Anatomical Therapeutic Chemical Research Articles

Prevalence and Incidence of Medication-Treated Diabetes and Pattern of Glucose-Lowering Treatment During the COVID-19 Pandemic: Real-World Data from the Electronic Greek Prescription Database.

This study aimed to investigate the prevalence and incidence of medication-treated diabetes mellitus and the evolving patterns of glucose-lowering treatments the year before and during the first two years of the coronavirus disease 2019 (COVID-19) pandemic. Data from the Greek electronic prescription database were analyzed for 2019, 2020, and 2021. The study population included individuals with active social security numbers. Prevalence and incidence rates were calculated based on the dispensing of glucose-lowering medications according to their unique anatomical therapeutic chemical (ATC) code. The study population comprised 10,289,140 individuals in 2019, 10,630,726 in 2020, and 11,246,136 in 2021. Diabetes prevalence rates were 8.06%, 6.89%, and 7.91%, and incidence rates were 16.8/1000, 8.6/1000, and 13.4/1000 individuals, respectively. Metformin was the most prescribed medication, and newer classes, like sodium-glucose cotransporter-2 inhibitors 2 (SGLT-2) inhibitors and glucagon like peptide-1 (GLP-1) receptor agonists exhibited increasing trends. The study identified a decrease in medication-prescribed diabetes prevalence and incidence during the initial year of the COVID-19 pandemic, attributed to healthcare access restrictions. Subsequently, figures returned close to baseline levels. Glucose-lowering medication trends reflected adherence to local and international guidelines, with metformin as the cornerstone, and increasing preference for newer classes such as GLP-1 receptor agonists and SGLT-2 inhibitors.

Antibiotic exposure and colon carcinogenesis: In-depth profiling of a 492-patient cohort, with a focus on antibiotic classifications and subtypes.

e15643 Background: To investigate whether the use of specific antibiotics is associated with an increased risk of colon cancer incidence. Methods: We conducted a retrospective cohort study comprising 492 patients diagnosed with colon cancer between 2012 and 2022, with no prior malignancies and a minimum 5-year follow-up period. We collected demographic data, medical histories, and records of antibiotic exposure, categorizing antibiotics systematically based on the Anatomical Therapeutic Chemical (ATC) classification system. Patient antibiotic histories, including drug names, dosages, durations, and therapeutic indications, were included. Antibiotics were classified as broad-spectrum, narrow-spectrum, or extended-course. We performed univariate and multivariate logistic regression models and used propensity score matching to control for potential confounding variables, such as age, gender, co-morbidities, and concurrent medications. Subgroup analyses were conducted to identify specific antibiotic classes associated with an increased risk of colon cancer. Results: The mean age of the cohort was 65.7 years (SD ± 8.3), with an equal gender distribution. Adenocarcinoma was the predominant histological subtype (429 cases, 87%), with rare subtypes accounting for the remaining cases. Common co-morbidities included hypertension (226 cases, 46%), diabetes mellitus (108 cases, 22%), and hyperlipidemia (88 cases, 18%). The most frequently prescribed antibiotics were fluoroquinolones (158 cases, 32%), followed by cephalosporins (108 cases, 22%), and macrolides (88 cases, 18%). Extended-course antibiotics were administered in 138 cases (28%). Preliminary analysis revealed a statistically significant correlation between the use of extended-course antibiotics and the risk of colon cancer (Odds Ratio = 1.89, 95% Confidence Interval: 1.32-2.71, p < 0.05). No substantial association was observed with broad-spectrum or narrow-spectrum antibiotics. Subgroup analysis identified specific agents within the extended-course antibiotics, such as fluoroquinolones and clindamycin, with an elevated risk profile. Conclusions: This study suggests a potential association between the use of extended-course antibiotics and the development of colon cancer. Further validation through larger-scale, prospective studies is strongly recommended to confirm these findings. Further in-depth mechanistic inquiries, particularly in cellular signaling pathways and microbial interactions within the gut microbiome, are warranted to elucidate the underlying biological mechanisms driving this association.

