Machine Learning Approaches for Predicting Psoriatic Arthritis Risk Using Electronic Medical Records: Population-Based Study.

BACKGROUND: Psoriasis (PsO) is a chronic, systemic, immune-mediated disease with multiorgan involvement. Psoriatic arthritis (PsA) is an inflammatory arthritis that is present in 6%-42% of patients with PsO. Approximately 15% of patients with PsO have undiagnosed PsA. Predicting patients with a risk of PsA is crucial for providing them with early examination and treatment that can prevent irreversible disease progression and function loss. OBJECTIVE: The aim of this study was to develop and validate a prediction model for PsA based on chronological large-scale and multidimensional electronic medical records using a machine learning algorithm. METHODS: This case-control study used Taiwan's National Health Insurance Research Database from January 1, 1999, to December 31, 2013. The original data set was split into training and holdout data sets in an 80:20 ratio. A convolutional neural network was used to develop a prediction model. This model used 2.5-year diagnostic and medical records (inpatient and outpatient) with temporal-sequential information to predict the risk of PsA for a given patient within the next 6 months. The model was developed and cross-validated using the training data and was tested using the holdout data. An occlusion sensitivity analysis was performed to identify the important features of the model. RESULTS: The prediction model included a total of 443 patients with PsA with earlier diagnosis of PsO and 1772 patients with PsO without PsA for the control group. The 6-month PsA risk prediction model that uses sequential diagnostic and drug prescription information as a temporal phenomic map yielded an area under the receiver operating characteristic curve of 0.70 (95% CI 0.559-0.833), a mean sensitivity of 0.80 (SD 0.11), a mean specificity of 0.60 (SD 0.04), and a mean negative predictive value of 0.93 (SD 0.04). CONCLUSIONS: The findings of this study suggest that the risk prediction model can identify patients with PsO at a high risk of PsA. This model may help health care professionals to prioritize treatment for target high-risk populations and prevent irreversible disease progression and functional loss.

Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual Population-Based Study.

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000-2016) and linked with Taiwan Cancer Registry (1979-2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85-0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20-39 years (aOR: 0.70, 95% CI: 0.58-0.85), 40-64 years (aOR: 0.77, 95% CI: 0.74-0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.91), and overall (aOR: 0.81, 95% CI: 0.79-0.84). Ovarian cancer risk was significantly lower in the groups aged 40-64 years (aOR: 0.76, 95% CI: 0.69-0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75-092), and overall (aOR: 0.79, 95% CI: 0.74-0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20-39 years (aOR: 2.54, 95% CI: 1.79-3.61), 40-64 years (aOR: 1.08, 95% CI: 1.02-1.14), and overall (aOR: 1.06, 95% CI: 1.01-1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40-64 years (aOR: 0.88, 95% CI: 0.84-0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.90), and overall (aOR: 0.88, 95% CI: 0.85-0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86-0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.

How Can Research on Artificial Empathy Be Enhanced by Applying Deepfakes?

We propose the idea of using an open data set of doctor-patient interactions to develop artificial empathy based on facial emotion recognition. Facial emotion recognition allows a doctor to analyze patients' emotions, so that they can reach out to their patients through empathic care. However, face recognition data sets are often difficult to acquire; many researchers struggle with small samples of face recognition data sets. Further, sharing medical images or videos has not been possible, as this approach may violate patient privacy. The use of deepfake technology is a promising approach to deidentifying video recordings of patients' clinical encounters. Such technology can revolutionize the implementation of facial emotion recognition by replacing a patient's face in an image or video with an unrecognizable face-one with a facial expression that is similar to that of the original. This technology will further enhance the potential use of artificial empathy in helping doctors provide empathic care to achieve good doctor-patient therapeutic relationships, and this may result in better patient satisfaction and adherence to treatment.

Risk of cancer in long-term levothyroxine users: Retrospective population-based study.

