Integrating Genome-wide Polygenic Risk Scores with Non-genetic Models to Predict Surgical Site Infection after Total Knee Arthroplasty Using United Kingdom Biobank Data.

BACKGROUND: Prediction of the risk of developing surgical site infection (SSI) in patients following total knee arthroplasty (TKA) is of clinical importance. Genetic susceptibility is involved in developing TKA-related SSI. Previously reported models for predicting SSI were constructed using non-genetic risk factors without incorporating genetic risk factors. To address this issue, we performed a genome-wide association study (GWAS) using the UK Biobank database. METHODS: Adult patients who underwent primary TKA (n = 19,767) were analyzed and divided into SSI (n = 269) and non-SSI (n = 19,498) cohorts. Non-genetic covariates, including demographic data and preoperative comorbidities, were recorded. Genetic variants associated with SSI were identified by GWAS and included to obtain standardized polygenic risk scores (zPRS, an estimate of genetic risk). Prediction models were established through analyses of multivariable logistic regression and the receiver operating characteristic (ROC) curve. RESULTS: There were four variants (rs117896641, rs111686424, rs8101598, and rs74648298) achieving genome-wide significance that were identified. The logistic regression analysis revealed seven significant risk factors: increasing zPRS, decreasing age, men, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, and peripheral vascular disease. The areas under the ROC curve (AUC) were 0.628 and 0.708 when zPRS (model 1) and non-genetic covariates (model 2) were used as predictors, respectively. The AUC increased to 0.76 when both zPRS and non-genetic covariates (model 3) were used as predictors. A risk-prediction nomogram was constructed based on model 3 to visualize the relative effect of statistically significant covariates on the risk of SSI and predict the probability of developing SSI. Age and zPRS were the top two covariates that contributed to the risk, with younger age and higher zPRS associated with higher risks. CONCLUSION: Our GWAS identified four novel variants that were significantly associated with susceptibility to SSI following TKA. Integrating genome-wide zPRS with non-genetic risk factors improved the performance of the model in predicting SSI.

The new era of lung cancer therapy: Combining immunotherapy with ferroptosis.

Ferroptosis is an unconventional programmed cell death mode caused by phospholipid peroxidation dependent on iron. Emerging immunotherapies (especially immune checkpoint inhibitors) have the potential to enhance lung cancer patients' long-term survival. Although immunotherapy has yielded significant positive applications in some patients, there are still many mechanisms that can cause lung cancer cells to evade immunity, thus leading to the failure of targeted therapies. Immune-tolerant cancer cells are insensitive to conventional death pathways such as apoptosis and necrosis, whereas mesenchymal and metastasis-prone cancer cells are particularly vulnerable to ferroptosis, which plays a vital role in mediating immune tolerance resistance by tumors and immune cells. As a result, triggering lung cancer cell ferroptosis holds significant therapeutic potential for drug-resistant malignancies. Here, we summarize the mechanisms underlying the suppression of ferroptosis in lung cancer, highlight its function in the lung cancer immune microenvironment, and propose possible therapeutic strategies.

Nrf2--a hidden bridge linking cancer stem cells to ferroptosis.

Cancer stem cells (CSCs), a small population of stem cells existing in cancer cells, are considered as the "culprits" of tumor recurrence, metastasis, and drug resistance. Ferroptosis is a promising new lead in anti-cancer therapy. Because of unique metabolic characteristics, CSCs' growth is more dependent on the iron and lipid than ordinary cancer cells. When the metabolism of iron/lipid is disordered, that is, imbalanced redox homeostasis, CSCs are more susceptible to ferroptosis. The expression of Nuclear factor E2-related factor 2 (Nrf2), a molecule playing a major regulatory role in redox homeostasis, determines whether the cells are under oxidative stress and ferroptosis occurs. Nrf2 expression level is higher in CSCs, indicating stronger dependence on Nrf2. Here we expound the unique biological and metabolic characteristics of CSCs, explore the mechanism of inducing ferroptosis by targeting Nrf2, thus providing promising new targets for eliminating aggressive tumors and achieving the goal of curing tumors.

Immune checkpoint inhibitors as a threat to reproductive function: A systematic review.

