The Use of San-Huang-Xie-Xin-Tang Reduces the Mortality Rate among Breast Cancer Patients.

Globally, breast cancer is the most common cause of cancer deaths. In Taiwan, it is the most prevalent cancer among females. Since San-Huang-Xie-Xin-Tang (SHXXT) exerts not only an anti-inflammatory but an immunomodulatory effect, it may act as a potent anti-tumor agent. Herein, the study aimed to explore the influence of SHXXT and its constituents on the mortality rate among breast cancer patients in Taiwan regarding the component effect and the dose-relationship effect. By using the Taiwan National Health Insurance (NHI) Research Database (NHIRD), the study analyzed 5387 breast cancer patients taking Chinese herbal medicine (CHM) and 5387 breast cancer patients not using CHM. CHM means SHXXT and its constituents in the study. The Kaplan-Meier method was utilized to determine the mortality probabilities among patients. Whether the CHM influences the mortality rate among patients was estimated by Cox proportional hazard regression analysis. The use of CHM could lower the cancer mortality rate by 59% in breast cancer patients. The protective effect was parallel to the cumulative days of CHM use and the annual average CHM dose. In addition, the mortality rate was lower in patients who used SHXXT compared to those who only used one of its constituents. SHXXT and its constituents were all promising therapeutic weapons against breast cancer.

Mortality Risk and Decompensation in Hospitalized Patients with Non-Alcoholic Liver Cirrhosis: Implications for Disease Management.

Here we aimed to assess the mortality risk and distribution of deaths from different complications and etiologies for non-alcoholic liver cirrhosis (NALC) adult inpatients and compare them with that of the general hospitalized adult population. Hospitalized patients with a primary diagnosis of NALC and aged between 30 and 80 years of age from 1999 to 2010 were identified using a population-based administrative claims database in Taiwan. They were matched with a general, non-NALC population of hospitalized patients. Causes of death considered were variceal hemorrhage, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatocellular carcinoma, jaundice, and hepatorenal syndrome. A total of 109,128 NALC inpatients were included and then matched with 109,128 inpatients without NALC. Overall mortality rates were 21.2 (95% CI: 21.0-21.4) and 6.27 (95% CI: 6.17-6.37) per 100 person-years, respectively. Among complications that caused death in NALC patients, variceal hemorrhage was the most common (23.7%, 11.9 per 100 person-years), followed by ascites (20.9%, 10.4 per 100 person-years) and encephalopathy (18.4%, 9.21 per 100 person-years). Among all etiologies, mortality rates were highest for NALC patients with HBV infection (43.7%, 21.8 per 100 person-years), followed by HBV-HCV coinfection (41.8%, 20.9 per 100 person-years), HCV infection (41.2%, 20.6 per 100 person-years), and NAFLD (35.9%, 17.9 per 100 person-years). In this study, we demonstrated that mortality risks in NALC patients may differ with their etiology and their subsequent complications. Patients' care plans, thus, should be formulated accordingly.

Forgone Health and Economic Benefits Associated with Socioeconomic Differences in Organized Cervical Cancer Screening.

OBJECTIVE: To describe cervical cancer screening participation among women in Taiwan under its population-based screening policy and to estimate the economic burden of disease attributable to avoidable disparities in cervical cancer (CC) screening. METHODS: We identified a nationally-representative sample of females aged 30 years or above who were eligible for Pap smear testing in Taiwan from 1 January to 31 December 2013. An administrative database with detailed claims of health care utilization under the universal coverage health care system was used. Socioeconomic position of the female subjects was defined using the occupation classification, and two groups were specifically identified: general (O1) and low-income (O5) groups. Differences in screening rate, CC prevalence, and CC-attributable deaths were assessed between the two groups. Economic consequences as a result of screening inequalities were estimated using actual total health care spending (health care expenditure), monetary value per life-year and years of life lost for ill health and screening disparities (health as consumption good), and productivity losses alongside costs of social benefits (health as capital good). RESULT: A total of 301,057 enrolled females aged 30 years and older eligible for screening were identified. Overall, 3-year and 1-year screening rates among all subjects were 0.601 and 0.372, respectively. Impact of observed differences in screening translated to US$59,568 of health care spending in one year, 90.4% of which was specific to hospital admissions. When we viewed health as a consumption good and capital good, the impact of screening disparity on health losses through CC would be equivalent to US$78,095 and US$190,868, respectively. CONCLUSION: Forgone health and economic benefits associated with inequalities in CC screening uptake can be considerable in productive women.

