Impacts of doctor-shopping behavior on diabetic patients' health: A retrospective longitudinal study in Taiwan.

The aim of this study was to clarify the relationship between doctor-shopping behavior and clinical conditions, and to clearly outline the effects of both the number of clinic visits and the number of doctor changes on patients' health conditions. Data from January 1, 2000 to December 31, 2004 was collected from the National Health Insurance Research Database in Taiwan. After randomly selecting one million people, we extracted 5-year longitudinal data, about the number of clinic visits, number of doctor changes, and changes in self-health status for each patient with diabetes over the age of 18. We developed a relationship among the variables by using the generalized estimating equation. The results revealed that the number of clinic visits on the change of health status is a U curve, suggesting that health condition could be optimal with an appropriate number of clinic visits. The effect of the number of doctor changes is linearly correlated with health deterioration. The results suggest that disease conditions can only be controlled with an adequate number of clinic visits. Excessively frequent clinic visits are not only unfavorable to patients' health status but are also wasteful of limited medical resources. For diabetic mellitus patients, the more they change doctors, the worse their health status. All of these results are important for patients to stay healthy and to save medical resources.

A study on the impact of poor medication adherence on health status and medical expense for diabetes mellitus patients in Taiwan: A longitudinal panel data analysis.

Medication adherence plays an important role in disease management, especially for diabetes. The aim of this study was to examine the impacts of demographic characteristics on medication nonadherence and the impacts of nonadherence on both health status and medical expenses for diabetic patients in Taiwan.A total of 1 million diabetes mellitus patients were randomly selected from the National Health Insurance Research Database between January 1, 2000 and December 31, 2004. All records with missing values and those for participants under 18 years of age were then deleted. Because many patients had multiple clinical visit records, all records within the same calendar year were summarized into 1 single record for each person. This pre-processing resulted in 14,602 total patients with a combined 73,010 records over the course of 5 years. Generalized estimating equation models were then constructed to investigate the effects of demographic characteristics on medication nonadherence and the effects of nonadherence on patient health status and medical expenses. The demographic characteristics examined for each patient include gender, age, residential area, and socioeconomic status.Our analysis of how demographic variables impacted nonadherence revealed that elderly patients exhibited better overall medication adherence, but that male patients exhibited poorer medication adherence than female patients. Next, our analysis of how nonadherence impacted health status revealed that patients who exhibited medication nonadherence had poorer health status than patients with proper medication adherence. Finally, our analysis of how nonadherence impacted medical expenses revealed that patients who exhibited medication nonadherence incurred more medical expenses than those who exhibited proper medication adherence.This study's empirical results corroborate the general relationships expressed in the current literature regarding medication nonadherence. However, this study's results were statistically more reliable and revealed the precise impact on health status in terms of the Charlson comorbidity index and increased annual medical expenses. This indicates the need to improve patient attitudes toward medication adherence, which can have substantial effects both medically and economically.

Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N-Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR Inhibition.

BACKGROUND/AIMS: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. METHODS: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan's National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. RESULTS: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. CONCLUSION: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.

Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells.

BACKGROUND: N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo and in vitro. The effect of BP in bladder cancer treatment is still unclear and worth for further investigate. METHODS: Changes of patients with bladder cancer after Angelica Sinensis exposure were evaluated by analysis of Taiwan's National Health Insurance Research Database (NHIRD) database. The anti-proliferative effect of BP on human bladder cancer cells was investigated and their cell cycle profiles after BP treatment were determined by flow cytometry. BP-induced apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the expressions of apoptosis-related proteins were determined by western blot. The migration inhibitory effect of BP on human bladder cancer cells were shown by trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by injection of BFTC human bladder cancer cells. RESULTS: The correlation of taking Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this herbal product is worth for further investigation. BP caused bladder cancer cell death in a time- and dose- dependent manner and induced apoptosis via the activation of caspase-9 and caspase-3. BP also suppressed the migration of bladder cancer cells as revealed by the trans-well and wound healing assays. Up-regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real-time RT-PCR analysis after BP treatment in vitro. Besides, in combination with BP, the sensitivity of these bladder cancer cells to cisplatin increased significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2% reduction of tumor volume after treatment for 26 days. CONCLUSIONS: BP caused bladder cancer cell death through activation of mitochondria-intrinsic pathway. BP also suppressed the migration and invasion of these cells, probably by modulating EMT-related genes. Furthermore, combination therapy of BP with a lower dose of cisplatin significantly inhibited the growth of these bladder cancer cell lines. The incidence of bladder cancer decreased in patients who were exposed to Angelica sinensis, suggesting that BP could serve as a potential adjuvant in bladder cancer therapy regimen.

Zolpidem and the risk of Parkinson's disease: a nationwide population-based study.

BACKGROUND: This nationwide population-based study investigated the risk of Parkinson's disease (PD) after zolpidem use in patients with sleep disturbance using the National Health Insurance Research Database (NHIRD) in Taiwan. MATERIAL AND METHODS: In total, 59,548 adult patients newly diagnosed with sleep disturbance and who used zolpidem were recruited as the study cohort, along with 42,171 subjects who did not use zolpidem as a comparison cohort from 2002 to 2009. Each patient was monitored for 5 years, and those who subsequently had PD were identified. A Cox proportional hazards model was used to compare the risk of PD between the study and comparison cohorts after adjusting for possible confounding risk factors. RESULTS: The patients who received zolpidem had a higher cumulative rate of PD than those who did not receive zolpidem during the 5-year follow-up period (1.2% vs. 0.5%, P < 0.001). The adjusted hazard ratios were 1.10 (95% CI, 0.88-1.37), 1.41 (95% CI, 1.17-1.72), and 1.27 (95% CI, 1.05-1.55) for zolpidem use with 28-90, 91-365, and more than 365 cumulative defined daily doses (cDDDs), respectively, compared to those who did not use zolpidem. CONCLUSIONS: Among the patients with sleep disturbance, zolpidem use increased the risk of PD after 5 years of follow-up. Further mechanistic research of zolpidem effect in PD is needed.