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Baloxavir marboxil (1; BXM) is a potent drug used for treating influenza infections. The current synthetic route to BXM (1) is based on optical resolution; however, this method results in the loss of nearly 50% of the material. This study aimed to describe an efficient and simpler method for the synthesis of BXM. We achieved a stereoselective synthesis of BXM (1). The tricyclic triazinanone core possessing a chiral center was prepared via diastereoselective cyclization utilizing the readily available amino acid l-serine. The carboxyl moiety derived from l-serine was removed via photoredox decarboxylation under mild conditions to furnish the chiral tricyclic triazinanone core ((R)-14). The synthetic route demonstrated herein provides an efficient and atomically economical method for preparing this potent anti-influenza agent.
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Dibenzotiepinas , Serina , Estereoisomerismo , Ciclización , Serina/química , Estructura Molecular , Dibenzotiepinas/química , Dibenzotiepinas/síntesis química , Triazinas/química , Triazinas/síntesis química , Oxidación-Reducción , Descarboxilación , Morfolinas/química , Morfolinas/síntesis química , Piridonas/química , Piridonas/síntesis química , Procesos Fotoquímicos , Antivirales/síntesis química , Antivirales/químicaRESUMEN
The incidence of gastric tube cancers has increased due to improved survival rates in patients after esophagectomy. However, the optimal surgical approach for gastric tube cancer remains controversial. Here, we report the case of a 70-year-old man with advanced gastric cancer arising from a retrosternally placed gastric conduit, 12 years after thoracic esophagectomy for esophageal cancer. Total resection of the gastric conduit was performed with robotic assistance. Although the working space was limited, secure resection was possible. Continuous en bloc mobilization was achieved with neck dissection, and reconstruction was performed via the same retrosternal route using the ileocolon. The patient was discharged on the 14th postoperative day without any adverse events. Robot-assisted surgery can overcome the technical limitations of laparoscopic mediastinal surgery and has advantages such as improved ergonomics, comfort, and elimination of hand tremors, and therefore may be an option for future minimally invasive surgeries.
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Neoplasias Esofágicas , Procedimientos Quirúrgicos Robotizados , Masculino , Humanos , Anciano , Procedimientos Quirúrgicos Robotizados/efectos adversos , Esofagectomía/efectos adversos , Resultado del Tratamiento , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/cirugíaRESUMEN
PURPOSE: The long-term prognosis of stapled and hand-sewn ileal pouch-anal anastomoses in familial adenomatous polyposis patients in Japan remains unknown. This study aimed to compare the overall survival in familial adenomatous polyposis patients who underwent stapled or hand-sewn ileal pouch-anal anastomosis. METHODS: This multicenter retrospective study was conducted at 12 institutions in Shizuoka Prefecture, Japan. The clinical outcomes of 53 eligible familial adenomatous polyposis patients who underwent stapled (n = 24) and hand-sewn (n = 29) ileal pouch-anal anastomosis were compared. RESULTS: The median follow-up duration was 171.5 months. The incidence of adenoma in the remnant rectum or anal transitional zone and metachronous rectal cancer was significantly more common in stapled ileal pouch-anal anastomosis (adenoma: stapled, 45.8%, vs. hand-sewn, 10.3%, p = 0.005; metachronous rectal cancer: 29.2%, vs. none, p = 0.002). The number of deaths was remarkably higher in stapled ileal pouch-anal anastomosis (p = 0.002). Metachronous rectal cancer was the most common cause of death. Overall survival was worse in stapled ileal pouch-anal anastomosis than in hand-sewn ileal pouch-anal anastomosis (120 months, 90.7% vs. 96.6%; 240 months, 63.7% vs. 96.6%; p = 0.044). Cox regression analysis revealed the independent effects of preoperative advanced colorectal cancer and stapled ileal pouch-anal anastomosis on overall survival. CONCLUSION: Stapled ileal pouch-anal anastomosis negatively affected the overall survival of familial adenomatous polyposis patients. Therefore, hand-sewn ileal pouch-anal anastomosis is recommended for better prognosis in these patients.