Levothyroxine is a widely prescribed medication for the treatment of an underactive thyroid. The relationship between levothyroxine use and cancer risk is largely underdetermined. To investigate the magnitude of the possible association between levothyroxine use and cancer risk, this retrospective case-control study was conducted using Taiwan's Health and Welfare Data Science Center database. Cases were defined as all patients who were aged ≥20 years and had a first-time diagnosis for cancer at any site for the period between 2001 and 2011. Multivariable conditional logistic regression models were used to calculate an adjusted odds ratio (AOR) to reduce potential confounding factors. A total of 601 733 cases and 2 406 932 controls were included in the current study. Levothyroxine users showed a 50% higher risk of cancer at any site (AOR: 1.50, 95% CI: 1.46-1.54; P < .0001) compared with non-users. Significant increased risks were also observed for brain cancer (AOR: 1.90, 95% CI: 1.48-2.44; P < .0001), skin cancer (AOR: 1.42, 95% CI: 1.17-1.72; P < .0001), pancreatic cancer (AOR: 1.27, 95% CI: 1.01-1.60; P = .03), and female breast cancer (AOR: 1.24, 95% CI: 1.15-1.33; P < .0001). Our study results showed that levothyroxine use was significantly associated with an increased risk of cancer, particularly brain, skin, pancreatic, and female breast cancers. Levothyroxine remains a highly effective therapy for hypothyroidism; therefore, physicians should carefully consider levothyroxine therapy and monitor patients' condition to avoid negative outcomes. Additional studies are needed to confirm these findings and to evaluate the potential biological mechanisms.

Correction: Artificial Intelligence-Based Prediction of Lung Cancer Risk Using Nonimaging Electronic Medical Records: Deep Learning Approach.

[This corrects the article DOI: 10.2196/26256.].

Artificial Intelligence-Based Prediction of Lung Cancer Risk Using Nonimaging Electronic Medical Records: Deep Learning Approach.

BACKGROUND: Artificial intelligence approaches can integrate complex features and can be used to predict a patient's risk of developing lung cancer, thereby decreasing the need for unnecessary and expensive diagnostic interventions. OBJECTIVE: The aim of this study was to use electronic medical records to prescreen patients who are at risk of developing lung cancer. METHODS: We randomly selected 2 million participants from the Taiwan National Health Insurance Research Database who received care between 1999 and 2013. We built a predictive lung cancer screening model with neural networks that were trained and validated using pre-2012 data, and we tested the model prospectively on post-2012 data. An age- and gender-matched subgroup that was 10 times larger than the original lung cancer group was used to assess the predictive power of the electronic medical record. Discrimination (area under the receiver operating characteristic curve [AUC]) and calibration analyses were performed. RESULTS: The analysis included 11,617 patients with lung cancer and 1,423,154 control patients. The model achieved AUCs of 0.90 for the overall population and 0.87 in patients ≥55 years of age. The AUC in the matched subgroup was 0.82. The positive predictive value was highest (14.3%) among people aged ≥55 years with a pre-existing history of lung disease. CONCLUSIONS: Our model achieved excellent performance in predicting lung cancer within 1 year and has potential to be deployed for digital patient screening. Convolution neural networks facilitate the effective use of EMRs to identify individuals at high risk for developing lung cancer.

Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan.

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor-tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population-based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non-statins and 41 statins users who had undergone EGFR-TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan-Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non-statins group (4-y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%-81.4% vs. 85.5%; 95% CI, 78.5%-98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29-0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41-0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR-TKIs and played a synergistic anticancer role.

Association between Use of Statin and Risk of Dementia: A Meta-Analysis of Observational Studies.

