TIP60 is required for tumorigenesis in non-small cell lung cancer.

Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.

The cumulative dose-dependent effects of metformin on the development of tuberculosis in patients newly diagnosed with type 2 diabetes mellitus.

BACKGROUND: Diabetes mellitus (DM) is a well-known risk factor for tuberculosis (TB). Metformin, which is an essential anti-diabetic drug, has been shown to exhibit anti-TB effects in patients with DM. Its effect on preventing the development of TB among patients who are newly diagnosed with DM remains unclear. METHODS: This was a retrospective cohort study using the claims database of the Korean Health Insurance Review and Assessment Service. The study population included patients who were newly diagnosed with type 2 DM and who were treated with anti-diabetic drugs between 1 January 2003 and 31 March 2011. A patient was defined as a metformin user if he/she had taken metformin for more than 28 days within 6 months since cohort entry, and as a metformin non-user if he/she had never been treated with metformin. The development of TB within 2 years after the index date was compared by Cox proportional hazard regression models between metformin users and 1:1 propensity score (PS)-matched non-users. RESULTS: Among 76,973 patients who were newly diagnosed with type 2 DM, 13,396 were classified as metformin users, 52,736 were classified as metformin non-users, and 10,841 were excluded from the final analysis. PS-matched Cox proportional hazard regression models revealed that metformin use was not associated overall with the prevention of TB development (HR 1.17; 95% CI 0.75-1.83; P = 0.482). There was a trend, however, towards a reduction in the development of TB among patients taking a higher cumulative dose of metformin. Patients who were in the highest quartile (Q4) of cumulative metformin dose had only a 10% risk of developing TB compared to metformin non-users. In contrast, during the early phases of metformin treatment, patients in the second quartile (Q2) of cumulative metformin use had a higher risk of developing TB than patients in the first quartile (Q1). CONCLUSIONS: Only the highest cumulative doses of metformin were protective against the development of TB among patients who were newly diagnosed with type 2 DM; lower cumulative doses of metformin did not appear to reduce the incidence of active TB infection.

Clinical Genomic Sequencing Reports in Electronic Health Record Systems Based on International Standards: Implementation Study.

BACKGROUND: To implement standardized machine-processable clinical sequencing reports in an electronic health record (EHR) system, the International Organization for Standardization Technical Specification (ISO/TS) 20428 international standard was proposed for a structured template. However, there are no standard implementation guidelines for data items from the proposed standard at the clinical site and no guidelines or references for implementing gene sequencing data results for clinical use. This is a significant challenge for implementation and application of these standards at individual sites. OBJECTIVE: This study examines the field utilization of genetic test reports by designing the Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) for genomic data elements based on the ISO/TS 20428 standard published as the standard for genomic test reports. The goal of this pilot is to facilitate the reporting and viewing of genomic data for clinical applications. FHIR Genomics resources predominantly focus on transmitting or representing sequencing data, which is of less clinical value. METHODS: In this study, we describe the practical implementation of ISO/TS 20428 using HL7 FHIR Genomics implementation guidance to efficiently deliver the required genomic sequencing results to clinicians through an EHR system. RESULTS: We successfully administered a structured genomic sequencing report in a tertiary hospital in Korea based on international standards. In total, 90 FHIR resources were used. Among 41 resources for the required fields, 26 were reused and 15 were extended. For the optional fields, 28 were reused and 21 were extended. CONCLUSIONS: To share and apply genomic sequencing data in both clinical practice and translational research, it is essential to identify the applicability of the standard-based information system in a practical setting. This prototyping work shows that reporting data from clinical genomics sequencing can be effectively implemented into an EHR system using the existing ISO/TS 20428 standard and FHIR resources.

Patient-Level Prediction of Cardio-Cerebrovascular Events in Hypertension Using Nationwide Claims Data.

