Anatomical Therapeutic Chemical Research Articles

Marketing analysis of the domestic pharmaceutical market of antiherpetic medicines

Aim. To conduct the marketing research of the pharmaceutical market of Ukraine in the segment of medicinal products (MP) used for the treatment and prevention of infections caused by HSV-1 and HSV-2.
 Materials and methods. To achieve this aim, methods of logical and meaningful problem formation, desk marketing research, content analysis of publications in scientific and practice-oriented medical and pharmaceutical literature, comparative analysis were used.
 Results. The paper presents the results of the marketing analysis of the Ukrainian pharmaceutical market of antiherpetic MP. For the study, according to the ATC classification, 5 groups of medicines registered at the domestic market were selected. In the drug package leaflets for these medicines herpes infection was one of the indications for use. As of October 1, 2021, the range of antiherpetic MP includes 194 trade names for systemic and local use. The market segmentation of these groups of medicines by manufacturing countries, drug form, conditions of dispensing, origin and composition was carried out. It has been found that the share of herbal medicinal products is 14.43 % (6 positions) and is represented by products for systemic use.
 Conclusions. The research of the market of antiherpetic medicines conducted can be considered as the basis for the search and development of new effective antiviral herbal medicinal products of domestic production for the local treatment of the herpes virus.

Analysis of Reports on Adverse Drug Reactions Related to Herbal Medicinal Products and Herbal Supplements in the Netherlands Received by the National Pharmacovigilance Centre Lareb.

The inclusion of herbal medicinal products and herbal supplements in pharmacovigilance systems is important because a systematic approach of collecting and analyzing adverse drug reactions related to these products will help practitioners, patients, and regulators to gain more knowledge and prevent harm. We aimed to categorize the adverse drug reaction reports on herbal medicinal products and herbal supplements submitted to the Pharmacovigilance Centre Lareb between 1991 and February 2021 on the basis oftheir regulatory status, herbsincluded, and adverse drug reactions involved. We categorized products on the basis of their registration status and herbal ingredients. The products were then categorized according to the Herbal Anatomical Therapeutic Chemical Classification System. We used descriptive statistics in Microsoft Excel 2019. Pivot tables were used for the analysis and presentation of the data. Until February 2021, a total of 789 reports of herbal medicinal products and herbal supplements were received by Lareb. In these reports, a total of 823 herbal products were labeled as suspect. These products caused a total of 1727 adverse drug reactions. Of the 823 products, 229 were registered as a medicine, and 594 were on the market as a herbal supplement. Of the 823 herbal products, 522 reports concerned single-herb products, 256 reports concerned combination products, 27 reports concerned vitamin products containing herbal ingredients, and 18 reports concerned product issues. Approximately 15% of reports concerned serious adverse drug reactions, and adulterated products harbored a high risk of causing serious adverse drug reactions. Analysis of the herbal medicinal products and herbal supplements in the Dutch pharmacovigilance database revealed a variety of suspected herbal ingredients. The reports provide insight into the variety of herbal products used in the Netherlands and the adverse reactions associated with their use. Pharmacovigilance of herbal products is essential to ensure their safe use.

Drug Utilization 90% Profile of Antibiotics Use during the Period of 2013 – 2017 at a Private Teaching Hospital in Yogyakarta

Evaluation of antibiotics use plays an important role in antimicrobial stewardship programs to support the rational use of antibiotics at all healthcare facilities. This study aimed to describe the profile of drug utilization 90% (DU90%) of antibiotics use for hospitalized patients at a private teaching hospital in Yogyakarta over period of 2013 – 2017. Aggregate data of all systemic antibiotics having an anatomic therapeutic chemical (ATC) code and used for hospitalized patients during 2013 – 2017 were included in this study. Quantity of antibiotics use was expressed in defined daily dose (DDD) and final quantity was expressed in DDD/100 bed days. DU90% profile was obtained by calculating the cumulative use of antibiotics from the highest to the lowest percentage. There were 44 antibiotic agents used each year over the period of 2013 – 2017. However, there were only 10 – 12 agents within the DU90% segment. Cephalosporins group was identified as the most used antibiotics consistently over the period and the top three antibiotics that were consistently prescribed were: ceftriaxone, levofloxacin, and cefixime. It can be concluded that only about a quarter of the total antibiotic agents used in hospitals are within the DU90% segment and those antibiotic agents are relatively consistent, especially for the top three of the highest used antibiotics.

