Research progress on the application of organoids in genetic diseases of childhood / 天津医药

Organoids are in vitro 3D tissue cultures that retain the characteristics of their source tissue and organs,and have been widely used in biomedical fields.Organoids have emerged as effective models for investigating diseases,contribute to further understanding of pathophysiology and molecular mechanisms of diseases,and provide technical support for personalized treatment of genetic diseases.This article specifically explores the application of organoid technology in childhood genetic diseases.It emphasizes the advantages and potential advancements of this technology in disease modeling,correction of genetic defects and personalized treatment,thereby serving as a valuable reference for future research endeavors.

Clinical study of sacubitril valsartan in the treatment of patients with heart failure of midrange ejection fraction after acute myocardial infarction / 天津医药

Objective To investigate the efficacy and safety of sacubitril valsartan in the treatment of heart failure(HF)of midrange ejection fraction(HFmrEF)in patients after acute myocardial infarction(AMI).Methods A total of 102 patients with HFmrEF after AMI were divided into the control group and the experimental group,with 51 cases in each group.The control group was given conventional treatment for AMI and anti-HF treatment,and the angiotensin-converting enzyme inhibitor(ACEI)/angiotensin Ⅱ receptor blocker(ARB)was used without contraindications.The experimental group was replaced by ACEI/ARB with sacubitril valsartan on the basis of the control group.After 6 months of treatment,the total effective rates of the two groups after treatment were analyzed,and the cardiac function,N-terminal pro-brain natriuretic peptide(NT-proBNP)and serum inflammatory factor C-reactive protein(CRP)were compared before and after treatment.The occurrence of adverse reactions after treatment was recorded.Kaplan-Meier method was used to analyze the cumulative cardiovascular mortality,HF rehospitalization rate and end-event-free survival after 6 months of treatment in two groups.Results After treatment,there was no significant difference in the occurrence of adverse reactions between the two groups(P>0.05).The total effective rate was higher in the experimental group than that of the control group(P<0.05).Compared with before treatment,left ventricular ejection fraction(LVEF),stroke volume(SV),mitral diastolic blood flow velocity E peak and A peak ratio(E/A)and 6 min walking distance(6MWD)were increased in the two groups,and left ventricular end-diastolic diameter(LVEDD)and left atrial diameter(LAD)were decreased in the two groups after treatment(all P<0.05).After treatment,LVEF,SV,E/A and 6MWD were higher in the experimental group than those in the control group(P<0.05).LVEDD and LAD were lower than those in the control group(all P<0.05).Compared with results before treatment,NT-proBNP and CRP were decreased after treatment in the experiment group than those in the control group(P<0.05).There was no significant difference in the cumulative cardiovascular mortality between the experiment group and the control group(3.9％vs.5.9％,P=0.524).The cumulative HF rehospitalization rate was lower in the experimental group than that of the control group(9.8％vs.23.5％,P=0.042).The cumulative end-point-free survival rate was higher in the experiment group than that of the control group(86.3％vs.70.6％,P=0.037).Conclusion Sacubitril valsartan is safer and more effective than ACEI/ARB in the treatment of AMI patients with HFmrEF,and it is worthy of clinical promotion.

Ozone therapy improves early stages of osseointegration in ovariectomized rats

Abstract Objective the aim of this study was to analyze the influence of ozone therapy (OZN) on peri-implant bone repair in critical bones by installing osseointegrated implants in the tibia of ovariectomized rats. Methodology ovariectomy was performed on 30 Wistar rats, aged six months (Rattus novergicus), and, after 90 days, osseointegrated implants were installed in each tibial metaphysis. The study groups were divided into the animals that received intraperitoneal ozone at a concentration of 700 mcg/kg — OZ Group (n=15) — and a control group that received an intraperitoneal saline solution and, for this reason, was named the SAL group (n=15). The applications for both groups occurred during the immediate post-operative period on the 2nd, 4th, 6th, 8th, 10th, and 12th day post-surgery. At various stages (14, 42, and 60 days), the animals were euthanized, and tests were performed on their tibiae. These tests include histomorphometric and immunohistochemical analyses, computerized microtomography, sampling in light-cured resin for calcified sections, and confocal microscopy. The obtained data were then analyzed using One-way ANOVA and the Shapiro-Wilk, Kruskal-Wallis, and student t-tests (P<0.05). Results our findings indicate that the OZ group (3.26±0.20 mm) showed better cellular organization and bone neoformation at 14 days (SAL group, 0.90±1.42 mm) (P=0.001). Immunohistochemistry revealed that osteocalcin labeling was moderate in the OZ group and mild in the SAL group at 14 and 42 days post-surgery. The data from the analysis of calcified tissues (microtomography, histometric, and bone dynamism analysis) at 60 days showed no statistically significant differences between the groups (P=0.32). Conclusion it was concluded that ozone therapy anticipated the initial phases of the peri-implant bone repair process.