In recent years, the indications for immunotherapy in cancer treatment have been expanding. The increased risk of cancer in young people, coupled with the fact that many women or men choose to delay childbearing, has made an increasing number of patients of childbearing age eligible for immunotherapy. Furthermore, with the improvements of various treatments, more young people and children are able to survive cancer. As a result, long-term sequelae of cancer treatments, such as reproductive dysfunction, are increasingly important for survivors. While many anti-cancer drugs are known to cause reproduction dysfunction, the effects of immune checkpoint inhibitors (ICIs) on reproduction function remain largely unknown. Through a retrospective analysis of previous reports and literature, this article aims to elucidate the causes of reproductive dysfunction induced by ICIs and focus on their specific mechanisms, in order to providing some guidance to clinicians and patients.

Eradicating Helicobacter pylori via 13C-urea breath screening to prevent gastric cancer in indigenous communities: a population-based study and development of a family index-case method.

OBJECTIVE: Screening and eradication of Helicobacter pylori help reduce disparities in the incidence of gastric cancer. We aimed to evaluate its acceptability and feasibility in the indigenous communities and develop a family index-case method to roll out this programme. DESIGN: We enrolled residents aged 20-60 years from Taiwanese indigenous communities to receive a course of test, treat, retest and re-treat initial treatment failures with the 13C-urea breath tests and four-drug antibiotic treatments. We also invited the family members of a participant (constituting an index case) to join the programme and evaluated whether the infection rate would be higher in the positive index cases. RESULTS: Between 24 September 2018 and 31 December 2021, 15 057 participants (8852 indigenous and 6205 non-indigenous) were enrolled, with a participation rate of 80.0% (15 057 of 18 821 invitees). The positivity rate was 44.1% (95% CI 43.3% to 44.9%). In the proof-of-concept study with 72 indigenous families (258 participants), family members of a positive index case had 1.98 times (95% CI 1.03 to 3.80) higher prevalence of H. pylori than those of a negative index case. The results were replicated in the mass screening setting (1.95 times, 95% CI 1.61 to 2.36) when 1115 indigenous and 555 non-indigenous families were included (4157 participants). Of the 6643 testing positive, 5493 (82.6%) received treatment. According to intention-to-treat and per-protocol analyses, the eradication rates were 91.7% (89.1% to 94.3%) and 92.1% (89.2% to 95.0%), respectively, after one to two courses of treatment. The rate of adverse effects leading to treatment discontinuation was low at 1.2% (0.9% to 1.5%). CONCLUSION: A high participation rate, a high eradication rate of H. pylori and an efficient rollout method indicate that a primary prevention strategy is acceptable and feasible in indigenous communities. TRIAL REGISTRATION NUMBER: NCT03900910.

The relationship between child development and small for gestational age among preschool children.

Objectives: This study aimed to assess the impact of small for gestational age (SGA) on the development of Taiwanese preschool children using the Chinese Child Developmental Inventory (CCDI). Materials and Methods: A total of 982 children were enrolled in this study between June 2011 and December 2015. The samples were divided into two groups: SGA (n = 116, mean age = 2.98) and non-SGA (n = 866, mean age = 3.33) groups. The development scores were based on the CCDI, which consist of eight dimensions of development between the two groups. The linear regression analysis was adopted to examine the relationship of SGA with child development. Results: On average, the children in the SGA group scored less in all eight subitems of the CCDI than those in the non-SGA group. However, regression analysis revealed that there was no significant difference in both performance and delay frequency in the CCDI between the two groups. Conclusion: SGA children had similar developmental scores in CCDI as non-SGA children for preschool age in Taiwan.

Impact of interhospital transfer on emergency department timeliness of care and in-hospital outcomes of adult non-trauma patients.