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Adenoma , Poliposis Adenomatosa del Colon , Reservorios Cólicos , Proctocolectomía Restauradora , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Anastomosis Quirúrgica/efectos adversos , Proctocolectomía Restauradora/efectos adversos , Poliposis Adenomatosa del Colon/cirugía , Pronóstico , Neoplasias del Recto/cirugía , Reservorios Cólicos/efectos adversos , Resultado del TratamientoRESUMEN
Solar cells are a promising optoelectronic device for the simultaneous solution of energy resource and environmental problems. However, their high cost and slow, laborious production process so far severely hinder a sufficient widespread of clean, renewable photovoltaic energy as a major alternative electricity generator. This undesirable situation is mainly attributed to the fact that photovoltaic devices have been manufactured through a series of vacuum and high-temperature processes. Here we realize a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS)/Si heterojunction solar cell fabricated only in ambient and room temperature conditions from a plain Si wafer, with an over 10% energy conversion efficiency. Our production scheme is based on our finding that PEDOT:PSS photovoltaic layers actively operate even on highly doped Si substrates, which substantially mitigates the condition requirements for electrode implementation. Our approach may pave the way for facile, low-cost, high-throughput solar cell fabrication, useful in various fields even including developing countries and educational sites.
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PURPOSE: To assess the validity and reliability of the Japanese version of the Daily Record of Severity of Problems (J-DRSP, 24 items) for evaluating symptoms of premenstrual syndrome (PMS), and to develop a short form version of the J-DRSP. METHODS: Using the "DRSP-JAPAN" smartphone app, we collected daily J-DRSP records from cycle day - 6 (CD - 6) to CD 10, with CD 1 representing the menstruation onset date. Factorial validity (exploratory factor analysis: EFA, confirmatory factor analysis: CFA) and criterion validity were examined, and test-retest reliability (intraclass correlation: ICC) evaluated. The short-form version of the J-DRSP was developed using classical test theory. RESULTS: In total, 304 women participated and 243 recorded symptoms on at least 4 days spanning the week of the luteal phase (CD - 6 to CD 0) and 4 days spanning the week of the follicular phase (CD 4 to CD 10), with CD 0 set as the day before menstruation started. The EFA revealed a two-factor structure. Kaiser-Meyer-Olkin was 0.992, and Bartlett's test of sphericity chi-square was 3653.89 (P < 0.001). However, the model fitness of CFA was found to be suboptimal (comparative fit index (CFI): 0.83, root mean square error of approximation (RMSEA): 0.12). Total scores for J-DRSP and the sum scores for each subscale were higher on CD 0 than on CD 10 (p < 0.001), suggesting validity for some criteria. ICC values for the total J-DRSP score from CD 0 to CD - 1, and between CD 9 to CD 10, were 0.60 (95% CI: 0.48-0.72) and 0.76 (95% CI: 0.69-0.82), respectively. Having eliminated some original items after considering factor loading for each item, we developed an 8-item Short-Form J-DRSP (J-DRSP (SF)) comprising 2 factors (S-Psychological and S-Physical, 4 items for each). CFA showed a better model fit (CFI: 0.99, RMSEA: 0.048), and ICC values in the luteal and follicular phases were 0.61 (95%CI: 0.51-0.68) and 0.70 (95%CI: 0.62-0.77), respectively. CONCLUSION: The J-DRSP has moderate to good reliability and a certain level of validity. The 8-item J-DRSP (SF) has a two-factor structure and can be used effectively among Japanese women to assess their PMS symptoms.