Drug clinical comprehensive evaluation of tetrandrine in the treatment of pneumoconiosis / 中华劳动卫生职业病杂志

Objective: To analyze the safety, effectiveness, economics, innovation, suitability and accessibility of tetrandrine in the treatment of pneumoconiosis, and provide evidence-based basis for health policy decision-making and clinical practice. Methods: In July 2022, the system searched PubMed, Embase, the Cochrane Library, CNKI, Wanfang, SinoMed databases (the retrieval time was from the establishment of the database to June 30, 2022), screened the documents that meet the standards, extracted and evaluated the data, and used the "HTA checklist" developed by the International Network of Agencies for Health Technology Assessment (INAHTA) to evaluate the HTA report. AMSTAR-2 Scale was used to evaluate the quality of systematic evaluation/Meta analysis. CHEERS Scale was used to evaluate the quality of pharmacoeconomics research. The included cohort study or case-control study was evaluated with the Newcastle-Ottawa Scale. The included randomized controlled trial (RCT) studies were evaluated using the Cochrane Risk Bias Assessment Tool (Cochrane RCT) quality evaluation criteria. Comprehensive comparison and analysis based on the characteristics of the data included in the study. Results: A total of 882 related literatures were detected from the initial screening. According to relevant standards, 8 RCT studies were finally selected for analysis. Statistical results showed that basic treatment with tetrandrine could better improve FEV(1) (MD=0.13, 95%CI: 0.06-0.20, P<0.001), FEV(1)/FVC (MD=4.48, 95%CI: 0.61-8.35, P=0.02) and clinical treatment efficiency. Tetrandrine had a low incidence of adverse reactions. The affordability coefficient of tetrandrine tablets was 0.295-0.492. Conclusion: Tetrandrine can improve the clinical symptoms and pulmonary ventilation function of pneumoconiosis patients, most of the adverse reactions are mild, and the clinical application is safe.

Progress in A Real-world Study of Abiraterone Acetate Versus Docetaxel in Patients with Metastatic Hormone-sensitive Prostate Cancer / 肿瘤防治研究

The safety and survival benefits of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer have been confirmed by randomized controlled trials and clinical studies abroad. However, real-world studies remain lacking. In this article, we review the progress of real-world studies of abiraterone acetate and docetaxel in the treatment of patients with metastatic hormone-sensitive prostate cancer and the problems faced in clinical practice against the background of differentiated real-world studies. Further research is needed to address clinically important issues, such as individualized dosing, combination dosing, and monitoring of adverse effects.

Comparison of Volume-based Procurement and Innovator Antihypertensive Drugs Based on Digital Pharmaceutical Model / 医药导报

Objective To comprehensively assess the strengths and weaknesses of the 24 antihypertensive drugs procured as Volume-based Procurement(VBP)and innovator drugs by using quantitative evaluation system,and to provide a reference for doctors and patients in medication guidance and pharmaceutical decision-making.Methods The Quantitative Evaluation Criteria in the"Quick Guide to Drug Evaluation and Selection in Chinese Medical Institutions"were refined and optimized.The 24 selected VBP and innovator antihypertensive drugs were quantitatively evaluated according to the optimized quantitative evaluation system with the help of Chinese and English databases such as China Knowledge Network,Wanfang data,Wipunet,Embased,PubMed,and Metstr,as well as guideline search tools such as Meikang MCDEX,Drugwise Data,Up To Date,Medical Pulse and other databases etc.Results Among the 24 antihypertensive drugs,only four innovator drug evaluation scores were higher than those of drugs selected as VBP,namely felodipine tablets,Fosinopril sodium tablets,indapamide extended-release capsules,Irbesartan hydrochlorothiazide tablets.there were five main differences in the evaluation scores,namely economy,consistency evaluation,drug expiry date,global use,and the status of manufacturing enterprises.It was found that 83%of the VBP drugs had higher evaluation scores than those of the innovator drugs.The economic score of the innovator drug was low,and the difference in the scores was between 1-11 points.Conclusion By using the quantitative evaluation system to evaluate the antihypertensive drugs,the advantages and disadvantages of the innovator and VBP antihypertensive drugs can be assessed comprehensively,and the digital characteristics of antihypertensive drugs can be given,and the evaluation score can provide the reference basis for the guidance and decision-making of medication for doctors and patients.

