Phung-Anh Nguyen

Benzodiazepine Use and Risk of Dementia in the Elderly Population: A Systematic Review and Meta-Analysis

Background: Benzodiazepines are a widely used medication in developed countries, particularly among elderly patients. However, benzodiazepines are known to affect memory and cognition and might thus enhance the risk of dementia. The objective of this review is to synthesize evidence from observational studies that evaluated the association between benzodiazepines use and dementia risk. Summary: We performed a systematic review and meta-analysis of controlled observational studies to evaluate the risk of benzodiazepines use on dementia outcome. All control observational studies that compared dementia outcome in patients with benzodiazepine use with a control group were included. We calculated pooled ORs using a random-effects model. Ten studies (of 3,696 studies identified) were included in the systematic review, of which 8 studies were included in random-effects meta-analysis and sensitivity analyses. Odds of dementia were 78% higher in those who used benzodiazepines compared with those who did not use benzodiazepines (OR 1.78; 95% CI 1.33-2.38). In subgroup analysis, the higher association was still found in the studies from Asia (OR 2.40; 95% CI 1.66-3.47) whereas a moderate association was observed in the studies from North America and Europe (OR 1.49; 95% CI 1.34-1.65 and OR 1.43; 95% CI 1.16-1.75). Also, diabetics, hypertension, cardiac disease, and statin drugs were associated with increased risk of dementia but negative association was observed in the case of body mass index. There was significant statistical and clinical heterogeneity among studies for the main analysis and most of the sensitivity analyses. There was significant statistical and clinical heterogeneity among the studies for the main analysis and most of the sensitivity analyses. Key Messages: Our results suggest that benzodiazepine use is significantly associated with dementia 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.

Is Long-term Use of Benzodiazepine a Risk for Cancer?

AbstractThe carcinogenicity of benzodiazepines (BZDs) is still unclear. We aimed to assess whether long-term benzodiazepines use is risk for cancer.We conducted a longitudinal population-based case-control study by using 12 years from Taiwan National Health Insurance database and investigated the association between BZDs use and cancer risk of people aged over 20 years. During the study period, 42,500 cases diagnosed with cancer were identified and analyzed for BZDs use. For each case, six eligible controls matched for age, sex, and the index date (ie, free of any cancer in the date of case diagnosis) by using propensity score. For appropriate risk estimation, we observed the outcomes according to their length of exposure (LOE) and defined daily dose (DDD). To mimic bias, we adjusted with potential confounding factors such as medications and comorbid diseases which could influence for cancer risk during the study period. The data was analyzed by using Cox proportional hazard regression and conditional logistic regression.The finding unveils benzodiazepines use into safe and unsafe groups for their carcinogenicity. The use of diazepam (HR, 0.96; 95%CI, 0.92–1.00), chlorodizepoxide (HR, 0.98; 95%CI, 0.92–1.04), medazepam (HR, 1.01; 95%CI, 0.84–1.21), nitrazepam (HR, 1.06; 95%CI, 0.98–1.14), oxazepam (HR, 1.05; 95%CI, 0.94–1.17) found safer among BZDs. However, clonazepam (HR, 1.15; 95%CI, 1.09–1.22) were associated with a higher risk for cancers. Moreover, specific cancer risk among BZDs use was observed significantly increased 98% for brain, 25% for colorectal, and 10% for lung, as compared with non-BZDs use.Diazepam, chlordiazepoxide, medazepam, nitrazepam, and oxazepam are safe among BZDs use for cancer risk. Our findings could help physicians to select safer BZDs and provide an evidence on the carcinogenic effect of benzodiazepines use by considering the LOE and DDD for further research.