BACKGROUND AND AIMS: The impact of statin on dementia risk reduction has been a subject of debate over the last decade, but the evidence remains inconclusive. Therefore, we performed a meta-analysis of relevant observational studies to quantify the magnitude of the association between statin therapy and the risk of dementia. METHODS: We systematically searched for relevant studies published from January 2000 to March 2018 using EMBASE, Google, Google Scholar, PubMed, Scopus, and Web of Science. Two authors performed study selection, data abstraction, and risk of bias assessment. We then extracted data from the selected studies and performed meta-analysis of observational studies using a random-effects model. Subgroup and sensitivity analyses were also conducted. RESULTS: A total of 30 observational studies, including 9,162,509 participants (84,101 dementia patients), met the eligibility criteria. Patients with statin had a lower all-caused dementia risk than those without statin (risk ratio [RR] 0.83, 95% CI 0.79-0.87, I2 = 57.73%). The overall pooled reduction of Alzheimer disease in patients with statin use was RR 0.69 (95% CI 0.60-0.80, p < 0.0001), and the overall pooled RR of statin use and vascular dementia risk was RR 0.93 (95% CI 0.74-1.16, p = 0.54). CONCLUSION: This study suggests that the use of statin is significantly associated with a decreased risk of dementia. Future studies measuring such outcomes would provide useful information to patients, clinicians, and policymakers. Until further evidence is established, clinicians need to make sure that statin use should remain restricted to the treatment of cardiovascular disease.

Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.

PURPOSE: Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. STUDY SELECTION: We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. DATA EXTRACTION: Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. RESULTS OF DATA SYNTHESIS: Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66). CONCLUSION: We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

Increase Risk of Multiple Sclerosis in Patients with Psoriasis Disease: An Evidence of Observational Studies.

BACKGROUND: Psoriasis, a common chronic inflammatory disease, increases the risk of developing multiple sclerosis (MS), but evidence for this outcome is still unclear. However, we performed a meta-analysis of relevant studies to quantify the magnitude of the association between psoriasis and MS. It will help to assess the current state of knowledge, fill the gaps in our existing concern, and make a recommendation for future research. METHODS: PubMed, EMBASE, and the bibliographies of articles were searched for studies published between January 1, 1990, and November 1, 2017, which reported on the association between psoriasis and MS. Articles were included if they (1) were published in English, (2) reported patients with psoriasis, and the outcome of interest was MS, (3) provided OR/RR/HR with 95% CI or sufficient information to calculate the 95% CI, and (4) if ≥50 patients. All abstracts, full-text articles, and sources were reviewed, with duplicate data excluded. Summary relative risk (ORs) with 95% CI was pooled using a random-effects model. Subgroup and sensitivity analyses were also conducted. RESULTS: We selected 11 articles out of 785 unique abstracts for full-text review using our predetermined selection criteria, and 9 out of these 11 studies met all of our inclusion criteria. The overall pooled increased of developing MS in patients with psoriasis was RR 1.607 (95% CI 1.322-1.953, p < 0.0001) with low heterogeneity (I2 = 37.41%, Q = 12.782, τ2 = 0.027) for the random effect model. In the subgroup analysis, the MS risk in the patient with psoriasis was also significantly higher in the 6 studies from Europe RR 1.57 (95% CI 1.26-1.94, p < 0.001) with moderate heterogeneity (I2 = 50.66%, Q = 10.13, τ2 = 0.03) for the random effect model. CONCLUSION: Our results showed that psoriasis is significantly associated with an increased risk of developing MS. Physicians should carefully be observed symptoms and empower their patients to improve existing knowledge and quality of life. Further studies are warranted to establish the mechanisms underlying this relationship.

Non-steroidal anti-inflammatory drugs and risk of Parkinson's disease in the elderly population: a meta-analysis.