Integrative Chinese herbal medicine therapy reduced the risk of type 2 diabetes mellitus in patients with polycystic ovary syndrome: A nationwide matched cohort study.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common condition that affects 5%-10% of women of reproductive age worldwide. Patients with PCOS have a high degree of insulin resistance and are at an increased risk of developing type 2 diabetes mellitus (T2DM). The currently available therapeutic approaches for PCOS mainly focus on symptomatic treatment. AIM OF THE STUDY: This study aimed to determine whether Chinese herbal medicine (CMH)-based interventions could reduce the risk of T2DM in PCOS patients. MATERIALS AND METHODS: This retrospective study randomly selected 1 million enrollees from the National Health Insurance Database and identified 3797 patients who were newly diagnosed with PCOS in 1997-2010. After 1:1 frequency-matched by age, diagnosis of PCOS year and index days, we selected 342 eligible patients in each group. RESULTS: The incidence of T2DM in the CHM group was significantly lower than that in the non-CHM group (hazard ratio = 0.31; 95% confidence interval, 0.15-0.64; p = 0.0014) after a mean follow-up period of 5.2 years (4.20 years for the comparison cohort). Five herbal formulas and two single herbs showed protective effects, and Paeonia lactiflora was a common ingredient in the five formulas. CONCLUSIONS: Thus, CHM may help prevent T2DM-related complications in patients with PCOS. Further clinical and pharmacological analysis based on these findings is expected in the future.

Adjunctive Chinese herbal medicine therapy for nasopharyngeal carcinoma: Clinical evidence and experimental validation.

BACKGROUND: To investigate the benefits of adjunctive Chinese herbal medicine (CHM) for patients with nasopharyngeal carcinoma (NPC). METHODS: We included all patients diagnosed with NPC during 1997-2009 and followed until 2011 in Taiwan. We used 1:1 frequency matching by age, sex, comorbidity, conventional treatment, and index year to compare the CHM users and non-CHM users (n = 2542 each). The prescribed CHM was further investigated with regard to its cytotoxicity. RESULTS: Compared with non-CHM users, adjunctive CHM users had a lower hazard ratio of mortality risk, and a better survival probability. Gan-Lu-Yin (GLY) was the most commonly prescribed CHM, and it reduced cell viability, inhibited tumor proliferation, and induced apoptosis through the poly (ADP-ribose) polymerase and caspase-3-dependent pathway in human NPC TW01 cells. Oral administration of GLY retarded NPC-TW01 tumor growth in the xenograft nude mouse model. CONCLUSION: Real-world data and laboratory experiments implied that adjunctive CHM might be beneficial for NPC patients.

Association of Traditional Chinese Medicine Therapy with Risk of Total Hip Replacement in Patients with Nontraumatic Osteonecrosis of the Femoral Head: A Population-Based Cohort Study.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) contributes to 45% of total hip replacements (THRs) annually in Taiwan. Nontraumatic ONFH (NONFH) is multifactorial; no effective Western medicine is available to delay the disease process. This population-based cohort study investigated the association of traditional Chinese medicine (TCM) therapy with risk of THR in patients with NONFH. METHODS: This retrospective study was conducted using claims data from all insured residents covered by the National Health Insurance from 2000 to 2010. We enrolled 1,680 newly diagnosed ONFH patients who had not undergone THR, before or within 6 months after diagnosis of ONFH; these patients did not exhibit hip fracture or dislocation before the endpoint. In total, 595 propensity score-matched pairs were selected from among 1,028 TCM users and 652 non-TCM users. The association between TCM use and risk of THR was analyzed using a Cox proportional hazard model. Kaplan-Meier and log rank tests were performed to plot the cumulative incidence of THR. RESULTS: The mean follow-up periods were 5.00 years and 3.57 years for TCM and non-TCM cohorts, respectively. Compared to the non-TCM cohort, the TCM cohort had fewer patients undergoing THR surgery (25.4% vs. 18.2%, adjusted hazard ratio: 0.60, p<0.0001). The risk of reduction was noted in the group aged 30-59 years (adjusted hazard ratio: 0.56, p<0.0001), but there was no association with gender nor socioeconomic status. There was a significantly lower cumulative incidence of THR in TCM users (p<0.0001). Shu-Jing-Huo-Xue-Tang and Yan Hu Suo were the most frequently prescribed formula and single herb, respectively. CONCLUSIONS: NONFH patients using TCM had a lower risk of THR; the risk of reduction was noted in the group aged 30-59 years but was not associated with gender nor socioeconomic status. TCM might be useful in conservative treatment for NONFH.

