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Pharmaceuticals can reach the environment at all stages of their lifecycle and accumulate in the ecosystem, potentially reaching toxic levels for animals and plants. In recent years, efforts have been made to map and control this hazard. Assessing country‐specific environmental risks could drive regulatory actions towards eco‐friendlier drug utilization and disposal practices. By starting from a list of 25 environmentally hazardous pharmaceuticals developed by Region Stockholm, we integrated eco‐toxicological and 2019–2021 Italian drug utilization data to estimate the environmental impact of pharmaceuticals in Italy. We calculated the risk as the ratio between the predicted environmental concentration (PEC) and the predicted no‐effect concentration (PNEC). We found a high risk for levonorgestrel, ciprofloxacin, amoxicillin, azithromycin, venlafaxine, sertraline and diclofenac and a moderate risk for ethinyloestradiol, oestradiol and clarithromycin. This analysis can be periodically performed to identify the pharmaceuticals with the highest risk for the environment and ascertain if containment measures should be implemented. [ABSTRACT FROM AUTHOR]

Purpose: The COVID‐19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. Methods: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID‐19 pandemic with the preceding 3 years. Results: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID‐19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID‐19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from −39.4% in Romagna to −14.2% in Scotland) and nasal preparations (from −34.4% in Lithuania to −5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. Conclusions: The findings from this first European cross‐national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas. [ABSTRACT FROM AUTHOR]

Through this structured review of the published literature, we aimed to provide an up-to-date description of strategies (human-related) and tools (mainly from the digital field) facilitating the appropriateness of drug use in older adults. The evidence of each strategy and tool's effectiveness and sustainability largely derives from local and heterogeneous experiences, with contrasting results. As a general framework, three main steps should be considered in implementing measures to improve appropriateness: prescription, acceptance by the patient, and continuous monitoring of adherence and risk-benefit profile. Each step needs efforts from specific actors (physicians, patients, caregivers, healthcare professionals) and dedicated supporting tools. Moreover, how to support the appropriateness also strictly depends on the particular setting of care (hospital, ambulatory or primary care, nursing home, long-term care) and available economic resources. Therefore, it is urgent assigning to each approach proposed in the literature the following characteristics: level of effectiveness, strength of evidence, setting of implementation, needed resources, and issues for its sustainability. [ABSTRACT FROM AUTHOR]

Background: Estimating the morbidity of a population is strategic for health systems to improve healthcare. In recent years administrative databases have been increasingly used to predict health outcomes. In 1992, Von Korff proposed a Chronic Disease Score (CDS) to predict 1-year mortality by only using drug prescription data. Because pharmacotherapy underwent many changes over the last 3 decades, the original version of the CDS has limitations. The aim of this paper is to report on the development of the modified version of the CDS. Methods: The modified CDS (M-CDS) was developed using 33 variables (from drug prescriptions within two-year before 01/01/2018) to predict one-year mortality in Bologna residents aged ≥50 years. The population was split into training and testing sets for internal validation. Score weights were estimated in the training set using Cox regression model with LASSO procedure for variables selection. The external validation was carried out on the Imola population. The predictive ability of M-CDS was assessed using ROC analysis and compared with that of the Charlson Comorbidity Index (CCI), that is based on hospital data only, and of the Multisource Comorbidity Score (MCS), which uses hospital and pharmaceutical data. Results: The predictive ability of M-CDS was similar in the training and testing sets (AUC 95% CI: training [0.760–0.770] vs. testing [0.750–0.772]) and in the external population (Imola AUC 95% CI [0.756–0.781]). M-CDS was significantly better than CCI (M-CDS AUC = 0.761, 95% CI [0.750–0.772] vs. CCI-AUC = 0.696, 95% CI [0.681–0.711]). No significant difference was found between M-CDS and MCS (MCS AUC = 0.762, 95% CI [0.749–0.775]). Conclusions: M-CDS, using only drug prescriptions, has a better performance than the CCI score in predicting 1-year mortality, and is not inferior to the multisource comorbidity score. M-CDS can be used for population risk stratification, for risk-adjustment in association studies and to predict the individual risk of death. [ABSTRACT FROM AUTHOR]

