Drug Names Research Articles

Critical review and mechanistic insights into the health-protective and Immunomodulatory activity of Tiryāq (Theriac) from the purview of Unani medicine

BackgroundThe theriac, known in Arabic as tiryāq, is a medicinal panacea and an alexipharmic which was conceptualized during the 2nd century BC. During medieval ages, the Unani physicians employed various theriac formulations as an antidote, health-protective, and therapeutic in various disorders. In general, the theriac formulations contained many drugs having heath-protective, preventive, and restorative effects. Since the advent of COVID-19 pandemic, there has been a renewed interest in theriac formulations, and researches are underway to elaborate the scientific basis of their action mechanism. This article is an attempt to provide a comprehensive overview of theriac in Unani literature, as well as to elaborate on the potential mode of actions. MethodsSelected authoritative and comprehensive textbooks of Unani medicine and leading scientific websites (MEDLINE, PubMed, ScienceDirect, Springer, and PubMed Central) were explored for information regarding the theriac in Unani classical literature, and its potential usefulness in the present era. No time duration was specified for the search as certain drugs are now relatively obsolete. The keywords used for the search were ‘theriac’, ‘health’, ‘bioactive constituents’, ‘infection’, and ‘antidote’, etc., accompanied by names of drugs. ResultsPharmacological researches on theriac ingredients have revealed the presence of several bioactive compounds, having anti-inflammatory, antioxidant, antipyretic, antivenin, neuroprotective, hepatoprotective, cytotoxic, etc. activities.‎ An interesting step in theriac preparation is the process of maturation. It is scientifically proven that during maturation, the drugs undergo biotransformation through fermentation. Besides, certain drugs like Saffron, Celery, and Fennel, etc. increase bioavailability of other drugs. Overall, the Theriac formulations are a complex mixture of health-preservative, protective, therapeutic and restorative drugs. ConclusionsThe theriac formulations contain a thoughtful mixture of ingredients, which have health-protective as well as restorative effects. It is known that most toxins as well as biological disease-causing agents damage the vital organs and processes which lead to complications and death. Hence, the theriac formulations can provide the much-needed protection to these organs, and also maintain the physiological processes, and gives the body the necessary time and strength to recover from these adverse effects.

“Assessment of potential drug-drug interactions and their associated risk factor in patients with rheumatoid arthritis: A cross-sectional study”

BackgroundRheumatoid arthritis patients poses high risk for the development of potential drug-drug interactions (PDDIs) due to polypharmacy. Data relating the assessment of PDDIs in rheumatoid arthritis patients is still limited. Therefore, we assessed the prevalence, severity and adverse events of PDDIs, and their risk factors in rheumatoid arthritis patients. MethodsA cross-sectional research was carried out for 36 months in a tertiary care teaching hospital. Patient who met study eligibility were enrolled and their drug therapies were reviewed thoroughly. Generic name of drug was entered into Micromedex® software to identify the PDDIs. Adverse events related to PDDIs were identified and subsequently managed. Logistic regression analysis was applied to identify the risk factors associated with PDDIs. ResultsOf 598 patients, 518 (86.6%) patients were presented with ≥1 PDDIs. A total of 1492 PDDIs were identified, and 43.1% were moderate in their severity. Corticosteroids (32.8%) was major class of drugs involved in PDDIs development. Aceclofenac plus prednisolone (7.9%) was most common drug pair involved in the development of PDDIs. About 2.7% adverse events related to PDDIs were found. Age and multiple comorbidities were the most common risk factors associated with PDDIs. ConclusionThe occurrence of PDDIs was high among rheumatoid arthritis patients, majority were moderate in their severity. Age and multiple comorbidities were the most common risk factors associated with development of PDDIs. Therefore, prescriber and pharmacists’ need to take urgent action in reviewing medications chart and subjected to identify PDDIs, and their associated risk factors to enhance drug safety.

The Use of AI in Diagnosing Diseases and Providing Management Plans: A Consultation on Cardiovascular Disorders With ChatGPT.

