Data mining of severe cutaneous adverse reactions related to immune checkpoint inhibitors in the FAERS / 中国药房

OBJECTIVE To mine and analyze severe cutaneous adverse reaction signals of 5 commonly used immune checkpoint inhibitors （ICIs）， and to provide reference for clinically safe use of drugs. METHODS Based on the FDA adverse events reporting system （FAERS） database，adverse drug events （ADEs） reports about severe cutaneous adverse reactions related to ipilimumab， nivolumab， pembrolizumab， atezolizumab and durvalumab were collected from listing in the United States to the fourth quarter of 2022. The ADE signals were mined and analyzed with reporting odds ratio （ROR） and Bayesian confidence propagation neural network （BCPNN）. RESULTS A total of 5 726 reports of severe cutaneous adverse reactions were collected， including 3 037 reports for nivolumab，1 465 reports for pembrolizumab， 130 reports for durvalumab， 429 reports for atezolizumab and 665 reports for ipilimumab. All 5 kinds of ICIs caused positive signals， the correlation degree of which was as follows： pembrolizumab＞atezolizumab＞nivolumab＞ipilimumab＞durvalumab. Stevens-Johnson syndrome（SJS） and toxic epidermal necrolysis （TEN） have been reported for all 5 ICIs， and the association was the strongest with pembrolizumab. CONCLUSIONS All 5 kinds of ICIs are associated with the risk of severe skin adverse reactions， and close attention should be paid to their clinical use， especially being cautious when using pembrolizumab. The combination of ICIs should be avoided as much as possible.

Data mining of adverse drug reaction of iodine contrast media based on spontaneous reporting system / 中国药房

OBJECTIVE To mine the risk sig nals o f iodine contrast media from spontaneous reporting system. METHODS Reporting odds ratio ，proportional reporting ratio ，Medicines and Healthcare Products Regulatory Agency and Bayesian confidence propagation neural network were used to mine risk signals of 5 iodine contrast media （iopamidol，iohexol，iopromide，ioversol， iodixanol）. RESULTS 1 164（2 446 case times ）adverse drug reaction of iodine contrast media were included ，a total of 14 risk signals involving systems/organs such as respiratory system （3，2，4，3，2 for the above 5 iodine contrast media ）and immune system and 32 specific adverse drug reaction signals including anaphylactic shock ，rash and flushing （11，7，7，3，4 for the above 5 iodine contrast media ）were found in 5 iodine contrast media. CONCLUSIONS The risk signals of 5 iodine contrast media verify that there is a certain correlation between these drugs and above adverse drug reactions. It is suggested that before using iodine contrast media in clinic ，it is necessary to pay attention to whether the patient has a history of tumor and combined medication ，evaluate the patient’s renal function ，and give preventive measures such as hydration in advance. When using iodine contrast media ，it is necessary to pay attention to the temperature ，dose and injection rate. And medical staff need to follow up the patient ’s situation in time after using iodine contrast media to avoiding the impact of delayed adverse reactions.

Analysis of β-blockers associated with acute renal failure signal based on data mining method / 中国药房

