The association between younger age and poorer mental health during the COVID-19 pandemic has been documented. Whether these changes were associated with a change in antidepressant (AD) use is not well understood. This study aimed to estimate the impact of the COVID-19 pandemic on AD use by young adults in the ASL TO4 Regione Piemonte (Italy). The impact of the pandemic on the weekly prevalence of AD users was assessed using interrupted time-series analysis with autoregressive integrated moving average models. A total of 1071 subjects (18-22 years with ≥1 AD dispensation) were included in the study. The observed prevalence was lower than the predicted value for several weeks after the introduction of the lockdown. However, it was consistently higher than the predicted values from week 134. The maximum difference between observed and predicted values (25 subjects per 10,000 young adults) was found at week 170. Changes in AD use were observed in both genders and were more pronounced for selective serotonin reuptake inhibitors. In conclusion, the impact of the COVID-19 pandemic on the mental health of young adults is likely to be significant in the coming years, which may place a future burden on pharmaceutical public health and community health.

Identification of Barriers for Active Disease Management and of Medication-Related Problems through Therapeutic Patient Education in Older Home-Care Patients.

Combining therapeutic patient education (TPE) with a medication review service could foster the adoption of appropriate lifestyles by patients and support care-providers in identifying strategies to improve the quality of prescribed care. This study aimed to identify barriers experienced by patients in managing their diseases and medication-related problems. This was a monocentric, case series, observational study involving home-care patients from the Local Health Authority ASL TO4. Patients were enrolled for a TPE intervention where drug therapies and patient habits were collected through narrative interviews. Medication review was performed to identify potentially inappropriate prescriptions (PIPs). Twenty patients (13 females) with a mean age of 74.7 years were enrolled. Patients had an average of 4.3 diseases and 80.0% of them were treated with ≥5 daily medications. The main PIPs involved ibuprofen, furosemide and pantoprazole. The qualitative analysis of the interviews identified seven macro-themes relating to different aspects of medication management: therapy; diseases; patient; patient journey; professionals; family and caregivers; drug information. The results of this study revealed some critical aspects related to the treatment path and healthcare professionals. These results will be used to plan educational interventions for polypharmacy patients to improve medication adherence and the understanding and management of diseases.

Assessing Therapeutic Choices and Adherence to Antidiabetic Therapy in Naïve Patients: A Retrospective Observational Study in a Local Health Authority of the Piedmont Region (Italy).

Due to its prevalence and socio-economic burden on health systems, diabetes mellitus (DM) is considered a major health emergency. This retrospective, observational study aimed to describe a population of DM-naïve patients of the Local Health Authority (LHA) ASL TO4 Regione Piemonte and the prescriptive behavior of LHA general practitioners. Drug dispensing data collected between January 2018 and December 2021 was analyzed. Adult patients were included if they received their first prescription for an antidiabetic drug (AD) in 2019 and had ≥2 prescriptions/year of ADs during the follow-up. Patients who started antidiabetic therapy with metformin were selected to investigate comorbidities, medication adherence, and first treatment intensification. Comorbidities were identified through a modified version of the Rx-Risk Index; adherence was measured as the continuous measure of medication availability (CMA). Among 1927 DM-naïve patients, 1361 started therapy with metformin. Most of them received drugs related to cardiovascular diseases, hypertension, and infectious diseases during the study period. Median CMA was 58.8%, with the majority of patients being partially adherent to ADs (40 ≤ CMA < 80). Initial antidiabetic therapy was mostly modified (switch, add-on) with SGLT-2 inhibitors and sulfonylureas. These findings help to identify areas of intervention to improve the use of ADs in the LHA.

Clinical decision support systems to improve drug prescription and therapy optimisation in clinical practice: a scoping review.