Cardiovascular diseases (CVDs) have remained the leading causes of death worldwide and substantially contribute to loss of health and excess health system costs. According to WHO, cardiovascular diseases (CVDs) take an estimated 17.9 million lives each year. One of the reasons for an immensely high fatality in CVDs is lack of efficient diagnosis and prompt treatment. Timely recognition and management are crucial to minimize mortality. In the advancing world, AI (artificial intelligence) and machine learning technologies continue to progress, this advancement has opened new avenues for innovative approaches in the field of medicine. Despite the rapid development in the field of AI, there is a limited understanding of the potential benefits among clinicians and medical practitioners. In this study, we aimed to investigate the potential that the AI language model holds to assist health practitioners in the diagnosis and treatment of cardiovascular disorders. We asked Chat Generative Pre-trained Transformer (ChatGPT) 10 hypothetical questions simulating clinical consultation. The responses given by ChatGPT were accessed for its accuracy and accessibility by a team of medical specialists and cardiologists with extensive experience in managing cardiovascular disorders. Result:Out of the 10 clinical scenarios inserted in ChatGPT, eight were perfectly diagnosed, however, the other two answers given by ChatGPT were not entirely incorrect since those conditions were associated with the actual diagnosis. Furthermore, the management plans and the treatment protocols that were given by ChatGPT were in line with the literature and current medical knowledge. The exact drug names and regimens were not provided but a general guideline that was given by this AI tool is definitely beneficial for junior doctors in getting an idea on how to proceed or refresh their previous knowledge. ChatGPT is a valuable resource in the field of medicine. Its comprehensiveand properly organized response in an understandable language has made it an effective and efficient tool to be used. However, it is crucial to note that its limitations, such as the need for all associated and typical signs, symptoms, and physical examination findings, and its inability to personalize treatments need to be acknowledged.

Are large prospective trials on antidepressants in mental disorders seeding trials? A descriptive study of trials registered on ClinicalTrials.gov

ObjectivesThis descriptive study of registered trials aimed to identify large clinical trials on antidepressants for mental disorders: (1) to assess what proportion could be labelled as ‘seeding trials’ (trials for...

Development of methodological approaches to the formation of a risk-based model to minimize the prevalence of adverse reactions in drug application in medical organizations of Moscow

Objective: development of approaches to predict the likelihood of adverse reactions (ARs) when using drugs based on a comprehensive assessment of risk factors.Material and methods. We used a database containing 1,450 drug-related ARs reports from January through December 2021. A list of antibacterial drugs by international nonproprietary name (INN) with 4 or more ARs reports was selected as a reference group to perform various types of statistical analysis. A cumulative multivariate regression analysis was carried out on a database of 187 ARs notifications for 13 INN of antibacterial drugs. The study was performed in two stages. In the first stage, a statistical method was used (classical multiple regression, linear discriminant analysis, factor analysis, principal component regression, partial least squares regression, estimation of variance accuracy); at the second stage a modeling method was used. As part of the modeling stage, the integral score of the risk of ARs was presented as a sum of values for individual risk factors. Two groups of risks were proposed to be assessed: 1) intrinsic risk value for each factor (attribute), which was equal to the sum of risks of all factors (conditions) in which the drug had been used; 2) intrinsic risk value for antibacterial drugs by each INN. The total risk value was defined as the sum of the risk of the drug and all factors (conditions) in which this drug had been used.Results. The results were visualized in the form of a two-level risk-based model matrix, with a “heat map” of the risk level overlaid on it. The maximum total risk of ARs was obtained for ceftriaxone – 404.96 points, depending on patient’s gender. The minimum total risk was calculated for azithromycin and cefotaxime depending on the International Classification of Diseases (10th revision) code – 88.46 points. The proposed methodological approach also allows combining all possible combinations of drugs and conditions of their use. For example, for the use of vancomycin in hospital conditions by intravenous administration: intrinsic risk of use – 42.93 points; risk of use in hospital conditions – 183.68 points; risk when administered intravenously – 209.95 points; the total risk value in the designated situation – 436.56 points.Conclusion. The proposed approach can allow medical organizations to reduce significantly the number of ARs when using drugs by categorizing and preventing risks before they occur. It also has significant prospects of application at the federal level, given its modification on a large volume of data.