OBJECTIVE To excavate and evaluate β-blockers associated with acute renal failure（ARF）signal. METHODS Using the report odds ratio （ROR）method and Bayesian confidence interval progressive neural network （BCPNN）method，signal detection and analysis were performed for 4 kinds of β-blockers（metoprolol，bisoprolol，atenolol，nebivolol）associated with ARF Δ 基金项目：重庆市临床药学重点专科建设项目 （No.渝卫办发 in FDA adverse event reporting system （FAERS）from the two 〔2020〕68号）；重庆医科大学未来医学青年创新团队发展支持计划项 dimensions of Standard International Dictionary of Medical 目（No.W0081） Terms （MedDRA） analysis query （SMQ） term set and ＊药师，硕士研究生。研究方向：药物警戒。电话：023-68485161。 preferred term （PT） level terms. When the two methods E-mail：2020121624@stu.cqmu.edu.cn detected positive signals at the same time ，it indicated that # 通信作者：主任药师，硕士生导师。研究方向：临床药学、药物警 suspicious signals were detected. RESULTS Totally 14 328 戒。电话：023-63625666。E-mail：jiayuntaomail@hospital.cqmu.edu.cn ARF reports of 4 kinds of β-blockers were retrieved within the ·1380· China Pharmacy 2022Vol. 33 No. 11 中国药房 2022年第33卷第11期 narrow sense of “acute renal failure ”in SMQ term set ，of which men （6 964）were more than women （6 206）. The age of patients was mainly concentrated in the middle-aged and elderly （≥45 years old ），and serious adverse events accounted for 77.23％. The results of signal retrieval based on SMQ term set showed that ROR values and 95％ confidence intervals of metoprolol ，bisoprolol， atenolol and nebivolol detected by ROR method were 2.58（2.51，2.65），5.30（5.14，5.47），2.80（2.69，2.91）and 3.28（3.04， 3.53）respectively. The signal components （IC）detected by BCPNN method and the lower limit of IC were 1.29（1.25），2.26 （2.22），1.42（1.36）and 1.64（1.53）respectively，suggesting suspicious signals were detected in these four kinds of β-blockers associated ARF. The results of signal detection based on PT level terms showed that 37 positive signals were detected by ROR method，38 positive signals were detected by BCPNN method ，and 36 suspicious signals were detected by the two methods at the same time. For each drug ，12 suspicious signals of metoprolol were detected at the same time ，9 suspicious signals of bisoprolol and atenolol were detected at the same time ，and 6 suspicious signals of nebivolol were detected at the same time ；the number and type of signals were different among the 4 kinds of drug. CONCLUSIONS Four kinds of β-blockers may cause ARF. Compared with metoprolol and atenolol ，bisoprolol and nebivolol have strong statistical correlation with ARF ，suggesting that medical personnel should pay attention to the possible renal related adverse reactions of these drugs in the process of clinical use.

Detection method of nonlinear magnetized harmonic signal of medical magnetic nanoparticles / 生物医学工程学杂志

Medical magnetic nanoparticles are nano-medical materials with superparamagnetism, which can be collected in the tumor tissue through blood circulation, and magnetic particle imaging technology can be used to visualize the concentration of magnetic nanoparticles in the living body to achieve the purpose of tumor imaging. Based on the nonlinear magnetization characteristics of magnetic particles and the frequency characteristics of their magnetization, a differential detection method for the third harmonic of magnetic particle detection signals is proposed. It was modeled and analyzed, to study the nonlinear magnetization response characteristics of magnetic particles under alternating field, and the spectral characteristics of magnetic particle signals. At the same time, the relationship between each harmonic and the amount of medical magnetic nanoparticle samples was studied. On this basis, a signal detection experimental system was built to analyze the spectral characteristics and power spectral density of the detected signal, and to study the relationship between the signal and the excitation frequency. The signal detection experiment was carried out by the above method. The experimental results showed that under the alternating excitation field, the medical magnetic nanoparticles would generate a spike signal higher than the background sensing signal, and the magnetic particle signal existed in the odd harmonics of the detected signal spectrum. And the spectral energy was concentrated at the third harmonic, that is, the third harmonic magnetic particle signal detection that meets the medical detection requirement could be realized. In addition, the relationship between each harmonic and the particle sample volume had a positive growth relationship, and the detected medical magnetic nanoparticle sample volume could be determined according to the relationship. At the same time, the selection of the excitation frequency was limited by the sensitivity of the system, and the detection peak of the third harmonic of the detection signal was reached at the excitation frequency of 1 kHz. It provides theoretical and technical support for the detection of medical magnetic nanoparticle imaging signals in magnetic particle imaging research.

2．A Checklist of Important Points in Research Using JADER / 薬剤疫学

Spontaneous reporting is an important source of information in pharmacovigilance. In Japan, the Japanese Adverse Drug Event Report database (JADER) was released in 2012, and this has led to numerous conference presentations and academic research papers that have reported the detection of signals based on the use of data mining methods. However, spontaneous reporting generally has certain limitations, including under-reporting, a lack of denominator information, and the effects of reporting bias, and these problems apply equally to JADER. The system of collecting spontaneous reports also influences the results obtained based on JADER analysis, as JADER in principle comprises serious adverse drug event reports and includes solicited reports. The detection of signals showing statistical significance does not necessarily imply a causal relationship between a particular drug and adverse events, and consequently, the cause of the signals detected requires careful interpretation. However, it has been pointed out that findings are sometimes accepted without considering the limitations.For pharmaceutical companies, the Guidance on good pharmacovigilance practices Module Ⅸ and Guidance for Industry - Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment are available in the European Union and United States, respectively, for the purpose of signal management in pharmacovigilance activities. In contrast, there are limited resources to which researchers can refer when they publish scientific findings obtained using spontaneous reporting databases. To rectify this deficiency, we created a “checklist of important points to be noted during research that uses the data mining method in JADER (mainly signal detection by disproportionality analysis)” for the benefit of researchers using JADER. That study was supported by a Grant for Research Projects of the Japanese Society of Drug Informatics in 2017. In this article, we provide an overview of the checklist, with reference to the “Report of CIOMS Working Group Ⅷ： practical aspects of signal detection in pharmacovigilance,” which was used as a source when creating the checklist.

