A Data-Driven Iterative Approach for Semi-automatically Assessing the Correctness of Medication Value Sets: A Proof of Concept Based on Opioids

Background Value sets are lists of terms (e.g., opioid medication names) and their corresponding codes from standard clinical vocabularies (e.g., RxNorm) created with the intent of supporting health information exchange and research. Value sets are manually-created and often exhibit errors. Objectives The aim of the study is to develop a semi-automatic, data-centric natural language processing (NLP) method to assess medication-related value set correctness and evaluate it on a set of opioid medication value sets. Methods We developed an NLP algorithm that utilizes value sets containing mostly true positives and true negatives to learn lexical patterns associated with the true positives, and then employs these patterns to identify potential errors in unseen value sets. We evaluated the algorithm on a set of opioid medication value sets, using the recall, precision and F1-score metrics. We applied the trained model to assess the correctness of unseen opioid value sets based on recall. To replicate the application of the algorithm in real-world settings, a domain expert manually conducted error analysis to identify potential system and value set errors. Results Thirty-eight value sets were retrieved from the Value Set Authority Center, and six (two opioid, four non-opioid) were used to develop and evaluate the system. Average precision, recall, and F1-score were 0.932, 0.904, and 0.909, respectively on uncorrected value sets; and 0.958, 0.953, and 0.953, respectively after manual correction of the same value sets. On 20 unseen opioid value sets, the algorithm obtained average recall of 0.89. Error analyses revealed that the main sources of system misclassifications were differences in how opioids were coded in the value sets—while the training value sets had generic names mostly, some of the unseen value sets had new trade names and ingredients. Conclusion The proposed approach is data-centric, reusable, customizable, and not resource intensive. It may help domain experts to easily validate value sets.

Evaluation of insecticidal potential of organochemicals on SF9 cell line

Background Organophosphates and Pyrethroids are the most widely used pesticides worldwide and are known to have significant toxicity on the nervous system of the target pest. Assessment for combined toxicity of Organophosphate and Pyrethroid on Sf9 (Spodoptera frugiperda) cells is less explored. The present study demonstrates and compares the two organochemicals whose trade names are Ammo and Profex, for its cytotoxic potential on the insect Sf9 cells. Ammo and Profex were selected as the test chemicals as toxicity of these insecticides at molecular and cellular level is poorly understood. Results The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay demonstrated that Ammo and Profex exhibited significant cytotoxicity to Sf9 cells in a time- and dose-dependent manner. In our study, the IC50 value was obtained by MTT assay and the sub-lethal concentrations (IC50/20-17.5 µg/ml, IC50/10-35 µg/ml, and IC50/5–70 µg/ml for Ammo and IC50/20-20 µg/ml, IC50/10-40 µg/ml, and IC50/5-80 µg/ml for Profex) were selected for further tests. Acridine orange/ethidium bromide staining proved the apoptotic cell death on exposure of both the insecticides confirming its toxic potential. Furthermore, antioxidant status was assessed using DCF-DA staining and both the insecticides resulted into an increased reactive oxygen species (ROS) generation. A dose- and time-dependent significant (p < 0.05) alterations in lipid peroxidase (LPO), glutathione (GSH) and catalase (CAT) activity were observed. Conclusion The results showed that both Ammo and Profex triggered apoptosis in Sf9 cells through an intrinsic mitochondrial pathway via the generation of ROS. Of the two insecticides, Ammo was found to be more toxic compared to Profex. The present study is important to evaluate the environmental safety and risk factors of Organochemicals’ exposure to crops and livestock.

Culture and Differentiation of Primary Human Tracheobronchial Epithelial Cells Using STEMCELL Technologies Pneumacult Media

NOTE: A PDF methods document is attached in the supplementary materials.SCOPE OF APPLICATION (LIMITATIONS)This method describes the culture and differentiation of primary human tracheobronchial epithelial cells (pHBEC). Cells used for this method can be obtained by brush biopsy during clinical bronchoscopy or purchased commercially. This method replaces the previous version described in (Dailey and McCullough, 2021a; b). Disclaimer: The contents of this article have been reviewed by the US Environmental Protection Agency and approved for publication and do not necessarily represent Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendations for use.

Culture of IMR90 Cells in Advanced MEM with Reduced Serum

NOTE: Methods document and worksheet versions of this method are attached as PDFs.SCOPE OF APPLICATION (LIMITATIONS)This method describes the thawing, culturing, and cryopreservation of the human lung fibroblast cell line IMR90 in Advanced MEM-based growth medium. Disclaimer: The contents of this article have been reviewed by the US Environmental Protection Agency and approved for publication and do not necessarily represent Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendations for use.