Evaluation of the Potential for Medication Error in Outpatient Elderly Patients at Siti Fatimah Az-Zahra Regional Hospital

Medication error is an event or situation that can be prevented and avoided, but if drugs cannot be controlled it can lead to inappropriate or harmful use of drugs. Medication error is an error made unintentionally in prescribing (Prescribing), reading prescriptions (transcribing), preparing prescriptions (dispensing) and administration. The purpose of this study was to determine the incidence of medication errors in the prescribing and transcribing phase in elderly patients. This study included descriptive observational research in a retrospective manner with purposive sampling method in the form of prescriptions of elderly patients at Siti Fatimah Az-Zahra Hospital Palembang. The results obtained in this study indicate that the occurrence of medication errors at the Prescribing stage, namely no prescription date 12%, no doctor's SIP 15%, no doctor's signature 10%, no dosage unit 35%, no amount of drug administration 3% and at the Transcribing stage, namely unclear / complete drug names 34%, unclear / complete drug doses 34% and unclear / complete drug amounts 3%.
 Keywords: medication error, prescribing, transcribing

Unlocking the Therapeutic Potential of Ulotaront as a Trace Amine-Associated Receptor 1 Agonist for Neuropsychiatric Disorders.

All antipsychotics currently used in clinic block D2 dopamine receptors. Trace amine-associated receptor 1 is emerging as a new therapeutic target for schizophrenia and several other neuropsychiatric disorders. SEP-363856 (International Nonproprietary Name: Ulotaront) is an investigational antipsychotic drug with a novel mechanism of action that does not involve antagonism of dopamine D2 receptors. Ulotaront is an agonist of trace amine-associated receptor 1 and serotonin 5-HT1A receptors, but can modulate dopamine neurotransmission indirectly. In 2019, the United States Food and Drug Administration granted Breakthrough Therapy Designation for ulotaront for the treatment of schizophrenia. Phase 2 clinical studies indicated that ulotaront can reduce both positive and negative symptoms of schizophrenia without causing the extrapyramidal or metabolic side effects that are inherent to most currently used antipsychotics. At present, it is in phase 3 clinical development for the treatment of schizophrenia and is expected to be introduced into clinical practice in 2023-2024. Clinical studies evaluating the potential efficacy of ulotaront in Parkinson's disease psychosis, generalized anxiety disorder, and major depressive disorder have also been started. The aim of this scoping review is to summarize all currently available preclinical and clinical evidence on the utility of ulotaront in the treatment of schizophrenia. Here, we show the main characteristics and distinctive features of this drug. Perspectives and limitations on the potential use of ulotaront in the pharmacotherapy of several other neuropsychiatric disorders are also discussed.

A Survey About How Much Physicians Give Information to Their Patients in Kerman, Iran

Background: Providing accurate information to patients is an important task of the medical staff that can help establish a relationship complying with current ethical principles. The present study aimed to clarify the current status of providing information to patients about their diseases by physicians. Methods: This cross-sectional study was conducted in the internal medicine and surgery wards of a teaching hospital at Kerman University of Medical Sciences. The participants, selected using the convenience sampling method, answered 13 yes/no questions about the information given to them by their physicians based on Braddock et al.’s study and the second part of the Patients’ Rights Charter in Iran. Results: Totally, 396 patients participated in this study. The results showed that less than half of the patients confirmed their physicians had given information to them. There was a significant difference in participants’ answers to the questions on knowing about drug names (P=0.002), drug side effects (P=0.002), paraclinical test results (P=0.002), and patient’s preference and consent to have awareness of adverse outcomes of the disease (P<0.001) between patients hospitalized at internal medicine and surgery wards, and the frequency of "yes" answers was higher in patients at internal medicine than surgery ward. Conclusion: It is recommended to offer appropriate training courses to physicians in order to further improve their relationship with patients to be able to make more informed decisions.

Flight safety risk assessment of self-medication among fighter pilots: a cross-sectional study.

Fighter pilots are a specific population in which any adverse drug reaction can unpredictably interact with aeronautical constraints and thus compromise flight safety. This issue has not been evaluated in risk assessments. To provide a semi-quantitative assessment of the risk to flight safety of self-medication in fighter pilots. A cross-sectional survey that aimed at identifying the determinants of self-medication in fighter pilots was conducted. All medications consumed within 8h preceding a flight were listed. A modified Failure Mode and Effects Analysis was performed, and any adverse drug reaction reported in the French marketing authorization document of a drug was considered a failure mode. The frequency of occurrence and severity were evaluated using specific scales to assign each to three risk criticality categories: acceptable, tolerable, and unacceptable. Between March and November 2020, the responses of 170 fighter pilots were analyzed, for an overall return rate of approximately 34%. Among them, 78 reported 140 self-medication events within 8h preceding a flight. Thirty-nine drug trade names (48 different international nonproprietary names) were listed, from which 694 potential adverse drug reactions were identified. The risk criticality was considered unacceptable, tolerable and acceptable for 37, 325 and 332 adverse drug reactions, respectively. Thus, the risk criticality was considered unacceptable, tolerable and acceptable for 17, 17, and 5 drugs, respectively. This analysis suggests that the overall risk to flight safety of the current practice of self-medication in fighter pilots may be considered at least tolerable, or even unacceptable.