Assessment of disease pattern and drug utilization among neurology intensive care unit patients in a developing country: an observational analysis

ABSTRACT Objective This study aimed to assess the disease pattern and drug utilization among admitted patients in a tertiary-care hospital’s neurology intensive care unit (neuro ICU). Methods A prospective observational cohort study was conducted between August 2022 and January 2023. Patients of any age and gender admitted to the neuro ICU were included, but those who declined to participate were excluded. Demographics, clinical, and medication details were consistently gathered and maintained until discharge. The World Health Organization (WHO)/International Network of Rational Use of Drugs (INRUD) prescribing indicators and the Anatomical Therapeutic Chemical (ATC) classification/Defined Daily Dose (DDD) system were used to evaluate drug use. Results A total of 516 patients were included, predominantly male (65.1%), with an average age of 54.62 ± 15.02 years. The most common diagnosis was stroke [72.3%, comprised of hemorrhagic (46.7%) and ischemic (25.6%)], followed by seizure disorders (6.6%), and central nervous system infections (5.4%). Patients received an average of 7.8 medications, 32.3% prescribed by generic name, 16.0% antibiotics, 74.1% injections, and 100% essential drugs. A (28.5%), C (19.2%), N (17.3%), J (19.2%), B (13.5%), and R (2.3%) were commonly prescribed ATC classes of medications. Number of DDDs was maximum for pantoprazole and furosemide. Based on discharged status, 41.0% were discharged on request, 24.8% against medical advice, 23.8% routine, and 10.2% mortality during hospitalization. Conclusion Our study reveals a high prevalence of hemorrhagic stroke, especially among men, diverging from global ischemic stroke trends. Irregular hypertension treatment is the primary cause, exacerbated by low healthcare knowledge in rural areas, where patients often discharge on request, probably due to poor socio-economic conditions. Urgent public awareness campaigns and further research are needed to address this elevated hemorrhagic stroke incidence.

Association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and macular degeneration in patients with diabetes: a nationwide population-based study in Taiwan.

Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes. The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications. Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75). We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.

#1018 Profiles of medication use in dialysis patients globally

Abstract Background and Aims Global patterns of medication use in dialysis have not been defined so far. This project aims to provide a real-world view of medication use in dialysis and to characterize therapeutic classes and types of medications. An anonymized dialysis dataset of a global kidney care network called Apollo Dial DB was used. The most common prescribed medications administered at home by the patients were assessed. Method This is a multi-center, retrospective study using real-life data from adult dialysis patients captured in the first version of the Apollo Dial DB dataset. This dataset contains anonymized dialysis data (longitudinal observation level data) on more than 540,000 unique dialysis patients in 40 countries from Jan 2018-Mar 2021. Home medications were analyzed based on Anatomical Therapeutic Chemical (ATC) codes. Top (most common) 5 ATC codes for home medication are presented, once as 4-digit ATC code classes (e.g., A12A for Calcium) and once as full/exact ATC code (e.g., A12AA04 as 7-digit code for Calcium carbonate). Results In Apollo Dial DB 497,723 patients had 10,538,324 documented home medication entries (on average 21 medication prescriptions per patient outside the dialysis clinic), thereof 114,978 patients had 1,607,168 ATC code entries. Each ATC code entry represents a documented prescription of individual length. All percentages shown below are related to 1,607,168 ATC code entries (not to patients). The top 4-digit ATC code classes of home medication were Calcium (8.60%), Vitamin A and D, including combinations (7.33%), All other Therapeutic Products (6.84%), Antithrombotic Agents (5.89%) and Selective Calcium Channel Blockers with mainly vascular Effects (5.39%) (Fig. 1). Out of the ATC class Calcium, Calcium carbonate (4.89%) and Calcium acetate (3.22%) are listed as number 1 and 3 of the top 5 ‘full’ ATC codes. Alfacalcidol (3.36%) of ‘Vitamin A and D, including combinations’ is also number 2 of the ‘full’ ATC code list. Amlodipine (3.07%), number 4 of the full ATC code list, represents the majority of ‘Selective Calcium Channel Blockers with mainly vascular Effects’. Sevelamer of ‘All other Therapeutic Products’ is listed as number 5 in the ATC code list with 2.91% (Fig. 2). Conclusion The top 5 home ATC classes of medications account for 34% of all home prescriptions in dialysis patients. They largely represent phosphate binders, vitamin A & D, antithrombotics, and antihypertensives/antiarrhythmic medications. Although, outside the dialysis clinic each patient has on average 21 medication prescriptions, a lot of these prescriptions represent the major medication classes. It is worthwhile to mention the presented data are related to prescriptions and not to duration of use, e.g., both a medication prescribed for 6 months and a prescription for 1 week are documented only once, even if time on drug varies. Further research is needed to explore global patterns, including further ATC code groups particularly on a patient level, accounting for duration of use and medication formulations, real-world application of various drugs (e.g., GLP1 drugs, HIF PH inhibitor) and accounting for US data with NDC codes.

