Anatomical Therapeutic Chemical Research Articles

Bioequivalence of recombinant factor VIII products: a position paper from the Italian Association of Hemophilia Centers.

Over the last three decades, the continuous evolution of recombinant factor VIII (rFVIII) concentrates for replacement treatment of hemophilia A, including recent extended half-life products, implies that patients may switch from one product to another, technologically more advanced, with the aim of improving treatment efficacy, safety, management and, ultimately, quality of life. In this scenario, the issues of bioequivalence of rFVIII products and the clinical implications of their interchangeability are keenly debated, in particular when economic reasons or purchasing systems influence product availability and choices. Although sharing the same Anatomical Therapeutic Chemical (ATC) level, rFVIII concentrates, as other biological products, show relevant differences in terms of molecular structure, source and manufacturing process, which make them unique products, recognized as new active substances by regulatory agencies. Moreover, data from clinical trials with both standard and extended half-life products clearly document the large inter-patient variability of pharmacokinetic profiles after administering the same dose of the same product; in cross-over evaluations, even when mean values are comparable, some patients show better patterns with one product or with the comparator one. Pharmacokinetic assessment thus reflects the response to a specific product in the individual patient, with his genetic determinants, only partially identified, affecting the behavior of exogenous FVIII. These concepts, consistent with the currently recommended approach of personalization of prophylaxis, are discussed in this position paper endorsed by the Italian Association of Hemophilia Centers (AICE), highlighting that ATC or other available classifications do not completely consider differences between drugs and innovations and that substitutions of rFVIII products will not invariably ensure the previously achieved clinical outcomes or generate benefits for all patients.

Quantitative and Qualitative Analysis of Antibiotics in the Intensive Care Unit (ICU)

The high incidence of infection in the ICU requires frequent use of antibiotics, thereby increasing the risk of developing antibiotic resistance when used irrationally. To assess the quantity and quality of antibiotic use, the World Health Organization (WHO) recommends using the Anatomical Therapeutic Chemical (ATC) classification system or the Defined Daily Dose (DDD) method. In that study, 25 articles were analyzed, including 21 quantitative research articles and four qualitative research articles. These articles were obtained from three databases: PubMed Central (PMC), Research Gate, and Google Scholar. The most commonly used antibiotics in the ICU are ceftriaxone (1×2g, IV) with a DDD value of 358,139/100 bed-days, meropenem (3×2g, IV) with a DDD value of 289,747/100 bed-days, and piperacillin-tazobactam (4×4.5g, IV) with a DDD value of 164,816/100 bed-days. These values indicate the number of antibiotics used in relation to 100 days of sleep. In addition, evaluation of the quality of antibiotic use in the ICU revealed that it is generally characterized by irrational use. By conducting such research, healthcare professionals can optimize the use of antibiotics in the ICU, leading to more effective treatment outcomes while minimizing the development of antibiotic resistance. Keywords: Antibiotics, ATC/DDD, Gyssens, intensive care unit

Analysis on the Marketing Trend and Approval Lag of Imported Orphan Drugs from 2010 to 2021 in China.

In order to meet the unmet needs of rare disease patients in China, importing orphan drugs is an important way. The objectives of this study were to investigate the marketing trend of orphan drugs approved by the US Food and Drug Administration (FDA) and imported by China, to examine the orphan drug lag between China and the United States. This study analyzes the orphan drugs approved by FDA and imported by China from January 2010 to December 2021. The approval lag for orphan drugs between China and the US was calculated and analyzed by approval time. Factors potentially affecting the approval lag, such as target disease, ATC classification, formulation, corporation name, drug type, and whether the indications belong to the first batch of rare diseases catalogue were investigated. The number of FDA-approved orphan drugs imported by China is increasing year by year, and the approval lag of these drugs is gradually decreasing, especially in the classification of Non-L, Injections, Non-United States, and biological product. Compared with 2010-2015, the approval lag of total drugs in the study was significantly improved in 2016-2021 (1977days) compared with 2010-2015 (3928days). China's groundbreaking regulatory reforms of drugs since 2015 had made significant progress in reducing orphan drug lags, but there is still considerable room for progress. We should more actively promote the approval of rare disease drugs in China, establish a better approval mechanism, and enable Chinese patients with rare diseases to receive drug treatment in a timely manner.