Animal Models of Pulmonary Arterial Hypertension and Their Application in Drug Research / 实验动物与比较医学

Pulmonary arterial hypertension is a clinical syndrome characterized by pulmonary vascular remodeling causing increased vascular resistance, which will lead to right heart failure and even death if left untreated. The pathogenesis of pulmonary arterial hypertension has not yet been clarified, and clinical treatments have not been effective in improving prognosis or reducing mortality. To investigate the pathogenesis of pulmonary arterial hypertension and to develop and evaluate more effective and safer drug treatments, establishing related animal disease models is very important. This paper outlines the pathological characteristics of pulmonary arterial hypertension and summarizes the various types of animal models of pulmonary arterial hypertension, as well as describes the progress of the application of these models in three therapeutic pathways and related drug research in the past five years, with a view to providing a reference for the selection of animal models of pulmonary arterial hypertension and research applications.

Research progress of microfluidic chips in age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Age-related macular degeneration(ARMD)is the primary cause of severe visual impairment and blindness in people over 60 years old. With the aging of the global population, the incidence of the disease is also rising year by year. However, the pathogenesis and treatment strategy of ARMD need to be further explored. As a cutting-edge science and technology, microfluidic chips can build a comprehensive microsystem that simulates the condition and function of human tissues and organs, which has the advantages of less sample consumption and short analysis time. In recent years, many studies have confirmed that microfluidic chips can bring brand new technology solutions to the basic and clinical research of ARMD. This article will discuss and review the application progress of microfluidic chips in the areas of ARMD mechanism research, drug evaluation and clinical translation, providing a theoretical reference for further research on the diagnosis and treatment of ARMD.

Quality control of the technology method of clinical comprehensive drug evaluation / 中国药房

At present， there are still some problems in China’s clinical comprehensive drug evaluation， such as the unscientific design of the evaluation content， the nonstandard evaluation method and organizational process， and the evaluation results not meeting the decision-making needs. It is urgent to carry out quality control over the whole process of the clinical comprehensive drug evaluation project. From the technical point of view， the quality control methods of clinical comprehensive drug evaluation are discussed through three links of the evaluation content and design （giving the quality control key points of the theme selection process and scheme design）， the evaluation method （discussing the quality control elements of two common evaluation methods， i. e. documentary evidence method and real-world research） and result application transformation （giving suggestions on quality control from the comprehensive analysis of evaluation results， transformation of evaluation results and decision-making）， so as to promote the quality improvement of clinical comprehensive drug evaluation.

Multi-factor combined biomarker screening strategy to rapidly diagnose Alzheimer's disease and evaluate drug effect based on a rat model / 药物分析学报

Alzheimer's disease(AD)represents the main form of dementia;however,valid diagnosis and treatment measures are lacking.The discovery of valuable biomarkers through omics technologies can help solve this problem.For this reason,metabolomic analysis using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)was carried out on plasma,hippocampus,and cortex samples of an AD rat model.Based on the metabolomic data,we report a multi-factor combined biomarker screening strategy to rapidly and accurately identify potential bio-markers.Compared with the usual procedure,our strategy can identify fewer biomarkers with higher diagnostic specificity and sensitivity.In addition to diagnosis,the potential biomarkers identified using our strategy were also beneficial for drug evaluation.Multi-factor combined biomarker screening strategy was used to identify differential metabolites from a rat model of amyloid beta peptide 1-40(Aβ1-40)plus ibotenic acid-induced AD(compared with the controls)for the first time;lysophosphati-dylcholine(LysoPC)and intermediates of sphingolipid metabolism were screened as potential bio-markers.Subsequently,the effects of donepezil and pine nut were successfully reflected by regulating the levels of the abovementioned biomarkers and metabolic profile distribution in partial least squares-discriminant analysis(PLS-DA).This novel biomarker screening strategy can be used to analyze other metabolomic data to simultaneously enable disease diagnosis and drug evaluation.