Background: Patients who present to the emergency department (ED) from interhospital transfer (IHT) and non-IHT are known to have differences in various clinical outcomes including mortality. The ED timeliness of care is an effective indicator of the quality of ED care and operational efficiency. The impact of IHT on ED timeliness of care remains unclear. We evaluated the association between IHT and ED timeliness of care or in-hospital outcomes in adult non-trauma patients. Methods: Data of consecutive hospital admission of adult non-trauma patients who visited the ED of a medical center from January 2018 to Jun 2020 were retrospectively analyzed. The patients were divided into IHT and non-IHT cohorts. Various data were recorded. The ED length of stay (LOS) was measured as the outcome of ED timeliness of care, while hospital LOS and in-hospital death were measured as the in-hospital outcomes. Multiple regression analyses were performed using unmatched and propensity-matched cohorts. In the later analyses, both groups were propensity matched for sex, age, and other covariates that showed significant differences between two groups to achieve a 1:4 balanced cohort. Results: Data on 1856 IHT patients and 16295 non-IHT patients were analyzed. IHT was associated with a shorter ED LOS, longer hospital LOS, and higher odds of in-hospital death compared with non-IHT in unmatched and propensity-matched analyses. The shorter ED LOS was due to the slightly longer interval of arrival to ED physicians (∼1 min) and considerably shorter intervals of ED physicians to decision (∼120 min) and decision to departure (∼105 min). Risk stratification revealed that IHT was associated with a shorter ED LOS in patients with all levels (1-5) of Taiwan Triage and Acuity Scale (TTAS) and associated with longer hospital LOS and higher odds of in-hospital death in patients with TTAS level ≥3. Conclusions: IHT was associated with a shorter ED LOS, longer hospital LOS, and higher odds of in-hospital death in adult non-trauma patients compared with non-IHT. The expedited ED timeliness of care in the IHT cohort was due to considerably shorter intervals of both ED physicians to decision and decision to disposition.

Using the Phecode System to Identify the Preoperative Clinical Phenotypes Associated with Surgical Site Infection in Patients Undergoing Primary Total Knee Arthroplasty: The Sex Differences.

Sex-related differences among comorbid conditions associated with surgical site infection (SSI) after total knee arthroplasty (TKA) are unclear. This population-based cohort study used a novel approach with a Phecode system to evaluate preoperative clinical phenotypes (i.e., comorbid conditions) associated with SSI after TKA and delineate sex-related differences in phenotypes. Using the Taiwan National Health Insurance Research Database (2014-2018), 83,870 patients who underwent TKA were identified. Demographic and SSI data during the 90-day postoperative follow-up were obtained. Comorbidities identified by the International Classification of Diseases within 1 year before TKA were recorded and mapped into Phecodes representing phenotypes. The overall rate of 90-day SSI was 1.3%. In total, 1663 phenotypes were identified among 83,870 patients-1585 and 1458 phenotypes for female (n = 62,018) and male (n = 21,852) patients, respectively. According to multivariate logistic regression analysis, the SSI odds ratio significantly increased with the presence of each of the 16 phenotypes. Subgroup analysis revealed that the presence of 10 and 4 phenotypes significantly increased SSI risk in both sexes; only one phenotype was common to both sexes. Therefore, comorbid conditions and sex should be considered in preoperative SSI risk evaluation in patients undergoing primary TKA. These findings provide new perspectives on susceptibility, prevention, and treatment in these patients.

Chinese Herbal Medicines Have Potentially Beneficial Effects on the Perinatal Outcomes of Pregnant Women.

Introduction: Tocolytic treatment is beneficial to pregnant women with a risk of premature labor or miscarriage. However, previous reports have shown that progestogen might not be effective and ritodrine may increase the risk of maternal vascular-related diseases. Chinese herbal products (CHP) are used as alternative therapies for pregnant women. The goal was to evaluate the efficacy of combined tocolytic therapy and CHP therapy in pregnancy outcomes for pregnant women in Taiwan. Materials and Methods: We conducted a retrospective cohort study based on the National Health Insurance Research Database. A total of 47,153 pregnant women treated with tocolytics aged 18-50 years from 2001 to 2015 were selected from two million random samples. According to the medical use of tocolytics and CHP, we divided the users into two groups: western medicine (WM) only (n = 40,961) and WM/CHP (n = 6,192) groups. A propensity score (PS)-matched cohort (6,192 pairs) was established based on baseline confounders. All participants were followed up to perinatal outcomes. Conditional logistic regression analysis was used to examine the effects of CHP use on the odds of miscarriage and preterm birth. Results: The adjusted odds ratio (OR) for premature birth in the WM/CHP group (n = 411, 6.64%) was significantly lower than in the WM group (n = 471, 7,61%) (0,86, 95% confidence interval [CI], 0.74-0.99). Further subgroup analysis based on the usage of formulae that activate blood and remove stasis or purgative formulae, the adjusted OR of preterm birth of those using these formulae was significantly lower in the WM/CHP group (n = 215, 6.32%) than that in the WM group (n = 265, 7.77%) (OR: 0.79, 95% CI: 0.65-0.96). Conclusion: We found that the combination of CHP and tocolytics can be beneficial to pregnant women in the prevention of premature birth. Further research is required to investigate causal relationships.