OBJECTIVE: Clinical decision support systems (CDSSs) can reduce medical errors increasing drug prescription appropriateness. Deepening knowledge of existing CDSSs could increase their use by healthcare professionals in different settings (ie, hospitals, pharmacies, health research centres) of clinical practice. This review aims to identify the characteristics common to effective studies conducted with CDSSs. MATERIALS AND METHODS: The article sources were Scopus, PubMed, Ovid MEDLINE and Web of Science, queried between January 2017 and January 2022. Inclusion criteria were prospective and retrospective studies that reported original research on CDSSs for clinical practice support; studies should describe a measurable comparison of the intervention or observation conducted with and without the CDSS; article language Italian or English. Reviews and studies with CDSSs used exclusively by patients were excluded. A Microsoft Excel spreadsheet was prepared to extract and summarise data from the included articles. RESULTS: The search resulted in the identification of 2424 articles. After title and abstract screening, 136 studies remained, 42 of which were included for final evaluation. Most of the studies included rule-based CDSSs that are integrated into existing databases with the main purpose of managing disease-related problems. The majority of the selected studies (25 studies; 59.5%) were successful in supporting clinical practice, with most being pre-post intervention studies and involving the presence of a pharmacist. DISCUSSION AND CONCLUSION: A number of characteristics have been identified that may help the design of studies feasible to demonstrate the effectiveness of CDSSs. Further studies are needed to encourage CDSS use.

Italian Translation and Validation of the Original ABC Taxonomy for Medication Adherence.

Medication adherence represents a complex and multifaceted process. Standardized terminology is essential to enable a reproducible process in various languages. The study's aim was to translate and adapt the original Ascertaining Barriers for Compliance (ABC) Taxonomy on medication adherence, first proposed in 2012, into Italian language. The study was carried out according to the Preferred Methods for Translation of the ABC Taxonomy for Medication Adherence adopted by the ESPACOMP. Key steps included: (1) a systematic literature review using PubMed and Embase according to the PRISMA Guidelines to identify published Italian terms and definitions, and Italian adherence experts; (2) a forward translation of terms and definitions; (3) panelists' selection; (4) a three-round Delphi survey. From the systematic review, 19 studies allowed detection of 4 terms, 4 definitions and 767 Italian experts. To these, Italian ESPACOMP members and experts though snowball sampling were added. The identified Italian adherence experts received the Delphi questionnaire. The Italian ABC Taxonomy was achieved after three rounds of Delphi survey by reaching at least a moderate consensus on unambiguous naming and definition of medication adherence-related terms. The Taxonomy is intended to be used in research, academic, and professional fields in order to harmonize adherence terminology and avoid confusion in comparing research findings.

Persistence to Medications for Benign Prostatic Hyperplasia/Benign Prostatic Obstruction-Associated Lower Urinary Tract Symptoms in the ASL TO4 Regione Piemonte (Italy).

BACKGROUND: Pharmacological treatment of benign prostatic hyperplasia (BPH)/benign prostatic obstruction (BPO)-associated lower urinary tract symptoms (LUTS) aims at improving patients' quality of life by managing urinary symptoms and preventing complications and disease progression. However, continuous use of drugs to treat BPH/BPO-associated LUTS decreases over time. The aim of this retrospective observational study was to describe use of α1-adrenoceptor antagonists (ABs) and steroid 5α-reductase inhibitors (5ARIs) by adult (age ≥ 40 years) men in the ASL TO4, a Local Health Authority in the northern area of the city of Turin (Italy). METHODS: Persistence measures were adopted as a robust, informative, and feasible way to understand medication-taking behavior and to assess patient compliance. RESULTS: A total of 4309 men (median age 71 years) were enrolled. Monotherapy was the treatment option prescribed to the largest part of the study population. However, ≥two drugs were prescribed to a substantial proportion of men (23%). Men prescribed alfuzosin or dutasteride had significantly greater persistence, which decreased over time. CONCLUSIONS: Unmet needs and areas of intervention for healthcare systems aimed at improving the use of drugs for BHP/BPO-associated LUTS in the ASL TO4 Regione Piemonte were identified.

A Network Approach for the Study of Drug Prescriptions: Analysis of Administrative Records from a Local Health Unit (ASL TO4, Regione Piemonte, Italy).