Pharmacological action and clinical evaluation of difelikefalin, a new drug for the treatment of uremic pruritus / 中国基层医药

Uremic pruritus is one of the skin complications that perplex patients with end-stage renal disease undergoing hemodialysis or peritoneal dialysis. Because the specific pathogenesis is not clear, there is no unified treatment plan in the world. In August 2021, the US Food and Drug Administration approved the use of difelikefalin (under the trade name Korsuva) for the treatment of moderate to severe pruritus associated with chronic kidney disease in adult patients undergoing hemodialysis. Studies have shown that difelikefalin can remarkably reduce the intensity of pruritus and improve sleep and pruritus-related quality of life. The recommended dose of difelikefalin is 0.5 μg/kg, and difelikefalin is well tolerated and has high safety. This paper reviews the pharmacological effects, pharmacokinetics, clinical efficacy and safety of difelikefalin.

Advances in research based on primary human hepatocytes in vitro / 中华肝胆外科杂志

Due to the special functions of liver, the topic of liver physiological function and pathophysiological changes has always been the main issue in life science area. Human liver is composed of multiple types of cells, among which the hepatocyte is the most essential one. Primary human hepatocytes are considered as the gold standard model in vitro for the liver study and the ideal cell for hepatocyte transplantation and bioartificial liver. Nowadays, primary human hepatocytes play a vital role in the field of basic science research and applied research. Therefore, we presented recent advances in research based on primary human hepatocytes in vitro.

Analysis of current situation of researches on comprehensive evaluation of drugs in China based on CiteSpace / 中国药房

OBJECT IVE To analyze the situation of comprehensive drug evaluation research in China. METHODS Using the method of bibliometrics ，CiteSpace 5.8.R3 analysis tool was used to summarize the research situation and hotspots from 6 dimensions，such as safety ，effectiveness，economy，innovation，suitability and accessibility. RESULTS & CONCLUSIONS At present，there were many types of researches on safety and effectiveness. The economic evaluation was increasing. There were still not much researches on the comprehensive evaluation of drugs from 6 dimensions. Researchers were concentrated ，and there was less collaboration between researchers or research institutions. In terms of methods ，systematic review ，meta-analysis，clinical observational research and retrospective research were more common. The topic selection of antibacterial drugs ，anti-tumor drugs ， and cardiovascular drugs were more popular. It is recommended to establish a unified method and standard for clinical comprehensive evaluation of drugs ，clarify the coordination medianism of the comprehensive drug evaluation ，make full use of real-world data to enrich the contents of 6 dimensions，implement quality control for all segments of the evaluation ，and form a comprehensive evaluation report with sufficient evidence and definite results ，so as to promote the clinical application of the results.

Ascending， Descending， Floating and Sinking Properties of Descurainiae Semen Lepidii Semen Based on Pulmonary Edema Model / 中国实验方剂学杂志