Acute surgical site infection after total knee arthroplasty in patients with rheumatoid arthritis versus osteoarthritis.

Osteoarthritis is the main cause for total knee arthroplasty (TKA), followed by rheumatoid arthritis. Previous studies have reported conflicting results concerning the risk of surgical site infection after TKA for rheumatoid arthritis and osteoarthritis patients. Thus, this study aimed to examine whether rheumatoid arthritis patients had a higher risk of acute surgical site infection after TKA compared to osteoarthritis patients. We conducted a retrospective cohort study using Taiwan's National Health Insurance Research Database of the whole population from 2012 to 2015, and collected the medical records of osteoarthritis patients or rheumatoid arthritis patients who underwent TKA. To evaluate the risk of acute surgical site infection in rheumatoid arthritis patients, propensity score matching was implemented for osteoarthritis patients. Acute surgical site infection was observed in 2.58% of TKA cases in rheumatoid arthritis patients and 2.66% of TKA cases in osteoarthritis patients. Rheumatoid arthritis and osteoarthritis patients had comparable risk for 90-day (odds ratio = 0.81, 95% confidence interval: 0.371-1.768) and 1-year (odds ratio = 0.463, 95% confidence interval: 0.121-1.766) surgical site infection. In conclusion, patients with rheumatoid arthritis were not at higher risk of acute surgical site infection after TKA compared to osteoarthritis patients. The current treatment strategy for patients with RA is safe and appropriate if they require TKA.

Profile of the Change in Depression during Proton-Pump Inhibitor Therapy in Patients with Gastroesophageal Reflux Disease: Influence of the Mucosal Break.

Given the frequent concomitance between depression and gastroesophageal reflux disease (GERD), it is important to evaluate the change of depression in patients with GERD, especially considering the presence of esophageal mucosal breaks (MB). This study aimed to examine the change in the levels of depression in patients with GERD during proton-pump inhibitors (PPI) therapy. We designed a prospective cohort study to explore the profile of the alteration in depression with respect to the impact of esophageal MB. This study recruited 172 eligible patients with GERD between February 2016 and May 2018. The change in depression was defined as the difference between the respective Taiwanese Depression Questionnaire (TDQ) scores obtained at baseline and after PPI therapy. Multivariate linear regression models were used to estimate the factors associated with the change in depression. The results revealed statistically significant improvements in the TDQ score (mean score: baseline = 13.2, after PPI therapy = 10.9, p < 0.01, Cohen's d = 0.30) during PPI therapy for GERD. Moreover, the MB was an independent variable associated with changes in the TDQ score [B = 3.31, 95% confidence interval (CI): (1.12, 5.51), p < 0.01] and the improvement in depression [odds ratio = 0.38, 95% CI: (0.17, 0.86), p = 0.02]. Our findings revealed that depressive symptoms improved slightly following PPI therapy. Moreover, MB was an unfavorable prognostic factor for the improvement in depression.

Sex-Specific Temporal Trends in Overweight and Obese Among Schoolchildren From 2009 to 2018: An Age Period Cohort Analysis.

Background: Our study examined the age, period, and cohort effects on overweight and obesity in children using a 10-year dataset collected from schoolchildren in Hualien, Taiwan. Methods: We used data from the annual health checkup of a total of 94,661 schoolchildren in primary schools and junior high schools in Hualien from 2009 to 2018. Children were defined as overweight or obese by the gender- and age-specific norm of the body mass index. We conducted the age-period-cohort (APC) analysis in boys and girls separately. Results: From 2009 to 2018, the rates of children overweight and obese were 12.78 and 14.23%, respectively. Boys had higher rates of overweight and obesity than girls (29.73 vs. 24.03%, P < 0.001). Based on APC analysis results, positive age effect existed regardless of gender. The risk of overweight or obesity of children aged 9 or 12 years was significantly higher compared to the average rate. As for period effect, a fluctuating downward trend in overweight was evident in 2016, and a similar trend in obesity was seen in 2017 across gender groups. The birth cohort of 2007 to 2009 had a significant higher proportion of overweight and obese than other birth cohorts. This indicated that the proportion of children overweight and obese in the young generation is higher than that in the old generation. Conclusion: An increased risk of children overweight or obese was associated with age and later birth cohort. For the period effect, the trend in the prevalence of overweight and obesity fluctuated downward slowly from 2016 to 2017.