Increase in Chronic Medications and Polypharmacy-The Multifaceted Burden of COVID-19 Disease on Public Health Care.

The long-term impact of COVID-19 disease is becoming a major global concern. In this retrospective monocentric analysis, we included consecutive subjects admitted to our COVID-19 Post-Acute Care Service for a SARS-CoV-2 infection that occurred between three and twelve months before. A home medication list relative to the period before SARS-CoV-2 infection (baseline) was recorded and compared with that one relative to the time of outpatient visit (follow-up). Drugs were coded according to the Anatomical Therapeutic Chemical Classification (ATC) System. In a total of 2007 subjects, at follow-up, a significant increase with respect to baseline was reported in the total median number of chronic medications (two [0-4] vs. one [0-3]) and in specific ATC-group drugs involving the alimentary, blood, cardiovascular, genitourinary, muscle-skeletal, nervous and respiratory systems. In a multivariate analysis, COVID-19 disease severity and age > 65 years resulted in the best predictors for an increase in the number of medications, while anti-SARS-CoV-2 vaccination played a significant protective role. The long-term care of patients infected by COVID-19 may be more complex than reported so far. Multidisciplinary and integrated care pathways should be encouraged, mainly in older and frailer subjects and for patients experiencing a more severe disease. Vaccination may also represent a fundamental protection against long-term sequelae.

Gender differences in the management of acute psychiatric episodes in the emergency department: a cross-sectional analysis of the 2017-2019 triennium.

There is growing evidence that gender is an important determinant of mental health and well-being. In this sense, both biological and socio-economic factors play a key role in how people experience psychological disturbances. This study examine whether there were sex- and gender-based differences in the management of psychiatric disorders in the emergency department (ED). A cross-sectional retrospective study was conducted in the ED over the 2017-2019 period. Sex was codified as female/male and socio-economic deprivation index was compiled to address the impact of social determinants. Episodes were reclassified according to four major clusters. Psychotropic drug prescription was categorized according to the ATC classification. Poisson regression models, adjusted for age and socioeconomic status, were used. A total of 9789 episodes (53.9% females) of individuals who required an acute-related psychiatric intervention were retrieved. Age distribution and socioeconomic quintiles revealed gender differences. Anxiety-related consultations accounted for up to 50% of all episodes. Female gender was found to be overrepresented in anxiety and stress-related disorders, mood disorders, and personality disorders. In contrast, Males accounted for 70% of all psychoactive substance use disorders. Considering main clinical syndromic clusters, analysis showed that female patients were more likely to be prescribed with anxiolytic treatment in ED treatment than men in the categories of "Common mental disorders" (PR = 1.122 [1.014-1.242; p = 0.025), "Severe Mental Disorders" (PR = 1.217[1.054-1.406] p = 0.007) and "Personality disorders" (PR = 1.398 (1.038 - 1.884); p = 0.028). This study highlights the relevance of considering sex and gender as potential determinants in both the clinical presentation and management of psychiatric emergencies.

Pharmacotherapeutic profile, polypharmacy and its associated factors in a cohort of people living with HIV in Brazil

BackgroundThe increased survival provided by the access, development, and evolution of antiretroviral drugs (ARV) greatly increased the life expectancy of people living with HIV (PWH). This has also led to an increased occurrence of diseases or morbidities related to aging. In individuals with multiple comorbidities, the simultaneous use of multiple medications, also known as polypharmacy, is common, and rational use of medications is essential. This study aims to describe the pharmacotherapeutic profile, estimate the prevalence of polypharmacy and identify factors associated with polypharmacy in a cohort of adult PWH from a referral unit in Rio de Janeiro, Brazil.MethodsCross-sectional study including PWH on ARV who received at least one medical prescription (outpatient/hospitalized) in 2019. We described the proportion of prescribed medications according to ARV and Anatomical Therapeutic Chemical (ATC) classes stratified by age (< 50 vs. ≥50 years). Polypharmacy was defined as ≥ 5 medications prescribed beyond ARV. Logistic regression models assessed demographic and clinical factors associated with polypharmacy.ResultsA total of 143,306 prescriptions of 4547 PWH were analyzed. Median age was 44.4 years (IQR:35.4–54.1) and 1615 (35.6%) were ≥ 50 years. A total of 2958 (65.1%) participants self-identified as cisgender man, 1365 (30.0%) as cisgender woman, and 224 (4.9%) as transgender women. Most self-declared Black/Pardo (2582; 65.1%) and 1984 (44.0%) completed elementary education or less. Median time since HIV diagnosis was 10.9 years (IQR:6.2–17.7). Most frequently prescribed concomitant medications were nervous system (64.8%), antiinfectives for systemic use (60.0%), alimentary tract and metabolism (45.9%), cardiovascular system (40.0%) and respiratory system (37.1%). Prevalence of polypharmacy was 50.6% (95%CI: 49.2–52.1). Model results indicated that being older, self-identify as cisgender woman, having less education and longer time since HIV diagnosis increased the odds of polypharmacy.ConclusionsWe found high rates of polypharmacy and concomitant medication use in a cohort of PWH in Brazil. Targeted interventions should be prioritized to prevent interactions and improve treatment, especially among individuals using central nervous system and cardiovascular medications, as well as certain groups such as cisgender women, older individuals and those with lower education. Standardized protocols for continuous review of patients’ therapeutic regimens should be implemented.