ObjectiveThe pulmonary edema （PE） model where the disease was located in the viscera was established according to the treatment principle that patients with the disease location inside should be treated with descending and sinking medicine， combined with changes in the disease tendency， to verify the scientificity of descending and sinking properties of Descurainiae Semen Lepidii Semen （SD）， and to preliminarily elucidate the scientific connotation of descending， ascending， floating and sinking of Chinese medicine. MethodSixty male SD rats were randomly divided into normal control group， model group （20 mg·kg-1）， positive drug group （dexamethasone， 0.075 mg·kg-1） and SD low （1.167 g·kg-1）， medium （2.334 g·kg-1）and high （4.668 g·kg-1） dose groups. The PE model was established by intrapleural injection of 1% carrageenan （2 mL·kg-1）. The evaluation indexes （lung autopsy， amount of pleural effusion， number of white blood cells， lung wet/dry weight ratio， lung water content and lung permeability） were tested to determine the optimal dose of SD decoction for intervention of PE. The relevant indexes of the five major systems （central nervous system， respiratory system， circulatory system， digestive system and urinary system） closely related to the body's Qi movement were detected and changes in the disease tendency in PE rats were analyzed， to determine the descending， ascending， floating and sinking properties of SD. In addition， histopathological changes were investigated by hematoxylin-eosin （HE） staining， and types and numbers of inflammatory cells and mediators were detected to preliminarily explore the mechanism of SD in improving PE. ResultCompared with the conditions in the normal control group， the amount of pleural effusion， number of white blood cells in pleural effusion， lung wet/dry weight ratio， lung water content and lung permeability were increased （P<0.01） in the model group， where the rats presented cough， dyspnea， shortness of breath and arched back， and a small number of them had wet nose and bubble liquid in nostrils. In the autopsy of the rats in the model group， the lungs were enlarged or accompanied by congestion and plenty of pink bubble liquid appeared at the trachea. Compared with the conditions in the model group， SD reduced the amount of pleural effusion， number of white blood cells in pleural effusion， lung coefficient， lung wet/dry weight ratio and lung water content （P<0.01）， and improved pulmonary edema symptoms such as damage， inflammation and infiltration around the lumen， thickening of the trachea， and accumulation of edema fluid， and the SD medium dose group had the best effect on the treatment of PE. In terms of respiratory system， compared with the normal control group， the model group had reduced latent time of cough and asthma （P<0.05， P<0.01） and elevated number of cough and wheezing （P<0.01）. The three SD groups had increased latent time of cough and asthma and decreased number of cough and wheezing （P<0.01）. In terms of urinary system， compared with the normal control group， the model group presented decreased urine volume. The SD low， medium and high dose groups had increased urine volume （P<0.05， P<0.01）， but they had no effect on perspiration. In terms of digestive system， compared with the conditions in the normal control group， the gastric residual rate and gastrin （GT） level were increased （P<0.05， P<0.01）， and the gastric emptying rate and small intestine transit rate were decreased （P<0.01）. The SD low dose group had elevated small intestine transit rate （P<0.01）， and the SD high and medium groups had enhanced gastric emptying rate and small intestine transit rate （P<0.01）， reduced gastric residual rate， lowered GT level to promote gastrointestinal movement and transportation （P<0.01）， and increased motilin （MTL） level to promote gastric emptying in rats （P<0.05， P<0.01）. In terms of circulatory system， compared with the normal control group， the model group displayed reduced left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS） and cardiac output （CO） （P<0.01）， and elevated tendency of heart rate， systolic blood pressure （SBP， P<0.01） and diastolic blood pressure （DBP， P<0.05）. Compared with the model group， the SD low dose group increased LVEF and decreased DBP （P<0.05）， while the SD medium dose group increased LVEF， LVFS， CO and SBP （P<0.01） and decreased DBP （P<0.05）， and the SD high dose group increased LVFS （P<0.01） and decreased SBP （P<0.01） and DBP （P<0.05）. In terms of central nervous system， compared with the conditions in the normal control group， the standing times dropped in the model group （P<0.01）. SD reduced the movement distance， movement time， standing times and activity time in the center of the open field， and increased the rest time and activity time at the edge of the open field （P<0.05， P<0.01）. Moreover， compared with the normal control group， the model group had serious inflammatory infiltration around the lung lumen， thickened trachea with accumulated edema fluid， seriously damaged lung tissue， increased number of white blood cells and percentage of neutrophils in blood （P<0.01）， elevated percentage of monocytes， interleukin-4 （IL-4）， immunoglobulin E （IgE） level and reactive oxygen species （ROS） level in lung tissue （P<0.05，P<0.01）， and decreased IFN-γ in alveolar lavage fluid （P<0.01）. Compared with the model group， SD decreased the number of white blood cells， neutrophil accumulation， pulmonary congestion and interstitial edema， IFN-γ and IL-4 levels in alveolar lavage fluid and ROS level in lung tissue， and increased IgE level （P<0.05， P<0.01）. ConclusionSD had a significant improvement effect on PE model where the disease was located in the viscera. It could regulate the excretion of water by purgation， regulate Qi movement and expel Qi stagnation by descending and sinking lung Qi， and promote purification and descent of lung qi to make Qi movement downward. This indicated SD had the descending and sinking properties. The medium dose of SD decoction exerted the best effect， and its mechanism of action might be through regulating the neutrophil inflammatory response.

Expert Consensus on the Application of Multiple criteria Decision Analysis in Comprehensive Clinical Evaluation of Orphan Drugs(2022) / 罕见病研究

@#Comprehensive clinical drug evaluation is an important technical tool for decision-making on drug supply. Traditional evaluation on health technology provides methodological references for comprehensive clinical evalu-ation of drugs. However, data from clinical trials for orphan drugs are often insufficient. It is difficult to evaluate the clinical and economic value of orphan drugs by using the criteria of ordinary drugs. Particularity of orphan drugs makes it difficult to use the traditional evaluation methods for health technology. Multiple criteria decision analysis explores the comprehensive value of drugs from different angles. It promotes the transparency and scientific thinking on the basis of evidence-based medicine, improves the quality of decision-making, and thus provides a possible solution to the comprehensive clinical evaluation of orphan drugs. However, its application in the comprehensive evaluation of orphan drugs in China is still in its infancy and trial stage, and no methodological guidelines is available. In order to optimize the construction of a diversified system for comprehensive clinical evaluation of orphan drugs in China, the Multi-disciplinary Team for Rare Diseases of Peking Union Medical College Hospital and China Alliance for Rare Disease organized experts in related fields to formulate this consensus, aiming to provide standardized methodological guideline to the comprehensive clinical evaluation of orphan drugs.