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BACKGROUND: Pervasive games aim to create more fun and engaging experiences by mixing elements from the real world into the game world. Because they intermingle with players' lives and naturally promote more casual gameplay, they could be a powerful strategy to stimulate physical activity among older adults. However, to use these games more effectively, it is necessary to understand how design elements of the game affect player behavior. OBJECTIVE: The aim of this study was to evaluate how the presence of a specific design element, namely social interaction, would affect levels of physical activity. METHODS: Participants were recruited offline and randomly assigned to control and intervention groups in a single-blind design. Over 4 weeks, two variations of the same pervasive game were compared: with social interaction (intervention group) and with no social interaction (control group). In both versions, players had to walk to physical locations and collect virtual cards, but the social interaction version allowed people to collaborate to obtain more cards. Changes in the weekly step counts were used to evaluate the effect on each group, and the number of places visited was used as an indicator of play activity. RESULTS: A total of 20 participants were recruited (no social interaction group, n=10; social interaction group, n=10); 18 participants remained active until the end of the study (no social interaction group, n=9; social interaction group, n=9). Step counts during the first week were used as the baseline level of physical activity (no social interaction group: mean 46,697.2, SE 7905.4; social interaction group: mean 45,967.3, SE 8260.7). For the subsequent weeks, changes to individual baseline values (absolute/proportional) for the no social interaction group were as follows: 1583.3 (SE 3108.3)/4.6% (SE 7.2%) (week 2), 591.5 (SE 2414.5)/2.4% (SE 4.7%) (week 3), and -1041.8 (SE 1992.7)/0.6% (SE 4.4%) (week 4). For the social interaction group, changes to individual baseline values were as follows: 11520.0 (SE 3941.5)/28.0% (SE 8.7%) (week 2), 9567.3 (SE 2631.5)/23.0% (SE 5.1%) (week 3), and 7648.7 (SE 3900.9)/13.9% (SE 8.0%) (week 4). The result of the analysis of the group effect was significant (absolute change: η2=0.31, P=.04; proportional change: η2=0.30, P=.03). Correlations between both absolute and proportional change and the play activity were significant (absolute change: r=0.59, 95% CI 0.32 to 0.77; proportional change: r=0.39, 95% CI 0.08 to 0.64). CONCLUSIONS: The presence of social interaction design elements in pervasive games appears to have a positive effect on levels of physical activity. TRIAL REGISTRATION: Japan Medical Association Clinical Trial Registration Number JMA-IIA00314; https://tinyurl.com/y5nh6ylr (Archived by WebCite at http://www.webcitation.org/761a6MVAy).
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The goal of this research was to design a solution to detect non-reported incidents, especially severe incidents. To achieve this goal, we proposed a method to process electronic medical records and automatically extract clinical notes describing severe incidents. To evaluate the proposed method, we implemented a system and used the system. The system successfully detected a non-reported incident to the safety management department.
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Registros Electrónicos de Salud , Aprendizaje Automático , Errores Médicos , Gestión de Riesgos , Administración de la SeguridadRESUMEN
Effective bed management is important for hospital management. Until now, bed allocation process is generally controlled by administrative staffs in centralized manner but it is not always effective. In the present study, we proposed and evaluated new method for bed allocation applying market mechanism via token. Evaluation was performed with newly-developed game-type simulation. Nurse managers as research participants played it and answered for survey. The result showed that the proposed method can be useful with appropriate operational design.
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Ocupación de Camas , Administración Hospitalaria , Enfermeras Administradoras , HumanosRESUMEN
Redesigning Electronic Medical Record (EMR) systems is needed to improve their usefulness and usability. For user-centered redesign, designers should consider which EMR features are the most important to the users. However, prioritizing the EMR features is complicated because: (i) EMR systems involve multiple users with different, and sometimes conflicting, priorities and (ii) targeting one feature will affect other features of the EMR system. In this work, we propose a method for prioritizing the features to target when redesigning an EMR system. The method takes into consideration the different priorities of the users and the relationships between the different features. We illustrate the method through a case study on redesigning EMR systems in Japanese antenatal care settings. Our results show the importance of considering the different types of EMR users and the relationships between different EMR features. Designers could use the proposed method as a decision-aid tool in EMR redesign projects.
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Registros Electrónicos de Salud , Atención Prenatal , Femenino , Humanos , EmbarazoRESUMEN
Nephrosis is disease characterized by abnormal protein loss from impaired kidney. We constructed early prediction model using machine learning from clinical time series data, that can predict onset of nephrosis for more than one month. Long short-term memory capable of recognizing temporal sequential data patterns, was adopted as early prediction model for nephrosis. We verified our proposed prediction model has higher accuracy compared with those of baseline classifiers by 5-fold cross validation.