Acupuncture treatment is associated with a decreased risk of developing stroke in patients with depression: A propensity-score matched cohort study.

BACKGROUND: Depression had a significantly increased risk of stroke. Some patients with depression seek acupuncture treatment. The aim of this study is to investigate the association between acupuncture treatment and risk of developing stroke in patients with depression. METHODS: Patients with newly diagnosed depression above 18 years old between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database, and followed up until the end of 2013. The 1:1 propensity score method was used to match an equal number of patients (N = 13,823) in the acupuncture and non-acupuncture cohorts, based on characteristics including sex, age, baseline comorbidity and drug used. The outcome measurement was the comparison of stroke incidence in the two cohorts. We used the Cox regression model and the Kaplan-Meier method to estimate the risk of developing stroke. RESULTS: Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a lower risk of stroke (adjusted hazard ratio (HR) = 0.49, 95% confidential interval = 0.45-0.52) after adjustment for age, sex, comorbidities and drugs used. Regarding the two types of stroke, acupuncture users also had lower risk of hemorrhagic or ischemic stroke (adjusted HR = 0.37 and 0.49, respectively). The cumulative incidence of stroke in the acupuncture cohort was significantly lower than that of the non-acupuncture cohort (log-rank test, p < 0.001). At the 5th year of follow-up, 7.22% of acupuncture users had stroke onset compared with 14% in the non-acupuncture cohort. LIMITATIONS: The database provided information of antidepressants but not the severity of depression. Details of the life style and selection of acupoints were also not provided. CONCLUSIONS: The present study revealed that acupuncture reduced the risk of developing stroke in depression patients in Taiwan. Further clinical studies investigating the mechanisms and efficacy of acupuncture are warranted.

All-cause mortality of insulin plus dipeptidyl peptidase-4 inhibitors in persons with type 2 diabetes.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors could effectively reduce HbA1C and postprandial hyperglycemia and could incur only minimal danger of hypoglycemia. Patients with uncontrolled diabetes might be treated by the complementary action of insulin plus DPP-4 inhibitors. Here, we compared the all-cause mortality risk between DPP-4 inhibitor users and nonusers with underlying insulin therapy. METHODS: Using the population-based National Health Insurance Research Database of Taiwan, we conducted an 11-year retrospective cohort study. A total of 3120 patients undergoing insulin therapy for type 2 diabetes mellitus (T2DM) during 2000-2010 were enrolled. The overall incidence rates for all-cause mortality of 1560 DPP-4 inhibitor users and 1560 matched DPP-4 inhibitor nonusers were compared. RESULTS: No significant difference was found in the baseline demographic and clinical variables of the two groups of patients. Median follow-up period for the matched cohort was 1.67 years. All-cause mortality was observed in 93 (6.0%) of 1560 DPP-4 inhibitor nonusers and 36 (2.3%) of 1560 DPP-4 users. The incidence rate of mortality was 11.72 for DPP-4 inhibitor users and 38.16 per 1000 person-years for DPP-4 inhibitor nonusers. After multivariate adjustment, DPP-4 inhibitor users ran a reduced mortality risk (adjusted hazard ratio 0.32, 95% CI 0.22-0.47; p < 0.0001) than did the nonusers. CONCLUSION: Risk of all-cause mortality may be reduced when using insulin plus DPP-4 inhibitors than when using insulin plus non-DPP-4 inhibitors.

Systemic autoimmune diseases are associated with an increased risk of obsessive-compulsive disorder: a nationwide population-based cohort study.