Acid suppressants use and the risk of dementia: A population-based propensity score-matched cohort study.

In this population-based propensity score matched (PSM) cohort study, we aimed to investigate the risk of developing dementia with the use of acid suppressants, including proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2 antagonists). Cohorts of PPI users (n = 2,778), H2 antagonist users (n = 6,165), and non-users (n = 86,238) were selected from a dataset covering the years 2000 to 2010 in Taiwan's National Health Insurance Research Database. Patients in the three groups were PSM at a ratio of 1:1 within each comparison cohort (CC). Three CCs were created: (1) PPI users compared to non-users (CC1, n = 2,583 pairs); (2) H2 antagonist users compared to non-users (CC2, n = 5,955 pairs); and (3) PPI users compared to H2 antagonist users (CC3, n = 2,765 pairs). A multivariable robust Cox proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and the 95% confidence interval (CI) for the risk of developing dementia. The multivariable analysis results show that the aHR of developing dementia during the follow-up period was 0.72 (CC1: 95% CI = 0.51-1.03, P = 0.07) for PPI users and 0.95 (CC2: 95% CI = 0.74-1.22, P = 0.69) for H2 antagonist users, when compared to non-users. Between the patients using acid suppressants, there was no difference between PPI and H2 antagonist users in the risk of developing dementia (CC3: aHR = 0.82, 95% CI = 0.58-1.17, P = 0.28). In conclusion, no association was observed between the use of acid suppressants and the risk of developing dementia in any of the three CCs. Further, randomized controlled trials are warranted to confirm this relationship.

Prescription patterns and factors influencing the use of Chinese herbal medicine among pregnant women in Taiwan: a population-based retrospective study.

BACKGROUND: The use of Chinese herbal medicine (CHM) has been widely promoted as a natural and safe way to treat illness during pregnancy. However, prescription patterns and factors influencing its use are largely unknown. Therefore, we conducted a population-based study to address these questions. METHODS: Pregnant women aged 18-50 years were selected from Taiwan's National Health Insurance Research Database between 2001 to 2011. CHM prescriptions and diagnostic records were collected. Demographic data and pre-existing diseases were compared between CHM users and non-users. A multivariate logistic regression analysis was performed to identify possible factors influencing the use of CHM during pregnancy. RESULTS: A total of 81,873 eligible prescription records were identified, and 16,553 pregnant women were prescribed CHM during pregnancy, yielding a CHM prescription rate of 20.2%. The three most frequently used herbs were Scutellariae Radix (Huang Qin) (4.4%), Eucommiae cortex (Du Zhong) (2.5%), and Atractylodes Rhizome (Bai Zhu) (2.4%). The most frequently used herbal formulae were Dang-Guei-Shao-Yao-San (4.1%), Jia-Wei-Xiao-Yao-San (3.5%), and Xiang-Sha-Liu-Jun-Zi-Tang (2.6%). Multivariate logistic regression revealed that subjects with an older age, a university education, a pre-pregnancy history of CHM use, asthma, chronic renal disease, and cardiac valvular disease and living in a residential area other than northern Taiwan had an increase in adjusted odds ratio for CHM use during pregnancy. CONCLUSIONS: In this population-based study, we found that demographic factors and pre-existing diseases were associated with the use of CHM among pregnant women. It is worth noting that Leonuri Herba (Yi Mu Cao) and Shao-Fu-Zhu-Yu-Tang should be used with caution in the first trimester. Further research is needed to explore the safety and effectiveness of the use of CHM in pregnant women.

Predicting factors of recurrence in patients with gastroesophageal reflux disease: a prospective follow-up analysis.