Opioid trends in Finland: a register-based nationwide follow-up study

The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009–2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3–6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain - a type of pain where the risk-benefit ratio of opioids is controversial.

FC 103: Matched Control Study on Applied Long-Term Anti-Thrombotic Therapies and Clinical Outcome of Atrial Fibrillation in HD-Patients Based on German Network Data

Abstract BACKGROUND AND AIMS Hemodialysis (HD) patients (pts) with atrial fibrillation (AF) are at high risk for cardiovascular events, severe bleeding and rapid vascular/valvular calcification. Thus, antivitamin-K based oral anticoagulation (VK-OAC) for HD patients is debated, since prospective trials are missing and US register studies are often limited to 3–6 months OAC use. We studied AF risk-factors, long-term antithrombotic therapies and clinical outcomes in a large German HD cohort. METHOD We analysed pseudonymized benchmarking data in a German out-patient dialysis center network (Verband Deutsche Nierenzentren, DN) based on quarterly electronically transmitted data. Diagnoses coded by ‘International Classification of Diseases (ICD)’ and ‘Anatomical Therapeutical Chemical (ATC)’ drug codes of adult HD patients 2013–2018. RESULTS In 2013, 2753 (18%) of 15 682 HD-pts had AF as coded diagnosis. Baseline CHA2DS2-VASc (4.0/1.5 mean/SD) and HAS-BLED (3.2/0.9) risk-scores indicated high risk for embolism and bleeding. Charlson Comorbidity Index (CCI) was high (6.4/2.8) and median observation was 2.1 years (range 0.01–6 years). Beside HD-related heparin, four main OAC approaches were applied: no active therapy, VK-OAC+/-aspirin/clopidogrel (VK-OAC+/-Asp/Clop), heparin-based therapy (heparin+/-Asp/Clop) or 1–2 antithrombocyte drugs (Asp/Clop). A total of 959 pts (35%) changed therapy, but 1794 pts (65%) had no change in OAC regime during the 6 year study period and were used for final therapy-related outcome analysis (Table 1). Both AF risk-scores overestimated de-novo events. Total 6-year event rate was low (7.5%; <1.3% per year) and comparable for all anticoagulant therapies, especially for cerebral ischemic events (2.8%; range 1.2–3.7; NS). All three antithrombotic therapies had similar overall events as without active therapy (7.6 versus 7.3%), including cerebral adverse events (ischemic: 3.0 versus 2.6%; bleeding: 0.7 versus 0.6%; NS). Survival (Kaplan–Meier) was analysed for matched controls by propensity-score based on mortality risk factors in multivariate Cox regression: age (HR 1.05), sex (female HR 0.78), CCI (HR 1.07) and albumin (HR 0.93). Six-year mortality rates were high (63%) and matched analysis showed significant lower survival (P < 0.001) without anticoagulant (median 1.8 years) or on heparin-based therapy (1.7 years) than on Asp/Clop (2.9 years) or VK-OAC based therapy (2.8 years). This relation was similar for subgroups on age, CCI or changed therapy. CONCLUSION Our large study showed that baseline CHA2DS2-VASc and HAS-BLED scores had no predictive value for clinical events in HD pts with AF. Cerebral ischemic event rates over 6 years were low (<0.7%/year) and similar for all three antithrombotic therapies and even no active therapy, suggesting major benefit of regular dialysis-related heparin supply. Since median survival on Asp/Clop is similar to VK-OAC therapy and even 1 year better than on no active or heparin-based therapy, we conclude that antithrombotic therapy in HD patients with AF can effectively be done with Asp/Clop and VK-OAC should be avoided. For future prospective trials, we recommend to apply Asp/Clop as first-line control therapy evaluating new direct-acting oral anticoagulants (DOAK) and/or interventional approaches (i.e. left atrial appendage closure) in HD patients with AF.