BACKGROUND: Prevention and management of chronic diseases are the main goals of national health maintenance programs. Previously widely used screening tools, such as Health Risk Appraisal, are restricted in their achievement this goal due to their limitations, such as static characteristics, accessibility, and generalizability. Hypertension is one of the most important chronic diseases requiring management via the nationwide health maintenance program, and health care providers should inform patients about their risks of a complication caused by hypertension. OBJECTIVE: Our goal was to develop and compare machine learning models predicting high-risk vascular diseases for hypertensive patients so that they can manage their blood pressure based on their risk level. METHODS: We used a 12-year longitudinal dataset of the nationwide sample cohort, which contains the data of 514,866 patients and allows tracking of patients' medical history across all health care providers in Korea (N=51,920). To ensure the generalizability of our models, we conducted an external validation using another national sample cohort dataset, comprising one million different patients, published by the National Health Insurance Service. From each dataset, we obtained the data of 74,535 and 59,738 patients with essential hypertension and developed machine learning models for predicting cardiovascular and cerebrovascular events. Six machine learning models were developed and compared for evaluating performances based on validation metrics. RESULTS: Machine learning algorithms enabled us to detect high-risk patients based on their medical history. The long short-term memory-based algorithm outperformed in the within test (F1-score=.772, external test F1-score=.613), and the random forest-based algorithm of risk prediction showed better performance over other machine learning algorithms concerning generalization (within test F1-score=.757, external test F1-score=.705). Concerning the number of features, in the within test, the long short-term memory-based algorithms outperformed regardless of the number of features. However, in the external test, the random forest-based algorithm was the best, irrespective of the number of features it encountered. CONCLUSIONS: We developed and compared machine learning models predicting high-risk vascular diseases in hypertensive patients so that they may manage their blood pressure based on their risk level. By relying on the prediction model, a government can predict high-risk patients at the nationwide level and establish health care policies in advance.

Impact of an Electronic Health Record-Integrated Personal Health Record on Patient Participation in Health Care: Development and Randomized Controlled Trial of MyHealthKeeper.

BACKGROUND: Personal health record (PHR)-based health care management systems can improve patient engagement and data-driven medical diagnosis in a clinical setting. OBJECTIVE: The purpose of this study was (1) to demonstrate the development of an electronic health record (EHR)-tethered PHR app named MyHealthKeeper, which can retrieve data from a wearable device and deliver these data to a hospital EHR system, and (2) to study the effectiveness of a PHR data-driven clinical intervention with clinical trial results. METHODS: To improve the conventional EHR-tethered PHR, we ascertained clinicians' unmet needs regarding PHR functionality and the data frequently used in the field through a cocreation workshop. We incorporated the requirements into the system design and architecture of the MyHealthKeeper PHR module. We constructed the app and validated the effectiveness of the PHR module by conducting a 4-week clinical trial. We used a commercially available activity tracker (Misfit) to collect individual physical activity data, and developed the MyHealthKeeper mobile phone app to record participants' patterns of daily food intake and activity logs. We randomly assigned 80 participants to either the PHR-based intervention group (n=51) or the control group (n=29). All of the study participants completed a paper-based survey, a laboratory test, a physical examination, and an opinion interview. During the 4-week study period, we collected health-related mobile data, and study participants visited the outpatient clinic twice and received PHR-based clinical diagnosis and recommendations. RESULTS: A total of 68 participants (44 in the intervention group and 24 in the control group) completed the study. The PHR intervention group showed significantly higher weight loss than the control group (mean 1.4 kg, 95% CI 0.9-1.9; P<.001) at the final week (week 4). In addition, triglyceride levels were significantly lower by the end of the study period (mean 2.59 mmol/L, 95% CI 17.6-75.8; P=.002). CONCLUSIONS: We developed an innovative EHR-tethered PHR system that allowed clinicians and patients to share lifelog data. This study shows the effectiveness of a patient-managed and clinician-guided health tracker system and its potential to improve patient clinical profiles. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200119; https://clinicaltrials.gov/ct2/show/NCT03200119 (Archived by WebCite at http://www.webcitation.org/6v01HaCdd).