Patterns of Prescription Medication Use Before Diagnosis of Early Age-Onset Colorectal Cancer: Population-Based Descriptive Study.

Colorectal cancer (CRC) is estimated to be the fourth most common cancer diagnosis in Canada (except for nonmelanoma skin cancers) and the second and third leading cause of cancer-related death in male and female individuals, respectively. The rising incidence of early age-onset colorectal cancer (EAO-CRC; diagnosis at less than 50 years) calls for a better understanding of patients' pathway to diagnosis. Therefore, we evaluated patterns of prescription medication use before EAO-CRC diagnosis. We used linked administrative health databases in British Columbia (BC), Canada, to identify individuals diagnosed with EAO-CRC between January 1, 2010, and December 31, 2016 (hereinafter referred to as "cases"), along with cancer-free controls (1:10), matched by age and sex. We identified all prescriptions dispensed from community pharmacies during the year prior to diagnosis and used the Anatomical Therapeutic Chemical Classification system Level 3 to group prescriptions according to the drug class. A parallel assessment was conducted for individuals diagnosed with average age-onset CRC (diagnosis at age 50 years and older). We included 1001 EAO-CRC cases (n=450, 45% female participants; mean 41.0, SD 6.1 years), and 12,989 prescriptions were filled in the year before diagnosis by 797 (79.7%) individuals. Top-filled drugs were antidepressants (first; n=1698, 13.1%). Drugs for peptic ulcer disease and gastroesophageal reflux disease (third; n=795, 6.1%) were more likely filled by EAO-CRC cases than controls (odds ratio [OR] 1.4, 95% CI 1.2-1.7) and with more frequent fills (OR 1.8, 95% CI 1.7-1.9). We noted similar patterns for topical agents for hemorrhoids and anal fissures, which were more likely filled by EAO-CRC cases than controls (OR 7.4, 95% CI 5.8-9.4) and with more frequent fills (OR 15.6, 95% CI 13.1-18.6). We observed frequent prescription medication use in the year before diagnosis of EAO-CRC, including for drugs to treat commonly reported symptoms of EAO-CRC.