Basic Dos and Don’ts in Applying Signal Detection Methods to Spontaneous Reporting Systems Databases / 医薬品情報学

“Signals are useless until they are read and possibly subjected to intensive study by appropriate investigators in WHO or in national centres”, cited from Finney’s 1974 first article on the theory of signal detection. Recently, freely available large-scale spontaneous reporting systems databases and improved computational power of personal computers have made it easier to perform signal detection in personal researches. However, adequate knowledge for the limitations of source spontaneous reports and understanding the differences with conventional clinical and epidemiological studies are imperatives for valid interpretation of signal indexes. This review describes the basic theory, aims and limitations of the signal detection method using spontaneous reporting systems databases and practical considerations.

Tocilizumab related adverse events: A cross-section analysis of FDA Adverse Event Reporting System / 中国临床药理学与治疗学

AIM: To analyze the adverse events (AE) of tocilizumab by using the FDA Adverse Event Reporting System (FAERS) database. METHODS: AE reports related to tocilizumab were extracted from the FAERS database. Disproportionality analysis of reporting odds ratio (ROR) and Medicines and Healthcare Products Regulatory Agency (MHRA) methods were performed for safety signal detection. RESULTS: A total of 19 773 reports associated with tocilizumab as the primary or secondary suspected drugs were extracted from the FAERS database between July 2014 to March 2019. AEs of drug ineffective, pain, drug intolerance, fatigue and rash were commonly reported. There were 13 642 serious AE reports, and 602 reports of death outcome. The proportion of serious and death outcome AEs of male patients was significantly higher than female, and these proportions were significantly higher in children and elderly compared with others. Respectively 602 and 490 of tocilizumab signals were detected by ROR method and MHRA method, including common AEs such as infection, drug hypersensitivity, leukopenia, and hepatic enzyme increased, and signals not indicated in label, for instance, pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, were also detected. CONCLUSION: The commonly reported AEs of tocilizumab include drug inefficiency, pain, drug intolerance, fatigue and rash. Pulmonary fibrosis, interstitial lung disease, pancreatic toxicity and demyelination, which not indicated in label, should be further assessed and be cautious in COVID-19 treatment.

Creating a Checklist and a Survey on Research That Used the Japanese Adverse Drug Event Report Database / 医薬品情報学

Objective: The purpose of this study was to create a checklist that summarizes checkpoints that should be noted when using the Japanese Adverse Drug Event Report database (JADER). After we created the checklist, we then used it to survey published academic papers that used JADER.Method: First, we created a draft checklist for research that uses JADER by citing the report of CIOMS working group VIII “Practical Aspects of Signal Detection in Pharmacovigilance”. Then, we conducted a pilot test and revised the draft checklist. Finally, the checklist was completed after the review by a pharmacoepidemiology expert. The checklist was applied to published academic papers that used JADER, and the fulfill rate of each checkpoints was calculated.Results: A “checklist of important points to be noted during research that uses the data mining method in JADER (mainly signal detection by disproportionality analysis)” was created. We also revealed problems with published academic papers that used JADER. For example, some researchers were thought to be inappropriately using JADER as a source of their research while others used an inappropriate version of MedDRA.Conclusion: The checklist created in this study summarizes key points that could be noted in research that uses JADER and is thought to contribute to an improvement in quality of research that uses JADER. Additionally, in our investigation of published academic papers that used JADER, we found the possibility that both the role of signal detection and the impact on analysis of JADER using the updated MedDRA version are not well understood.