GENDER CHARACTERISTICS OF ADVERSE DRUG REACTIONS DEVELOPMENT: EXPERIENCE OF REGIONAL DATABASE ANALYSIS

The aim of the article is the gender characteristics study of the adverse drug reactions (ADRs) development based on the data of the notification forms registered in the regional database ARCADe (Adverse Reactions in Crimea, Autonomic Database), for the period from 2009 to 2018.Materials and methods. The objects of the study were 6903 notification forms about adverse drug reactions recorded in the regional database called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2009 to 2018. The classification of drugs for separate pharmacological groups was carried out using the codes of the Anatomical Therapeutic Chemical (ATC) classification system of the World Health Organization (WHO) medicinal products, the instructions data of the State Registers of medicinal preparations used in the Russian Federation and Ukraine (for the cases registered before the entry of the Republic of Crimea into the Russian Federation).Results. A general analysis of the number of cases of the adverse drug reactions (ADRs) development in patients of different genders made it possible to determine that 59.9% (4132 notification forms) of ADRs cases were observed in female patients; 37.7% (2602 cases) – in male patients. In 169 cards (2.4%), information about a patient’s gender was missing. The groups with the largest number of the registered cases of ADRs were antimicrobial agents for a systemic use (2864 cases, 41.5% of the total number of the ADRs registered cases), the drugs affecting the cardiovascular (811 cases, 11.7%) and nervous (734 cases, 10.6%) systems. In each of the presented groups, the incidence rate of ADRs in female patients exceeded that in men.Conclusion. The study of the gender characteristics of the pharmacotherapy safety, carried out on the basis of the notification forms of the ADRs data registered in the Republic of Crimea, confirmed a higher likelihood of developing ADRs in female patients. This may be due to the peculiarities of the pharmacokinetics and pharmacodynamics of drugs in the female body, psychological factors, a more frequent use of drugs by this category of people. The implementation of the drug, taking into account specific features of each gender, can lead not only to better treatment outcomes, but also to increased patients’ compliance.

Methodological approaches for medication error analyses in patient safety and pharmacovigilance reporting systems: a scoping review protocol

IntroductionMedication errors (MEs) are associated with patient harm and high economic costs. Healthcare authorities and pharmacovigilance organisations in many countries routinely collect data on MEs via reporting systems to improve...

Influence of Drugs on Mild Cognitive Impairment in Parkinson's Disease: Evidence from the PACOS Study.

polytherapy and the anticholinergic activity of several drugs negatively influence cognition in the elderly. However, little is known on the effect on Mild Cognitive Impairment (MCI) in Parkinson's Disease (PD). patients with PD belonging to the baseline PACOS cohort with full pharmacological data have been included in this study. MCI diagnosis was made according to the MDS level II criteria. Polytherapy was defined as patients assuming ≥6 drugs. The anticholinergic burden has been calculated using the Anticholinergic Drug Scale (ADS). Molecules have been classified according to the ATC classification. Association with MCI has been assessed with a multivariate logistic regression analysis with MCI as the dependent variable. pharmacological data were available for 238 patients (mean age 64.7±9.7). One hundred (42.0%) were diagnosed with MCI. No association was found in the full multivariate model (correcting for age, sex, disease duration, education, UPDRS-ME, LEDD-DAs) with either polytherapy or the ADS. Concerning drug classes, anti-hypertensive medications were positively associated with PD-MCI (OR 2.02;95%CI 1.04-3.89; p=0.035) while gastroprotective agents were negatively associated (OR 0.51; 95%CI 0.27-0.99; p=0.047). the magnitude of polytherapy and anticholinergic drugs burden does not appear to modulate MCI risk in PD, probably due to cautious prescription patterns. The effect of antihypertensive and gastroprotective agents on PD-MCI risk, while needing further confirmations, could be relevant for clinical practice.