Prescription de l'oxygène dans le service d'urgence d'un hôpital de référence de Mahajanga

Introduction : L'oxygène est un médicament. Une prescription non appropriée peut occasionner une insuffisance ou un excès d'apport source de dépenses hospitalières dans les pays en développement. L'objectif était d'évaluer la prescription de l'oxygénothérapie dans un service d'urgence et de soins intensifs et d'observer les modalités d'utilisation pour permettre d'ajuster les objectifs et les cibles thérapeutiques en prenant comme référence les recommandations. Matériels et Méthodes : Il s'agit d'une étude prospective descriptive sur trois mois, en 2018, de la prescription de l'oxygène au service des urgences et de soins intensifs dans un hôpital de référence de Mahajanga. Quatre obus et quatre extracteurs étaient les sources d'oxygène pour 18 lits d'accueil, de déchoquage et de soins intensifs. Ni un générateur d'oxygène ni des matériels de ventilation spécifique n'étaient disponibles. L'étude statistique a été réalisée avec le logiciel SPSS® v.20, le test Khi2 utilisé pour la comparaison des valeurs avec un seuil de signification p˂0,05. Résultats : Sur 599 admissions, 244 patients (40,7%) bénéficiant d'un apport en oxygène ont été inclus dans l'étude. L'âge moyen était de 47,6 ans avec prédominance masculine (sex-ratio de 1,4). Une saturation d'au plus 90% a été retrouvée dans 25% des cas. Les 40% des patients ont été référés pour une « oxygénothérapie ¼. Les pathologies en cause étaient neurologiques dans 34,4% des cas, touchant la tranche d'âge de 40 à 60 ans (p=0,006), respiratoires pour 21,7% et cardio-vasculaires dans 13,9%. Les lunettes à oxygène étaient utilisées à 71,7%, l'obus à oxygène à 69,3% dans les premières 24 heures (p=0,001). La mortalité était de 22,5% avec 60,6% des patients décédés qui avaient une saturation en oxygène de 90% au maximum (p=0,05). Conclusion : Un algorithme standard avec une saturation pulsée en oxygène ciblée et des techniques plus appropriées auraient permis d'économiser l'oxygène hospitalier et de réduire la mortalité.

Background: Oxygen is a drug. An inappropriate prescription can lead to insufficient or excessive intake, which is a source of hospital expenditure in low-income countries. The aim of the study was to assess the prescription of oxygen therapy in an emergency and intensive care unit and to observe the modalities of its use to allow adjustment of the therapeutic objectives and targets according to the current recommendations. Materials and Methods: We conducted a prospective descriptive study over three months, in 2018, of the prescription of oxygen in the Emergency and Intensive Care Department, of a referral hospital in Mahajanga. Four oxygen cylinder and 4 concentrators were available as oxygen sources for 18 beds intended for patient reception, destock and intensive care. The hospital did not have an oxygen generator or specific ventilation equipment. The statistical study was carried out with SPSS® v.20 software, the Khi2 test used for the comparison of values with a significance level p˂0.05. Results: Of 599 admissions, 244 patients (40.7%) receiving oxygen were included in the study. The average age was 47.6 years with a male predominance (sex ratio : 1.4). Oxygen saturation ≤90% was found in 25% of cases. The 40% of patients were referred for "oxygen therapy". The main disease were neurological in 34.4%, affecting the age group of 40 to 60 years (p=0.006); respiratory for 21.7% and cardiovascular in 13.9%. Nasal cannulas were used in 71.7%, the oxygen cylinder in 69.3% in the first 24 hours (p=0.001). Mortality was 22.5% of which 60.6% had oxygen saturation ≤90% (p=0.05). Conclusion: Using a standard algorithm with targeted SpO2 and more appropriate techniques would have saved hospital oxygen and reduced mortality.