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Aprendizaje Profundo , Nefrosis , Diagnóstico Precoz , Humanos , Aprendizaje Automático , Nefrosis/diagnósticoRESUMEN
The amount of text of electronic medical records and its changes over time are not clear. In designing an electronic medical records system, prediction of the amount of text is important. We analyzed the number of characters described in the electronic medical records. As a result, it became clear that the annual text quantity of electronic medical records follows the lognormal distribution, and also the amount has been increasing year by year.
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Registros Electrónicos de SaludRESUMEN
BACKGROUND: The novel genre of pervasive games, which aim to create more fun and engaging experiences by promoting deeper immersion, could be a powerful strategy to stimulate physical activity among older adults. To use these games more effectively, it is necessary to understand how different design elements affect player behavior. OBJECTIVE: The aim was to vary a specific design element of pervasive games for older adults, namely social interaction, to test the effect on levels of physical activity. METHODS: Over 4 weeks, two variations of the same pervasive game were compared: social interaction for the test group and no social interaction for the control group. In both versions, players had to walk to physical locations and collect virtual cards, but the social interaction version allowed people to collaborate to obtain more cards. Weekly step counts were used to evaluate the effect on each group, and the number of places visited was used as an indicator of play activity. RESULTS: A total of 32 participants were recruited (no social interaction=15, social interaction=17); 18 remained until the end of the study (no social interaction=7, social interaction=11). Step counts during the first week were used as the baseline (no social interaction: mean 17,099.4, SE 3906.5; social interaction: mean 17,981.9, SE 2171.1). For the following weeks, changes to individual baseline were as follows for no social interaction (absolute/proportional): 383.8 (SE 563.8)/1.1% (SE 4.3%), 435.9 (SE 574.5)/2.2% (SE 4.6%), and -106.1 (SE 979.9)/-2.6% (SE 8.1%) for weeks 2, 3, and 4, respectively. For social interaction they were 3841.9 (SE 1425.4)/21.7% (SE 5.1%), 2270.6 (SE 947.1)/16.5% (SE 4.4%), and 2443.4 (SE 982.6)/17.9% (SE 4.7%) for weeks 2, 3, and 4, respectively. Analysis of group effect was significant (absolute change: η2=.19, P=.01; proportional change: η2=.27, P=.009). Correlation between the proportional change and the play activity was significant (r=.34, 95% CI 0.08 to 0.56), whereas for absolute change it was not. CONCLUSIONS: Social interaction design elements of the pervasive game may have some positive effects on the promotion of physical activity, although other factors might also have influenced this effect. TRIAL REGISTRATION: Japan Medical Association Clinical Trial Registration Number JMA-IIA00314; https://dbcentre3.jmacct.med.or.jp/JMACTR/App/JMACTRS06/JMACTRS06.aspx?seqno=7274 (Archived by WebCite at http://www.webcitation.org/761a6MVAy).
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BACKGROUND: Redesigning electronic medical record (EMR) systems is needed to improve their usability and usefulness. Similar to other artifacts, EMR systems can evolve with time and exhibit situated roles. Situated roles refer to the ways in which a system is appropriated by its users, that is, the unintended ways the users engage with, relate to, and perceive the system in its context of use. These situated roles are usually unknown to the designers as they emerge and evolve as a response by the users to a contextual need or constraint. Understanding the system's situated roles can expose the unarticulated needs of the users and enable redesign opportunities. OBJECTIVE: This study aimed to find EMR redesign opportunities by understanding the situated roles of EMR systems in prenatal care settings. METHODS: We conducted a field-based observational study at a Japanese prenatal care clinic. We observed 3 obstetricians and 6 midwives providing prenatal care to 37 pregnant women. We looked at how the EMR system is used during the checkups. We analyzed the observational data following a thematic analysis approach and identified the situated roles of the EMR system. Finally, we administered a survey to 5 obstetricians and 10 midwives to validate our results and understand the attitudes of the prenatal care staff regarding the situated roles of the EMR system. RESULTS: We identified 10 distinct situated roles that EMR systems play in prenatal care settings. Among them, 4 roles were regarded as favorable as most users wanted to experience them more frequently, and 4 roles were regarded as unfavorable as most users wanted to experience them less frequently; 2 ambivalent roles highlighted the providers' reluctance to document sensitive psychosocial information in the EMR and their use of the EMR system as an accomplice to pause communication during the checkups. To improve the usability and usefulness of EMR systems, designers can amplify the favorable roles and minimize the unfavorable roles. Our results also showed that obstetricians and midwives may have different experiences, wants, and priorities regarding the use of the EMR system. CONCLUSIONS: Currently, EMR systems are mainly viewed as tools that support the clinical workflow. Redesigning EMR systems is needed to amplify their roles as communication support tools. Our results provided multiple EMR redesign opportunities to improve the usability and usefulness of EMR systems in prenatal care. Designers can use the results to guide their EMR redesign activities and align them with the users' wants and priorities. The biggest challenge is to redesign EMR systems in a way that amplifies their favorable roles for all the stakeholders concurrently.