Long-term medical treatment and adherence in patients with left ventricular assist devices: a Danish nationwide cohort study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Grant from Karen Elise Jensen Foundation and Helse Foundation. Introduction An increasing number of patients with advanced heart failure (HF) live with a left ventricular assist device (LVAD). Data regarding medical treatment after LVAD implantation is sparse, including the impact of socioeconomic factors and multimorbidity. Purpose To describe medication use and assess the influence of socioeconomic factors and multimorbidity on medication use in the first two years following LVAD implant. Methods We conducted a nationwide cohort study based on data from the Danish clinical LVAD databases, the Scandiatransplant Database, and Danish nationwide administrative and medical registries. We identified patients with LVAD implantation between January 1, 2008, and December 31, 2018, who were discharged with LVAD therapy. Patients were followed until heart transplantation, LVAD explant, death, or December 31, 2018. Medication use was defined as a redeemed prescription from the Danish National Prescription Registry using ATC codes. Socioeconomic factors included cohabitation status, highest education attained, employment status, and personal income. Multimorbidity was defined as two or more chronic conditions. Medical treatment 90 days before LVAD implant and 720 days post-LVAD were assessed using descriptive statistics in 90 days intervals. Results We identified 119 patients; 88.2% were male, and the mean age (standard deviation) was 52.6 (14.5) years. The median (IQR) follow-up time was 0.8 years (0.4;1.8 years). 44.5% of patients underwent heart transplantation, and 4.2% had the LVAD explanted during follow-up. 27.7% of the patients were living alone, 27.7% had a low educational level, 37.8% were unemployed, 15.1% were in the lowest income (25 percentile), and 16.8% were categorized with multimorbidity (without cardiovascular disease group). The proportion of medication users of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (88.7%), beta-blocker (67%), mineralocorticoid receptor antagonists (62.9%), warfarin (87.6%), and aspirin (55.7%) within 90 days post-LVAD were substantially higher than pre-LVAD and were stable during the follow-up (Figure 1). In contrast, the proportion of diuretic users was lower post-LVAD implant than pre-LVAD, decreased further, and plateaued up to 180 days after hospital discharge. Stratified analyses according to socioeconomic factors and multimorbidity showed no differences in medication use (Figure 2). Conclusions Guideline-derived medical therapies for HF increased after LVAD implantation and were stable during long-term follow-up. As expected, the proportion of warfarin users increased substantially after LVAD implantation. Surprisingly, the percentage of aspirin users was not at the same level as for warfarin users. Socioeconomic factors and comorbidity burden did not influence long-term medication use of guideline-derived HF therapies, warfarin and aspirin in LVAD recipients.

Prescribing of valproate and oral antiepileptics for women of childbearing age and during pregnancy in Germany between 2010 and 2020.

To examine prescriptions of valproate and oral antiepileptic drugs (OAED) in Germany irrespective of the indication in women in general and particularly in women of childbearing age (13-49 years) and during pregnancy between 2010 and 2020, that is, before, during and after the implementation of the EU risk minimization measures (RMMs). Analysis of claims data. all women continuously insured with the AOK health insurance fund in the respective observation year (2010-2020) and the previous year. OAED were identified by ATC code N03. Period of pregnancy was calculated based on birth information in claims data. (i) prevalent use of valproate/OAED: number of women with at least one prescription of valproate/OAED per year divided by all women of the study population (rate per 1000 women); (ii) percentage of OAED recipients with at least one valproate prescription during pregnancy (13-49 years) in the respective observation year. Prevalence rate/1000 women for valproate use decreased by -31.33% across all age groups (2010-2014: -7.48%; 2014-2018: -16.47%; 2018-2020: -11,17%) with a strong reduction in women 13-49 years between 2014 and 2018 (-28.74%). The rate for OAED across all age groups rose from 33.43/1000 women in 2010 to 41.03/1000 (+22,73%). Valproate use during pregnancy of women with OAED declined from 1.29% in 2010 to 0.59% in 2020 (-54,26%) (2010-2014: -5.14%; 2014-2018: -42.31%; 2018-2020: -16.69%). Even if, due to the descriptive nature of the study, no causal relationship can be postulated between the RMMs and the strong decrease in valproate prescriptions, our results are compatible with the hypothesis that the measures have improved drug therapy safety.

The place of sclerotherapy in the treatment of varicose vein disease

Aim. To evaluate effectiveness of the scleroobliteration in the treatment of small-diameter varicose veins.Materials and Methods. The analysis incorporated the results of sclerotherapy in 135 patients, comprising those with telangiectasias and reticular varicose veins (n=95) and those with varicose dilation of aberrant subcutaneous veins (n=40) with intact trunks of major and/or minor subcutaneous veins of the lower extremities. The sample included 111 women (82.2%) and 24 men (17.8%), with an average age of 35.2±6.5 years.For the obliteration of expanded subcutaneous veins, two sclerotherapy techniques were employed: liquid (n=65) and foam-form (n=70), prepared as per the L. Tessari method. Sclerosants used were a 0.5–3% sodium tetradecyl sulfate solution (“Fibro vein”) (ATC code: C05BB04) (n=69) or a 1-3% polidocanol solution (“Ethoxisclerol”) (ATC code: C05BB02) (n=66).A detailed analysis was carried out of all complications that developed during and at various times post-sclerotherapy, and the effectiveness of the treatment, which depended on the diameter of the expanded veins and the thoroughness of the procedure.Results. The technical success of the procedure was registered at 100%. The overall frequency of complications post-sclerotherapy was 20.7%, including 27.7% with the liquid form and 14.3% with the foam form of sclerosants (p&lt;0.001). Intradermal and subcutaneous hemorrhages were observed in 10 (7.4%) patients, allergic reactions in 8 (5.9%), localized skin necrosis in 3 (2.2%), folliculitis in 3 (2.2%), and localized purulent complications in 2 (1.5%). Micro-air embolism of the pulmonary artery branches due to exceeding the established norm of air volume during foam sclerotherapy was recorded in 2 (2.9%) cases.Following one session, a positive sclerotherapy effect was noted in 45.9% of patients. The necessity for additional sclerotherapy courses was indicated for over half the patients, with the effectiveness rising to 97.8% after 3 or more courses.Conclusion. Sclerotherapy, being an effective minimally invasive method, is significantly impactful in treating reticular varices and telangiectasias. Greater efficiency and a lower rate of complications have been observed with the use of foam form sclerosant. Proper selection of sclerosant volume and concentration is essential for the prevention and reduction of sclerotherapy complications.