PURPOSE: Studies suggested autoimmunity plays a role in the etiology of obsessive-compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD. METHODS: Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41-2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07-2.54) dermatomyositis (3.25, 1.04-10.17), and Sjögren's syndrome (2.38, 1.53-3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD. CONCLUSIONS: This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Risk of obstructive sleep apnea in patients with bipolar disorder: A nationwide population-based cohort study in Taiwan.

AIM: Previous studies have found a high prevalence of risk factors for obstructive sleep apnea (OSA) in patients with bipolar disorder (BD). This study aimed to determine whether BD patients are associated with an increased risk of incident OSA. METHODS: Using the National Health Insurance Research Database of Taiwan, 3650 BD patients and 18 250 non-BD controls matched by sex and age were enrolled between 2000 and 2010 and followed until the end of 2013. Patients who developed OSA confirmed by a polysomnographic examination during the follow-up period were identified. Cox regression analysis was performed to examine the risk of OSA between BD patients and comparative controls. RESULTS: BD patients were prone to developing OSA in the crude analysis (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.07-2.49). After adjusting for demographics and comorbidities, the HR declined and was only marginally significant (HR: 1.54, 95%CI: 0.99-2.37). The stratification analysis by sex revealed that the risk trend with BD and subsequent OSA was mainly contributed by male BD patients (HR: 1.72, 95%CI: 1.02-2.91) and female BD patients weakened the overall association. Additionally, this study found that older age, higher income, living in urbanized areas, and some metabolic comorbidities were potential risk factors for developing OSA. CONCLUSION: This study shows that male BD patients are associated with an increased risk of OSA, which has direct implications for the development of targeted prevention interventions or the implementation of a screening algorithm for OSA to reduce its negative health impact.

Hyperthyroidism is not a significant risk of benign prostatic hyperplasia: A nationwide population-based study.

Benign prostatic hyperplasia (BPH) is a common disorder in the aging male population. Despite evidence that thyroid status impacts the prostate, the objective of this study was to examine whether patients with hyperthyroidism were at a greater risk for BPH.This study is a retrospective nationwide population-based cohort study of the Chinese population. Data for this study were retrieved from the Taiwan National Health Insurance Research Database (NHIRD). Overall, 1032 male patients aged 40 years or older with hyperthyroidism diagnosed between 2000 and 2006 were included in the hyperthyroidism group, and 4128 matched controls without hyperthyroidism were included in the non-hyperthyroidism group. Both groups were monitored until the end of 2011. A Cox proportional hazards regression model was used to compute and compare the risk of BPH between study participants with and those without hyperthyroidism.Patients with hyperthyroidism exhibited a greater incidence of BPH (18.51% vs 15.53%) than did the controls. Furthermore, the hazard ratio (HR) of the hyperthyroidism group was 1.24 times that of the control group [95% confidence interval (95% CI 1.05-1.46)] signifying that there is a significant 24% increase in the risk of BPH with the presence of hyperthyroidism. This increased risk of BPH with hyperthyroidism, however, failed to remain significant (adjusted HR = 1.11, 95% CI = 0.94-1.3) after adjusting for covariates of age (adjusted HR = 2.72, 95% CI = 2.32-3.2), diabetes (adjusted HR = 1.4, 95% CI = 1.17-1.68), hypertension (adjusted HR = 1.74, 95% CI = 1.49-2.03), hyperlipidemia (adjusted HR = 1.25, 95% CI = 1.03-1.53), neurogenic bladder, cystitis (adjusted HR = 1.23, 95% CI = 0.58-2.59), urethral stricture (adjusted HR = 2.01, 95% CI = 0.28-14.47), urethritis (adjusted HR = 1.52, 95% CI = 0.72-3.21), and urinary tract infection (adjusted HR = 1.77, 95% CI = 1.31-2.39).After adjustment for comorbidities and covariates, hyperthyroidism was not found to be a significant risk factor of BPH in our male study subjects. Further research is warranted to validate our results and elucidate the association of the pathophysiology of these 2 diseases.

HGK-sestrin 2 signaling-mediated autophagy contributes to antitumor efficacy of Tanshinone IIA in human osteosarcoma cells.