Pediatric Outpatient Prescriptions in Countries With Advanced Economies in the 21st Century

An international comparison of pediatric outpatient prescriptions (POPs) is pivotal to investigate inadequate practices at the national scale and guide corrective actions. To compare annual POP prevalence among Organisation for Economic Co-operation and Development (OECD) member countries. Two independent reviewers systematically searched PubMed, Embase, and institutes of public health or drug agency websites for studies published since 2000 and reporting POP prevalence (expressed as number of patients aged <20 years with ≥1 POP per 1000 pediatric patients per year) in OECD member countries or large geographic areas within them. Risk of bias was assessed for exhaustiveness and representativeness. Prevalence ratios (PRs) were used to compare the highest and lowest POP prevalence among countries overall, by levels of Anatomical Therapeutic Chemical (ATC) classification for the overall pediatric population, and by age group (ie, ages <5-6 vs ≥5-6 years), stratifying on prescription-only drug (POD) status. Among 11 studies performed on 3 regional and 8 national medicoadministrative databases in 11 countries, 35 552 550 pediatric patients were included. The overall risk of bias was low (10 studies were representative [90.9%], and the prevalence denominator included nonusers of health care for 9 studies [81.8%]). Prevalence of 1 or more POP per year ranged from 480 to 857 pediatric patients per 1000 in Sweden and France, respectively (PR, 1.8 [95% CI, 1.8-1.8]). Overall, among 8 studies reporting ATC level 1 drugs, Denmark had the lowest POP prevalence (eg, systemic hormonal preparations: 9 pediatric patients per 1000 per year) and France the highest (eg, systemic hormonal preparation: 216 pediatric patients per 1000 per year). Among 8 studies reporting ATC level 2 drugs for PODs, the PR between France and Denmark was 108.2 (95% CI, 108.2-108.2) for systemic corticosteroids and 2.1 (95% CI, 2.1-2.1) for drugs for obstructive airway disease. The PR for antibiotics was 3.4 (95% CI, 3.4-3.4) between New Zealand and Sweden. For pediatric patients aged 5 to 6 years or older, the PR for sex hormones was 2.1 (95% CI, 2.1-2.1) between Denmark and France. Among 7 studies reporting ATC level 5 drugs, the prevalence of the 10 most prevalent PODs was less than 100 pediatric patients per 1000 per year in Scandinavian countries and the Netherlands and less than 300 pediatric patients per 1000 per year in France and New Zealand. This study found large between-country variations in POPs, which may suggest substantial inappropriate prescriptions. The findings may suggest guidance for educational campaigns and regulatory decisions in some OECD member countries.

Medication Persistence to Lipid-lowering Agents As A Cost-saving Opportunities on Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention in Indonesia

Medication persistence is known to reduce acute coronary syndrome (ACS) disease mortality. As much as 13% of Indonesia's budget on national health insurance programs was used for cardiovascular disease. The number of population-based studies discussing the cost-saving opportunities of medication persistence in ACS patients undergoing percutaneous coronary syndrome (PCI) is still minimal. This study aimed to investigate the estimated cost saving of persistence to lipid-lowering agents in patients with ACS after their first PCI. Hospital-based, retrospective cohort study with 2 years of follow-up was conducted with 367 patients. Patients were deemed as having medication persistence if the gap between prescriptions was ≤ 30 days. Persistence assessment was done for lipid-modifying agents (WHO ATC Code: C10). The main outcome is cost-saving opportunities assessed by dividing the difference in total costs resulting from medication persistence with the difference in the proportion of major adverse cardiovascular events (MACE) and major adverse cardiovascular and cerebrovascular events (MACCE) prevented by medication persistence. The study found that direct medical costs incurred by persistent patients were significantly lower than non-persistent patients with lipid-lowering agents (IDR 9,535,209.76 versus IDR 15,933,959.28). Persistence to lipid-lowering therapy can prevent one MACE incident with cost-saving of IDR 996,192.41 when compared to non-persistence patients, while one MACCE incident can be prevented with cost-saving of IDR 733,103.02. Our study indicates that among ACS patients who underwent their first PCI, medication persistence with lipid-lowering agents can contribute to cost-saving in preventing one MACE or MACCE event. These data will be useful for policymakers to help budget allocation and reemphasize the important role of medication persistence with lipid-lowering therapy in the management of ACS after PCI.