Literature Review : Potensi Tanaman Mawar Merah (Rosa damascena) Beserta Kandungan Senyawa di Dalamnya

Processing of plants as medicine or as industrial products is mostly done nowadays, for example in the beauty industry. Rossa damascena is a plant that can be used as a medicinal plant. This flower has many benefits, its essential oil and extract have long been used in body wash products, perfumes, skin lotions and medicines. However, there is not much management and distribution of drugs circulating in the community. The processing of these medicinal plants is a promising matter for pharmacists, because utilizing medicinal plants to be used as medicine can expand the nomenclature of drugs. The method used is the collection and screening of data that has inclusion and exclusion criteria. The results obtained are various information regarding the compound content and its potency contained in Rosa damascena.

Prevalence of Outpatient Use of Medicines by the Elderly Population in Portugal: A Cross-Sectional Study

Like in other countries, the age pyramid in Portugal has been changing considerably, with a substantial increase in the size of the older population and a significant reduction in the number of young people. With aging, co-occurrence of several conditions becomes frequent, often leading to the use of multiple medications (polypharmacy). Polypharmacy in the older population is particularly relevant considering the physiological changes of the ageing process, which increase the risk of drug interactions, poor adherence to treatment, and adverse drug reactions, especially in the oldest-old population (85 years or older). As the size of the older population is likely to increase significantly, it is important to characterize the pattern of medicines' use by the elderly while also identifying cases of polypharmacy in order to obtain evidence that can be used to develop specific measures to tackle the high prevalence of use and its associated risks. To this end, the aim of this study was to characterize medication use by older individuals in Portugal. Cross-sectional study with data from the National Health System's Control and Monitoring Center on reimbursed medicines that were prescribed and dispensed to individuals aged 65 years or older in 2019 in all community pharmacies of the Portuguese mainland. We performed a demographic and geographic analysis of the data by international nonproprietary name and therapeutic group. The number of reimbursed packages and the number of reimbursed packages per capita were the metrics used (data from Instituto Nacional de Estatística). A higher consumption of medicines was observed in women, increasing with age, except in the oldest olds, in which the sex difference tended to shrink. Use per capita showed an opposite trend, with the oldest-old men surpassing the oldest-old women (mean reimbursed packages: 55.5 in men versus 55.1 in women). In women, consumption was led by cardiovascular medicines (31%), followed by central nervous system medications (30%) and antidiabetics (13%); in men, 37% of TOP 10 consumption was due to cardiovascular medications, antidiabetics (16%) and drugs for benign prostatic hypertrophy (14%). In the elderly, there were sex differences in the pattern of medicines' use, and there were also significant age-related differences in 2019. To the best of our knowledge, our study is the first nationwide analysis of reimbursed medicines' consumption data in the elderly, which is essential to characterize the use of medicines in this age group in Portugal.

Botulinum toxin preparations: areas for improvement and issues of standardisation

Scientific relevance. Botulinum toxin preparations are a good example of using a deadly toxin as a unique therapeutic agent. However, there are many unresolved issues related to biotechnology, biological activity, interchangeability, and standardisation of botulinum toxin preparations. Aim. To review current opportunities for improving therapeutic botulinum toxin preparations.Discussion. This review covers botulinum toxin type A preparations and unresolved issues related to them. In the absence of international non-proprietary names recommended by the World Health Organisation or by the Board of the Eurasian Economic Commission, domestic and imported botulinum toxin type A preparations approved in Russia have only similarity-based grouping names. In addition, manufacturers name botulinum toxin preparations at their discretion. Therefore, classifying these preparations under a common nomenclature is essential for clear identification, adequate selection, and correct prescription. Several studies have shown significant variability across botulinum toxin type A preparations. Due to the identified differences in qualitative and quantitative characteristics, botulinum toxin type A preparations cannot be considered similar, which raises the issue of their interchangeability and bioequivalence. To resolve this issue, a unified classification and naming system for botulinum toxin preparations should be established and documented in regulatory standards. According to the literature, manufacturers of botulinum toxin preparations use in-house reference standards. Hence, the same activity unit resulting from toxicity and efficacy studies may express a different protein load for each botulinum toxin preparation. Keeping that in mind, the authors discuss the development of a single international potency standard for existing and pipeline botulinum toxin type A preparations. Conclusions. The article describes novel pharmaceutical compositions containing botulinum toxin, including those in late development. Summarised data from clinical studies on the safety, efficacy, and cost-effectiveness of botulinum toxin type A preparations can guide prescribing decisions.