Tanshinone IIA (TIIA) is a diterpenoid naphthoquinone isolated from the herb Salvia miltiorrhiza with antitumor effects manifested at multiple levels that are mechanistically obscure. In our previous studies, we illustrated that TIIA treatment triggered apoptosis in human osteosarcoma 143B cells both in vitro and in vivo, accompanied with mitochondrial dysfunction. Importantly, the overall survival rate of patients with osteosarcoma who were randomly recruited to S. miltiorrhiza treatment was significantly higher than those without. Pursuing this observation, we evaluated the potential effect of TIIA on autophagy induction in osteosarcoma both in vivo and in vitro. We discovered that TIIA inhibited osteosarcoma cell survival through class I PI3K and Akt signaling pathways. In contrast, expression of class III PI3K required in the early stages of autophagosome generation was predominantly enhanced by TIIA treatment. Our study indicated that treatment of TIIA effectively induced autophagy in human osteosarcoma cells, which contributed to the blockade of anchorage-independent growth of osteosarcoma cells and ameliorated tumor progression in NOD/SCID mice. We demonstrated that TIIA-mediated autophagy occurred in a sestrin 2 (SESN2)-dependent but not Beclin 1-dependent manner. In addition, we defined the activation of HGK (MAP4K4 or mitogen-activated protein kinase kinase kinase kinase)/SAPK/JNK1/Jun kinase pathways in upregulating transcription of SESN2, in which TIIA triggered HGK/JNK1-dependent Jun activation and led to increased Jun recruitment to AP-1-binding site in the SESN2 promoter region. Our results offer novel mechanistic insight into how TIIA inhibits osteosarcoma growth and suggest TIIA as a promising therapeutic agent for the treatment of cancer.

Schizophrenia is associated with an increased risk of sexually transmitted infections: A nationwide population-based cohort study in Taiwan.

OBJECTIVES: In Taiwan, there has been a growing emphasis on physical health screening, health education and improving access to treatment in patients with schizophrenia (SCZ). However, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are neglected in this population. The study aimed to investigate the association between SCZ and the subsequent incident STI and to examine potential risk factors. METHODS: Using the National Health Insurance Research Database of Taiwan, 58,948 SCZ patients and 235,784 controls matched by gender and age were enrolled between 2000 and 2010 and followed until the end of 2011. Participants who developed any STI (HIV, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis) during the follow-up period were identified. Cox regression analysis was performed to examine the risk of STI between SCZ patients and controls. RESULTS: SCZ patients were predisposed to developing STI (hazard ratio (HR): 1.11, 95% confidence interval (95% CI): 1.01-1.21) that could be caused by syphilis (HR: 2.58, 95% CI: 2.14-3.10) or possibly HIV (Crude HR: 1.39, 95% CI: 1.04-1.86; adjusted HR: 1.11, 95% CI: 0.81-1.52). Additionally, this study found that female, young adults, low-income, living in less urbanized areas, and comorbid substance abuse were potential risk factors for developing STI. CONCLUSION: This study shows that SCZ is associated with an increased risk of developing STI, which has direct implications for the development of targeted prevention interventions or regular sexual health screening in mental health clinics to reduce the disproportionate burden of HIV and other STI in SCZ patients.

Autoimmune diseases are associated with an increased risk of schizophrenia: A nationwide population-based cohort study.

OBJECTIVES: Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. METHODS: Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23-2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07-6.72), rheumatoid arthritis (2.89, 1.97-4.23), dermatomyositis (5.85, 1.32-25.94) and autoimmune vasculitis (2.44, 1.17-5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. CONCLUSIONS: This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances.

A Controlled Trial of Sheng-Yu-Tang for Post-Hematopoietic Stem Cell Transplantation Leukemia Patients: A Proposed Protocol and Insights From a Preliminary Pilot Study.

INTRODUCTION: Hematopoietic stem cell transplantation has become a well-established treatment for hematologic disorders including acute leukemia. However, long-term survival rates following this procedure are still extremely low, due to posttransplantation relapse, infections, and graft-versus-host disease. We propose that adjunctive Chinese herbal medicine may benefit posttransplantation patients. In preparation for a randomized clinical trial, we conducted a pilot trial. Methods and Analysis: Between September 2015 and June 2017, 18 patients were consecutively enrolled at China Medical University Hospital and followed for up to 1 year. Fresh blood samples were obtained on a monthly basis, and immune reconstitution was analyzed. In addition to the standard-care treatment administered by their oncologist, a number of patients also received a Chinese herbal formula (Sheng-Yu-Tang) for up to 6 months. Results were used to improve on study protocol and estimate required sample size for a future randomized trial. Ethics and Dissemination: Study protocol was approved by the institutional review board of China Medical University Hospital (DMR-105-005), and all participants provided informed consent.