BACKGROUND: Recurrence of gastroesophageal reflux disease (GERD) is common among patients who are no longer receiving proton pump inhibitors (PPIs). This study investigated factors associated with GERD recurrence. METHODS: We included 499 consecutive GERD patients who completed validated reflux and psychological questionnaires before undergoing upper endoscopy. All patients were treated with PPIs and followed up. RESULTS: Recurrence was observed in 89 (30.4%) of 293 patients during the 1-year follow up. Patients with recurrence had a higher prevalence of diabetes mellitus (p = 0.037), higher baseline GERD Questionnaire (GERDQ) scores (p = 0.002), and higher Pittsburgh Sleep Quality Index scores (p = 0.045). Log-rank analysis showed that a GERDQ score of ⩾8 was independently associated with an increased recurrence risk (p = 0.002). The scores of all psychological questionnaires and health-related quality of life questionnaire worsened more at the end of follow up in patients with recurrence than in those without recurrence. Multivariate analysis revealed that a higher GERDQ score was the only independent risk factor for GERD recurrence (p = 0.024). GERD patients who have greater initial symptom burden will have a higher recurrence rate after discontinuing PPIs. CONCLUSIONS: GERD patients with greater initial symptom burden are more likely to have recurrence after discontinuing PPIs. This study highlights the importance of developing a new strategy to prevent GERD recurrence in the management of this common disorder.

The role of tea and coffee in the development of gastroesophageal reflux disease.

OBJECTIVE: The incidence of gastroesophageal reflux disease (GERD) is increasing, and the disease has a close association with dietary habits. This study aims to investigate the role of tea and coffee drinking in the development of GERD. MATERIALS AND METHODS: This study prospectively enrolled individuals who underwent an upper gastrointestinal endoscopy during a health checkup. Each participant completed the reflux disease questionnaire (RDQ). Coffee or tea drinking was defined as drinking the beverage at least 4 days/week for 3 months. Heavy coffee or tea consumption was defined as drinking at least two cups every day. RESULTS: A total of 1837 participants (970 men; age 51.57 ± 10.21 years), who had data on clinical characteristics and consumption of coffee and tea with or without additives such as milk or sugar were included for final analysis. Among them, 467 (25.4%) were diagnosed as having symptomatic GERD based on the RDQ score, and 427 (23.2%) had erosive esophagitis (EE) on endoscopy. Drinking coffee or tea was not associated with reflux symptoms or EE in univariate and multivariate analyses. In contrast, drinking coffee with milk was associated with reflux symptoms and drinking "tea and coffee" was associated with EE in univariate analysis. However, these associations became insignificant after multivariate analysis. CONCLUSION: Drinking coffee or tea and adding milk or sugar was not associated with reflux symptoms or EE.

Taiwanese depression questionnaire revisit: Factor structure and measurement invariance across genders.

BACKGROUND/PURPOSE: Taiwanese Depression Questionnaire (TDQ) was widely used in Taiwan to measure individuals' proneness to depression. In light of well-established gender differences in the manifestation of depression, TDQ's structure invariance and measurement invariance across genders were examined in this study. METHODS: Data from 2604 adults was analyzed. Exploratory factor analysis was first performed to explore the factor structure. Possible factor structures and the original 2-factor structure were then compared by confirmatory factor analysis (CFA). The best fitting model was tested for measurement invariance across genders using multi-group CFA. RESULTS: EFA revealed 2 possible factor structures and suggested cross-loaded items deletion needed. This resulted in 4 models along with the original 2-factor structure to be tested in the follow-up CFA. Among the 5 models tested, the best-fitting model was the 3-factor solution with 3 cross-loaded items removed. The multi-group CFA performed on this 15-item TDQ revealed that the configural invariance, metrix invariance, and scalar invariance were all supported; partial strict invariance was supported when residual variances of items 1, 9, and 18 were set to vary. CONCLUSION: The 15-item TDQ with a 3-factor structure reflects the manifestations of depression of Taiwanese general population well. Although the results of measurement invariance suggest no gender difference in factor structure, the partial strict invariance suggests that there is gender difference in the amount of variance captured by TDQ. Hence, examining gender differences in the predictive value of different factors regarding health behaviors or medical conditions may bring fruitful results.

Sleep Disturbance and Its Association with Gastrointestinal Symptoms/Diseases and Psychological Comorbidity.