PURPOSE: Several studies have explored the impact of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD). However, the extent to which NSAIDs may increase or decrease the risk of PD remains unresolved. We, therefore, performed a meta-analysis of relevant studies to quantify the magnitude of the association between NSAID use and PD risk in the elderly population. METHODS: The electronic databases such as PubMed, EMBASE, Scopus, Google Scholar, and Web of Science were used to search the relevant articles published between January 1990 and December 2017. Large (n ≥ 1000) observational design studies with a follow-up at least 1 year were considered. Two authors independently extracted information from the included studies. Random effect model was used to calculate risk ratios (RRs) with 95% confidence interval (Cl). RESULTS: A total of 17 studies with 2,498,258 participants and nearly 14,713 PD patients were included in the final analysis. The overall pooled RR of PD was 0.95 (95%CI 0.860-1.048) with significant heterogeneity (I2 = 63.093, Q = 43.352, p < 0.0001). In the subgroup analysis, the overall pooled RR of PD was 0.90 (95%CI 0.738-1.109), 0.96 (95%CI 0.882-1.055), and 0.99 (95%CI 0.841-0.982) from the studies of North America, Europe, and Asia. Additionally, long-term use, study design, individual NSAID use, and risk of PD were also evaluated. CONCLUSION: Despite the neuroprotective potential of NSAIDs demonstrated in some experimental studies, our findings suggest that there is no association between NSAIDs and the risk of Parkinson disease at the population level. Until further evidence is established, clinicians need to be vigilant ensuring that the use of NSAIDs remains restricted to their approved anti-inflammatory and analgesic effect.

Opportunities and challenges in Taiwan for implementing the learning health system.

Due to the low ratio of medical decisions made upon solid scientific evidence (4%) and the low efficiency of deploying knowledge in practice (17 years), the concept of a learning health system (LHS) was initiated to speed up knowledge generation and adoption and systematically approach continuous improvement in clinical practice. This concept can be illustrated by a so-called learning health cycle. This cycle, the first version as well as its variants, provides a framework for discussion on a common basis and has been well-accepted by the medical communities. Though the idea attracted major attention widely, very little has been done in way of actual adoption in real practices in the past 10 years. Nevertheless, as one of the pioneers in Taiwan, we have been involved in the effort to implement the LHS locally since 2016. In this article, we systematically summarize the evolution of the learning health cycle, review cases of its applications and briefly introduce the work we have done for promoting LHSs in Taiwan. Based on the experience we have gained, we try to identify the challenges and opportunities in Taiwan. While full-scale electronic medical records powered by the National Health Insurance system give Taiwan a special advantage in achieving a nationwide LHS, the medical community is not yet ready for a dramatic change. The lack of infrastructure for this use and motivation to take action right away makes the implementation of a LHS in Taiwan challenging.

Risk of Hemorrhagic Stroke in Patients Exposed to Nonsteroidal Anti-Inflammatory Drugs: A Meta-Analysis of Observational Studies.

BACKGROUND AND AIM: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most common pain relief medications, but the risk of hemorrhagic stroke in patients taking these medications is unclear. In this study, our aim was to systematically review, synthesize, and critique the epidemiological studies that evaluate the association between NSAIDs and hemorrhagic stroke risk. We therefore assessed the current state of knowledge, filling the gaps in our existing concern, and make a recommendation for future research. METHODS: We searched for articles in PubMed, EMBASE, Scopus, and Web of Science between January 1, 1990, and July 30, 2017, which reported on the association between the use of NSAIDs and hemorrhagic stroke. The search was limited to studies published in English. The quality of the included studies was assessed in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Summary risk ratios (RRs) with 95% CI were pooled using a random-effects model. Subgroup and sensitivity analyses were also conducted. RESULTS: We selected 15 out of the 785 unique abstracts for full-text review using our selection criteria, and 13 out of these 15 studies met all of our inclusion criteria. The overall pooled RR of hemorrhagic stroke was 1.332 (95% CI 1.105-1.605, p = 0.003) for the random effect model. In the subgroup analysis, a significant risk was observed among meloxicam, diclofenac, and indomethacin users (RR 1.48; 95% CI 1.149-1.912, RR 1.392; 95% CI 1.107-1.751, and RR 1.363; 95% CI 1.088-1.706). In addition, a greater risk was found in studies from Asia (RR 1.490, 95% CI 1.226-1.811) followed by Europe (RR 1.393, 95% CI 1.104-1.757) and Australia (RR 1.361, 95% CI 0.755-2.452). CONCLUSION: Our results indicated that the use of NSAIDs is significantly associated with a higher risk of developing hemorrhagic stroke. These results should be interpreted with caution because they may be confounded owing to the observational design of the individual studies. Nevertheless, we recommend that NSAIDs should be used judiciously, and their efficacy and safety should be monitored proactively.