Persistence with Antiplatelet and Risk of Major Adverse Cardiac and Cerebrovascular Events in Acute Coronary Syndrome Patients after Percutaneous Coronary Intervention in Indonesia: A Retrospective Cohort Study

BACKGROUND: Acute coronary syndrome (ACS) is a life-threatening condition that carries high risk of recurrent cardiovascular events and death. Persistence with treatment is known to reduce morbidity and mortality in patients with ACS. AIM: This study focuses on ACS patients undergoing their first percutaneous coronary intervention (PCI) to investigate the association between persistence with antiplatelet therapy and clinical outcomes. MATERIALS AND METHODS: A retrospective cohort study with 2 years of follow-up was conducted with 367 patients recruited. Patients were deemed as having persistence with antiplatelet therapy (WHO ATC code: B0A1C), if the gap between prescriptions was ≤30 days. The clinical outcomes were defined as a composite of major adverse cardiac event (MACE), major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction, recurrent PCI, stroke, all-cause death, cardiovascular death, and hospitalization. RESULTS: Cumulative persistence with antiplatelet showed that 72.3% of all ACS patients were still taking antiplatelet 1 year after PCI. Persistence to treatment with antiplatelet therapy can be used as a predictor of MACE or MACCE, because it was associated with recurrent PCI (RR 3.09, 95% CI = 1.18−8.05). History of cardiovascular disease in non-persistence patients was associated with increased risk of MACE (RR 4.90 95% CI = 1.37−17.48) and MACCE (RR 3.67 95% CI = 1.12−11.98) events. CONCLUSION: After PCI, not all ACS patients continued taking their drug exactly as prescribed. Our study indicates that among ACS patients who underwent their first PCI, non-persistence with antiplatelet therapy might lead to worse clinical outcomes. This data will help promote secondary prevention among ACS patients after PCI.

Development and consensus testing of quality indicators for geriatric pharmacotherapy in primary care using a modified Delphi study

Background Polypharmacy is associated with an increased risk of adverse drug events in older people. Although national guidance on geriatric pharmacotherapy exists in Japan, tools to routinely monitor the quality of care provided by community pharmacists are lacking. Aim To develop a set of quality indicators (QIs) to measure the quality of care provided by community pharmacists in improving geriatric pharmacotherapy in primary care in Japan, using a modified Delphi study. Method The development of QIs for the Japanese community pharmacy context followed a two–step process: national guidance review and consensus testing using a modified Delphi study. The latter involved two rounds of rating with a face–to–face meeting between the rounds. Ten experts in geriatric pharmacotherapy in primary care were recruited for the panel discussion. QIs were mapped to three key taxonomies and frameworks: the Anatomical Therapeutic Chemical (ATC) classification system, problems and causes of drug–related problems (DRPs) taxonomy and Donabedian’s framework. Results A total of 134 QIs for geriatric pharmacotherapy were developed. This QI set included 111 medicine specific indicators, covering medicines in 243 third–level ATC classifications. QIs were classified into the problem of treatment safety (80%) and causes of drug selection (38%) based on validated classification for DRPs. In Donabedian's framework, most QIs (82%) were process indicators. There were no structure indicators. Conclusion A set of 134 QIs for geriatric pharmacotherapy was rigorously developed. Measurement properties of these QIs will be evaluated for feasibility, applicability, room for improvement, sensitivity to change, predictive validity, acceptability and implementation issues in a subsequent study.

Pediatric Adverse Drug Reactions: An Observational Cohort Study After Health Care Workers' Training.

Adverse drug reactions (ADRs) in children are an important but underestimated public health issue. This study describes ADRs in a registered pediatric population of Bologna and demonstrates that ADRs might be better detected after health care personnel training. A prospective cohort was recruited from July 1, 2016, to June 30, 2019, after health care worker sensitization, and compared to a retrospective cohort enrolled from 2013 to 2016. The ADRs are classified by system organ classes and drugs are categorized according to the Anatomical Therapeutic Chemical classification system. We retrospectively recruited 78 pediatric patients with ADRs in the 2013 to 2016 period, and we prospectively enrolled 127 children in the 2016 to 2019 period. In both periods, most of the ADRs reported were classified as non-serious reactions (68.8%). The most frequent ADRs were general and administration site disorders. During 2013 to 2016 vaccines were the most frequent cause of ADRs (83.3%;) and the main reporters were health care workers other than physicians (84.6%), whereas during the second period, medical doctors become the main signalers (65.4%) and ADRs related to vaccines significantly decreased (55.1%). During the 2016 to 2019 period the number of drug categories was higher than in the 2013 to 2016 period (24 vs 8). Patients with ADRs due to vaccinations present more frequently a favourable outcome (63%). This study demonstrates that active pharmacovigilance and health care personnel sensitization are associated with improved ADR detection, providing valuable information about drugs' safety profile in pediatric patients.