Cereblon Deficiency Contributes to the Development of Elastase-Induced Emphysema by Enhancing NF-κB Activation.

Cereblon (CRBN) has been shown to play an essential role in regulating inflammatory response and endoplasmic reticulum stress, thus mediating the development of various diseases. However, little is known about the roles of CRBN in chronic obstructive pulmonary disease (COPD) pathogenesis. We found that the protein levels of CRBN in lung homogenates from patients with COPD were lower than those from never smokers and smokers. The CRBN protein level was positively correlated with the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). To investigate the role of CRBN in modulating elastase-induced emphysema, we used Crbn knockout (KO) mice. Elastase-induced emphysematous changes were significantly aggravated in Crbn KO mice. Neutrophil infiltration, lung cell injury, and protein leakage into the bronchoalveolar space were more severe in Crbn KO mice than in wild-type (WT) mice. Furthermore, Crbn KO resulted in the elevated release of neutrophilic chemokines and inflammatory cytokines in lung epithelial cells and macrophages. The transcriptional activity of nuclear factor-κB (NF-κB) was significantly increased in Crbn knocked-down cells. In conclusion, Crbn deficiency might be involved in the development of emphysema by enhancing NF-κB activation, suggesting that targeting CRBN might be an effective therapeutic approach for the treatment of COPD.

Impact of Personal Health Records and Wearables on Health Outcomes and Patient Response: Three-Arm Randomized Controlled Trial.

BACKGROUND: Although using the technologies for a variety of chronic health conditions such as personal health record (PHR) is reported to be acceptable and useful, there is a lack of evidence on the associations between the use of the technologies and the change of health outcome and patients' response to a digital health app. OBJECTIVE: This study aimed to examine the impact of the use of PHR and wearables on health outcome improvement and sustained use of the health app that can be associated with patient engagement. METHODS: We developed an Android-based mobile phone app and used a wristband-type activity tracker (Samsung Charm) to collect data on health-related daily activities from individual patients. Dietary record, daily step counts, sleep log, subjective stress amount, blood pressure, and weight values were recorded. We conducted a prospective randomized clinical trial across 4 weeks on those diagnosed with obstructive sleep apnea (OSA) who had visited the outpatient clinic of Seoul National University Bundang Hospital. The trial randomly assigned 60 patients to 3 subgroups including 2 intervention groups: (1) mobile app and wearable device users (n=20), (2) mobile app-only users (n=20), and (3) controls (n=20). The primary outcome measure was weight change. Body weights before and after the trial were recorded and analyzed during clinic visits. Changes in OSA-related respiratory parameters such as respiratory disturbance, apnea-hypopnea, and oxygenation desaturation indexes and snoring comprised the secondary outcome and were analyzed for each participant. RESULTS: We collected the individual data for each group during the trial, specifically anthropometric measurement and laboratory test results for health outcomes, and the app usage logs for patient response were collected and analyzed. The body weight showed a significant reduction in the 2 intervention groups after intervention, and the mobile app-only group showed more weight loss compared with the controls (P=.01). There were no significant changes in sleep-related health outcomes. From a patient response point of view, the average daily step counts (8165 steps) from the app plus wearable group were significantly higher than those (6034 steps) from the app-only group because they collected step count data from different devices (P=.02). The average rate of data collection was not different in physical activity (P=.99), food intake (P=.98), sleep (P=.95), stress (P=.70), and weight (P=.90) in the app plus wearable and app-only groups, respectively. CONCLUSIONS: We tried to integrate PHR data that allow clinicians and patients to share lifelog data with the clinical workflow to support lifestyle interventions. Our results suggest that a PHR-based intervention may be successful in losing body weight and improvement in lifestyle behavior. TRIAL REGISTRATION: ClinicalTrials.gov NCT03200223; https://clinicaltrials.gov/ct2/show/NCT03200223 (Archived by WebCite at http://www.webcitation.org/74baZmnCX).