Levothyroxine use and the risk of breast cancer: a nation-wide population-based case-control study.

PURPOSE: To investigate whether the use of levothyroxine was associated with breast cancer risk. METHODS: We conducted a population-based case-control study in Taiwan. Cases consisted of all patients who were aged 20 years and older, and had a first-time diagnosis of breast cancer for the period between 2001 and 2011. The controls were matched to the cases by age, sex, year, and month of diagnosis. Adjusted odd ratios (ORs) and 95% confidence intervals (CIs) were estimated by a conditional logistic regression. RESULTS: We examined 65,491 breast cancer cases and 261,964 controls. We found that use of levothyroxine was associated with a significant increase in breast cancer risk (OR 1.24, 95% CI 1.15-1.33; P < 0.001). Compared with no use levothyroxine, the adjusted odd ratio was 1.22 (95% CI 1.11-1.35; P = 0.01) for the group having been prescribed levothyroxine 2 months to 1 year, and 1.26 (95% CI 1.12-1.41; P < 0.01) for the group with more than 1 year. When stratified by age, the adjusted odd ratio was 1.45 (95% CI 1.23-1.71; P < 0.01) for the patients aged 65 years or more and 1.19 (95% CI 1.09-1.29, P < 0.01) for the patients aged less than 65 years. CONCLUSION: The results of the present study are the first to suggest that levothyroxine use increased the risk of breast cancer. However, a larger long-term prospective randomized-controlled trial specifically designed to assess the effect of levothyroxine use on the risk of developing breast cancer is needed.

Exploring the Association between Statin Use and the Risk of Parkinson's Disease: A Meta-Analysis of Observational Studies.

BACKGROUND: Parkinson's disease (PD) is a progressive disorder of the central nervous system. The prevalence of PD varies considerably by age group; it has a higher prevalence in patients aged 60 years and more. Several studies have shown that statin, a cholesterol-lowering medication, reduces the risk of developing PD, but evidence for this is so far inconclusive. The objective of this study is to evaluate the association between statin use and the risk of developing PD. METHODS: PubMed, EMBASE, and the bibliographies of articles were searched for studies published between January 1, 1990, and January 1, 2017, which reported on the association between statin use and PD. Articles were included if they (1) were published in English, (2) reported patients treated with statin, and the outcome of interest was PD, (3) provided OR/HR with 95% CI or sufficient information to calculate the 95% CI. All abstracts, full-text articles, and sources were reviewed, with duplicate data excluded. Summary relative risk (RRs) with 95% CI was pooled using a random-effects model. Subgroup and sensitivity analyses were also conducted. RESULTS: We selected 16 out of 529 unique abstracts for full-text review using our selection criteria, and 13 out of these 16 studies, comprising 4,877,059 persons, met all of our inclusion criteria. The overall pooled RR of PD was 0.70 (95% CI 0.58-0.84) with significant heterogeneity between estimates (I2 = 93.41%, p = 0.000) for the random-effects model. In subgroup analysis, the greater decreased risk was found in studies from Asia (RR 0.62 95% CI 0.51-0.76), whereas a moderate reduction was observed in studies from North America (RR 0.69 95% CI 0.47-1.00), but less reduction was observed in studies from Europe (RR 0.86 95% CI 0.80-0.92). Also, long-term statin use, simvastatin, and atorvastatin showed a higher rate of reduction with significance heterogeneity. CONCLUSION: Our results showed that statin use is significantly associated with a lower risk of developing PD. Physicians should consider statin drug therapy, monitor its outcomes, and empower their patients to improve their knowledge, therapeutic outcomes, and quality of life. However, preventive measures and their associated mechanisms must be further assessed and explored.