Purpose: Antidepressant consumption has risen in recent years, driven by longer treatment duration. The objective of this study was to measure the prevalence of antidepressant long-term and chronic use in the Bologna area, Italy, and to identify their main determinants. Materials and Methods: We conducted a retrospective claims-based cohort study by using the Bologna Local Health Authority data. A cohort of 18,307 incident users of antidepressant drugs in 2013 was selected, and subjects were followed for three years. A long-term utilization was defined as having at least one prescription claimed during each year of follow-up, while chronic utilization was defined as claiming at least 180 defined daily doses per year. Factors associated with chronic and long-term use were identified by univariate and multivariate logistic regressions. Results: In our cohort, 5448 (29.8%) and 1817 (9.9%) subjects were dispensed antidepressants for a long-term course and in a chronically way, respectively. Older age, antidepressant polytherapy, polypharmacy, and being prescribed the first antidepressant by a hospital physician were all factors independently associated with chronic and long-term prescriptions of antidepressant drugs. Results were reported separately for men and women. Conclusion: Antidepressant long-term and chronic prescriptions are common in the Bologna area. Because longer treatment should be clinically motivated, these results strongly prompt the need to evaluate the actual relevance, as they may indicate potentially inappropriate prescription patterns. [ABSTRACT FROM AUTHOR]

The article presents the authors' response to a letter from Drs. J. Holstiege and D. Pieper which raised concerns about whether their study allows meaningful comparison of antibiotic use between countries. They stand by their findings that there substantial differences in the prevalence and amount of antibiotic use across European cohorts.

Background: There is appreciable utilisation of antihistamines (H1) in European countries, either prescribed by physician and purchased by patients for self-medication. Terfenadine and astemizole underwent regulatory restrictions in ’90 because of their cardiac toxicity, but only scarce clinical data are available on other antihistamines. Aim: To investigate the pro-arrhythmic potential of antihistamines by combining safety reports of the FDA Adverse Event Reporting System (FAERS) with drug utilization data from 13 European Countries. Methods: We identified signals of antihistamine arrhythmogenic potential by analyzing FAERS database for all cases of Torsades de Pointes (TdP), QT abnormalities (QTabn), ventricular arrhythmia (VA) and sudden cardiac death/cardiac arrest (SCD/CA). Number of cases ≥3 and disproportionality were used to define alert signals: TdP and QTabn identified stronger signals, whereas SCD/CA identified weaker signals. Drug utilization data from 2005 to 2010 were collected from administrative databases through health authorities and insurance. Results: Antihistamines were reported in 109 cases of TdP/QT prolongation, 278 VA and 610 SCD/CA. Five agents resulted in stronger signals (cetirizine, desloratadine, diphenhydramine, fexofenadine, loratadine) and 6 in weaker signals (alimemazine, carbinoxamine, cyclizine, cyproeptadine, dexchlorpheniramine and doxylamine). Exposure to antihistamines with stronger signal was markedly different across European countries and was at least 40% in each Country. Cetirizine was >29 Defined Daily Doses per 1000 inhabitants per day (DID) in Norway, desloratadine >11 DID in France and loratadine >9 DID in Sweden and Croatia. Drugs with weaker signals accounted for no more than 10% (in Sweden) and in most European countries their use was negligible. Conclusions: Some second-generation antihistamines are associated with signal of torsadogenicity and largely used in most European countries. Although confirmation by analytical studies is required, regulators and clinicians should consider risk-minimisation activities. Also antihistamines without signal but with peculiar use in a few Countries (e.g., levocetirizine) or with increasing consumption (e.g., rupatadine) deserve careful surveillance. [ABSTRACT FROM AUTHOR]

Purpose: Our aim was to evaluate whether dronedarone authorization impacts antiarrhythmic drug prescribing in Sweden and Emilia Romagna (Italy). Methods: Prescriptions of classes I and III antiarrhythmics, expressed as defined daily doses per thousand inhabitants per day (DDD/TID) were monthly using information collected from pharmacy-reimbursed databases. Interrupted time series analysis was applied to compare prescription data over the 2009-2011 period. Results: In Emilia Romagna, the overall consumption of antiarrhythmics was six times as high as in Sweden (7.6 vs. 1.2 DDD/TID). In the first year on the market, dronedarone represented 1.0 % in Italy and 10.7 % in Sweden of the overall antiarrhythmic prescriptions. In Sweden, dronedarone authorization generated an increase in the prescription trend of antiarrhythmics (trend change +0.02; p < 0.001) without variation in amiodarone use In Emilia Romagna, dronedarone marketing did not influence the prescription pattern of either overall antiarrhythmics or amiodarone. Conclusions: Emilia Romagna and Sweden substantially differ in terms of overall antiarrhythmic use. Although clinical guidelines place dronedarone among first-choice treatments for atrial fibrillation, amiodarone prescribing was not affected in either country by the entry of dronedarone, probably due to a cautious approach by clinicians in line with regulatory recommendations and safety warnings. [ABSTRACT FROM AUTHOR]