Association of adverse cutaneous reactions with drug exposure: A case control analysis of a Tunisian pharmacovigilance database

Introduction (contexte de la recherche) Although case-control studies have been described as an excellent approach for validation and assessment of adverse drug reactions, no studies of this type have been published on adverse cutaneous reactions so far. To assess adverse cutaneous reactions using a case-control approach to qualify drug risks. The study used the Tunisian pharmacovigilance database of Monastir. The association between drugs and cutaneous reactions was assessed using a case/non-case method. Drugs were grouped according to the ATC Classification System. Patients were defined as “cases” if they have developed cutaneous reaction regardless of the causality assessment. Allother reports were “non-cases”. Association between reactions and drugs was calculated using the reporting odds ratio (ROR) with 95% confidence intervals (CIs). A P value < 0.05 was considered significant. The analysis was carried out on 3752 reports, of which 1908 concerned “cases” and 1768 concerned « non-cases ». The calculated risk estimates were significant for alimentary tract and metabolism group (ROR 1.3; 95% CI 1.1 to 1.6), blood and blood forming organs agents (ROR 1.5; 95% CI 1.1 to 2.1), cardiovascular system group (ROR 1.6; 95% CI 1.3 to 1.9), antiinfectives for systemic use (ROR 1.3; 95% CI 1.1 to 1.5), nervous system drugs (ROR 1.5; 95% CI 1.2 to 1.7). Dealyed cutaneous recations were associated to alimentary tract and metabolism ( P < 0.001), blood and blood forming organs ( P < 0.004), cardiovascular system ( P < 10-3), antiinfectives for systemic use ( P < 10-3), nervous system ( P < 0.001). Immediate cutaneous reactions were associated to musculo-skeletal system ( P < 0.02) and nervous system ( P < 0.009). Dealing with sublevels, antibacterials for systemic use, mainly penicillins and cephalosporins were associated to immediate reactions ( P < 10-3). Our findings corroborate risks for a number of drugs in inducing cutaneous reactions with a particular association between some reactions and specific drugs. Given the widespread use of these drug classes, awareness should be raised among patients and prescribers about these risks.

Non-bullous Impetigo: Incidence, Prevalence, and Treatment in the Pediatric Primary Care Setting in Italy.

Impetigo is a common skin infection in children. The worldwide prevalence in children is estimated to be 12%, but this may be lower since high-income countries are under-represented. This research aims to evaluate the incidence, prevalence, and management of children with non-bullous impetigo (NBI) residing in Italy. This retrospective cohort study included children up to 14 years of age enrolled in the Pedianet database from January 2004 to June 2018. Events were identified searching ICD9-CM codes (684 and 694.3) and free text fields for a diagnosis of NBI reported during a primary care visit. Diagnoses were manually validated, and events registered within 30-days after the index date were considered follow-ups. Incidence (IR) and prevalence (PR) rates of NBI were stratified by sex, age group, and calendar year. Topical and systemic antibiotic treatments were grouped based on ATC codes. 15,136 NBI episodes occurred in a total cohort of 225,979 children. The overall IR of NBI was 9.5 per 1,000 person-years, and children aged 1–4 years had the highest IR (13.2 per 1,000 person-years). A significant decrease in NBI IR from 13 per 1,000 person-years in 2004 to 7.46 per 1,000 person-years in 2018 (p < 0.0001) was noted. Most of the episodes were treated; systemic antibiotics were preferred over topical.ConclusionThe prevalence of NBI in children in Italy is less than one third than the global estimate and the trend in time is decreasing. Over prescriptions of systemic antibiotics pose a threat to the diffusion of antimicrobial resistance.