Complementary Chinese Herbal Medicine Therapy Improves Survival of Patients With Pancreatic Cancer in Taiwan: A Nationwide Population-Based Cohort Study.

BACKGROUND: Pancreatic cancer is a difficult-to-treat cancer with a late presentation and poor prognosis. Some patients seek traditional Chinese medicine (TCM) consultation. We aimed to investigate the benefits of complementary Chinese herbal medicine (CHM) among patients with pancreatic cancer in Taiwan. METHODS: We included all patients with pancreatic cancer who were registered in the Taiwanese Registry for Catastrophic Illness Patients Database between 1997 and 2010. We used 1:1 frequency matching by age, sex, the initial diagnostic year of pancreatic cancer, and index year to enroll 386 CHM users and 386 non-CHM users. A Cox regression model was used to compare the hazard ratios (HRs) of the risk of mortality. The Kaplan-Meier curve was used to compare the difference in survival time. RESULTS: According to the Cox hazard ratio model mutually adjusted for CHM use, age, sex, urbanization level, comorbidity, and treatments, we found that CHM users had a lower hazard ratio of mortality risk (adjusted HR = 0.67, 95% CI = 0.56-0.79). Those who received CHM therapy for more than 90 days had significantly lower hazard ratios of mortality risk than non-CHM users (90- to 180-day group: adjusted HR = 0.56, 95% CI = 0.42-0.75; >180-day group: HR = 0.33, 95% CI = 0.24-0.45). The survival probability was higher for patients in the CHM group. Bai-hua-she-she-cao (Herba Oldenlandiae; Hedyotis diffusa Spreng) and Xiang-sha-liu-jun-zi-tang (Costus and Chinese Amomum Combination) were the most commonly used single herb and Chinese herbal formula, respectively. CONCLUSIONS: Complementary Chinese herbal therapy might be associated with reduced mortality among patients with pancreatic cancer. Further prospective clinical trial is warranted.

Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: A nationwide population-based cohort study.

BACKGROUND: Studies suggested autoimmunity plays a role in the etiology of bipolar disorder (BD). This study aimed to investigate the association between systemic autoimmune diseases (SADs) and the subsequent development of BD, and examine the potential risk factors for developing BD. METHODS: Patients with SADs were identified in the Taiwan National Health Insurance Program (NHIP). A comparison cohort was created by matching patients without SADs with age. The SADs cohort consisted of 65,498 while the comparison cohort consisted of 261,992 patients. The incidence of BD was evaluated in both cohorts. RESULTS: The major finding was the discovery of a higher incidence of subsequent BD among patients with SADs (adjusted hazard ratio: 1.98). Specifically, the risk of BD was observed to be significant increase in systemic lupus erythematosus, rheumatoid arthritis, autoimmune vasculitis, Sicca syndrome and Crohn's disease. Furthermore, our study revealed some potential risk factors for developing BD including female, younger age and patients who lived in eastern Taiwan. Also, some comorbidities including dyslipidemia, chronic obstructive pulmonary disease, diabetes mellitus, asthma, cerebrovascular disease, alcohol used disorder, liver cirrhosis, and malignancies were potential risk factors for incident BD. LIMITATIONS: The diagnosis of SADs was based on the catastrophic illness certificate defined by Taiwanese NHIP. Thus, not every form of SADs was explored for subsequent developing BD. CONCLUSION: This study confirms that SADs are associated with higher incidence of BD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Selective serotonin reuptake inhibitors and the risk of hepatocellular carcinoma in hepatitis B virus-infected patients.