Study of physicians' preferences for optimizing the pharmacy assortment of glocose-lowering drugs

For the stable operation of the pharmacy and the proper support of patients with diabetes, it is necessary to optimize the assortment of glucose-lowering drugs (GLD), taking into account the significant prevalence of this disease. The demand for prescription drugs is formed by doctors who choose therapy and prescribe drugs.
 The purpose of this study was to determine the factors that influence of choosing GLD for the treatment of type 2 diabetes and the preferences of doctors when choosing GLD for therapy.
 They used a remote questionnaire form using Google forms. 732 doctor questionnaires were processed. Statistical processing was carried out using structural, comparative and graphic analysis.
 A survey of doctors established the factors that influence the prescription of drugs for the treatment of type 2 diabetes: high effectiveness and inclusion of drugs in treatment standards, their safety, and their own positive experience in prescribing drugs. It was also found that when choosing a GLD type, almost half of doctors take into account the patient's purchasing power and the presence of a GLD in the reimbursement program. The survey showed that a third of doctors prefer domestic GLD, and half of the respondents do so sometimes. When choosing foreign medical medications, doctors prefer German, French, and Swiss-made medical drugs. A significant part of doctors do not have preferences when choosing trade name (TN), but the majority of doctors who have preferences prefer TN mainly of foreign production and prolonged forms. It was found that about 10% of the responding doctors do not prescribe combined GLD. The majority of respondent doctors have preferences for combinations: metformin/glimepiride, dapagliflozin propanediol/metformin and sitagliptin/metformin. Problems have been identified at the stage of pharmacological supervision of GLD. Despite the fact that doctors noted in their practice the side effects of drugs in patients, only a fourth (22.7%) of respondents recorded these effects in accordance with the current legislation and made reports.
 It is advisable to use the results of the questionnaire to improve the care of patients with diabetes and to meet their needs by optimizing the pharmacy assortment.
 It is advisable to increase the list of International Nonproprietary Name of GLDs for reimbursement, which will contribute to the availability of modern treatment regimens, because the price of medicines limits the quality of modern treatment regimens for type 2 diabetes.

TRLS-01. FDA ANALYSIS OF EXPANDED ACCESS USE IN PEDIATRIC PATIENTS WITH CNS TUMORS FROM 2015 TO 2020

Abstract Few therapies are approved for children with central nervous system (CNS) tumors, and their prognosis is often poor. Expanded Access (EA) is a regulatory mechanism enabling patients with life-threatening or serious diseases to receive treatment with investigational drugs outside of clinical trials when no comparable or satisfactory options are available. FDA’s central database was queried for single-patient investigational new drug (spIND) applications submitted to the Office of Oncologic Diseases between January 2015-December 2020. Data collection included IND date/type/status, drug name, patient demographics. Duplicate/exempt INDs, those cancelled by physician-sponsor before initiating therapy, and those for indications occurring almost exclusively in adults or missing patient age were excluded. Of 2,901 unique spINDs granted, 534 (18%) were for patients <18 years old; of those, 229 (43%) were for patients with nervous system tumors. Demographics included: 53% male, median age 5.0 years (range 0.3-17); race/ethnicity reported in <1%. Patients were treated in 78 zip codes across 33 states; one-third of submissions were from 5 large academic hospitals. Tumor types included low-grade glioma (71), plexiform neurofibroma (35), high-grade glioma (32), DIPG/DMG (30), ATRT (27), medulloblastoma (11), ependymoma (11), other CNS tumors (12). Thirty-eight unique drugs were requested (1 to 56 spINDs per drug); 60% for kinase inhibitors, 30% for other small molecule inhibitors, and the remainder for immunotherapies/other drug types. Median time for FDA to review and deem safe to proceed was 1 day. While pediatric CNS tumors are rare, these patients made up almost half of spINDs granted for pediatric patients. Ongoing efforts are needed to assess the impact of EA on patient outcomes and ensure availability to patients, families, and institutions more widely. These data highlight interest within the pediatric neuro-oncology community in accessing innovative therapies, which supports early investigation of promising new drugs for these patients.