Design of a Hospice Referral System for Terminally Ill Cancer Patients Using a Standards-Based Health Information Exchange System.

OBJECTIVES: The demand for hospice has been increasing among patients with cancer. This study examined the current hospice referral scenario for terminally ill cancer patients and created a data form to collect hospice information and a modified health information exchange (HIE) form for a more efficient referral system for terminally ill cancer patients. METHODS: Surveys were conducted asking detailed information such as medical instruments and patient admission policies of hospices, and interviews were held to examine the current referral flow and any additional requirements. A task force team was organized to analyze the results of the interviews and surveys. RESULTS: Six hospices completed the survey, and 3 physicians, 2 nurses, and 2 hospital staff from a tertiary hospital were interviewed. Seven categories were defined as essential for establishing hospice data. Ten categories and 40 data items were newly suggested for the existing HIE document form. An implementation guide for the Consolidated Clinical Document Architecture developed by Health Level 7 (HL7 CCDA) was also proposed. It is an international standard for interoperability that provides a framework for the exchange, integration, sharing, and retrieval of electronic health information. Based on these changes, a hospice referral scenario for terminally ill cancer patients was designed. CONCLUSIONS: Our findings show potential improvements that can be made to the current hospice referral system for terminally ill cancer patients. To make the referral system useful in practice, governmental efforts and investments are needed.

Effect of Lifestyle Modification Using a Smartphone Application on Obesity With Obstructive Sleep Apnea: A Short-term, Randomized Controlled Study.

OBJECTIVES: To investigate the short-term effects of a lifestyle modification intervention based on a mobile application (app) linked to a hospital electronic medical record (EMR) system on weight reduction and obstructive sleep apnea (OSA). METHODS: We prospectively enrolled adults (aged >20 years) with witnessed snoring or sleep apnea from a sleep clinic. The patients were randomized into the app user (n=24) and control (n=23) groups. The mobile app was designed to collect daily lifestyle data by wearing a wrist activity tracker and reporting dietary intake. A summary of the lifestyle data was displayed on the hospital EMR and was reviewed. In the control group, the lifestyle modification was performed as per usual practice. All participants underwent peripheral arterial tonometry (WatchPAT) and body mass index (BMI) measurements at baseline and after 4 weeks of follow-up. RESULTS: Age and BMI did not differ significantly between the two groups. While we observed a significant decrease in the BMI of both groups, the decrease was greater in the app user group (P <0.001). Apnea-hypopnea index, respiratory distress index, and oxygenation distress index did not change significantly in both groups. However, the proportion of sleep spent snoring at >45 dB was significantly improved in the app user group alone (P =0.014). In either group, among the participants with successful weight reduction, the apnea-hypopnea index was significantly reduced after 4 weeks (P =0.015). Multiple regression analyses showed that a reduction in the apnea-hypopnea index was significantly associated with BMI. CONCLUSION: Although a short-term lifestyle modification approach using a mobile app was more effective in achieving weight reduction, improvement in OSA was not so significant. Long-term efficacy of this mobile app should be evaluated in the future studies.

Technology and Policy Challenges in the Adoption and Operation of Health Information Exchange Systems.

OBJECTIVES: This study aimed to identify problems and issues that arise with the implementation of online health information exchange (HIE) systems in a medical environment and to identify solutions to facilitate the successful operation of future HIE systems in primary care clinics and hospitals. METHODS: In this study, the issues that arose during the establishment and operation of an HIE system in a hospital were identified so that they could be addressed to enable the successful establishment and operation of a standard-based HIE system. After the issues were identified, they were reviewed and categorized by a group of experts that included medical information system experts, doctors, medical information standard experts, and HIE researchers. Then, solutions for the identified problems were derived based on the system development, operation, and improvement carried out during this work. RESULTS: Twenty-one issues were identified during the implementation and operation of an online HIE system. These issues were then divided into four categories: system architecture and standards, documents and data items, consent of HIE, and usability. We offer technical and policy recommendations for various stakeholders based on the experiences of operating and improving the online HIE system in the medical field. CONCLUSIONS: The issues and solutions identified in this study regarding the implementation and operate of an online HIE system can provide valuable insight for planners to enable them to successfully design and operate such systems at a national level in the future. In addition, policy support from governments is needed.