In a Drug Prescription Network (DPN), each drug is represented as a node and two drugs co-prescribed to the same patient are represented as an edge linking the nodes. The use of DPNs is a novel approach that has been proposed as a means to study the complexity of drug prescription. The aim of this study is to demonstrate the analytical power of the DPN-based approach when it is applied to the analysis of administrative data. Drug prescription data that were collected at a local health unit (ASL TO4, Regione Piemonte, Italy), over a 12-month period (July 2018-June 2019), were used to create several DPNs that correspond to the five levels of the Anatomical Therapeutic Chemical classification system. A total of 5,431,335 drugs prescribed to 361,574 patients (age 0-100 years; 54.7% females) were analysed. As indicated by our results, the DPNs were dense networks, with giant components that contain all nodes. The disassortative mixing of node degrees was observed, which implies that non-random connectivity exists in the networks. Network-based methods have proven to be a flexible and efficient approach to the analysis of administrative data on drug prescription.

Prescription of proton pump inhibitors in older adults with complex polytherapy.

OBJECTIVES: Prescription of proton pump inhibitors (PPIs) may be a source of potentially clinically relevant drug-drug interactions (DDIs) and related complications for elderly patients with complex polytherapy at discharge from hospital. The aim of the study was to identify, through the analysis of hospital discharge records, the co-administrations (PPIs + one or more drugs potentially generating DDIs) hypothetically leading to severe consequences according to the literature and online databases. Subsequently, alternatives to PPIs were evaluated for the treatment of gastric acidity and ulcers. METHODS: The medical records of 1288 patients, discharged from a geriatric ward at the Città della Salute e della Scienza Hospital in Turin from January 2012 to December 2013, were collected in an Excel database for analysis of DDIs using the literature and online sources such as Micromedex. RESULTS : Six hundred and sixty-three of the 1288 clinical folders had a PPI prescription. A list of 18 drugs considered potentially hazardous and able to trigger a DDI when co-administrated with PPIs was drafted; the frequencies of the co-prescriptions of each PPI with one of the listed drugs were esomeprazole 65.38%, lansoprazole 52.87%, omeprazole 48.19% and pantoprazole 37.11%. An analysis of these co-prescriptions, according to Micromedex classification, gave a percentage of major interactions of 11.01% over 663 clinical folders including a PPI. CONCLUSIONS: This study provides a collection of potentially hazardous drug associations and helpful suggestions to improve the quality of prescriptions for elderly patients and strengthens the case for synergic work between doctors and pharmacists in the wards.

Prevalence of frailty status among the European elderly population: Findings from the Survey of Health, Aging and Retirement in Europe.

AIM: In the present study, we aimed to update the data of frailty status in the European community-dwelling population of older adults, based on the latest data released (wave 6) of the Survey of Health, Aging and Retirement in Europe database, and to study the impact of each criterion on frailty assessment. METHODS: Frailty status was assessed applying a version of the Fried phenotype operationalized for the Survey of Health, Aging and Retirement in Europe. We included all participants who answered all the questions used in a frailty assessment and who disclosed their sex and, furthermore, who were aged ≥50 years. Our final sample was 60 816 individuals. Of these, the mean age was 67.45 ± 9.71 years; 38 497 (56.4%) were women. RESULTS: The overall prevalence of pre-frailty was 42.9% (ranging from 34.0% in Austria to 52.8% in Estonia), and frailty was 7.7% (ranging from 3.0% in Switzerland to 15.6% in Portugal). Pre-frailty and frailty prevalence increased along with age, and were more frequent among women. Regarding the five criteria considered on frailty assessment, exhaustion seems to be the criterion that contributes most to frailty status, followed by low activity, weakness, loss of appetite and slowness. CONCLUSIONS: With this work, we showed that >50% of the European population aged >50 years are pre-frail/frail, which must be considered when designing interventions to reduce/postpone/mitigate the progression of this condition, thus reducing the burden associated with it. Geriatr Gerontol Int 2019; 19: 723-729.

Chemical modifications of Tonda Gentile Trilobata hazelnut and derived processing products under different infrared and hot-air roasting conditions: a combined analytical study.