Gender-based personalized pharmacotherapy: a systematic review

PurposeIn general, male and female are prescribed the same amount of dosage even if most of the cases female required less dosage than male. Physicians are often facing problem on appropriate drug dosing, efficient treatment, and drug safety for a female in general. To identify and synthesize evidence about the effectiveness of gender-based therapy; provide the information to patients, providers, and health system intervention to ensure safety treatment; and minimize adverse effects.MethodsWe performed a systematic review to evaluate the effect of gender difference on pharmacotherapy. Published articles from January 1990 to December 2015 were identified using specific term in MEDLINE (PubMed), EMBASE, and the Cochrane library according to search strategies that strengthen the reporting of observational and clinical studies.ResultsTwenty-six studies fulfilled the inclusion criteria for this systematic review, yielding a total of 6309 subjects. We observed that female generally has a lower the gastric emptying time, gastric PH, lean body mass, and higher plasma volume, BMI, body fat, as well as reduce hepatic clearance, difference in activity of Cytochrome P450 enzyme, and metabolize drugs at different rate compared with male. Other significant factors such as conjugation, protein binding, absorption, and the renal elimination could not be ignored. However, these differences can lead to adverse effects in female especially for the pregnant, post-menopausal, and elderly women.ConclusionThis systematic review provides anxa0evidence for the effectiveness of dosage difference to ensure safety and efficient treatment. Future studies on the current topic are, therefore, recommended to reduce the adverse effect of therapy.

Profiling phenome-wide associations: a population-based observational study.

OBJECTIVESnTo objectively characterize phenome-wide associations observed in the entire Taiwanese population and represent them in a meaningful, interpretable way.nnnSTUDY DESIGNnIn this population-based observational study, we analyzed 782 million outpatient visits and 15 394 unique phenotypes that were observed in the entire Taiwanese population of over 22 million individuals. Our data was obtained from Taiwans National Health Insurance Research Database.Results We stratified the population into 20 gender-age groups and generated 28.8 million and 31.8 million pairwise odds ratios from male and female subpopulations, respectively. These associations can be accessed online at http://associations.phr.tmu.edu.tw. To demonstrate the database and validate the association estimates obtained, we used correlation analysis to analyze 100 phenotypes that were observed to have the strongest positive association estimates with respect to essential hypertension. The results indicated that association patterns tended to have a strong positive correlation between adjacent age groups, while correlation estimates tended to decline as groups became more distant in age, and they diverged when assessed across gender groups.nnnCONCLUSIONSnThe correlation analysis of pairwise disease association patterns across different age and gender groups led to outcomes that were broadly predicted before the analysis, thus confirming the validity of the information contained in the presented database. More diverse individual disease-specific analyses would lead to a better understanding of phenome-wide associations and empower physicians to provide personalized care in terms of predicting, preventing, or initiating an early management of concomitant diseases.

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

BackgroundElectronic 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.MethodsWe 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.ResultsThis 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.ConclusionsWe 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.

Interactions between traditional Chinese medicine and western drugs in Taiwan

BACKGROUNDnDrug-drug interactions have long been an active research area in clinical medicine. In Taiwan, however, the widespread use of traditional Chinese medicines (TCM) presents additional complexity to the topic. Therefore, it is important to see the interaction between traditional Chinese and western medicine.nnnOBJECTIVEn(1) To create a comprehensive database of multi-herb/western drug interactions indexed according to the ways in which physicians actually practice and (2) to measure this databases impact on the detection of adverse effects between traditional Chinese medicine compounds and western medicines.nnnMETHODSnFirst, a multi-herb/western medicine drug interactions database was created by separating each TCM compound into its constituent herbs. Each individual herb was then checked against an existing single-herb/western drug interactions database. The data source comes from the National Health Insurance research database, which spans the years 1998-2011. This study estimated the interaction prevalence rate and further separated the rates according to patient characteristics, distribution by county, and hospital accreditation levels. Finally, this new database was integrated into a computer order entry module of the electronic medical records system of a regional teaching hospital. The effects it had were measured for two months.nnnRESULTSnThe most commonly interacting Chinese herbs were Ephedrae Herba and Angelicae Sinensis Radix/Angelicae Dahuricae Radix. Ephedrae Herba contains active ingredients similar to in ephedrine. 15 kinds of traditional Chinese medicine compounds contain Ephedrae Herba. Angelicae Sinensis Radix and Angelicae Dahuricae Radix contain ingredients similar to coumarin, a blood thinner. 9 kinds of traditional Chinese medicine compounds contained Angelicae Sinensis Radix/Angelicae Dahuricae Radix. In the period from 1998 to 2011, the prevalence of herb-drug interactions related to Ephedrae Herba was 0.18%. The most commonly prescribed traditional Chinese compounds were MA SHING GAN SHYR TANG (23.1%), followed by SHEAU CHING LONG TANG (15.5%) and DINQ CHUAN TANG (13.2%). The prevalence of herb-drug interactions related to Angelicae Sinensis Radix, Angelicae Dahuricae Radix was 4.59%. The most common traditional Chinese compound formula were TSANG EEL SAAN (32%), followed by HUOH SHIANG JENQ CHIH SAAN (31.4%) and SHY WUH TANG (10.7%). Once the multi-herb drug interaction database was deployed in a hospital system, there were 480 prescriptions that indicated a TCM-western drug interaction. Physicians were alerted 24 times during two months. These alerts resulted in a prescription change four times (16.7%).nnnCONCLUSIONnDue to the unique cultural factors that have resulted in widespread acceptance of both western and traditional Chinese medicine, Taiwan stands well positioned to report on the prevalence of interactions between western drugs and traditional Chinese medicine and devise ways to reduce their incidence. This study built a multi-herb/western drug interactions database, embedded inside a hospital clinical information system, and then examined the effects that drug interaction alerts had on clinician prescribing behaviour. The results demonstrated that western drug/traditional Chinese medicine interactions are prevalent and that western-trained physicians tend to change their prescribing behaviour more than traditional Chinese medicine physicians in their response to medication interaction alerts.