Design and Implementation of Ultra-micro Nucleic Acid Protein Analyzer / 中国医疗器械杂志

In this paper, a nucleic acid protein analyzer based on Lambert-Beer law and ultraviolet spectrophotometry is introduced, which is composed of ultraviolet monochromatic light generator, photoelectric signal detection module, vortex mixer, touch screen and embedded central controller. For ultra-micro measurement, a continuous-wavelength full-spectrum spectrophotometric detection circuit is designed in the hardware part. The transmitted light signal is collected by silicon photodiode, amplified and processed by subsequent circuit, and then transmitted to a single chip computer STM32F407VGT6 with CortexTM-M4 core after A/D conversion. The concentration and purity of nucleic acid protein are evaluated by assistant software detection algorithm. The instrument has the characteristics of compact size, flexible use, simple operation, high sensitivity and high detection efficiency. The experimental results show that the instrument has good sensitivity, repeatability and accuracy, and is suitable for the ultra-micro measurement of nucleic acid sample concentration, purity and protein concentration.

Data Analysis of the Risks of Abnormal Female Reproductive System Haemorrhages Induced by Novel Oral An- ticoagulants Based on FAERS / 中国药房

OBJECTIVE：To eva luate the risk of abno rmal female reproductive system haemorrhage induced by novel oral anticoagulants （NOACs）. METHODS ：The abnormal female reproductive system haemorrhage reports induced by 4 kinds of NOACs as “dabigatran etexilate ”，“rivaroxaban”，“apixaban”and“edoxaban”were used as the first suspected dugs to collected from FDA adverse event reporting system （FAERS）database during Jan. 1st，2004-May 31st，2019. The report odd ratio （ROR） method was used to detect the signal of abnormal female reproductive system haemorrhage induced by NOACs. RESULTS ：A total of 2 658 adverse events related to abnormal female reproductive system haemorrhage were collected from FAERS database ， involving 330 reports of dabigatran etexilate ，2 049 reports of rivaroxaban ，267 reports of apixaban ，and 12 reports of edoxaban. The abnormal female reproductive system haemorrhage caused by dabigatran etexilate ，apixaban and edoxaban mainly occurred in patients aged 75 and older ，accounting for 37.27％，36.70％ and 58.33％ respectively；that of rivaroxaban mainly occurred in patients with 45-64 years old ，accounting for 33.04％. The incidence of severe adverse events （SAE）induced by dabigatran etexilate，rivaroxaban，apixaban and edoxaban were 96.36％，84.53％，47.19％ and 58.33％，respectively. All of patients in the included reports were mainly hospitalized and hospitalization stay wa s prolonged ，accounting for 64.78％，90.01％，86.51％ and 71.43％ ，respectively. A total of 12 suspected signals were detected，involving cervix uteri ，fallopian tube ，ovary，pelvis cavity，uterus，vagina，urinary tract ，etc. Among them ，there were 11 positive signals of rivaroxaban ，and the bleeding events were concentrated in vaginal hematoma [ROR ＝12.07， 药。95％CI（8.51，17.12）]，postmenopausal hemorrhage [ROR ＝ 9.89，95％CI（8.31，11.77）]，pelvic hematoma [ROR ＝7.68，95％CI（5.66，10.43）]. There were 4，4 and 2 suspicious signals for dabigatran etexilate ，apixaban and edoxaban. The main bleeding events of both apixaban [ ROR＝5.18，95％CI（1.81，5.85）] and edoxaban [ROR ＝48.19，95％CI（6.76，343.77）] were vaginal hematoma ；dabigatran etexilate-induced pelvic hematoma [ROR ＝ 12.56，95％CI（8.92，17.70）] had the strongest signal ，followed by urinary tract bleeding [ROR ＝5.41，95％CI（3.34，8.76）] and pelvic hemorrhage [ ROR＝2.53，95％CI（1.88，3.40）]. CONCLUSIONS ：Totally 4 kinds of NOACs can cause abnormal female reproductive system haemorrhage ，and the incidence of SAE is high ，of requiring hospitalization or prolonging hospitalization time. The risk of haemorrhage in rivaroxaban is the highest ，usually manifesting as vaginal hematoma ，postmenopausal hemorrhage and pelvic hematoma. Dabigatran etexilate mainly induce pelvic hematoma ，while apixaban and edoxaban are mainly cause vaginal hematoma.