BACKGROUND: For the processing industry, it is crucial to know what effect the roasting process and conditions have on hazelnut quality. The present study investigates, for the first time, the effects of hot-air and infrared (IR) roasting at different time-temperature combinations on Tonda Gentile Trilobata hazelnut: whole kernels and derived processing products (paste and oil). RESULTS: The nutritional and physical characteristics of hazelnuts and processing products were investigated to determine the influence of the different roasting conditions as a function of intended use. The antioxidant profile (2.2-diphenyl-1-picrylhydrazyl radical, oxygen radical absorbance capacity and total phenolic content) were analyzed on roasted hazelnut and paste extracts. For a comprehensive understanding of the complex biochemical phenomena occurring during roasting, E-nose and near-IR spectroscopy were also applied. All analytical data were processed using univariate and multivariate data analyses. Hazelnuts derived from IR roasting at higher temperatures (195 °C) showed a richer antioxidant profile and a more intense flavour. On the other hand, the yield associated with the oil extraction under the same conditions was unsatisfactory, making this process completely inadequate for oil production. Oil obtained by hot-air roasting and IR roasting at lower temperature (135 °C) was found to be of good quality, showing rather similar acidity grade, peroxide number and acidic composition. In particular, a slightly but significantly lower acidity was related to lower roasting temperatures (0.21-0.22% versus 0.27% for higher temperatures). All roasting conditions tested allowed the quantitative homogeneous hazelnut paste to be obtained and, from a rheological point of view, a higher roasting temperatures resulted in pastes characterized by higher density and viscosity values. CONCLUSION: The use of IR was found to be a promising alternative method for hazelnut roasting, as a result of its capability with respect to preserving nutritional values and enhancing organoleptic quality. © 2018 Society of Chemical Industry.

A cooperation project between hospital pharmacists and general practitioners about drug interactions in clinical practice.

OBJECTIVES: (1) To evaluate drug-drug interactions (DDIs) in general practitioners' (GPs) prescriptions; (2) to implement a cooperation project between pharmacists and GPs to improve DDI management and patient care. METHODS: In 2013, pharmacists from the Community Drug Assistance ASL TO1 launched a cooperation project involving 48 GPs. As a first step, GPs were asked to select, from a list, drug associations for which they recommended analysis of occurrence in their prescriptions. The pharmacists (1) analysed GPs' prescriptions dated 2012-2014, according to the list of DDIs selected (n= 9); (2) evaluated solutions for DDI management, using the Micromedex DDI checker database and literature analysis; they then (3) disseminated DDI-related information to GPs through training meetings and (4) assessed the efficacy of these actions through a questionnaire submitted to the GPs in 2013. RESULTS: (1) Prescriptions analysis: a reduction in the number of DDIs was observed (-14% in 2013 vs 2012, -9% in 2014 vs 2012); in some cases these reductions were statistically significant (calcium carbonate + proton pump inhibitors (PPIs) -50%, p<0.0041, amoxicillin+lansoprazole -42%, p<0.0088). (2) Questionnaire: this was completed by 75% of GPs. The literature analysis was considered interesting by 94% of GPs; solutions were adopted by 89% of GPs and 34% of GPs affirmed that clinical improvements after application of the measures were observed in their patients, even if they could not provide quantitative data for this outcome. CONCLUSION: The cooperation project between pharmacists and GPs was effective because it established a professional exchange between the two health professionals. The pharmacist gave support to GPs, which benefited the patients, who gained clinical improvements and improved satisfaction with their medical care, as declared by the GPs in answers to the questionnaire.

Hydroxytriazole derivatives as potent and selective aldo-keto reductase 1C3 (AKR1C3) inhibitors discovered by bioisosteric scaffold hopping approach.