Cloud-based BP system integrated with CPOE improves self-management of the hypertensive patients

BACKGROUNDnLess than 50% of patients with hypertensive disease manage to maintain their blood pressure (BP) within normal levels.nnnOBJECTIVEnThe aim of this study is to evaluate whether cloud BP system integrated with computerized physician order entry (CPOE) can improve BP management as compared with traditional care.nnnMETHODSnA randomized controlled trial done on a random sample of 382 adults recruited from 786 patients who had been diagnosed with hypertension and receiving treatment for hypertension in two district hospitals in the north of Taiwan. Physicians had access to cloud BP data from CPOE. Neither patients nor physicians were blinded to group assignment. The study was conducted over a period of seven months.nnnRESULTSnAt baseline, the enrollees were 50% male with a mean (SD) age of 58.18 (10.83) years. The mean sitting BP of both arms was no different. The proportion of patients with BP control at two, four and six months was significantly greater in the intervention group than in the control group. The average capture rates of blood pressure in the intervention group were also significantly higher than the control group in all three check-points.nnnCONCLUSIONSnCloud-based BP system integrated with CPOE at the point of care achieved better BP control compared to traditional care. This system does not require any technical skills and is therefore suitable for every age group. The praise and assurance to the patients from the physicians after reviewing the Cloud BP records positively reinforced both BP measuring and medication adherence behaviors.

The concomitant association of thyroid disorders and Myasthenia gravis

Abstract Background Some of the thyroid disorders (TD) and Myasthenia gravis (MG) are autoimmune related disease. The purpose of the study to evaluate the relationship of MG with all morphological and functional thyroid disorders. Methods: We constructed a population-based cohort study during the period from January 2000-December 2002 by using reimbursement data from the Bureau National Health Insurance (NHI) system in Taiwan. Patients with TD and MG were identified by referring to the ICD-9-CM codes. (ICD-10-CM as reference) .The association of TD with MG occurred only in the same person within the study period. The Q value was used to measure the strength of disease-disease associations. Results We obtained 520628 TD and 7965 MG records for analysis. Diffuse toxic goiter had highest association rate, followed by nontoxic nodular goiter, simple goiter, chronic lymphocytic thyroiditis, thyroid cancer, and toxic nodular goiter. Female and older patients had a higher rate than their male and younger counterparts, respectively. Functional abnormalities revealed higher incidence of thyrotoxicosis and hypothyroidism in both sexes. We also found the strongest association in men with chronic thyroiditis, diffuse toxic goiter, thyrotoxicosis, acquired hypothyroidism, thyroid cancer, and simple goiter. While an intermediate association was observed in female with diffuse toxic goiter, in a male with toxic and nontoxic nodular/multinodular goiters, in female with thyrotoxicosis, thyroid cancer and acquired hypothyroidism. Conclusion This population based cohort study showed potential association of all types of TD with MG, and observed a higher association rate in female autoimmune TD whereas males showed a higher strength of association.

Contents Vol. 47, 2016

125 New Zealand Applied Neurosciences Conference Auckland, New Zealand, November 24–26, 2016 Editors: Feigin, V.L.; Barber, P.A. (Auckland)