Measuring population health using health expectancy estimates from morbidity and mortality databases.

The progressive incorporation of quality of life indicators in health planning meets a critical need: The evaluation of the performance of health services, which are under stress by multiple causes, but in particular by an ageing population. In general, national health plans rely on health expectancies obtained using the Sullivan method. The Sullivan health expectancy index combines age-specific mortality rates and age-specific prevalence of healthy life, obtained from health surveys. The objective of this work is to investigate an equivalent estimation, using available information from morbidity and mortality datasets. Mortality and morbidity information, corresponding to years 2016 and 2017, was obtained for the population of the county of Baix Empordà (Catalonia), N = 91,130. Anonymized individual information on diagnoses, procedures and pharmacy consumption contained in the individual clinical record (ICD and ATC codes), were classified into health states. Based on the observed health transitions and mortality, life expectancies by health state were obtained from a multistate microsimulation model. Healthy life expectancies at birth and 65 years for females and males were respectively HLE0female = 39.94, HLE0male = 42.87, HLE65female = 2.43, HLE65male = 2.17. These results differed considerably from the Sullivan equivalents, e.g., 8.25 years less for HLE65female, 9.26 less for HLE65male. Point estimates for global life expectancies at birth and 65 years of age: LE0female = 85.82, LE0male = 80.58, LE65female = 22.31, LE65male = 18.86. Health indicators can be efficiently obtained from multistate models based on mortality and morbidity information, without the use of health surveys. This alternative method could be used for monitoring populations in the context of health planning. Life Expectancy results were consistent with the standard government reports. Due to the different approximation to the concept of health (data-based versus self-perception), healthy life expectancies obtained from multistate micro simulation are consistently lower than those calculated with the standard Sullivan method.

A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.

To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation. We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs. We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis. Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.

Management of Prescription Medicines in Ukraine: Continuation of the Experimental Study on the Organization of Pharmaceutical Provision

Conducted the experimental study on the organization of pharmaceutical provision, complaints of patients from the position of management of prescription medicines in Ukraine. It has been proven that the level of organization of pharmaceutical supply affects patient complaints. 750 complaints from patients about unsatisfactory on the organization of the pharmaceutical provision were processed. Found that 77% of complaints of patients (women accounted for 70%; men – 30%) were related to late or incomplete on the organization of the pharmaceutical provision of prescription medicines. Violation of the rights of patients to receive medicines on discounted and free prescriptions of doctors was recorded in 88% of complaints. The matrix of complaints based on patient reports of unsatisfactory of prescription medicines of different clinical and pharmacological, classification and legal and nomenclature and legal groups was constructed. In accordance to the ATC classification, the clinical and pharmacological groups were distributed of medicines on 9 clinical and pharmacological groups. According to ATC code A, 5 INN medicines were not available to patients, and more complaints were received. According to ATC code B, 7 INN medicines were not available to patients, and more complaints were received. According to ATC code C, 25 INN medicines were not available to patients, and more complaints were received. According to ATC code D, 1 INN medicines were not available to patients, and more complaints were received. According to ATC code L, 2 INN medicines were not available to patients, and more complaints were received. According to ATC code M, 1 INN medicines were not available to patients, and more complaints were received. According to ATC code N, 13 INN medicines were not available to patients, and more complaints were received. According to ATC code R, 5 INN medicines were not available to patients, and more complaints were received. According to ATC code S, 2 INN medicines were not available to patients, and more complaints were received. The organization of pharmaceutical provision of these drugs was at a low level. It is substantiated that the main feature of pharmaceutical provision of patients is social orientation. It is proved that it is necessary to actively develop the social potential of health care facilities in the format of transparency, completeness, reliability, and efficiency of information about the costs that form the cost of drugs. In the course of the study, a matrix of complaints based on patient reports of unsatisfactory pharmaceutical provision of drugs of different clinical and pharmacological, classification and legal, nomenclature and legal groups was constructed. On the basis of the matrix of complaints, three national lists of drugs were developed with the further development of organizational and legal measures to increase the level of pharmaceutical provision of patients. It is noted that the reference mechanism of drug pricing is aimed at establishing the level of reimbursement at the expense of the state and reducing costs to 50% for pharmaceutical provision of patients.