Measurement of Trans-Epithelial Electrical Resistance with EVOM2 and EndOhm Cup

Trans-epithelial Electrical Resistance (TEER) can be used as a measure of cell monolayer confluence, health, and integrity. An EndOhm chamber connected to an Epithelial Voltohmmeter (EVOM) may be used to take TEER measurements that are more reproducible than the chopsticks electrode. This method details how to take TEER readings using an EndOhm-12 chamber and EVOM2 resistance reader. Read the manufacturer’s manual carefully before adjusting any of the parameters below as the conditions described here were determined to meet the manufacturer’s specifications. Volumes will need to be adjusted to accommodate substitution of the EndOhm-6 or EndOhm-24.Disclaimer: The contents of this article have been reviewed by the US Environmental Protection Agency and approved for publication and do not necessarily represent Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendations for use.

ANTIHISTAMINES: RESEARCH AND ANALYSIS OF THE REGIONAL RETAIL MARKET

the aim. Focused on optimizing the assortment portfolio of pharmacy organizations and improving the process of drug supply to end-consumers, the aim of the study was to analyze the regional pharmaceutical market for antihistamines.Materials and methods. In the study, the following methods were used: a content analysis of regulatory documents; a documentary observation method of the volume of antihistamines sales; a sociological survey method. The objects of the study were accounting registers in 32 pharmacy organizations for 2020, as well as the sociological survey results of 174 respondents – consumers of antihistamines.Results. The classification analysis of 38 international non-proprietary trade names of antihistamines, represented by 187 names of drugs, revealed the prevalence of the first-generation drugs (63%). On the Russian pharmaceutical market, there were also 55% of foreign production drugs. At the regional level, there are 66 types of drugs in circulation, 50% of which are second-generation ones. The cost analysis showed rather a wide rage of the pricing proposal and the economic availability of antihistamines for patients. The sociological survey revealed the fact that 46% of the consumers were ready to pay for the necessary drugs in the price range “over 100 and up to 500 rubles” (over $ 1.38 and up to $ 6.88) for one conventional package. A medical-demographic profile of the antihistamines consumer at the regional level has been made up, and guidelines for pharmaceutical specialists on managing the assortment portfolio of pharmaceutical organizations have been developed.Conclusion. As a result of the study, the following facts have been established: the seasonal peaks in the antihistamines consumption; a gradual renewal of the pharmacies assortment portfolio due to the increased consumption of the second and third generation antihistamines. The medical and demographic profile of the consumer should be taken into consideration when planning a drug provision for the patients with allergic pathologies, and it is connected with the growth in pharmacies profits due to the sale of drugs in the range from 100 to 500 rubles (from $ 1.38 to $ 6.88). The methodical recommendations have been brought to the attention of the management of regional pharmacy organizations.

The analysis of prolonged-release drugs at the Ukrainian pharmaceutical market

Aim. To analyze the range of prolonged-release dosage forms at the Ukrainian pharmaceutical market focusing on the pharmacotherapeutic groups that are insufficiently saturated with prolonged-release drugs, in particular to determine the proportion of non-steroidal anti-inflammatory drugs (NSAIDs). Materials and methods. The research was conducted in accordance with the data of the State Registry of Medicines of Ukraine and the АТС classification system. The methods of scientific analysis, in particular methods of grouping and comparison, marketing methods of analysis were applied. Results. The study of the assortment of prolonged-release drugs registered at the Ukrainian pharmaceutical market has been performed. The structure of the assortment by manufacturer, dosage forms, the АТС classification system has been analyzed. As a result of the study, it has been found that 202 trade names of prolonged-release drugs are registered in Ukraine. Most of them (196 names, 84 %) are medicines of foreign manufacturers. Prolonged-release drugs registered in Ukraine are mostly presented in the form of tablets and capsules, but tablets (72.77 %) are the largest part. The analysis of distribution of prolonged-release drugs by the ATC classification groups has shown that a significant number of prolonged-release drugs belongs to group N – Nervous system (80 trade names), and group C – Cardiovascular system (44 trade names). The share of group M – Musculoskeletal system, in particular prolonged-release NSAIDs, is insignificant (9 trade names). Conclusions. The marketing research of the prolonged-release drugs conducted allowed us to characterize the structure of the assortment of the Ukrainian market by pharmacotherapeutic groups, manufacturers and dosage forms. As a result of the research, the current assortment of prolonged-release NSAIDs has been determined.