Proposal for Handling of Medicine Shortages Based on a Comparison of Retrospective Risk Analysis.

Introduction: We reviewed and compared current drug shortages and shortage management practices in six selected countries (Hungary, Belgium, Spain, Switzerland, Australia, United States) based on the most comprehensive national shortage databases for each country, for four Anatomical Therapeutic Chemical (ATC) groups, to analyze the criticality of drug shortages across countries and identify best practices in shortage management strategies. Materials and Methods: Countries were selected to cover a wide geographical range of high-income nations where a lack of economic power as a potential source of drug shortages is not observable. ATC groups were selected based on a pre-examination of the databases to analyze groups most often in shortage, and groups where the absence of which could have a severe negative impact on treatment outcomes. The bias originating from the different reporting systems had to be reduced to gain comprehensive and comparable information. The first bias-reducing mechanism was transforming the raw number of shortages into proportion per million people. Secondly, critical cases were classified, and thirdly, critical cases were compared with the Word Health Organization (WHO) Essential Medicine Lists. Results: The results indicate that every European country studied reports significantly higher total and critical shortages per population compared to the US and Australia. Within Europe, Hungary reports the highest number of cases both for total and critical shortages, while Spain has the lowest results in both aspects. While in the US and Australia critical shortages were observable in similar proportions across all ATC groups, in European countries ATC groups of anti-infectives for systemic use (J) and the nervous system (N) were found to account for a notably higher proportion of critical shortages. Current shortage management practices were examined in each country and classified into five groups to identify common best practices. Conclusions: Due to the different characterization of reporting systems, several bias-reducing mechanisms should be applied to compare and evaluate shortages. In addition, European harmonization should be initiated to create mutually acknowledged definitions and reporting systems, which could be the basis of good drug shortage handling practices in Europe.

Identifying Potential Drug-Related Problems Among Geriatric Patients With Use of an Integrated Clinical Decision Support Tool.

Background: Drug-related problems (DRPs) which arise from potentially inappropriate medications (PIMs) are a common problem in older people with multi-morbidity and polypharmacy. Aim: To develop an integrated PIM clinical decision support tool for identification of DRPs in geriatric multi-morbid polypharmacy patients, using the EU(7)-PIM and EURO-FORTA lists, with a focus on high-risk medications. Methods: The integrated PIM tool used the information on PIMs in both databases—the EU(7)-PIM and EURO-FORTA. PIMs were classified into four color groups based on risk profile: high-risk PIMs (should be avoided in older patients) as red, moderate-risk PIMs (require dose and/or treatment duration adjustment) as yellow, low-risk PIMs (low DRP risk) as green, and questionable PIMs (incomplete/missing information) as grey. Results: The summarized list of the high-risk (red and some grey) PIMs contained 81 active substances and medication classes. According to the ATC classification, most of the high-risk PIMs (n = 60, 74.1%) belong to the A, C, and N medication groups and 50.6% (n = 41) of the high-risk PIMs have currently marketing authorization in Estonia. The preliminary list of the moderate- and low-risk (yellow, green, and other grey) PIMs contained 240 active substances and medication classes, but sub-classification of this category into one or another group depends mainly on an individual patient´s clinical characteristics in a concrete analyzed study sample and needs further research. Conclusion: The integrated clinical decision support tool based on the EU(7)-PIM and EURO-FORTA criteria addresses the need for more efficient identification of DRPs. It can be applied to identify PIMs and geriatric prescribing problems in different health care settings, and also in a context of little clinical information available.