BACKGROUND: This study aimed to investigate the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. METHODS: We conducted a population-based cohort study by using claims data from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised 1380 newly diagnosed HBV-infected patients with SSRI use who were frequency matched by age, sex, liver cirrhosis, and index year with HBV-infected patients without SSRI use in the comparison cohort. Each patient case was followed from 2000 to 2012 to identify incident HCC cases. Cox proportional hazards regression was performed to evaluate the association between SSRI use and HCC risk. The further sensitivity analysis used case-control study design. A total of 9070 HCC subjects retrieved from NHIRD, and equal non-HCC subjects were analyzed after matching for age and sex. RESULTS: We identified 9 and 24 HCC cases in the study and comparison cohorts during the follow-up period of 7056 and 6845 person-years, respectively. The incidence rate of HCC was 1.28 and 3.51 per 1000 person-years for SSRI and non-SSRI users, respectively. After adjusting for potential confounders, the adjusted hazard ratio (HR) for SSRI use was 0.28 (95% confidence interval [CI], 0.12-0.64; p = 0.0027). For SSRI users with a cumulative defined daily dose (cDDD) of 28-89, 90-364, and ≥365, the adjusted HRs were 0.51, 0.22, and 0.12, respectively, (95% CI, 0.21-1.25, 0.05-0.94, and 0.02-0.90, respectively) compared with non-SSRI users (<28 cDDD). The sensitivity analysis showed that the SSRI presented with a dose-response protective effect for HCC in the multivariate analysis. CONCLUSION: SSRIs use may possibly reduce the risk of HCC in HBV-infected patients in a dose-responsive manner.

Chinese Herbal Medicine as an Adjunctive Therapy Ameliorated the Incidence of Chronic Hepatitis in Patients with Breast Cancer: A Nationwide Population-Based Cohort Study.

We conducted a National Health Insurance Research Database-based Taiwanese nationwide population-based cohort study to evaluate whether Chinese herbal medicine (CHM) treatment decreased the incidence of chronic hepatitis in breast cancer patients receiving chemotherapy and/or radiotherapy. A total of 81171 patients were diagnosed with breast cancer within the defined study period. After randomly equal matching, data from 13856 patients were analyzed. Hazard ratios of incidence rate of chronic hepatitis were used to determine the influence and therapeutic potential of CHM in patients with breast cancer. The patients with breast cancer receiving CHM treatment exhibited a significantly decreased incidence rate of chronic hepatitis even across the stratification of age, CCI score, and treatments. The cumulative incidence of chronic hepatitis for a period of seven years after initial breast cancer diagnosis was also reduced in the patients receiving CHM treatment. The ten most commonly used single herbs and formulas were effective in protecting liver function in patients with breast cancer, where Hedyotis diffusa and Jia-Wei-Xiao-Yao-San were the most commonly used herbal agents. In conclusion, our study provided information that western medicine therapy combined with CHM as an adjuvant modality may have a significant impact on liver protection in patients with breast cancer.

Interaction and joint effect of ALT and chronic liver disease on liver cancer in type 2 diabetes patients.

BACKGROUND: This study examined whether serum alanine transaminase (ALT) and chronic liver diseases were interactively, jointly, or independently associated with hepatocellular carcinoma (HCC) risk in type 2 diabetic patients. MATERIALS AND METHODS: A retrospective cohort study was conducted in 46,369 Chinese type 2 diabetic patients, aged 30 and older, in National Diabetes Care Management Program in 2002-2004. These data were analyzed by multivariate Cox proportional hazards models. RESULTS: Mean follow-up period was 8.20 years. Multivariate-adjusted hazard ratios of HCC were 2.85 (95% confidence interval, CI: 2.45-3.31), 3.80 (3.04-4.76), and 3.89 (3.08-4.91) for patients with a level of ALT 40-80, 80-120, and >120 U/L, respectively, compared with patients with a level of ALT < 40 U/L after multivariable adjustment. Significant hazard ratios of HCC for patients with a level of ALT ≥ 40 U/L and alcoholic liver damage, nonalcoholic fatty liver disease, liver cirrhosis, hepatitis B virus and hepatitis C virus infection, or any one of these chronic liver diseases compared with patients with ALT level < 40 U/L and no counterpart comorbidity were observed. Significant effect modifications were observed between ALT level with liver cirrhosis and HBV. CONCLUSIONS: Results suggest significant effect modification and joint associations of ALT ≥ 40 U/L and chronic liver diseases. Diabetes care should provide lifestyle or treatment interventions to manage ALT level, liver cirrhosis and hepatitis B virus infection for reducing burden of HCC.