Psychotropic medication use and mortality in patients with acute myocardial infarction complicated by cardiogenic shock

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Danish Heart Foundation the Research Foundation of Odense University Hospital & Rigshospitalet. Background The impact of pre-existing mental illness on mortality in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains unclear. Purpose This study aims to assess the relation between pharmacologically treated mental disorders at the time of AMICS admission with patient characteristics and mortality. A surrogate marker for mental illness was defined as having at least one reimbursed prescription for psychotropic medication (Anatomical Therapeutic Chemical (ATC) group and subgroups N05, N06) within one year prior to admission with AMICS. Patients were divided into three therapy categories: None, one ATC subgroup, or two or more ATC subgroups. One-year survivors were further stratified by therapy status one year before admission and one year after discharge. Mortality was assessed at 30 days (5 years for one-year survivors). Kaplan-Meier estimates and univariable and multivariable Cox proportional hazards models were used to assess mortality rates stratified by treatment group. Results Of the cohort, 425 patients (25%) received therapy with psychotropic medication within the previous year at the time of presentation with AMICS. Polypharmacy (two or more ATC N05, N06 subgroups) was identified in 132 patients (8%). In these patients, there was a higher prevalence of comorbidities and a greater proportion of females (42% vs. 21%, p<0.001), compared to no treatment. More patients in the polypharmacy group presented with chest pain (60% vs. 52%, p=0.031), they were less often triaged directly to an invasive center (55% vs. 70%, p<0.001), and 30-day mortality was higher (73% vs. 51%, p<0.001). Among the 712 one-year survivors, 121 (17%) were treated with one or more drugs within one year before and after their AMICS admission. 149 (21%) began receiving therapy in the year following their AMICS admission. 422 (59%) never received psychotropic medication. In an unadjusted Cox model, therapy with two or more drugs, compared to no therapy, was associated with higher 30-day mortality (hazard ratio (HR) 1.77, 95% confidence interval (CI) 1.43-2.19, p<0.001). This association remained significant in multivariable analysis (HR 1.66, 95%CI 1.22-2.26, p=0.001). Among one-year survivors, therapy with one or more drugs before and after AMICS was tied to an almost two-fold increase in five-year mortality (adjusted HR 1.95, 95%CI 1.23-3.10, p=0.004). Conclusions AMICS patients with pharmacologically treated mental illnesses were associated with higher mortality rates, as well as less favorable clinical profiles and treatment patterns. This increased risk remains evident among one-year survivors.

Recommendations for national registers of medicinal products with validated ATC codes and DDD values

Medicines have important effect on population health and it is important to have a system for assessing their effects and monitoring their use, expenditure and price. The basis for all these objectives is the availability of an internationally valid classification system of medicines and a measurement system of their utilisation. Since 1996 the WHO Headquarter has adopted and proposed the ATC (Anatomical Therapeutical Chemical) classiifcation and the DDD (Defined Daily Dose) as the global standard for medicine classification and utilisation sudies, respectively. The EURO-MED-STAT project has defined the criteria for the production, validation and maintenance of national registers with validated ATC codes and DDD values, as suggested by WHO. A register with a valid ATC code and DDD value is able to provide reliable information allowing calculation of utilisation and expenditure indicators (Utilisation in DDD; DDD/1000inh/day and Expenditure per DDD).