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INTRODUCTION: Promoting active lifestyles among older adults can bring drastic benefits for their quality of life. The innovative mechanics of pervasive games - that mix real and virtual worlds - can further engage and motivate elderly people into that goal. Using social interaction as a study case, we designed and evaluated the feasibility of a pervasive game to investigate how game design elements can affect the levels of physical activity of older adults. METHODS: A mobile, location-based pervasive game was developed, and a study with community dwelling elderly volunteers from Kyoto, Japan was performed to evaluate its feasibility as an experiment system. RESULTS: Participants reported that the theme and visual style of the game was adequate, and that game rules and goals could be easily understood. The game was considered enjoyably challenging and engaging. Further analysis showed that next iterations of the system must pay special attention to the level of complexity of controls, and that new ways to connect players when there are few people playing or when they are too far apart are necessary. CONCLUSIONS: The design allowed to test for variations on pervasive mechanics and was effective to engage elderly people, encouraging further investigation.
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Background: There are limited data on the prevalence and burden of severe eosinophilic asthma (SEA) both in Japan and globally. This study aimed to assess the prevalence and burden of SEA in Japan. Methods: This study was a retrospective, observational cohort analysis using health records or health insurance claims from patients with severe asthma treated at Kyoto University Hospital. The primary outcome was the prevalence of SEA, defined as a baseline blood eosinophil count ≥300 cells/µL. Secondary outcomes included frequency and risk factors of asthma exacerbations, and asthma-related healthcare resource utilization and costs. Results: Overall, 217 patients with severe asthma were included; 160 (74%) had eosinophil assessments. Of these, 97cases (61%), 54cases (34%), and 33cases (21%) had a blood eosinophil count ≥150, ≥300, and ≥500 cells/µL, respectively. Proportion of SEA was 34%. Blood eosinophil count was not associated with a significantly increased frequency of exacerbations. In the eosinophilic group, lower % forced expiratory volume in 1 second and higher fractional exhaled nitric oxide were predictive risk factors, while the existence of exacerbation history was a predictive risk factor for asthma exacerbations in the non-eosinophilic group. Severe asthma management cost was estimated as ¥357,958/patient-year, and asthma exacerbations as ¥26,124/patient-year. Conclusions: Approximately, one-third of patients with severe asthma in Japan have SEA. While risk factors for exacerbations differed between SEA and severe non-eosinophilic asthma, both subgroups were associated with substantial disease and economic burden. From subgroup analysis, blood eosinophil counts could be an important consideration in severe asthma management.