BACKGROUND/AIMS: We aimed to investigate gastrointestinal symptoms, clinical characteristics, and psychological factors in subjects with and without sleep disturbance (SD) in a health screening cohort. METHODS: We enrolled 2,752 consecutive subjects during their health checkups. All participants underwent an evaluation with questionnaires. Demographic characteristics and biochemical data were recorded. SD was confirmed when Pittsburgh Sleep Quality Index score was greater than 5. RESULTS: Among the study population (n = 2,674), 956 (36%) individuals had SD. SD was associated with female gender, older age, lower level of education, higher systolic blood pressure, higher serum high-density lipoprotein levels and higher prevalence of functional dyspepsia and irritable bowel syndrome (IBS). SD subjects also had more depression, more anxiety, more severe gastrointestinal reflux disease symptoms and higher prevalence of non-erosive reflux disease (NERD; p < 0.001). SD was -independently associated with female gender (OR 1.75, p < 0.001), older age (OR 1.03, p < 0.001), NERD (OR 1.88, p = 0.004), IBS (OR 1.51, p = 0.043), and depression (OR 1.16, p < 0.001) by multivariate analysis. CONCLUSIONS: Future studies will be needed to clarify the interrelationships among SD, psychological stress, and functional gastrointestinal disorders.

Impact of concomitant dyspepsia and irritable bowel syndrome on symptom burden in patients with gastroesophageal reflux disease.

BACKGROUND: Patients with gastroesophageal reflux disease (GERD) frequently report symptoms like dyspepsia or/and irritable bowel syndrome (IBS). The aim of the study was to investigate the impact of symptom overlap on GERD symptom burden. We also investigate whether GERD overlapping dyspepsia or/and IBS would have different clinical and psychological features as compared with GERD alone. METHODS: A total of 2752 subjects were screened from a health check-up population. We compared the clinical and psychological factors among subjects with GERD alone and with overlap of two or all three diseases. All participants underwent an evaluation with questionnaires including Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory before receiving endoscopic exam. RESULTS: Among the GERD population, we identified 26 with IBS (GERD-IBS), 60 with dyspepsia (GERD-D), and 25 subjects with overlap of all three conditions (GERD-D-IBS). GERD-D and GERD-D-IBS subjects had more severe GERD symptoms as compared subjects with GERD alone (p < 0.001). Subjects with overlapping dyspepsia or/and IBS showed a significant increase in the severity of depression and poorer sleep quality than subjects with GERD alone. Notably, anxiety scores did not differ significantly between subjects with overlapping diseases and GERD alone. CONCLUSION: Our study demonstrates that disease overlap in GERD population is associated with greater symptom burden, higher depression and poorer sleep quality, but not with anxiety. This study highlights the importance of identifying overlapping conditions as a therapeutic strategy for better management of GERD.

Concurrent use of Chinese herbal medicine among hormone users and its association with ischemic stroke risk: A population-based study.

ETHNOPHARMACOLOGICAL RELEVANCE: Previous studies had indicated that hormone therapy (HT) may increase the risk of ischemic stroke (IS) in menopausal women. However, little is known about the benefits and risks of use of Chinese herbal medicine (CHM) in conditions related to hormone use. The aim of this study is to explore the risk of IS in menopausal women treated with HT and CHM. MATERIALS AND METHODS: A total of 32,441 menopausal women without surgical menopause aged 40-65 years were selected from 2003 to 2010 using the 2-million random samples of the National Health Insurance Research Database in Taiwan. According to the medication usage of HT and CHM, we divided the current and recent users into two groups: an HT use-only group (n = 4989) and an HT/CHM group (n = 9265). Propensity-score matching samples (4079 pairs) were further created to deal with confounding by indication. The adjusted hazard ratios (HR) of IS were estimated by the robust Cox proportional hazards model. RESULTS: The incidence rate of IS in the HT/CHM group was significantly lower than in the HT group (4.5 vs. 12.8 per 1000 person-year, p < 0.001). Multivariate analysis results indicated that additional CHM use had a lower risk of IS compared to the HT group (HR = 0.3; 95% confidence interval [CI], 0.21-0.43). Further subgroup analyses and sensitivity analyses had similar findings. CONCLUSION: We found that combined use of HT and CHM was associated with a lower risk of IS. Further study is needed to examine possible mechanism underlying this association.