The comparative analysis of the economic availability of antihypertensives from the group of beta-blockers in Ukraine

The comparative analysis of the economic availability of antihypertensives from the group of beta-blockers in Ukraine

The analysis of medical prescriptions for patients with duodenal ulcer in hospital setting

The analysis of medical prescriptions for patients with duodenal ulcer in hospital setting

Administration of Drugs for Pharmacotherapy of Tuberculosis According to GSP Requirements

This research paper outlines the findings from a comprehensive investigation focused on the dispensation and management of antituberculosis medications in pharmaceutical practices. The examination of antituberculosis medications was conducted using various classification systems, including ATC codes, clinical and pharmacological, classification and legal, nomenclature and legal groups. The study provides a detailed analysis of the harmonization process for GxP standards within Ukraine, offering a thorough understanding of the current practices. Additionally, the research looks into the supply chain dynamics of antituberculosis medication distribution. Developed within the study are strategic guidelines for the proper storage of these medications, essential for maintaining their efficacy and safety. A systematic proposal for the spatial organization of storage facilities in the wholesale sector is presented, ensuring compliance with GSP. The study’s goal was to refine the methodologies involved in the storage and management of antituberculosis drugs, with the ultimate aim of enhancing the efficiency of tuberculosis treatment protocols. This, in turn, is expected to elevate the caliber of healthcare delivery and pharmaceutical care available to patients afflicted with tuberculosis. Expanding on the study's contributions, the paper highlights the implications of these findings for public health policy and the potential to streamline pharmaceutical organization. By drawing attention to the criticality of adherence to rigorous storage protocols, the research underscores the necessity of meticulous oversight in the pharmaceutical supply chain. The insights gained from the study are not only pivotal for healthcare providers but also for policymakers tasked with the mandate of curbing the tuberculosis epidemic. The proposed recommendations provide a scaffold for future enhancements in drug management practices.

Utilization Trends of Phosphodiesterase Type-5 Inhibitors for Erectile Dysfunction Between 2019 and 2023 in Tanzania.

Introduction Erectile dysfunction (ED) profoundly affects millions of people globally, including interfering with mental health and quality of life. Phosphodiesterase type-5 inhibitors (PDE5Is) such as sildenafil are pivotal in ED treatment. This study aimed to examine the utilization patterns ofPDE5Is in Tanzania. Materials and methods In this retrospective longitudinal study, data on sildenafil and other similar PDE5Is imported between 2019 and 2023 were sourced from the Tanzania Medicines and Medical Devices Authority (TMDA). Pre-processing and visualization were performed using Microsoft Power BI Desktop, and further analysis was performed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). Utilization trends were ascertained through curve fitting, Holt's linear trend model, and autoregressive integrated moving average (ARIMA) models. The defined daily doses (DDDS) per 1000 inhabitants (DID) were calculated using the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) Classification System and the DDD methodology endorsed by the WHO Collaborating Centre for Drug Statistics Methodology. Results Between 2019 and 2023, there was a pronounced increase in the importation of approximately 587 consignments of PDE5Is. Employing the Holt model (R-square = 0.843), a substantial increase from 0.220910 DID in 2019 to 0.534272 DID by 2025 was observed and anticipated. The period witnessed sildenafil dominating 75.5% of the total use, with Erecto being the most consumed brand (37.6% of totalDID). Notably, 2022 had the highest surge (27.2% of the total), albeit a slight decline was observed in 2023 (20.5%). This trend was supported by a linear regression model (R-square = 0.889). Conclusion We found increasing annual trends of PDE5Is of utilization. This requires critical oversight and effective policies to ensure appropriate use and risk minimization.