Reacciones adversas a medicamentos utilizados para la COVID-19 en cinco países de América Latina / Adverse reactions to drugs used for COVID-19 in five Latin American countries / Reações adversas a medicamentos utilizados para a COVID-19 em cinco países da América Latina

RESUMEN Objetivo. Caracterizar y describir las notificaciones de sospechas de reacciones adversas de un grupo de medicamentos que se utilizaron en Colombia, Costa Rica, Cuba, Chile, El Salvador, México y Perú para tratar o prevenir la enfermedad por el coronavirus (COVID-19, por su sigla en inglés) entre el 1 de marzo y el 31 de agosto del 2020. Métodos. Se elaboró una lista de los 13 medicamentos utilizados para tratar o prevenir la COVID-19, según fuentes oficiales y no oficiales. Desde las bases de datos de los programas nacionales de farmacovigilancia de los países participantes, se recopilaron las notificaciones de sospechas de reacciones adversas a estos medicamentos recibidas en el período comprendido entre el 1 de marzo y 31 de agosto de año 2020. Resultados. Se recibieron 3 490 notificaciones de sospechas de reacciones adversas desde los programas de farmacovigilancia de Perú (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72) y El Salvador (n = 3). Los medicamentos con mayor número de notificaciones de reacciones adversas fueron la azitromicina, la ivermectina y la hidroxicloroquina. La diarrea fue el evento más frecuente (15,0%). Del total de las sospechas de reacciones adversas, 11,9% fueron notificadas como graves. La más frecuente fue la prolongación del intervalo QT posterior al uso de hidroxicloroquina. De estas sospechas de reacciones adversas graves, 54,5% ocurrieron en personas mayores de 65 años. Conclusión. Si bien no es posible establecer una relación causal a partir de la evaluación de informes espontáneos, el presente estudio confirma la presencia de reacciones adversas, algunas graves, con medicamentos que se utilizaron para tratar o prevenir la COVID-19.

ABSTRACT Objective. Characterize and describe reports of suspected adverse reactions to a group of drugs used in Colombia, Costa Rica, Cuba, Chile, El Salvador, Mexico, and Peru to treat or prevent coronavirus disease (COVID-19) between 1 March and 31 August 2020. Methods. A list of the 13 drugs used to treat or prevent COVID-19 was prepared, based on official and unofficial sources. Drawing on the databases of the national pharmacovigilance programs of the participating countries, reports of suspected adverse reactions to these drugs were collected for the period from 1 March and 31 August 2020. Results. A total of 3 490 reports of suspected adverse reactions were received from the pharmacovigilance programs of Peru (n = 3 037), Cuba (n = 270), Colombia (n = 108), Chile (n = 72), and El Salvador (n = 3). The drugs with the highest number of reported adverse reactions were azithromycin, ivermectin, and hydroxychloroquine. Diarrhea was the most frequent event (15.0%). Of the total suspected adverse reactions, 11.9% were reported as serious. The most frequent was QT prolongation following use of hydroxychloroquine. Of these suspected serious adverse reactions, 54.5% occurred in people over 65 years of age. Conclusions. While it is not possible to establish a causal relationship from the evaluation of spontaneous reports, the present study confirms the presence of adverse reactions—some of them serious—involving drugs used to treat or prevent COVID-19.

RESUMO Objetivo. Caracterizar e descrever as notificações de suspeitas de reações adversas a um grupo de medicamentos utilizados na Colômbia, Costa Rica, Cuba, Chile, El Salvador, México e Peru, para tratar ou prevenir a doença do coronavírus (COVID-19), entre 1º de março e 31 de agosto de 2020. Métodos. Foi elaborada uma lista dos 13 medicamentos usados para tratar ou prevenir a COVID-19, segundo fontes oficiais e não oficiais. A partir das bases de dados dos programas nacionais de farmacovigilância dos países participantes, foram coletadas notificações de suspeitas de reações adversas a esses medicamentos, recebidas no período entre 1º de março e 31 de agosto de 2020. Resultados. Foram recebidas 3.490 notificações de suspeitas de reações adversas dos programas de farmacovigilância do Peru (n = 3.037), Cuba (n = 270), Colômbia (n = 108), Chile (n = 72) e El Salvador (n = 3). Os medicamentos com maior número de notificações de reações adversas foram azitromicina, ivermectina e hidroxicloroquina. A diarreia foi o evento mais frequente (15,0%). Do total de suspeitas de reações adversas, 11,9% foram notificadas como graves. A mais frequente foi o prolongamento do intervalo QT após o uso de hidroxicloroquina. Dessas suspeitas de reações adversas graves, 54,5% ocorreram em pessoas com mais de 65 anos. Conclusão. Embora não seja possível estabelecer uma relação causal com base na avaliação de relatos espontâneos, o presente estudo confirma a presença de reações adversas - algumas graves - a medicamentos que foram usados para tratar ou prevenir a COVID-19.