KNOWLEDGE, ATTITUDES, AND PRACTICES TOWARD MALARIA AND ANTIMALARIAL MASS DRUG ADMINISTRATION AMONG HEADS OF HOUSEHOLDS IN VILLAGES ON GRANDE COMORE ISLAND, THE COMOROS.

Knowledge, attitudes, and practices (KAP) surveys on malaria and antimalarial mass drug administration (MDA) have not received much attention in the Union of the Comoros. This study is a household-based cross-sectional survey using a multi-stage sampling technique aiming at investigating KAP toward malaria and antimalarial MDA with artemisinin-piperaquine among heads of households on Grande Comore Island, the largest island of the Comoros. A predefined structured questionnaire containing socio-demographic characteristics and questions about malaria and antimalarial MDA was administered to 1,368 randomly selected heads of households from 10 malaria-endemic villages on Grande Comore Island. The results showed that 81.4% of the heads of households knew that malaria is a transmissible disease, 77.6% recognized mosquitoes as the vectors of malaria, and 70.8% recognized fever as one of the frequent symptoms of malaria; 40.8% of respondents remembered the name of the antimalarial drug used for MDA, and 62.1% remembered the color of the antimalarial tablets; and 65.1% chose to go to a public health center to seek treatment as their first option within 24 hr of the onset of initial malaria symptoms. This study found that most heads of households had a reasonable level of knowledge about malaria and antimalarial MDA. However, only 7.3% obtained full points on all knowledge-related questions. Misconceptions about malaria cause, transmission, diagnostic method, and antimalarial MDA exist in the community of Grande Comore Island. As the Comoros continues to put great efforts to go toward malaria elimination, the community's KAP on malaria and antimalarial MDA is crucial to guarantee the community's long-term adherence to malaria elimination interventions and could become key to guaranteeing malarial elimination in the Comoros. Therefore, there is a great need to improve malaria prevention awareness through strengthening malaria education and promoting behavioral change. Heads of households should be the core target of malaria education and behavioral change for malaria elimination.

Utilizing Drug Combo to improve the design of phase 1 trials for anticancer drugs.

1571 Background: Accurate prior knowledge of a single drug or drug combination on toxicity, pharmacokinetics (PK), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) can help oncologists and statisticians design an efficient phase 1 clinical trial. However, most of the relevant knowledge is shattered in various databases. More importantly, MTD and DLT are missing in any databases. This study constructed a comprehensive knowledge base with expert-curated MTD and DLT knowledge from published anticancer drug combination phase 1 clinical trial results. We also demonstrated the utility of the knowledgebase to design a more efficient phase 1 trial. Methods: Toxicity, pharmacology, and PK knowledge were integrated from publicly available data sources, including DrugBank, SIDER, and drug labels. An interdisciplinary team manually curated the MTD and DLT knowledge. Relevant papers were discovered by PubMed keyword search (drug name + MTD or RP2D). Details regarding patient eligibility, treatment information (dose, formula, and schedule), trial design method, dose levels, DLT definition, MTD or Recommended phase 2 dose, and DLT incident were curated in the structured data format and stored in a database. Rxnorm and MedDRA were used for normalizing drug names and DLT. Results: Currently, 2358 papers on cancer drugs phase 1 trial have been curated. Additionally, pharmacological and PK knowledge of 197 cancer drugs, ADE information from 1094 drug labels, and more than 500000 pieces of DDI evidence were integrated into the knowledge base. This knowledge base (drugcombo.info) could help researchers design an efficient phase 1 trial. For example, based on knowledge from Drug Combo, the combination of nivolumab and axitinib did not have potential PK DDI and severe overlapping toxicity. The reviewing physician considered a phase 1b study to start at a curated 5 mg maximum dose of axitinib with dose reduction to 3 and 2 mg and maintenance of a 3-mg/kg dose of nivolumab based on guidelines. With such additional preliminary knowledge, the reviewing statistician felt the adaptive statistical methods could be applied to redesign this phase I combination trial and minimize patient exposure to sub-therapeutic dose levels. Conclusions: To our knowledge, Drug Combo is the first knowledge that integrated curated MTD and DLT knowledge. It would promote applying curated knowledge to better design phase I trials to treat cancer.