Improving the prescriptive appropriateness of vitamin D: The Italian experience

At the Asl Napoli 3 SUD a local, regional and national level analysis of prescription and spending related to the prescription and dispensing of drugs intended to increase vitamin D levels in the human body was carried out. The Italian Pharmacy Regulatory Agency (AIFA) in late 2019 introduced a prescriptive note of appropriateness (note 96) to regulate the prescribing activity of a drug that is widely used on the Italian national population, significantly affecting spending by the National Health System (NHS). Despite this action there has been an increase in prescription and expenditure of calcifediol at all levels of analysis (national, regional and local) while regarding the remaining Anatomical Therapeutic Chemical (ATC) referring to drugs used as vitamin D supplement in the Campania Region and at the Asl Napoli 3 SUD there is a slower decrease in expenditure and prescription, sometimes even increasing and in countertendency to the Italian national average. For these reasons, the Campania Region instituted two executive decrees (DD 405/2021 and 91/2022) that led to a marked reduction in spending and prescription in 2022 even higher than in other Italian regional realities. This analysis aims to show how vitamin D prescription is widespread and often inappropriate, attested by wide regional variability. In addition, the main recommendations for the use of these drugs are highlighted in order to raise awareness among all healthcare professionals of the informed use of these molecules ensuring sustainability and governance.

Predictive modeling of skin permeability for molecules: Investigating FDA-approved drug permeability with various AI algorithms.

The transdermal route of drug administration has gained popularity for its convenience and bypassing the first-pass metabolism. Accurate skin permeability prediction is crucial for successful transdermal drug delivery (TDD). In this study, we address this critical need to enhance TDD. A dataset comprising 441 records for 140 molecules with diverse LogKp values was characterized. The descriptor calculation yielded 145 relevant descriptors. Machine learning models, including MLR, RF, XGBoost, CatBoost, LGBM, and ANN, were employed for regression analysis. Notably, LGBM, XGBoost, and gradient boosting models outperformed others, demonstrating superior predictive accuracy. Key descriptors influencing skin permeability, such as hydrophobicity, hydrogen bond donors, hydrogen bond acceptors, and topological polar surface area, were identified and visualized. Cluster analysis applied to the FDA-approved drug dataset (2326 compounds) revealed four distinct clusters with significant differences in molecular characteristics. Predicted LogKp values for these clusters offered insights into the permeability variations among FDA-approved drugs. Furthermore, an investigation into skin permeability patterns across 83 classes of FDA-approved drugs based on the ATC code showcased significant differences, providing valuable information for drug development strategies. The study underscores the importance of accurate skin permeability prediction for TDD, emphasizing the superior performance of nonlinear machine learning models. The identified key descriptors and clusters contribute to a nuanced understanding of permeability characteristics among FDA-approved drugs. These findings offer actionable insights for drug design, formulation, and prioritization of molecules with optimum properties, potentially reducing reliance on costly experimental testing. Future research directions include offering promising applications in pharmaceutical research and formulation within the burgeoning field of computer-aided drug design.

Mental health services in Gauteng, South Africa: A proxy evaluation using pharmaceutical data.

South African legislation advocates for equitable access to mental healthcare services integrated into general healthcare settings. Mental, neurological, and substance use (MNS) disorders are often comorbid. Pharmacoepidemiology provides indirect evidence of service provision for conditions amenable to medicine treatment. The study aims to evaluate medicine procurement for MNS disorders at different service levels in the health system. The Public health sector, Gauteng province formed the setting for the study. A secondary analysis of the Gauteng pharmaceutical database was conducted using Anatomic Therapeutic Chemical (ATC) and defined daily dose (DDD) methodology. Anatomic Therapeutic Chemical classes of medicines for MNS disorders were included. Defined daily doses and costs were calculated per 1000 population served by each facility and service level. Statistical comparisons were made using chi-square testing. General healthcare settings accounted for 90% (R118 638 248) and specialised hospitals for 10% (R13 685 032) of expenditure on medicines for MNS disorders, procuring 94% (n = 49 442 474) and 6% (n = 3 311 528) of DDDs, respectively. Although district clinics procured 60% of DDDs, they procured the least per 1000 population served, whereas district hospitals procured the most. For almost all ATC classes, procurement differed significantly between municipalities at every service level and between specialised hospitals. In Gauteng province, most medicines for MNS disorders are procured by general healthcare services, but access to care may not be equitable. While population coverage at district clinics appears low, district hospitals may experience the greatest care burden. Research regarding quality of care at each service level is recommended. This study provides insight into service provision for MNS disorders.