Effect of Prophylactic Use of Silymarin on Anti-tuberculosis Drugs Induced Hepatotoxicity.

BACKGROUND: The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs. METHODS: This is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > 2× UNL within the first 8 weeks of anti-TB treatment. RESULTS: We enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >2× ULN at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043). CONCLUSION: Our findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.

Antiviral activity of gemcitabine against human rhinovirus in vitro and in vivo.

Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model. Intranasal administration of gemcitabine significantly lowered pulmonary viral load and inflammation by decreasing proinflammatory cytokines, including TNF-α and IL-1ß, and reduction in the number of lung-infiltrating lymphocytes. Interestingly, we found that the addition of UTP and CTP significantly attenuated the antiviral activity of gemcitabine. Thus the limitation of UTP and CTP by the addition of gemcitabine may inhibit the viral RNA synthesis. These results suggest that gemcitabine, an antineoplastic drug, can be repositioned as an antiviral drug to inhibit HRV infection.

Trans-scirpusin A showed antitumor effects via autophagy activation and apoptosis induction of colorectal cancer cells.

Trans-Scirpusin A (TSA) is a resveratrol oligomer found in Borassus flabellifer L. We found that TSA inhibited the growth of colorectal cancer Her2/CT26 cells in vivo in mice. Although some cytotoxic T lymphocytes (CTLs) were induced against the tumor-associated antigen Her2, TSA treatment did not significantly increase the level of Her2-specific CTL response compared to that with vehicle treatment. However, there was a significant increase in the level of TNF-α mRNA in tumor tissue and Her2-specific Ab (antibody) production. More importantly, we found that TSA overcomes the tumor-associated immunosuppressive microenvironment by reducing the number of CD25+FoxP3+ regulatory T cells and myeloid-derived suppressor cells (MDSCs). We detected the induction of autophagy in TSA-treated Her2/CT26 cells, based on the increased level of the mammalian autophagy protein LC3 puncta, and increased conversion of LC3-I to LC3-II. Further, TSA induced 5' AMP-activated protein kinase (p-AMPK) (T172) and inhibited mammalian target of rapamycin complex 1 (mTORC1) activity as estimated by phosphorylated ribosomal protein S6 kinase beta-1 (p-p70S6K) levels, thereby suggesting that TSA-mediated AMPK activation and inhibition of mTORC1 pathway might be associated with autophagy induction. TSA also induced apoptosis of Her2/CT26 cells, as inferred by the increased sub-G1 mitotic phases in these cells, Annexin V/PI-double positive results, and TUNEL-positive cells. Finally, we found that the combined treatment of mice with docetaxel and TSA successfully inhibited tumor growth to a greater extent than docetaxel alone. Therefore, we propose the use of TSA for supplementary anticancer therapy to support anti-neoplastic drugs, such as docetaxel, by inducing apoptosis in cancer cells and resulting in the induction of neighborhood anti-cancer immunity.

Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial.