The association between prescription drugs and colorectal cancer prognosis: a nationwide cohort study using a medication-wide association study

BackgroundWith the availability of health insurance claim data, pharmacovigilance for various drugs has been suggested; however, it is necessary to establish an appropriate analysis method. To detect unintended drug effects and to generate new hypotheses, we conducted a hypothesis-free study to systematically examine the relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients.MethodsWe used the Korean National Health Insurance Service-National Sample Cohort database. A total of 2,618 colorectal cancer patients diagnosed between 2004 and 2015 were divided into drug discovery and drug validation sets (1:1) through random sampling. Drugs were classified using the Anatomical Therapeutic Chemical (ATC) classification system: 76 drugs classified as ATC level 2 and 332 drugs classified as ATC level 4 were included in the analysis. We used a Cox proportional hazard model adjusted for sex, age, colorectal cancer treatment, and comorbidities. The relationship between all prescription nonanticancer drugs and the mortality of colorectal cancer patients was analyzed, controlling for multiple comparisons with the false discovery rate.ResultsWe found that one ATC level-2 drug (drugs that act on the nervous system, including parasympathomimetics, addictive disorder drugs, and antivertigo drugs) showed a protective effect related to colorectal cancer prognosis. At the ATC level 4 classification, 4 drugs were significant: two had a protective effect (anticholinesterases and opioid anesthetics), and the other two had a detrimental effect (magnesium compounds and Pregnen [4] derivatives).ConclusionsIn this hypothesis-free study, we identified four drugs linked to colorectal cancer prognosis. The MWAS method can be useful in real-world data analysis.

Exposure to systemic antibiotics in outpatient care and the risk of multiple sclerosis

Background: Infections, early life exposures and the microbiome have been associated with the aetiology of multiple sclerosis (MS). Data on any possible roles of antibiotics is scarce and conflicting. Objective: The objective of this study was to investigate associations between outpatient systemic antibiotic exposure and the risk of MS in a nationwide case-control setting. Methods: Patients with MS were identified from the nation MS registry and their exposure to antibiotics was compared with that of persons without MS, provided by the national census authority. Antibiotic exposure was investigated using the national prescription database and analyzed by Anatomical Therapeutic Chemical (ATC) category. Results: Among the 1830 patients with MS and 12765 control persons, there were no associations between exposure to antibiotics in childhood (5–9 years) or adolescence (10–19 years) and the subsequent risk of MS. There was also no association between antibiotic exposure 1–6 years before disease onset and the risk of MS, save for exposure to fluoroquinolones in women (odds ratio: 1.28; 95% confidence interval: 1.03, 1.60; p = 0.028) which is probably associated with the increased infection burden in the MS prodrome. Conclusion: Use of systemic prescription antibiotics was not associated with subsequent MS risk.