Use of Severe ADR-inducing Drugs in Special Population in Our Hospital Guided by the Detailed Quantitative Scoring Rules of Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions / 中国药房

OBJECTIVE：To promote the safe use of severe ADR-inducing drugs in special population in our hospital. METHODS：According to detailed quantitative scoring rules of Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions，comprehensive evaluation database of drugs in our hospital was established. Drugs with ADR rating or ADE general terminology standard rating of 1，2，3 and 4 under the "safety" dimension were obtained from the database. According to the difference of the incidence of ADR ，4 kinds of severe ADR-inducing drugs ，such as very common （incidence≥10％），common （incidence 1％-＜10％），occasional（incidence 0.1％-＜1％）and rare （incidence ＜0.1％），were obtained. According to the quantitative scores of these 4 kinds of drugs in six special groups ，such as children ，pregnant women ，lactating women ，the elderly，patients with abnormal liver function ，and patients with abnormal kidney function ，the feasibility for special population to use drugs that cause severe ADR was analyzed. RESULTS ：Among 1 172 chemical drugs in drug comprehensive evaluation database of our hospital ，18，73，61，and 357 kinds can cause very common ，common，occasional and rare severe ADR ， respectively. Among them ，the incidence of severe ADR caused by tumor drugs was high ，so it was necessary to pay close attention to the use of tumor drugs in special populations. Totally 173 kinds of drugs were prohibited for children because the instructions clearly showed organ toxicity ，cytotoxicity and there were no guidelines recommending their use in children ，so the clinical medication should be used with extraordinary caution. There were 278 and 228 drugs prohibited for pregnant women and lactating women，which were prohibited for pregnant or lactating period due to embryonic toxicity and reproductive toxicity. There were 13 prohibited drugs for the elderly ，most of which were specialized drugs. Five kinds of drugs were prohibited in patients with abnormal liver function and seven were prohibited in patients with abnormal kidney function ，most of which were tumor drugs with strong hepatorenal toxicity. CONCLUSIONS ：Established quantitative score system can provide effective guidance for the safe use of severe ADR-inducing drugs among 6 special populations as children ，pregant women ，lactating women ，the elderly ，the patients with abnormal liver function and the patients with renal

Analysis on new research and development ideas and technical points of traditional Chinese medicine for prevention and treatment of chronic heart failure / 中国中药杂志

Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.

Perfil de seleção e consumo de medicamentos em uma instituição de ensino superior: diagnóstico situacional para promoção da saúde / Profile of drug selection and consumption in a higher education institution: situational diagnosis for health promotion

Resumo A seleção de medicamentos é um processo interdisciplinar baseado no perfil epidemiológico, econômico e técnico local. Os medicamentos selecionados devem apresentar eficácia e segurança, de acordo com a Política Nacional de Medicamentos. Este trabalho teve como objetivo identificar o perfil de seleção e consumo de medicamentos dispensados em uma instituição de ensino superior. A partir de pesquisa descritiva com característica quantitativa e qualitativa, foram utilizados os mapas de dispensação de medicamentos para a enfermagem da Divisão de Saúde de 2018 e 2019. Em 2018, 21% dos medicamentos padronizados não foram consumidos. Por esta razão, em 2019 houve nova seleção e 17,2% dos medicamentos foram excluídos. De acordo com o perfil de consumo de medicamentos, observou-se que o consumo de analgésicos foi superior ao consumo de fármacos com propósito anti-inflamatório, de acordo com a classificação Anatomical Therapeutic Chemical (ATC). Conclui-se que o perfil abordado neste estudo possibilita um diagnóstico situacional de seleção e consumo, tendo como necessidade a implantação do seguimento farmacoterapêutico com o intuito de minimizar as possíveis reações adversas produzidas por medicamentos, como estratégia de prevenção e promoção da saúde.

Abstract Drug selection is an interdisciplinary process based on the local epidemiological, economic and technical profile. The selected drugs must be effective and safe, in accordance with the National Drug Policy. This study aimed to identify the profile of selection and consumption of drugs dispensed in a higher education institution. From descriptive research with quantitative and qualitative characteristics, drug dispensing maps for the Nursing Division of the Health Division of 2018 and 2019 were used. In 2018, 21% of standardized medicines were not consumed. For this reason, in 2019 there was a new selection and 17.2% of medicines were excluded. According to the medication consumption profile, the consumption of analgesics was higher than the consumption of drugs with anti-inflammatory purposes, according to the Anatomical Therapeutic Chemical (ATC) classification. It is concluded that the profile addressed in this study allows a situational diagnosis of selection and consumption, with the need to implement pharmacotherapeutic follow-up in order to minimize the possible adverse reactions produced by drugs, as a health promotion strategy.