Detection and Analysis of Safety Signals of Chloroquine Based Upon FDA Adverse Event Database / 中国药学杂志

OBJECTIVE: To analyze and evaluate the safety signals of chloroquine in the patients, and to provide a valuable reference for rational use in clinic. METHODS: Both the reporting odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) were applied to analyze safety signals of chloroquine based upon the adverse drug events (ADEs) data ranging from 2004 to 2020 as reported in the Adverse Event Reporting System (FAERS) database of the Food and Drug Administration (FDA), and to systematically assesse the safety signals of chloroquine phosphate on various organs systems. RESULTS: Among the 2 063 reports of ADEs studied, 557 reports were considered to be mainly caused by chloroquine. The results demonstrated that the high-risk ADEs signals of chloroquine involved various systems, such as atrioventricular block complete (ROR=2.90, IC-2SD=1.64), ventricular fibrillation (ROR=3.40, IC-2SD=1.27), blindness (ROR=27.51, IC-2SD=0.55), cardiogenic shock (ROR=6.86, IC-2SD=0.54), vomiting (ROR=1.70, IC-2SD=1.83). Moreover, some rare ADEs with high-risk signals showed a correlation with chloroquine, including hypokalaemia (ROR=4.18,IC-2SD=1.51), renal failure acute (ROR=3.08, IC-2SD=0.30), methaemoglobinaemia (ROR=4.37, IC-2SD=0.03), and pyrexia (ROR=1.80, IC-2SD=1.84), which were consistent with literature reports. However, these ADEs were not listed in instruction and worth much attention in clinic. Moreover, basic diseases of patients and drug incompatibility need much attention to prevent the occurrence and exacerbation of chloroquine-related adverse reactions. CONCLUSION: A comprehensive analysis of the ADEs signals of chloroquine could shed some light on understanding of its safety characteristics and would provide valuable information for rational use of chloroquine in clinic, especially in treatment of COVID-19.

Signal Detection of Adverse Events Following Pneumococcal Vaccines from the Korea Adverse Event Reporting System Database, 2005–2016

PURPOSE: We aimed to analyze the surveillance reports of adverse events (AEs) due to different types of pneumococcal vaccines, in addition to detecting and validating signals of pneumococcal vaccines by comparing AEs with labels.MATERIALS AND METHODS: We analyzed the percentages of AEs according to vaccine type [pneumococcal polysaccharide vaccines (PPSVs) and pneumococcal conjugate vaccines (PCVs)] in children and adults using data from the Korea Adverse Event Reporting System (KAERS) database from 2005 to 2016. A signal was defined as an AE that met all three indices of data mining: proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC). We validated the detected signals by calculating sensitivity, specificity, as well as positive and negative predictive values of the signals against label information.RESULTS: Of the 39933 AE reports on vaccination, 5718 (7.0%) were related to pneumococcal vaccine. The most frequent AE after vaccination with PPSV was fever (23.9%) in children and injection-site reaction in adults. The most frequent AE after vaccination with PCV in children was pharyngitis (26.2%). In total, 13 AEs met all three indices for signal detection. Among these, hypotension, apathy, sepsis, and increased serum glutamic oxaloacetic transaminase level were not listed on vaccine labels. In validation analysis, PRR and ROR performed slightly better than IC for adults who were vaccinated with PPSVs.CONCLUSION: Overall, 13 new signals of PPSVs, including four signals not listed on the labels, were detected. Further research based on additional AE reports is required to confirm the validity of these signals for children.

Deep Learning-Based Electrocardiogram Signal Noise Detection and Screening Model / 대한의료정보학회지

OBJECTIVES: Biosignal data captured by patient monitoring systems could provide key evidence for detecting or predicting critical clinical events; however, noise in these data hinders their use. Because deep learning algorithms can extract features without human annotation, this study hypothesized that they could be used to screen unacceptable electrocardiograms (ECGs) that include noise. To test that, a deep learning-based model for unacceptable ECG screening was developed, and its screening results were compared with the interpretations of a medical expert. METHODS: To develop and apply the screening model, we used a biosignal database comprising 165,142,920 ECG II (10-second lead II electrocardiogram) data gathered between August 31, 2016 and September 30, 2018 from a trauma intensive-care unit. Then, 2,700 and 300 ECGs (ratio of 9:1) were reviewed by a medical expert and used for 9-fold cross-validation (training and validation) and test datasets. A convolutional neural network-based model for unacceptable ECG screening was developed based on the training and validation datasets. The model exhibiting the lowest cross-validation loss was subsequently selected as the final model. Its performance was evaluated through comparison with a test dataset. RESULTS: When the screening results of the proposed model were compared to the test dataset, the area under the receiver operating characteristic curve and the F1-score of the model were 0.93 and 0.80 (sensitivity = 0.88, specificity = 0.89, positive predictive value = 0.74, and negative predictive value = 0.96). CONCLUSIONS: The deep learning-based model developed in this study is capable of detecting and screening unacceptable ECGs efficiently.