A 6-Year Review of the Electronic Drug Prescription System in the Republic of Türkiye

Pharmacoepidemiological studies are important for the development of health systems. The aim of this study is to examine the seasonal and branch changes of prescriptions written in the light of national data. Drug and prescription information between 01.01.2016 and 31.12.2022 analyzed retrospectively from electronic data. In addition to gender and age distribution, the specialty and hospital level at which the prescription was written were examined in temporal terms. Prescribed drugs have been classified according to Anatomical Therapeutic Chemical (ATC) codes previously created by the World Health Organization. It was determined that 1,452,128,177 prescriptions were written during the study period. These included a total of 4,602,556,489 drugs with the ATC code. The most written ATC code group was A (alimentary tract and metabolism), followed by M (musculo-skeletal system), and R (respiratory system) group drugs. In terms of specialization, the group that wrote the most prescriptions was family physicians, followed by emergency physicians, and internal medicine specialists. Examining prescription software trends is important when creating healthcare policies. Developing strategies to reduce prescription costs will contribute to the efficient use of resources and improving the quality and sustainability of health services delivery.

Medication-Wide Study: Exploring Medication Use 10 Years Before a Diagnosis of Inflammatory Bowel Disease.

There is growing interest in the prediagnostic phase of inflammatory bowel disease (IBD) and in the overlap of IBD with other diseases. We described and compared use of any prescription medication between individuals with and without IBD in a 10-year period preceding diagnosis. Based on cross-linked nationwide registers, we identified 29,219 individuals diagnosed with IBD in Denmark between 2005 and 2018 and matched to 292,190 IBD-free individuals. The primary outcome was use of any prescription medication in years 1-10 before IBD diagnosis/matching date. Participants were considered as medication users if they redeemed ≥1 prescription for any medication in the World Health Organization Anatomical Therapeutic Chemical (ATC) main groups or subgroups before diagnosis/matching. The IBD population had a universally increased use of medications compared with the matched population before IBD diagnosis. At 10 years before diagnosis, the proportion of users was 1.1-fold to 1.8-fold higher in the IBD population in 12 of 14 ATC main groups of medication ( P -value < 0.0001). This applied across age, sex, and IBD subtypes, although it was the most pronounced for Crohn's disease (CD). Two years before diagnosis, the IBD population had a steep increase in medication use for several organ systems. When analyzing therapeutic subgroups of medication, the CD population exhibited 2.7, 2.3, 1.9, and 1.9 times more users of immunosuppressants, antianemic preparations, analgesics, and psycholeptics, respectively, than the matched population 10 years before diagnosis ( P -value < 0.0001). Our findings demonstrate universally increased medication use years before IBD, especially CD, diagnosis and indicates multiorgan involvement in IBD.

UPDATE ON THE IVERMECTIN’ MODE OF ACTION AND RESISTANCE MECHANISMS: A GENERAL MEDICAL LITERATURE OVERVIEW

Ivermectin (IVM) is an antiparasitic drug, and it belongs to the avermectin family ofmedications. After its discovery in 1975, its first uses were in veterinary medicine toprevent and treat heartworm and acariasis. Approved for human use in 1987, today it isused to treat infestations including head lice, scabies, river blindness (onchocerciasis),strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through manymechanisms to kill the targeted parasites, and can be taken orally, or applied to the skinfor external infestations. It is on the World Health Organization's List of EssentialMedicines, it is available as a generic medicine, and is approved by the U.S. Food andDrug Administration as an antiparasitic agent. By the year 2022, it was the 420th mostcommonly prescribed medication in the United States, with more than 100,000prescriptions.The pioneering drug IVM, a dihydro derivative of avermectin originating solely froma single microorganism isolated at the Kitasato Intitute, Tokyo, Japan from Japanese soilhas had an immeasurably beneficial impact in improving the lives and welfare of billionsof people throughout the world. Originally introduced as a veterinary drug, it kills a widerange of internal and external parasites in commercial livestock and companion animals. Itwas quickly discovered to be ideal in combating two of the world’s most devastating anddisfiguring diseases which have plagued the world’s poor throughout the tropics forcenturies. It is now being used free-of-charge as the sole tool in campaigns to eliminateboth diseases globally. It has also been used to successfully overcome several other humandiseases and new uses for it are continually being found.IVM with many global trade names of Stromectol®, Soolantra®, Sklice® or Vietnamtrade names of Stromectin®, Pizar®, A.T Ivermectine®. IVM can be use in oral or topicalroute administration by ATC code D11AX22 (WHO) , P02CF01 (WHO), QP54AA01(WHO), QS02QA03 (WHO).