The aldo-keto reductase 1C3 isoform (AKR1C3) plays a vital role in the biosynthesis of androgens, making this enzyme an attractive target for castration-resistant prostate cancer therapy. Although AKR1C3 is a promising drug target, no AKR1C3-targeted agent has to date been approved for clinical use. Flufenamic acid, a non-steroidal anti-inflammatory drug, is known to potently inhibit AKR1C3 in a non-selective manner as COX off-target effects are also observed. To diminish off-target effects, we have applied a scaffold hopping strategy replacing the benzoic acid moiety of flufenamic acid with an acidic hydroxyazolecarbonylic scaffold. In particular, differently N-substituted hydroxylated triazoles were designed to simultaneously interact with both subpockets 1 and 2 in the active site of AKR1C3, larger for AKR1C3 than other AKR1Cs isoforms. Through computational design and iterative rounds of synthesis and biological evaluation, novel compounds are reported, sharing high selectivity (up to 230-fold) for AKR1C3 over 1C2 isoform and minimal COX1 and COX2 off-target inhibition. A docking study of compound 8, the most interesting compound of the series, suggested that its methoxybenzyl substitution has the ability to fit inside subpocket 2, being involved in π-π staking interaction with Trp227 (partial overlapping) and in a T-shape π-π staking with Trp86. This compound was also shown to diminish testosterone production in the AKR1C3-expressing 22RV1 prostate cancer cell line while synergistic effect was observed when 8 was administered in combination with abiraterone or enzalutamide.

In vitro pharmacological evaluation of multitarget agents for thromboxane prostanoid receptor antagonism and COX-2 inhibition.

PURPOSE: Patients with high cardiovascular risk due to ageing and/or comorbidity (diabetes, atherosclerosis) that require effective management of chronic pain may take advantage from new non-steroidal anti-inflammatory drugs (NSAIDs) that at clinical dosages may integrate the anti-inflammatory activity and reduced gastrointestinal side effects of selective cyclooxygenase-2 (COX-2) inhibitor (coxib) with a cardioprotective component involving antagonism of thromboxane A2 prostanoid (TP) receptor. METHODS: New compounds were obtained modulating the structure of the most potent coxib, lumiracoxib, to obtain novel multitarget NSAIDs endowed with balanced coxib and TP receptor antagonist properties. Antagonist activity at TP receptor (pA2) was evaluated for all compounds in human platelets and in an heterologous expression system by measuring prevention of aggregation and Gq-dependent production of intracellular inositol phosphate induced by the stable thromboxane A2 (TXA2) agonist U46619. COX-1 and COX-2 inhibitory activities were assessed in human washed platelets and lympho-monocytes suspension, respectively. COX selectivity was determined from dose-response curves by calculating a ratio (COX-2/COX-1) of IC50 values. RESULTS: The tetrazole derivative 18 and the trifluoromethan sulfonamido-isoster 20 were the more active antagonists at TP receptor, preventing human platelet aggregation and intracellular signalling, with pA2 values statistically higher from that of lumiracoxib. Comparative data regarding COX-2/COX-1 selectivity showed that while compounds 18 and 7 were rather potent and selective COX-2 inhibitor, compound 20 was somehow less potent and selective for COX-2. CONCLUSION: These results indicate that compounds 18 and 20 are two novel combined TP receptor antagonists and COX-2 inhibitors characterized by a fairly balanced COX-2 inhibitor activity and TP receptor antagonism and that they may represent a first optimization of the original structure to improve their multitarget activity.

Designing multitarget anti-inflammatory agents: chemical modulation of the lumiracoxib structure toward dual thromboxane antagonists-COX-2 inhibitors.

A series of lumiracoxib derivatives were designed to explore the influence of isosteric substitution on balancing COX-2 inhibition and thromboxane A(2) prostanoid (TP) receptor antagonism. The compounds were synthesized through a copper-catalyzed coupling procedure and characterized for their pK(a) values. TP receptor antagonism was assessed on human platelets; COX-2 inhibition was determined on human isolated monocytes and human whole blood. TPα receptor binding of the most promising compounds was evaluated through radioligand binding assays. Some of the isosteric substitutions at the carboxylic acid group afforded compounds with improved TP receptor antagonism; of these, a tetrazole derivative retained good COX-2 inhibitory activity and selectivity. The identification of this tetrazole acting as a balanced dual-acting compound in human whole blood, along with SAR analysis of the synthesized lumiracoxib derivatives, might contribute to the rational design of a new class of cardioprotective anti-inflammatory agents.