Clinical pharmacist interventions in a hospital emergency

Objective: To identify the types of interventions performed by clinical pharmacists in an intensive care unit and in the emergency of a hospital in the interior of Bahia. Methods: Cross-sectional study, carried out in a regional reference hospital for 27 cities, from May to August 2019. A form designed for the research was used, considering the interventions registered in the patient’s medical record. Pearson’s chi-square test was used to compare the proportions of categorical variables. Results: 814 interventions were performed in 102 patients, with a median of 14 and an interquartile range of 23. Of the most frequent interventions, 36.2% were related to drug interactions, with 99.2% being monitored (p&lt;0.001); 10.8% dosage adjustment in renal failure interventions with 72.7% not accepted (p&lt;0.001); 8.5% for dose interval with 73.9% not accepted (p&lt;0.001) and 6.1% of interventions that involved orientation (nursing guidelines) with 73.9% that were monitored (p&lt;0.001). Of the total interventions, 63.8% took place in the intensive care unit, 52.7% in male patients and 66.7% in people aged ≥ 60 years. Regarding the use of alerts, 53.4% of the interventions that were accepted had alerts (p&lt;0.001). 46.7% were directed to the medical team; 44.9% for more than one professional; 5.8% for nurses; and 2.6% for nursing technicians. The drugs related to the interventions performed were grouped according to the ATC classification, as follows: 20.5% in group J-Antiinfectives for systemic use, 18.8% in group A-Alimentary tract and metabolism; 12.4% of the C-Cardiovascular sistem device group. Conclusion: The number of interventions performed, as well as the population and sectors assisted demonstrate the importance of the clinical pharmacist inserted in the multidisciplinary team in the care of critically ill patients.

Neural networks for anatomical therapeutic chemical (ATC) classification

PurposeAutomatic anatomical therapeutic chemical (ATC) classification is progressing at a rapid pace because of its potential in drug development. Predicting an unknown compound's therapeutic and chemical characteristics in terms of how it affects multiple organs and physiological systems makes automatic ATC classification a vital yet challenging multilabel problem. The aim of this paper is to experimentally derive an ensemble of different feature descriptors and classifiers for ATC classification that outperforms the state-of-the-art.Design/methodology/approachThe proposed method is an ensemble generated by the fusion of neural networks (i.e. a tabular model and long short-term memory networks (LSTM)) and multilabel classifiers based on multiple linear regression (hMuLab). All classifiers are trained on three sets of descriptors. Features extracted from the trained LSTMs are also fed into hMuLab. Evaluations of ensembles are compared on a benchmark data set of 3883 ATC-coded pharmaceuticals taken from KEGG, a publicly available drug databank.FindingsExperiments demonstrate the power of the authors’ best ensemble, EnsATC, which is shown to outperform the best methods reported in the literature, including the state-of-the-art developed by the fast.ai research group. The MATLAB source code of the authors’ system is freely available to the public at https://github.com/LorisNanni/Neural-networks-for-anatomical-therapeutic-chemical-ATC-classification.Originality/valueThis study demonstrates the power of extracting LSTM features and combining them with ATC descriptors in ensembles for ATC classification.

Matching Drug Metabolites from Non-Targeted Metabolomics to Self-Reported Medication in the Qatar Biobank Study.

Modern metabolomics platforms are able to identify many drug-related metabolites in blood samples. Applied to population-based biobank studies, the detection of drug metabolites can then be used as a proxy for medication use or serve as a validation tool for questionnaire-based health assessments. However, it is not clear how well detection of drug metabolites in blood samples matches information on self-reported medication provided by study participants. Here, we curate free-text responses to a drug-usage questionnaire from 6000 participants of the Qatar Biobank (QBB) using standardized WHO Anatomical Therapeutic Chemical (ATC) Classification System codes and compare the occurrence of these ATC terms to the detection of drug-related metabolites in matching blood plasma samples from 2807 QBB participants for which we collected non-targeted metabolomics data. We found that the detection of 22 drug-related metabolites significantly associated with the self-reported use of the corresponding medication. Good agreement of self-reported medication with non-targeted metabolomics was observed, with self-reported drugs and their metabolites being detected in a same blood sample in 79.4% of the cases. On the other hand, only 29.5% of detected drug metabolites matched to self-reported medication. Possible explanations for differences include under-reporting of over-the-counter medications from the study participants, such as paracetamol, misannotation of low abundance metabolites, such as metformin, and inability of the current methods to detect them. Taken together, our study provides a broad real-world view of what to expect from large non-targeted metabolomics measurements in population-based biobank studies and indicates areas where further improvements can be made.