Comparing self-reported health interview survey and pharmacy billing data in determining the prevalence of diabetes, hypertension, and hypercholesterolemia in Belgium

BackgroundAdministrative and health surveys are used in monitoring key health indicators in a population. This study investigated the agreement between self-reported disease status from the Belgian Health Interview Survey (BHIS) and pharmaceutical insurance claims extracted from the Belgian Compulsory Health Insurance (BCHI) in ascertaining the prevalence of diabetes, hypertension, and hypercholesterolemia.MethodsLinkage was made between the BHIS 2018 and the BCHI 2018, from which chronic condition was ascertained using the Anatomical Therapeutic Chemical (ATC) classification and defined daily dose. The data sources were compared using estimates of disease prevalence and various measures of agreement and validity. Multivariable logistic regression was performed for each chronic condition to identify the factors associated to the agreement between the two data sources.ResultsThe prevalence estimates computed from the BCHI and the self-reported disease definition in BHIS, respectively, are 5.8% and 5.9% diabetes cases, 24.6% and 17.6% hypertension cases, and 16.2% and 18.1% of hypercholesterolemia cases. The overall agreement and kappa coefficient between the BCHI and the self-reported disease status is highest for diabetes and is equivalent to 97.6% and 0.80, respectively. The disagreement between the two data sources in ascertaining diabetes is associated with multimorbidity and older age categories.ConclusionThis study demonstrated the capability of pharmacy billing data in ascertaining and monitoring diabetes in the Belgian population. More studies are needed to assess the applicability of pharmacy claims in ascertaining other chronic conditions and to evaluate the performance of other administrative data such as hospital records containing diagnostic codes.

Developing an Artificial Intelligence-Guided Signal Detection in the Food and Drug Administration Adverse Event Reporting System (FAERS): A Proof-of-Concept Study Using Galcanezumab and Simulated Data.

Time- and resource-demanding activities related to processing individual case safety reports (ICSRs) include manual procedures to evaluate individual causality with the final goal of dismissing false-positive safety signals. Eminent experts and a representative from pharmaceutical industries and regulatory agencies have highlighted the need to automatize time- and resource-demanding procedures in signal detection and validation. However, to date there is a sparse availability of automatized tools for such purposes. ICSRs recorded in spontaneous reporting databases have been and continue to be the cornerstone and the most important data source in signal detection. Despite the richness of this data source, the incessantly increased amount of ICSRs recorded in spontaneous reporting databases has generated problems in signal detection and validation due to the increase in resources and time needed to process cases. This study aimed to develop a new artificial intelligence (AI)-based framework to automate resource- and time-consuming steps of signal detection and signal validation, such as (1) the selection of control groups in disproportionality analyses and (2) the identification of co-reported drugs serving as alternative causes, to look to dismiss false-positive disproportionality signals and therefore reduce the burden of case-by-case validation. The Summary of Product Characteristics (SmPC) and the Anatomical Therapeutic Chemical (ATC) classification system were used to automatically identify control groups within and outside the chemical subgroup of the proof-of-concept drug under investigation, galcanezumab. Machine learning, specifically conditional inference trees, has been used to identify alternative causes in disproportionality signals. By using conditional inference trees, the framework was able to dismiss 20.00% of erenumab, 14.29% of topiramate, and 13.33% of amitriptyline disproportionality signals on the basis of purely alternative causes identified in cases. Furthermore, of the disproportionality signals that could not be dismissed purely on the basis of the alternative causes identified, we estimated a 15.32%, 25.39%, and 26.41% reduction in the number of galcanezumab cases to undergo manual validation in comparison with erenumab, topiramate, and amitriptyline, respectively. AI could significantly ease some of the most time-consuming and labor-intensive steps of signal detection and validation. The AI-based approach showed promising results, however, future work is needed to validate the framework.

Antineoplastic and immunomodulating agent effects on immunization outcomes.