ANALYSIS OF PHARMACEUTICAL WORKERS RECOMMENDATIONS FOR WOUND-HEALING DRUGS IN UKRAINE

The occurrence of superficial wounds remains one of the most significant problems all the time among different types of household injuries. Up to 40 % persons annually have such damages of the skin like abrasions, scratches, cracks, suppurations, cuts, bedsores, and others. The problem of choosing a suitable drug arises acutely, since most pharmacists consider the issue of treatment by themselves. Patient’s referral to hospital departments for doctors advise remains minimal. Pharmacy specialists carry out pharmaceutical care and perform a personal analysis due to the given initial information about the mechanism, place of occur, size of wound and stage of the process of wound healing. Considering previous experience in fulfilling customer needs, they select optimal remedy, determine the majority of choice and thus, may be identified as the sales leaders. As for January 2021, the range of topical drugs used for the treatment of wounds numbered 270 trade names according to the State registry of medicines of Ukraine. They included 62 types of active pharmaceutical ingredients. Antimicrobial (antiseptic), anti-inflammatory, decongestant, protective and emollient action properties are underlined in their pharmaceutical inserts. It is similar for most of the medicines that are available on the Ukrainian pharmaceutical market. After all, their effectiveness to satisfy a patient need is as different as the price point. The choice of the optimal in composition and rational in the dosage form causes certain difficulties among the available wide range of medicines. Registrated semi-solid wound-healing drugs are represented by three groups of ATC classification: D03 – drugs for wounds and ulcers, D06 – antibiotics and chemotherapeutic drugs for use in dermatology, D08 – antiseptic and disinfectant drugs (table 1). Ointments predominate among semi-solid dosage forms with range 67.3 %, creams –26.5 %, gels – 10.2 %, liniments – 6.1 %, and jellies only 2.0 % of the market. 59.2 % of semi-solid wound-healing drugs are produced by domestic enterprises, and 40.8 % – by foreign manufacturers. The recommendations for the use of semi-solid drugs were distributed as follows: for the first phase of wound process – 48.9 %, for the first and second phases – 12.2 %, for the second phase – 10.2 %, for the second and third phases – 26.4 %, for the third phase – 2.0 %. The article summarizes the results of a questionnaire of pharmaceutical specialists on the available and free sale wound-healing medicines among registered on the Ukrainian market, that are most promoted and recommended. The purpose of our work was to single out available and free sale wound-healing medicines among registered on the Ukrainian market, that are most promoted and recommended by pharmaceutical specialists. This would help to highlight the real picture of sales, to analyze the components of leading products and, as a result of additional research, to propose a model for the complex pharmaceutical development of a new wound-healing medicine in a rational dosage form with safe and effective active ingredients of plant origin, and, consequently, competitive for pharmaceutical manufacturers. The list of registered medicines was composed in accordance with the data from the State Register of Medicines of Ukraine (registrated trade names). The total number of respondents was 176. Questionnaire survey was the main method of information’s collecting: 46 respondents were interviewed individually, 130 persons of the target audience – by electronic form. Questionnaire contained the same questions for the individual survey and online one. Questionnaire contained particular situational tasks and questions related to the practical experience of the pharmaceutical specialists: 12 questions, among which 5 questions provided an answer in detail. Whole data was analyzed systematically and statistically. 342 reviews on 36 medicines trade names were received while answering the question about the drug’s recommendation for quick healing of abrasions and scratches. Various drugs promoting rapid injury healing («Bepanten®» ointment, «Levomekol» ointment, «Pantestin-Darnitsa®» gel and «Riativnyk®» cream) determined in the most mentioned requests. We found out that most pharmaceutical specialists chose semi-solid dosage forms containing dexpanthenol for light burn wounds healing («Bepanten®» cream and ointment, «D-panthenol», «Pantecream», «Pantexol-Jadran», «HepiDerm-Zdorovye»). Pharmaceutical specialists recommend «Contractubex®» and «Solcoseryl» mostly to improve wound healing and minimizing the development of a cosmetic scar. Only 1/3 of respondents would recommend to a pharmacy visitor to exam skin defect by doctor or cosmetician and get reliable advice. The recommendations of pharmaceutical specialists for shallow cuts were predominantly determined by antiseptic drugs – most of them chose iodine solutions. 264 reviews were received for 32 trade names of medicines as effective treatment for bedsores. Respondents preferred zinc oxide preparations usage. According to the investigation, the opinions of the interviewed pharmaceutical specialists were focused on the semi-solid dosage forms (ointments, creams etc) for various wound care (abrasions and scratches, burns, scars, bedsores). Dosage forms of medicines for the treatment of cut wounds were an exception. Solutions and new kind of plasters – Skin glue, were the drugs of choice in this group. Phytomedicines practically did not appear among the respondents answers.