BACKGROUND: Linezolid, an oxazolidinone, substantially improves treatment outcomes of multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We started a trial to test whether the use of linezolid instead of ethambutol could increase the rate of sputum culture conversion as of 8 weeks of treatment in patients with drug-susceptible tuberculosis. METHODS/DESIGN: This is a phase II, multicenter, randomized study with three arms. We are enrolling patients with pulmonary tuberculosis without rifampicin resistance screened by the Xpert MTB/RIF® assay. The standard treatment arm uses isoniazid (6 months), rifampicin (6 months), pyrazinamide (2 months), and ethambutol (2 months). Experimental arm 1 uses linezolid (600 mg/day) for 4 weeks instead of ethambutol. Experimental arm 2 uses linezolid (600 mg/day) for 2 weeks instead of ethambutol. The primary outcome is the sputum culture conversion rate on liquid media after 2 months of treatment. Secondary outcomes include the sputum culture conversion rate on solid media after 2 months of treatment, time to sputum culture conversion on liquid and solid media, cure rate, and treatment success rate. The frequencies of total adverse events (AEs) and serious AEs will be described and documented. Based on an α = 0.05 level of significance, a power of 85%, a 15% difference in the culture conversion rate after 2 months between the control arm and experimental arm 1 (75% vs. 90%), a 10% default (loss to follow-up) rate, and a 10% culture failure, the required number per arm was calculated to be 143 (429 in total). DISCUSSION: This trial will reveal the effectiveness and safety of 2 or 4 weeks of use of linezolid instead of ethambutol for patients with drug-susceptible pulmonary tuberculosis. If a new regimen including linezolid shows a higher culture conversion rate by week 8, and is safe, it could be tested as a 4-month antituberculosis treatment regimen in the future. TRIAL REGISTRATION: ClincalTrials.gov, NCT01994460 . Registered on 13 November 2013.

Choice between Levofloxacin and Moxifloxacin and Multidrug-Resistant Tuberculosis Treatment Outcomes.

RATIONALE: We previously showed that the choice of levofloxacin or moxifloxacin for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (MDR-TB) did not affect sputum culture conversion at 3 months of treatment. OBJECTIVES: To compare final treatment outcomes between patients with MDR-TB randomized to levofloxacin or moxifloxacin. METHODS: A total of 151 participants with MDR-TB who were included for the final analysis in our previous trial were followed through the end of treatment. Treatment outcomes were compared between 77 patients in the levofloxacin group and 74 in the moxifloxacin group, based on the 2008 World Health Organization definitions as well as 2013 revised definitions of treatment outcomes. In addition, the time to culture conversion was compared between the two groups. MEASUREMENTS AND MAIN RESULTS: Treatment outcomes were not different between the two groups, based on 2008 World Health Organization definitions as well as 2013 definitions. With 2008 definitions, cure was achieved in 54 patients (70.1%) in the levofloxacin group and 54 (73.0%) in the moxifloxacin group (P = 0.72). Treatment success rates, including cure and treatment completed, were not different between the two groups (87.0 vs. 81.1%, P = 0.38). With 2013 definitions, cure rates (83.1 vs. 78.4%, P = 0.54) and treatment success rates (84.4 vs. 79.7%, P = 0.53) were also similar between the levofloxacin and moxifloxacin groups. Time to culture conversion was also not different between the two groups (27.0 vs. 45.0 d, P = 0.11 on liquid media; 17.0 vs. 42.0 d, P = 0.14 on solid media). Patients in the levofloxacin group had more adverse events than those in the moxifloxacin group (79.2 vs. 63.5%, P = 0.03), especially musculoskeletal ones (37.7 vs. 14.9%, P = 0.001). CONCLUSIONS: The choice of levofloxacin or moxifloxacin made no difference to the final treatment outcome among patients with fluoroquinolone-sensitive MDR-TB. Clinical trial registered with www.clinicalrials.gov (NCT01055145).

Architecture Design of Healthcare Software-as-a-Service Platform for Cloud-Based Clinical Decision Support Service.