1539 Background: Oncologists face a challenge in advising patients on the infection risk associated with antineoplastic and immunomodulating medications, as the extent of risk posed by each medication is not well understood. The rapid administration of COVID-19 immunizations across the population provides an opportunity to assess the influence of immunosuppressing medications on infection outcomes post-vaccination. This study evaluated the effect of antineoplastic and immunomodulating medications as classified by the World Health Organization Anatomical Therapeutic Chemical Classification System (WHO ATC) on post-vaccination risk of COVID-19 infection and antibody response to multiple SARS-CoV-2 epitopes using serial serologic assessments. Methods: At a large, tertiary healthcare system in San Diego, we conducted an observational cohort study from December 11, 2020, to September 22, 2022, comparing vaccinated adult patients taking WHO ATC-classified immunosuppressing medications (“immunosuppressed” group) with matched control patients not prescribed these medications (“immunocompetent” group) for the outcome of PCR+ COVID-19 infection. A subset of immunosuppressed and immunocompetent individuals was consented to provide serial assessments of antibody response to multiple SARS-CoV-2 epitopes using the Genalyte serologic platform. Results: 12,709 vaccinated immunosuppressed patients and 197,151 immunocompetent controls were identified for matched analysis. Receiving an immunosuppressing medication conferred increased risk of COVID-19 infection post-immunization (HR: 1.5, 95% CI: 1.38 – 1.63, p &lt; 0.0001). Among immunosuppressing medications, PD1/PD-L1 inhibiting monoclonal antibodies and calcineurin inhibitors were associated with increased risk of COVID-19 infection (HR: 2.33, 95% CI: 1.35 – 4.04, p = 0.0038; HR 2.72, 95% CI: 1.78 – 4.16, respectively). Receiving three and four COVID-19 immunizations reduced this risk, except in patients taking calcineurin inhibitors. Among 87 consented participants, 218 samples from multiple timepoints revealed a decreased antibody response to both spike S1 and S2 subunits following third and fourth immunization. Despite decreased seroconversion, this study found medications like CD20 inhibiting monoclonal antibodies and folic acid analogs did not increase the post-immunization risk of COVID-19. Conclusions: These results help elucidate the relationship between antineoplastic and immunomodulating medications and COVID-19 immunization outcomes. In our patients, seroconversion efficacy did not always correspond to post-immunization infection, consistent with COVID-19 disease risk being multifactorial. The findings of this study inform oncologists’ shared decision-making process in advising patients of the risk of infection associated with immunomodulating medications and the potential impact on their vaccination response.

HPR117 Cross-Category Competition in Chinese Basic Medical Insurance Drug Formulary

China has established a new national dynamic adjustment mechanism of drug formulary covered by the basic medical insurance. In addition to the decision on including or excluding drugs within the same Anatomical Therapeutic Chemical (ATC) category, may the budget constraint of medical insurance fund pressure the decision maker to consider cross-category competition is still understudied.

Discrepancies in type of first major osteoporotic fracture and anti-osteoporotic therapy in elderly people with type 2 diabetes mellitus: A retrospective Danish cohort study.

Subjects with diabetes mellitus have an increased risk of fractures. We aimed to identify discrepancies in the first type of major osteoporotic fracture (MOF) and anti-osteoporotic therapy between subjects with type 2 diabetes (T2D) and subjects without diabetes. Methods and research design. We conducted a retrospective national cohort study by access to all discharge diagnoses (ICD-10 system) and redeemed drug prescriptions (ATC classification system). We included all subjects alive and Danish citizens in 2010 and identified subjects with T2D diagnosed after the age of 50 between 1998 and 2018. Only subjects with a MOF after the index date were included in the main analysis. The type of MOF was identified by diagnosis codes and categorized into Humerus, Forearm, Spine, and Hip. Multinomial logistic regression modeling was used to assess the predicted probability changes in MOF type between T2D and control subjects. Data on first anti-osteoporotic therapy after the MOF was assessed by redeemed drug prescriptions. Mortality and time to therapy after the MOF were evaluated by cox proportional hazards. We included 26,588 subjects with T2D and 97,982 subjects without diabetes. The mean age was age 69.33 (±10.34) for T2D and 69.85 (±10.19) for control subjects. The cohort was primarily females (67%). Subjects with T2D had a higher probability of hip (3.98% [95% CI 3.29; 4.67]) and humerus (2.82% [95% CI 2.17; 3.46]) fractures as the first MOF compared to control subjects. However, the probability of forearm fractures as the first MOF was 6.77% (95% CI 6.08; 7.46) lower among subjects with T2D. The multiple adjusted hazard ratio for anti-osteoporotic treatment after the first MOF was 0.80 (95% CI 0.77; 0.88) for T2D compared to controls among treatment-naïve subjects. Forearm fractures were the most frequent type of MOF and were more prevalent in control subjects. Subjects with T2D had a significantly higher probability of hip and humerus fractures as the first MOF but had a 20% lower chance of anti-osteoporotic treatment afterwards.