Data Mining and Analysis of Safety Signals of Osimertinib after Marketing / 中国药房

OBJECTIVE： To mine the signals of osimertinib adverse drug event （ADEs） and to provide reference for clinical drug safety. METHODS： By reporting odd ratio （ROR） and Bayesian confidence propagation neural network （BCPNN） algorithms， data mining and signal detection were carried out on osimertinib-related ADEs reports with case number ≥3 reported by American Adverse Event Reporting System （FAERS） from Nov. 2015 to Jun. 2018. RESULTS & CONCLUSIONS： A total of 2 044 osimertinib-related ADEs were found， among which the female （1 285 cases） was more than the male （615 cases）， mainly aged 45-64 years （228 cases）， 65-74 years （241 cases）， ≥75 years （248 cases）； most of reporters were physicians （887 cases）. A total of 63 and 57 osimertinib ADEs signals were mined by ROR and BCPNN methods， and the latter signals overlapped with the former. The obtained signals included skin toxicity （dermatitis acneiform， rash， dry skin， onychoclasis， nail disorder， paronychia）， gastrointestinal tract reaction （decreased appetite， diarrhea， stomatitis）， respiratory diseases （interstitial pneumonia， pneumonia）， hematological diseases （platelet count decreased， white blood cell count decreased， neutrophil count decreased）， vascular events （pulmonary embolism， deep vein thrombosis）， electrocardiogram QT prolonged （RORs were 2.04-56.70， ICs were 0.97-4.43）， all of which had been recorded in drug instructions； obtained signals also included new suspicious signals not indicated in the drug instructions， such as liver damage， cerebral infarction， hyponatremia， atrial fibrillation， renal impairment， dehydration， dysgeusia， and so on （RORs were 2.06-161.74， ICs were 1.00-4.58）. In clinical use of osimertinib， besides paying close attention to known safety problems such as nail toxicity of finger （toe） and rash， interstitial pneumonia， electrocardiogram QT prolonged， we should also be alert to the occurrence of potential ADEs such as liver damage to ensure drug safety.

Hydraulic System Onboard Monitoring and Fault Diagnostic in Agricultural Machine

Abstract Agricultural Machinery as an off-road vehicle is the backbone of the World agricultural industry. Its main function is to operate as a prime mover and support the power requirements to function the various type of draft implements. In this regards, the hydraulic system is an important part and is controlled by the propagated oil which is cleaned by impurities and debris using a filter system. Once it blocks, the bypass opens to avoid any pressure burst of the system, and the particles find their way into the hydraulic system and get lodged in the gears, pumps, valves, and drive train to hinder the performance of the Agricultural Machinery. This research presents an onboard Multiple Signal Classification Algorithm (MUSIC) and pseudo-spectrum analysis as a computational tool used by cellphones to analyze the particle pollution level of the hydraulic filter. This analysis is carried out on the soundtracks recorded from different cell phones in different incremental stages of fluid contamination to the particles until it being choked, based on the standard of ISO4406.

Efeito do álcool na ilusão da máscara côncava: uma revisão / Effect of alcohol on the hollow-face illusion: a review / Efecto del alcohol en la ilusión de la máscara cóncava: una revisión

A ilusão da máscara côncava ocorre quando o observador a determinada distância percebe uma máscara facial côncava como convexa. Isso pode ser explicado pela sobreposição dos processos de alta ordem da percepção visual sobre os de baixa ordem. Pesquisas com indivíduos intoxicados e em Síndrome de Abstinência do Álcool (SAA) revelaram um prejuízo em perceber essa ilusão. O objetivo foi realizar uma revisão da literatura sobre o tema. Após buscas em bases indexadas, cinco pesquisas foram encontradas. Os resultados para os alcoolistas em SAA moderada revelaram uma menor frequência nas respostas de percepção da ilusão. Os resultados foram contraditórios quanto ao grupo de alcoolistas com SSA leve. Pesquisas futuras com metodologias diferentes são necessárias para testar as hipóteses explicativas da ilusão da máscara côncava em alcoolistas. É importante considerar os processos de tomada de decisão do observador diante da observação dos objetos como base a Teoria de Detecção de Sinal (TDS)