Is access to adjuvant treatments prioritized over therapies for metastatic cancer? The Israeli experience.

e18599 Background: The Israeli National Insurance Law determines a uniform benefits package ('the Health Basket') for all residents. A public committee advises each year on which new medications should be added to the Health Basket, subject to the fixed annum budget allocated by the government for this purpose. The clinical benefit of the proposed health technologies is the committee's prime consideration; however, the committee also considers the professional medical societies' prioritizations, the expected budget impact, and other social and ethical aspects. Towards the annual discussions for 2023, 63 new indications for 41 cancer drugs were proposed for the annual update. Of those, 8 were for novel neo-adjuvant/ adjuvant indications, all given high priority ranks by the Israeli Oncologists Society based on the significant disease-free survival (DFS) figures from the phase III clinical trials. Varying the adjuvant treatment practice patterns based solely on DFS figures without available overall survival (OS) data has been in much debate recently between global key opinion leaders. We, therefore, aimed to evaluate whether the Israeli decision-makers have de-facto accepted the attitude of prioritizing budgets for adjuvant/neo-adjuvant therapies as the Israeli Oncologists Society recommended. Methods: We collected data on all cancer therapies proposed for inclusion in the 2023 Health Basket update; drug name, indication, treatment setting (curative intent vs. metastatic disease therapy), ESMO-MCBS grade, and whether or not accepted for reimbursement. All data were extracted from the official Israeli Ministry of Health website publications and press releases. Results: 20% of the allocated budget for updating the National Health basket for 2023 was provided to treat solid tumor cancers. 7 out of the 8 candidate therapies in the neo-adjuvant/adjuvant settings received reimbursement approval (88%) vs. 11 out of 55 therapies for advanced/ metastatic stages of disease (20%). 13 of the 16 candidate metastatic disease therapies that had a high ESMO-MCBS score (4 or 5) were not approved for reimbursement in the 2023 annual committee discussions. Conclusions: Our retrospective evaluation of the Israeli reimbursement prioritization process reveals that decision-makers have accepted the approach of prioritizing potentially curative adjuvant therapies over treatments for patients with incurable cancer. In an era of prosperity of adjuvant therapies in a range of tumor types, concerns might arise regarding restrictions on access to novel therapies for metastatic cancer, even those with proven benefits of significantly improving patients' OS and quality of life. Future analysis should determine the impact of this trend adopted by decision-makers in Israel on disease progression and overall survival in the real-world setting.

Research on named entity recognition of adverse drug reactions based on NLP and deep learning.

Introduction: Adverse drug reactions (ADR) are directly related to public health and become the focus of public and media attention. At present, a large number of ADR events have been reported on the Internet, but the mining and utilization of such information resources is insufficient. Named entity recognition (NER) is the basic work of many natural language processing (NLP) tasks, which aims to identify entities with specific meanings from natural language texts. Methods: In order to identify entities from ADR event data resources more effectively, so as to provide valuable health knowledge for people, this paper introduces ALBERT in the input presentation layer on the basis of the classic BiLSTM-CRF model, and proposes a method of ADR named entity recognition based on the ALBERT-BiLSTM-CRF model. The textual information about ADR on the website "Chinese medical information query platform" (https://www.dayi.org.cn) was collected by the crawler and used as research data, and the BIO method was used to label three types of entities: drug name (DRN), drug component (COM), and adverse drug reactions (ADR) to build a corpus. Then, the words were mapped to the word vector by using the ALBERT module to obtain the character level semantic information, the context coding was performed by the BiLSTM module, and the label decoding was using the CRF module to predict the real label. Results: Based on the constructed corpus, experimental comparisons were made with two classical models, namely, BiLSTM-CRF and BERT-BiLSTM-CRF. The experimental results show that the F 1 of our method is 91.19% on the whole, which is 1.5% and 1.37% higher than the other two models respectively, and the performance of recognition of three types of entities is significantly improved, which proves the superiority of this method. Discussion: The method proposed can be used effectively in NER from ADR information on the Internet, which provides a basis for the extraction of drug-related entity relationships and the construction of knowledge graph, thus playing a role in practical health systems such as intelligent diagnosis, risk reasoning and automatic question answering.