Genetic evidence for T-wave area from 12-lead electrocardiograms to monitor cardiovascular diseases in patients taking diabetes medications.

Aims Many studies indicated use of diabetes medications can influence the electrocardiogram (ECG), which remains the simplest and fastest tool for assessing cardiac functions. However, few studies have explored the role of genetic factors in determining the relationship between the use of diabetes medications and ECG trace characteristics (ETC). Methods Genome-wide association studies (GWAS) were performed for 168 ETCs extracted from the 12-lead ECGs of 42,340 Europeans in the UK Biobank. The genetic correlations, causal relationships, and phenotypic relationships of these ETCs with medication usage, as well as the risk of cardiovascular diseases (CVDs), were estimated by linkage disequilibrium score regression (LDSC), Mendelian randomization (MR), and regression model, respectively. Results The GWAS identified 124 independent single nucleotide polymorphisms (SNPs) that were study-wise and genome-wide significantly associated with at least one ETC. Regression model and LDSC identified significant phenotypic and genetic correlations of T-wave area in lead aVR (aVR_T-area) with usage of diabetes medications (ATC code: A10 drugs, and metformin), and the risks of ischemic heart disease (IHD) and coronary atherosclerosis (CA). MR analyses support a putative causal effect of the use of diabetes medications on decreasing aVR_T-area, and on increasing risk of IHD and CA. ConclusionPatients taking diabetes medications are prone to have decreased aVR_T-area and an increased risk of IHD and CA. The aVR_T-area is therefore a potential ECG marker for pre-clinical prediction of IHD and CA in patients taking diabetes medications.

Classifying Multimorbidity Using Drug Concepts via the Rx-Risk Comorbidity Index: Methods and Comparative Cross-Sectional Study.

The study objective was to update a method to identify comorbid conditions using only medication information in circumstances in which diagnosis codes may be undercaptured, such as in single-specialty electronic health records (EHRs), and to compare the distribution of comorbidities across Rx-Risk versus other traditional comorbidity indices. Using First Databank, RxNorm, and its web-based clients, RxNav and RxClass, we mapped Drug Concept Unique Identifiers (RxCUIs), National Drug Codes (NDCs), and Anatomical Therapeutic Chemical (ATC) codes to Rx-Risk, a medication-focused comorbidity index. In established rheumatoid arthritis (RA) and osteoarthritis (OA) cohorts within the Rheumatology Informatics System for Effectiveness registry, we then compared Rx-Risk with other comorbidity indices, including the Charlson Comorbidity Index, Rheumatic Disease Comorbidity Index (RDCI), and Elixhauser. We identified 965 unique ingredient RxCUIs representing the 46 Rx-Risk comorbidity categories. After excluding dosage form and ingredient related RxCUIs, 80,911 unique associated RxCUIs were mapped to the index. Additionally, 187,024 unique NDCs and 354 ATC codes were obtained and mapped to the index categories. When compared to traditional comorbidity indices in the RA cohort, the median score for Rx-Risk (median 6.00 [25th percentile 2, 75th percentile 9]) was much greater than for Charlson (median 0 [25th percentile 0, 75th percentile 0]), RDCI (median 0 [25th percentile 0, 75th percentile 0]), and Elixhauser (median 1 [25th percentile 1, 75th percentile 1]). Analyses of the OA cohort yielded similar results. For patients with a Charlson score of 0 (85% of total), both the RDCI and Elixhauser were close to 1, but the Rx-Risk score ranged from 0 to 16 or more. The misclassification and under-ascertainment of comorbidities in single-specialty EHRs can largely be overcome by using a medication-focused comorbidity index.

Clinical aspects of reimbursement policies for orphan drugs in Central and Eastern European countries.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications. Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs. Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a "strong" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a "moderate" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the "positive HTA recommendation guarantees reimbursement" policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001). Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.