The hollow-face illusion happens when the observer perceives a concave facial mask as convex, at a given distance. This can be explained by the overlap of top-down on bottom-up visual processes. Researches demonstrated that intoxicated and Alcohol Withdrawal Syndrome (AWS) individuals had deficit in perceiving this illusion. This study aimed to review the literature on this topic. A survey of indexed databases found five studies. The results for alcoholics with moderate AWS were similar and showed a lower frequency in the answers of illusion perception. However, results were contradictory to the alcoholic group with mild AWS. Future researches with different methodologies are necessary to test the hollow-face illusion hypotheses in alcoholics. Therefore, it is also important to consider the observer's decision-making processes in the objects observation based on the Signal Detection Theory (SDT)

La ilusión de la máscara cóncava ocurre cuando el observador a cierta distancia percibe una máscara facial cóncava como convexa. Esto puede ser explicado por la superposición de los procesos de alto orden de la percepción visual sobre los de bajo orden. Las investigaciones con individuos intoxicados y en el Síndrome de Abstinencia del Alcohol (SAA) revelaron un perjuicio en percibir esa ilusión. El objetivo fue realizar una revisión de la literatura sobre el tema. Después de buscar en bases indexadas, se encontraron cinco encuestas. Los resultados para los alcohólicos en SAA moderada revelaron una menor frecuencia en las respuestas de percepción de la ilusión. Los resultados fueron contradictorios en cuanto al grupo de alcohólicos con SSA leve. Las investigaciones futuras con metodologías diferentes son necesarias para probar las hipótesis explicativas de la ilusión de la máscara cóncava en alcohólicos. Es importante considerar los procesos de toma de decisión del observador ante la observación de los objetos como base la Teoría de Detección de Señal (TDS)

Efeito do álcool na ilusão da máscara côncava: uma revisão / Effect of alcohol on the hollow-face illusion: a review / Efecto del alcohol en la ilusión de la máscara cóncava: una revisión

A ilusão da máscara côncava ocorre quando o observador a determinada distância percebe uma máscara facial côncava como convexa. Isso pode ser explicado pela sobreposição dos processos de alta ordem da percepção visual sobre os de baixa ordem. Pesquisas com indivíduos intoxicados e em Síndrome de Abstinência do Álcool (SAA) revelaram um prejuízo em perceber essa ilusão. O objetivo foi realizar uma revisão da literatura sobre o tema. Após buscas em bases indexadas, cinco pesquisas foram encontradas. Os resultados para os alcoolistas em SAA moderada revelaram uma menor frequência nas respostas de percepção da ilusão. Os resultados foram contraditórios quanto ao grupo de alcoolistas com SSA leve. Pesquisas futuras com metodologias diferentes são necessárias para testar as hipóteses explicativas da ilusão da máscara côncava em alcoolistas. É importante considerar os processos de tomada de decisão do observador diante da observação dos objetos como base a Teoria de Detecção de Sinal (TDS)

The hollow-face illusion happens when the observer perceives a concave facial mask as convex, at a given distance. This can be explained by the overlap of top-down on bottom-up visual processes. Researches demonstrated that intoxicated and Alcohol Withdrawal Syndrome (AWS) individuals had deficit in perceiving this illusion. This study aimed to review the literature on this topic. A survey of indexed databases found five studies. The results for alcoholics with moderate AWS were similar and showed a lower frequency in the answers of illusion perception. However, results were contradictory to the alcoholic group with mild AWS. Future researches with different methodologies are necessary to test the hollow-face illusion hypotheses in alcoholics. Therefore, it is also important to consider the observer's decision-making processes in the objects observation based on the Signal Detection Theory (SDT)

La ilusión de la máscara cóncava ocurre cuando el observador a cierta distancia percibe una máscara facial cóncava como convexa. Esto puede ser explicado por la superposición de los procesos de alto orden de la percepción visual sobre los de bajo orden. Las investigaciones con individuos intoxicados y en el Síndrome de Abstinencia del Alcohol (SAA) revelaron un perjuicio en percibir esa ilusión. El objetivo fue realizar una revisión de la literatura sobre el tema. Después de buscar en bases indexadas, se encontraron cinco encuestas. Los resultados para los alcohólicos en SAA moderada revelaron una menor frecuencia en las respuestas de percepción de la ilusión. Los resultados fueron contradictorios en cuanto al grupo de alcohólicos con SSA leve. Las investigaciones futuras con metodologías diferentes son necesarias para probar las hipótesis explicativas de la ilusión de la máscara cóncava en alcohólicos. Es importante considerar los procesos de toma de decisión del observador ante la observación de los objetos como base la Teoría de Detección de Señal (TDS)