Use of adjuvant bisphosphonate therapy in breast cancer by Indian oncologists: An implementation science study.

e13667 Background: Several clinical trials, expert consensus and guidelines have recommended the use of bisphosphonates (BP) in reducing the breast cancer recurrence risk in postmenopausal women. The 2019 St. Gallen Panel voted 83.7% in favour of the routine use of bisphosphonates in postmenopausal women. Similarly, the 2022 ASCO-Ontario Health guidelines for breast cancer supports the recommendation. However, the uptake of these recommendations in routine clinical practice is poorly studied. We aimed to investigate the use of adjuvant BP therapy by Indian oncologists (implementation science study). Methods: A cross sectional survey study design was used to investigate our research question. Physicians in India who treat patients with breast cancer were presented with a clinical vignette of a young woman with postmenopausal (induced) non-metastatic high risk hormone receptor-positive breast cancer. A snowball sampling strategy was employed to avoid sampling bias. Participants were requested to state their gender, primary qualification, practice setting, number of years of practice as an oncologist and proportion of patients with breast cancer in their practice. Instead of providing the option of BP therapy, we asked an open-ended question whether they would recommend any additional therapy other than surgery, radiation, chemotherapy and anti-estrogen therapy. We asked them to write in the name or class of drug if they would prescribe an additional therapy to the patient. Results: The survey was completed by 74 Oncologists. The response rate is unknown as a snowball sampling strategy was employed. Majority of the respondents were male (74%), were non-teaching private practitioners (42%), medical oncologists (62%) with up to 10 years of experience (65%), and breast cancer patients make up to 50% of their patients (84%). Most of the oncologists responded no to our question on additional therapy (76%). Of those who responded yes, only 8 suggested BP therapy (11%). Conclusions: Despite strong evidence and guidelines, adjuvant BP therapy in high-risk early breast cancer was only recommended by very few oncologists in our survey study. Steps to bridge this gap between academic research and clinical application is urgently warranted. Implementation of clinical guidelines has to be monitored routinely which may be facilitated by provider and patient surveys. This can also assist in identifying and addressing the concerns with newer recommendations.

Medication and prescription rules for treating spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary

ObjectiveTo explore the prescriptions related to the treatment of spleen and stomach diseases in Prescriptions of Peaceful Benevolent Dispensary (Tai Ping Hui Min He Ji Ju Fang,《太平惠民和剂局方》, TPHMHJJF), and investigate the medication and prescription rules. MethodsThe prescriptions of TPHMHJJF for treating spleen and stomach diseases were screened, and the data set was established by entering the prescriptions and standardized drug names using WPS Excel 2019. Herb frequency statistics, efficacy categorization, property, flavor, meridian tropism, association rules, cluster analysis, factor analysis, and complex network analysis were performed using Python 3.6.8 programming language and Gephi 0.9.2 visualization software. ResultsA total of 239 prescriptions were included after the screening, and the dosage forms were mainly pills and powders. The study involved 200 herbal medicines, among which 40 herbs had a frequency of ≥ 12. The herb with the highest frequency was Ganjiang (Zingiber Rhizoma). The herb properties were mainly warm in nature, with the most pungent herbs. Most herbs were attributed to the spleen and stomach meridians, and tonifying medicine were the main species. The association rule analysis identified 26 second-order association rules and 16 third-order association rules, with "Renshen (Ginseng Radix et Rhizoma) → Fuling (Poria)" as the leading rule in the former and "Fuling (Poria) + Baizhu (Atractylodis Macrocephalae Rhizome) → Renshen (Ginseng Radix et Rhizoma)" as the leading rule in the latter. Also, cluster analysis divided the top 30 herbs into six herb combinations that can warm the middle, move Qi, and dry dampness effectively. Factor analysis extracted 13 common factors, with Renshen (Ginseng Radix et Rhizoma), Fuling (Poria), and Baizhu (Atractylodis Macrocephalae Rhizome) as the highest contributing factors. Lastly, complex network analysis yielded the core prescription of 14 herbs, with Ganjiang (Zingiber Rhizoma), Renshen (Ginseng Radix et Rhizoma), Gancao (Glycyrrhizae Radix et Rhizome), and Chenpi (Citri Reticulatae Pericarpium) among the herbs with a higher weighting degree. ConclusionTPHMHJJF is mainly based on the use of warming herbs to treat spleen and stomach diseases, and its medication rule can be summarized into three aspects: (i) primarily using warming and tonifying to warm the middle and dissipate cold, (ii) using the method of moving Qi with aromatic nature to delight the spleen and appetize the stomach, and (iii) emphasizing the regulation of Qi and blood to calm the five zang-organs.