Benzodiazepines use and breast cancer risk: A population-based study and gene expression profiling evidence.

The aim of this study was to investigate whether long-term use of Benzodiazepines (BZDs) is associated with breast cancer risk through the combination of population-based observational and gene expression profiling evidence. We conducted a population-based case-control study by using 1998 to 2009year Taiwan National Health Insurance Research Database and investigated the association between BZDs use and breast cancer risk. We selected subjects age of >20years old and six eligible controls matched for age, sex and the index date (i.e., free of any cancer at the case diagnosis date) by using propensity scores. A bioinformatics analysis approach was also performed for the identification of oncogenesis effects of BZDs on breast cancer. We used breast cancer gene expression data from the Cancer Genome Atlas and perturbagen signatures of BZDs from the Library of Integrated Cellular Signatures database in order to identify the oncogenesis effects of BZDs on breast cancer. We found evidence of increased breast cancer risk for diazepam (OR, 1.16; 95%CI, 0.95-1.42; connectivity score [CS], 0.3016), zolpidem (OR, 1.11; 95%CI, 0.95-1.30; CS, 0.2738), but not for lorazepam (OR, 1.04; 95%CI, 0.89-1.23; CS, -0.2952) consistently in both methods. The finding for alparazolam was contradictory from the two methods. Diazepam and zolpidem trends showed association, although not statistically significant, with breast cancer risk in both epidemiological and bioinformatics analyses outcomes. The methodological value of our study is in introducing the way of combining epidemiological and bioinformatics approaches in order to answer a common scientific question. Combining the two approaches would be a substantial step towards uncovering, validation and further application of previously unknown scientific knowledge to the emerging field of precision medicine informatics.

Psychotropic medications prescribing trends in adolescents: A nationwide population-based study in Taiwan.

OBJECTIVE: To describe psychotropic medications prescription patterns among adolescents in Taiwan; focusing on age, gender, duration of treatments and various classes of psychotropic medications. DESIGN: A retrospective description analysis. SETTING: Taiwan National Health Insurance Database. PARTICIPANTS: Twelve to seventeen years' patients treated with psychotropic medications. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Percentage and duration of treatment with psychotropic medications during the study periods by medication classes and age groups were calculated. In addition, top three prescribed psychotropic medications were also determined. RESULTS: A total of 3,120 patients were prescribed psychotropic drugs. The percentage of adolescent patients that received anxiolytics and antidepressants in 2002-2012 were 2.89% and 2.15%, respectively. Also, 851 patients (1.21%) were prescribed hypnotics and 638 (0.91%) were given sedatives. The prevalence rate of the prescription of psychotropic drugs increased steadily with age and females were more treated than males except antipsychotic. Among psychotropic drugs, antidepressants (mean: 8.6 times) were refilled more but antipsychotics (mean 188 days) were the long-term treatment drugs. Additionally, the trend of hospital visits fluctuated over the year while May and December showed a higher rate of visits. CONCLUSIONS: These findings show that the prevalence of psychotropic drug prescriptions in Taiwanese adolescents is even low but increasing trends in the prescription of these medications raises some concern. As the evidence of psychotropic drug safety and effectiveness in adolescents is still inadequate; we recommend that healthcare providers should consider psychotropic drugs therapy, continuously monitor for outcomes and empower their patients to improve their knowledge, therapeutic outcomes and quality of life.

Exploring association between statin use and breast cancer risk: an updated meta-analysis.