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Antiasmáticos/uso terapéutico , Asma/economía , Asma/epidemiología , Costo de Enfermedad , Eosinofilia Pulmonar/epidemiología , Adolescente , Adulto , Distribución por Edad , Análisis de Varianza , Asma/sangre , Asma/tratamiento farmacológico , Estudios de Cohortes , Bases de Datos Factuales , Manejo de la Enfermedad , Progresión de la Enfermedad , Eosinófilos/inmunología , Femenino , Costos de la Atención en Salud , Hospitales Universitarios , Humanos , Japón/epidemiología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Prevalencia , Eosinofilia Pulmonar/sangre , Eosinofilia Pulmonar/tratamiento farmacológico , Pruebas de Función Respiratoria , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Adulto JovenRESUMEN
Aim: The aim of this study was to investigate epidemiological and clinical aspects of severe postpartum hemorrhage (PPH) in Japan. Methods: We used national health insurance claims from 2011 to 2014 provided by the Ministry of Health, Labour and Welfare. The data included randomly selected claims that covered 10% of all inpatients in October, a so-called sampling dataset (covering 1/120 inpatients per year). We extracted claims for transfused blood, and further narrowed down the claims by names of diseases linked to PPH. As most referral obstetric facilities have adopted the diagnosis procedure combination (DPC)-based payment system while small-scale obstetric facilities have not (non-DPC facilities), the claims were also analyzed separately for DPC and non-DPC facilities. We assessed the incidence and causes of PPH, transfusion volume of red blood cells (RBC) and fresh frozen plasma (FFP), and surgical hemostatic management. Results: The number of PPH cases that required blood transfusion in the sampling dataset was 29, 29, 32, and 36 in 2011, 2012, 2013, and 2014, respectively. The leading cause of PPH was uterine atony followed by placental abruption. Although no specific trends were observed for the volume of transfused RBC (1467 ± 234 ml in 2014), there was a steady increase in the rate of FFP utilization in non-DPC facilities from 37% to 79% over the 4-year sampling period. Intrauterine balloon tamponade emerged in 2014. Conclusion: This nationwide survey indicates that the annual incidence of severe PPH is increasing. Furthermore, FFP has become more prevalent in small-scale obstetric facilities.
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Hemorragia Posparto , Adolescente , Adulto , Transfusión Sanguínea/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Humanos , Revisión de Utilización de Seguros , Japón/epidemiología , Persona de Mediana Edad , Hemorragia Posparto/diagnóstico , Hemorragia Posparto/epidemiología , Hemorragia Posparto/patología , Hemorragia Posparto/terapia , Embarazo , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Electronic Medical Records (EMR)s are intrinsic to modern-day clinics. Understanding the roles, i.e., the unintended functions of EMR systems in their context of use can guide the design of EMR systems and clinics to better integrate them. To understand the roles of EMR systems in antenatal care check-ups, we conducted a field-based observational study at an antenatal care clinic in a Japanese university hospital. We observed 37 antenatal care check-ups where we looked at how the EMR system affects the communication between the involved parties and supports or hinders the clinical process. Our data analysis resulted in 10 EMR roles, namely: the wingman, the third wheel, the accomplice, the bouncer, the messenger, the summarizer, the bureaucrat, the assistant, the gossip, and the alien. Through the roles, this study reveals multiple EMR design considerations and opportunities for improving both the human-EMR and human interactions in antenatal care settings.
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Registros Electrónicos de Salud , Atención Prenatal , Rol Profesional , Femenino , Hospitales Universitarios , Humanos , Japón , EmbarazoRESUMEN
OBJECTIVE: For chronic diseases, medical history reconstruction is essential for retrospective database analyses. One important aspect is determining which prescriptions belong to the same episode. However, a standard framework for this task is still lacking, particularly for multitherapy datasets. This paper presents a medication episode construction framework for the medical history of patients with chronic diseases. METHODS: Allen's relaxed temporal relations (i.e., temporal relations with time constraints relaxed by ) is used to define the consecutive prescription relations considering the patients' behavior. For example, patients occasionally arrive earlier or later than their appointment. RESULTS: influences the generation of stable periods (i.e., periods of time, at least three months, in which a medication is continuously taken by a patient). When using the lowest selected value (7 days), considerably fewer shorter stable periods (for durations less than 300 days) are produced and more longer stable periods are produced compared to cases without using . Furthermore, the results show that by using , regarding the number of events, where a stable period continues the previous stable period, decreases and the number of medication transition events available to be observed increases. CONCLUSION: Using in medication episode construction from multitherapy prescription datasets enables the longer expression of short-duration fragmented prescriptions and pruning repetitive prescriptions. SIGNIFICANCE: Our proposed framework is designed for multitherapy datasets, which has not been addressed by previous studies. The concept of relaxes the prescription relation against noise caused by the patient behavior and consequently provides a compact, but informative search space for observing medication transition events in a longitudinal analysis.