Design of magneto-acoustic-electrical detection system and verification of its linear sweep theory / 生物医学工程学杂志

Clinical studies had demonstrated that early diagnosis of lesion could significantly reduce the risk of cancer. Magneto-acoustic-electrical tomography (MAET) is expected to become a new detection method due to its advantages of high resolution and high contrast. Based on thinking of modular design, a low-cost, digital magneto-acoustic conductivity detection system was designed and implemented in this study. The theory of MAET using chirp continuous wave excitation was introduced. The results of homogeneous phantom experiment with 0.5% NaCl clearly showed that the conductivity curve of homogeneous phantom was highly consistent with the actual physical size, which indicated that the chirp excitation theory in our proposed system was correct and feasible. Besides, the resolution obtained by 1 000 μs sweep time was better than that obtained by 500 μs and 1 500 μs, which means that sweep time is an important factor affecting the detection resolution of the conductivity. The same result was obtained in the experiments carried out on homogeneous phantoms with different concentrations of NaCl, which demonstrated the repeatability of our proposed MAET system.

Using PMDA Drug Adverse Event Report Database, Study on Collective Background of Adverse Events Caused by the Total Cold Medicine ： Classification of Onset Cases Using Latent Class Analysis / 薬剤疫学

Objective： Using PMDA's medication side effect database （JADER), the aim of this study is to explore the collective background and characteristics of cases in which adverse events were caused by the total cold medicine.Methods：Latent class analysis is performed on 990 subject cases reported from April 2004 to June 2015. The target group is classified into plural, and each characteristic is clearly indicated. Furthermore, the number of adverse events is counted for each class, and specialization coefficients are calculated. In addition, the signal detection is performed with the same data.Results：The population was divided into three classes. Class 1 was a group which do not have the original disease or medication, 53.7％ of the whole, and it was set as “health group” . Adverse events specialized were immune system diseases. Class 2 was 33.2％, a positive group for self-treatment, it was set as “self-treatment oriented group” . A specialized adverse event was a serious skin disorder. Class 3 was 13.1％, and 90％ of the class was over 60 years old and almost people had primary diseases and medicines, so they were “high age outpatient treatment group” . The main adverse events were lung disease and nervous system disorder. It was possible to relate the characteristic of the group as a background factor.Conclusion：By applying Latent class analysis to the adverse event, it was possible to clarify the relationship between the occurrence of adverse event and its background.This research is applicable to other medicines, and expected to contribute as a new application method of JADER.

Evaluation of an Automatic Vigilance System for Detecting Adverse Drug Reactions from Electronic Medical Records / 医薬品情報学

Objective: We have developed an automatic vigilance system (AVS) that automatically reports adverse drug reactions (ADR) based on laboratory finding abnormalities and symptom keywords in electronic medical records.　In this study, we aimed to evaluate the impact of detecting ADR using AVS on medical treatment.Methods: In AVS, drugs and their ADR signals, which would be detected and reported by AVS to pharmacists, were defined.　Pharmacists evaluated the severity of these signals to identify whether these signals should be discussed with the doctor, continued to be followed up, or ignored.　We investigated detection of ADR at University of Fukui Hospital between April 2016 and March 2017 along with whether prescriptions were modified because of ADR and the contribution of AVS.　Assuming that ADR had worsened without appropriate treatment, medical expenses needed for treating severe ADR were calculated.Results: In total, 325 signals were defined for 146 drugs.　There were 9,103 ADR signals confirmed by pharmacists for 8,531 subjects.　Of these, 12 and 164 signals were discussed with the doctor and continuously observed, respectively.　The pharmacist's suggestions based on AVS led to prescription modifications in 10 cases, corresponding to a reduction of 2.56 million yen in medical expenses in the event that these cases become severe.Conclusion: AVS assisted prescription revisions because of ADR and is thought to contribute to the prevention of worsening of ADR and reduction of medical expenses.