PURPOSE: The benefits of statin treatment for preventing cardiac disease are well established. However, preclinical studies suggested that statins may influence mammary cancer growth, but the clinical evidence is still inconsistent. We, therefore, performed an updated meta-analysis to provide a precise estimate of the risk of breast cancer in individuals undergoing statin therapy. METHODS: For this meta-analysis, we searched PubMed, the Cochrane Library, Web of Science, Embase, and CINAHL for published studies up to January 31, 2017. Articles were included if they (1) were published in English; (2) had an observational study design with individual-level exposure and outcome data, examined the effect of statin therapy, and reported the incidence of breast cancer; and (3) reported estimates of either the relative risk, odds ratios, or hazard ratios with 95% confidence intervals (CIs). We used random-effect models to pool the estimates. RESULTS: Of 2754 unique abstracts, 39 were selected for full-text review, and 36 studies reporting on 121,399 patients met all inclusion criteria. The overall pooled risks of breast cancer in patients using statins were 0.94 (95% CI 0.86-1.03) in random-effect models with significant heterogeneity between estimates (I 2 = 83.79%, p = 0.0001). However, we also stratified by region, the duration of statin therapy, methodological design, statin properties, and individual stain use. CONCLUSIONS: Our results suggest that there is no association between statin use and breast cancer risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

An automated technique to identify potential inappropriate traditional Chinese medicine (TCM) prescriptions.

PURPOSE: Medication errors such as potential inappropriate prescriptions would induce serious adverse drug events to patients. Information technology has the ability to prevent medication errors; however, the pharmacology of traditional Chinese medicine (TCM) is not as clear as in western medicine. The aim of this study was to apply the appropriateness of prescription (AOP) model to identify potential inappropriate TCM prescriptions. METHODS: We used the association rule of mining techniques to analyze 14.5 million prescriptions from the Taiwan National Health Insurance Research Database. The disease and TCM (DTCM) and traditional Chinese medicine-traditional Chinese medicine (TCMM) associations are computed by their co-occurrence, and the associations' strength was measured as Q-values, which often referred to as interestingness or life values. By considering the number of Q-values, the AOP model was applied to identify the inappropriate prescriptions. Afterwards, three traditional Chinese physicians evaluated 1920 prescriptions and validated the detected outcomes from the AOP model. RESULT: Out of 1920 prescriptions, 97.1% of positive predictive value and 19.5% of negative predictive value were shown by the system as compared with those by experts. The sensitivity analysis indicated that the negative predictive value could improve up to 27.5% when the model's threshold changed to 0.4. CONCLUSION: We successfully applied the AOP model to automatically identify potential inappropriate TCM prescriptions. This model could be a potential TCM clinical decision support system in order to improve drug safety and quality of care.

A richly interactive exploratory data analysis and visualization tool using electronic medical records.

BACKGROUND: Electronic medical records (EMRs) contain vast amounts of data that is of great interest to physicians, clinical researchers, and medial policy makers. As the size, complexity, and accessibility of EMRs grow, the ability to extract meaningful information from them has become an increasingly important problem to solve. METHODS: We develop a standardized data analysis process to support cohort study with a focus on a particular disease. We use an interactive divide-and-conquer approach to classify patients into relatively uniform within each group. It is a repetitive process enabling the user to divide the data into homogeneous subsets that can be visually examined, compared, and refined. The final visualization was driven by the transformed data, and user feedback direct to the corresponding operators which completed the repetitive process. The output results are shown in a Sankey diagram-style timeline, which is a particular kind of flow diagram for showing factors' states and transitions over time. RESULTS: This paper presented a visually rich, interactive web-based application, which could enable researchers to study any cohorts over time by using EMR data. The resulting visualizations help uncover hidden information in the data, compare differences between patient groups, determine critical factors that influence a particular disease, and help direct further analyses. We introduced and demonstrated this tool by using EMRs of 14,567 Chronic Kidney Disease (CKD) patients. CONCLUSIONS: We developed a visual mining system to support exploratory data analysis of multi-dimensional categorical EMR data. By using CKD as a model of disease, it was assembled by automated correlational analysis and human-curated visual evaluation. The visualization methods such as Sankey diagram can reveal useful knowledge about the particular disease cohort and the trajectories of the disease over time.