OBJECTIVES: To design a cloud computing-based Healthcare Software-as-a-Service (SaaS) Platform (HSP) for delivering healthcare information services with low cost, high clinical value, and high usability. METHODS: We analyzed the architecture requirements of an HSP, including the interface, business services, cloud SaaS, quality attributes, privacy and security, and multi-lingual capacity. For cloud-based SaaS services, we focused on Clinical Decision Service (CDS) content services, basic functional services, and mobile services. Microsoft's Azure cloud computing for Infrastructure-as-a-Service (IaaS) and Platform-as-a-Service (PaaS) was used. RESULTS: The functional and software views of an HSP were designed in a layered architecture. External systems can be interfaced with the HSP using SOAP and REST/JSON. The multi-tenancy model of the HSP was designed as a shared database, with a separate schema for each tenant through a single application, although healthcare data can be physically located on a cloud or in a hospital, depending on regulations. The CDS services were categorized into rule-based services for medications, alert registration services, and knowledge services. CONCLUSIONS: We expect that cloud-based HSPs will allow small and mid-sized hospitals, in addition to large-sized hospitals, to adopt information infrastructures and health information technology with low system operation and maintenance costs.

Can a health information exchange save healthcare costs? Evidence from a pilot program in South Korea.

OBJECTIVE: Governments and institutions across the world have made efforts to adopt and diffuse the health information exchange (HIE) technology with the expectation that the technology would improve the quality and efficiency of care by allowing providers online access to healthcare information generated by other providers at the point of care. However, evidence concerning the effectiveness of the technology is limited hindering the wide adoption of a HIE. The objective of this study was to assess impacts of a HIE on healthcare utilization and costs of patient episodes at a tertiary care hospital following referrals by clinic physicians. MATERIAL/METHODS: We studied 1265 HIE and 2702 non-HIE episodes after physicians referred patients from 35 HIE and 59 non-HIE clinics to Seoul National University Bundang Hospital (SNUBH) during a 17-month period from June 2009. We examined 9 measures of healthcare utilization and the magnitude of clinical information exchanged in 4 categories. We estimated the savings resulting from HIE use through linear regression models with dummy variables for HIE participation and patient classification codes controlling the case-mix differences between HIE and non-HIE cases. RESULTS: The total charges incurred by the HIE group during episodes at SNUBH were approximately 13% lower (P<0.001), and the charges for clinical laboratory tests, pathological diagnosis, function tests, and diagnostic imaging were 54% (P<0.001), 76% (P<0.001), 73% (P<0.001), and 80% (P<0.001) lower for the HIE group than for the non-HIE group. SNUBH physicians had access to more clinical information for HIE than for non-HIE patients. CONCLUSIONS: HIE technology improved physicians' access to past clinical information, which appeared to reduce diagnostic test utilization and healthcare costs. The payer was the major beneficiary of HIE cost savings whereas providers paid for the technology. Fair allocation of benefits and costs among stakeholders is needed for wide HIE adoption.

Developing a common health information exchange platform to implement a nationwide health information network in South Korea.

OBJECTIVES: We aimed to develop a common health information exchange (HIE) platform that can provide integrated services for implementing the HIE infrastructure in addition to guidelines for participating in an HIE network in South Korea. METHODS: By exploiting the Health Level 7 (HL7) Clinical Document Architecture (CDA) and Integrating the Healthcare Enterprise (IHE) Cross-enterprise Document Sharing-b (XDS.b) profile, we defined the architectural model, exchanging data items and their standardization, messaging standards, and privacy and security guidelines, for a secure, nationwide, interoperable HIE. We then developed a service-oriented common HIE platform to minimize the effort and difficulty of fulfilling the standard requirements for participating in the HIE network. The common platform supports open application program interfaces (APIs) for implementing a document registry, a document repository, a document consumer, and a master patient index. It could also be used for testing environments for the implementation of standard requirements. RESULTS: As the initial phase of implementing a nationwide HIE network in South Korea, we built a regional network for workers' compensation (WC) hospitals and their collaborating clinics to share referral and care record summaries to ensure the continuity of care for industrially injured workers, using the common HIE platform and verifying the feasibility of our technologies. CONCLUSIONS: We expect to expand the HIE network on a national scale with rapid support for implementing HL7 and IHE standards in South Korea.