Background: In a previous questionnaire-based survey, we found extensive use of nonsteroidal anti-inflammatory drugs (NSAIDs) in subjects with risk factors for serious gastrointestinal complications. Aim: This study focused on the use of NSAIDs in subjects who reported either (a) pre-existing disorders which would have required caution in using NSAIDs (e.g. dyspepsia/heartburn or peptic ulcer) or (b) co-medication with drugs having a high risk of interacting with NSAIDs. Methods: Between March and September 2002, 65 general practitioners (GPs) submitted a validated self-administered questionnaire on health status and drug use to 3,250 subjects (age ≥18 years, stratified by sex and age). The questionnaire was divided into three parts: (1) sociodemographic information, (2) symptoms/illnesses (in the previous 6 months) and (3) drugs taken during the previous week. Results: Of the 2,738 subjects who filled in the questionnaire (84% of responders), 633 (23%) used NSAIDs and, among them, 114 (18%) were chronic users. Among the subjects reporting dyspepsia/heartburn or ulcer (n=909 of 2,738), 24% were occasional NSAID users and 6% chronic users. Of the chronic NSAID users reporting gastrointestinal symptoms, 35% also used a drug for acid-related disorders, but only 14% used daily a proton pump inhibitor (PPI). One hundred six subjects used concomitantly more than one NSAID. Eighteen percent of the subjects using corticosteroids also reported NSAID use; similar proportions were seen in subjects using selective serotonin reuptake inhibitor (SSRI) antidepressants or calcium channel blockers, whereas 6% of the subjects with oral anticoagulants used NSAIDs. Conclusions: Our study shows that NSAIDs are frequently used in patients with upper gastrointestinal complaints or in combination with potentially interacting medications. Adverse effects and untoward drug interactions should be monitored in patients treated with NSAIDs in order to minimise their occurrence. [ABSTRACT FROM AUTHOR]

Aims Many drugs belonging to different therapeutic classes appear to share a potentially fatal side-effect: ventricular tachyarrhythmias associated with QT prolongation. The aim of this study was to assess the relevance and the magnitude of the problem in seven countries by grouping all nonantiarrhythmic drugs according to the type of evidence on QT prolongation and analysing their sales data. Methods We divided all nonantiarrhythmic QT-prolonging agents into the following categories (in increasing order of clinical relevance): group A, drugs with published clinical or preclinical evidence on QT prolongation or with relevant official warnings; group B, drugs with published clinical or preclinical evidence; group C, drugs with published clinical evidence; group D, drug with published clinical evidence on torsades de pointes or ventricular arrhythmias associated with QT prolongation; group E, drugs belonging to group D with official warnings. We retrieved 1998 sales data from community pharmacies in seven countries (Australia, Denmark, England, Germany, Greece, Italy and Sweden). Data for individual agents were expressed as defined daily doses per 1000 inhabitants per day (DDD/1000/day). Overall use in each country was calculated for each drug group. Groups D and E were considered as the most clinically relevant. Results Among the 102 nonantiarrhythmic agents meeting at least one of the inclusion criteria, 33 drugs had sales data ≥1 DDD/1000/day and 71 drugs had a use ≥0.1 DDD/1000/day in at least one country. Among the 37 nonantiarrhythmic agents with published reports of ventricular arrhythmias associated with QT prolongation, 12 compounds had sales data ≥1 DDD/1000/day. Total consumption in each country ranged: from 51.9 to 94.7 DDD/1000/day for group A; from 51.6 to 92.7 DDD/1000/day for group B; from 37.1 to 76.6 DDD/1000/day for group C; from 12.9 to 29.1 DDD/1000/day for group D; and from 5.8 to 15.3 DDD/1000/day for group E.... [ABSTRACT FROM AUTHOR]

Background:Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods:FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Results: Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). Conclusions:This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and Country-specific scenarios requiring potential regulatory consideration: levomepromazine (Serbia), fluphenazine (Slovenia), olanzapine (across Europe), cyamemazine (France). This synergy should be encouraged to support future pharmacovigilance activities. [ABSTRACT FROM AUTHOR]