Searching for new NO-donor aspirin-like molecules: Furoxanylacyl derivatives of salicylic acid and related furazans.

A new group of derivatives of salicylic acid containing NO-donor furoxans, and the related des-NO-furazans, were synthesized and evaluated as new aspirin-like molecules. Their stability was assessed in acid (pH 1) and physiological solutions (pH 7.4), and in human serum. No compound exhibited COX-inhibitory activity against COX-1 and COX-2 isoforms, when tested up to 100µM, respectively, on isolated platelets and on monocytes. Phenylsulfonyl- and cyano-substituted furoxans inhibited platelet aggregation induced by collagen in human platelet-rich plasma, through a cGMP dependent mechanism. Furoxan derivatives displayed cGMP-dependent vasodilator activities, tested on rat aorta strips precontracted with phenylephrine. All products showed anti-inflammatory activity similar to that of ASA, tested on rats by the carrageenan-induced paw edema assay. Unlike ASA, all products showed markedly reduced gastrotoxicity in a rat lesion model.

Nitrooxyacyl derivatives of salicylic acid: aspirin-like molecules that covalently inactivate cyclooxygenase-1.

A recently described series of nitrooxyacyl derivatives of salicylic acid, displaying aspirin-like anti-inflammatory and platelet anti-aggregatory properties, were evaluated for their abilities to inhibit cyclooxygenase (COX). A number of these compounds irreversibly inhibited both COX-1 and COX-2 isoforms when tested in isolated human platelets and monocytes. Further studies using COX-1 expressed in human HEK293T cells showed that this inhibition mechanism is similar to that of aspirin; namely, the products are able to covalently bind to the Ser 530 residue present in the active cleft of the enzyme. Molecular modeling enabled us to rationalize this behavior. Because these products were previously found to display NO-dependent properties in rat animal models, particularly as they decreased in vivo gastrotoxicity and induced in vitro vasodilation, they represent a new and interesting class of potential aspirin-like antithrombotic agents worthy of further study.

Nitrooxymethyl-substituted analogues of rofecoxib: synthesis and pharmacological characterization.

Nitrooxymethyl-substituted derivatives of Rofecoxib were synthesized and tested for their cyclooxygenase (COX)-inhibiting activity in whole human blood, vasodilator potency on rat aorta strips, and for their capacity of inhibiting platelet aggregation of human platelet-rich plasma. The results show that their potency and selectivity in inhibiting COX isoforms, as well as their anti-aggregatory properties, are closely dependent on the position at which the NO-donor nitrooxymethyl function is introduced into the Rofecoxib scaffold. All the products were capable of dilating rat aorta strips precontracted with phenylephrine in a dose-dependent manner, through a cGMP-dependent mechanism. Compound 10 emerged as a quite potent COX-2-selective inhibitor endowed with good vasodilator activity. Interestingly, compound 19 behaved as a potent selective COX-1 inhibitor, and displayed good vasodilator and anti-aggregatory properties. The hydroxymethyl derivatives, potential metabolites of the nitrooxymethyl analogues, were similarly studied for a comparison.

Nitrooxymethyl-substituted analogues of celecoxib: synthesis and pharmacological characterization.

Nitrooxymethyl-substituted analogues of celecoxib were synthesized and tested for their cyclooxygenase (COX)-inhibiting, vasodilator, and anti-aggregatory activities, as well as for their metabolic stability in human serum and whole blood. The results showed their potency and selectivity in inhibiting the COX isoforms, evaluated in whole human blood, as well as their anti-aggregatory activity to depend closely on the position at which the NO-donor moiety is introduced. All products dilated rat aorta strips precontracted with phenylephrine in a dose-dependent manner through a cGMP-dependent mechanism. They were stable in human serum while, in blood, they were metabolically transformed, principally to the related alcohols.