Integrating Genome-Wide Polygenic Risk Scores With Nongenetic 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 nongenetic 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. Nongenetic 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 curve. RESULTS: There were 4 variants (rs117896641, rs111686424, rs8101598, and rs74648298) achieving genome-wide significance that were identified. The logistic regression analysis revealed 7 significant risk factors: increasing zPRS, decreasing age, men, chronic obstructive pulmonary disease, diabetes mellitus, rheumatoid arthritis, and peripheral vascular disease. The areas under the receiver operating characteristic curve were 0.628 and 0.708 when zPRS (model 1) and nongenetic covariates (model 2) were used as predictors, respectively. The areas under the receiver operating characteristic curve increased to 0.76 when both zPRS and nongenetic 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 2 covariates that contributed to the risk, with younger age and higher zPRS associated with higher risks. CONCLUSIONS: Our GWAS identified 4 novel variants that were significantly associated with susceptibility to SSI following TKA. Integrating genome-wide zPRS with nongenetic risk factors improved the performance of the model in predicting SSI.

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.

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.

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.

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.

Overlap of Dyspepsia in Patients with Gastroesophageal Reflux Disease: Impact of Clinical, Metabolic, and Psychosocial Characteristics.

BACKGROUND: Gastroesophageal reflux disease (GERD) and dyspepsia are highly prevalent in the general population with significant symptom overlap, while the interaction between both remains poorly understood. AIM: To examine whether GERD overlapping dyspepsia would have an impact on clinical and psychological features as compared with GERD alone. METHODS: We performed a cross-sectional study in a GERD cohort (n = 868) that was previously recruited from a population-based GERD survey (n = 2752). We compared the clinical and psychological factors between patients with and without dyspeptic symptoms "epigastric pain or burning." All participants were evaluated with Reflux Disease Questionnaire score, Pittsburgh Sleep Quality Index score, Taiwanese Depression Questionnaire score, and State-Trait Anxiety Inventory score. Endoscopic findings were classified according to the Los Angeles classification. RESULTS: Among the GERD population, 107 subjects had overlapping "epigastric pain or burning" (GERD-D), and 761 did not have these symptoms (GERD alone). GERD-D subjects had more severe GERD symptoms and were more often associated with irritable bowel syndrome (IBS) (OR 3.54, 95% CI 1.92-6.52) as compared subjects with GERD alone. In addition, GERD-D subjects had lower quality of sleep (OR 1.11, 95% CI 1.01-1.21), higher depression (OR 1.06, 95% CI 1.02-1.10), lower blood pressure (OR 0.45, 95% CI 0.22-0.95), and higher serum total cholesterol levels (OR 2.78, 95% CI 1.36-5.67) than GERD alone. CONCLUSIONS: GERD-D subjects are characterized with worsening clinical symptoms as well as higher psychosocial, IBS, and metabolic comorbidities, but less erosive esophagitis. Our results indicate that clinical awareness of such overlapping condition would help optimize the management of GERD in clinical practice.

Low dose tranexamic acid reduces blood transfusion rate after total knee arthroplasty: A population-based study in Taiwan.

BACKGROUND/PURPOSE: Previous reports, mostly small clinical trials conducted in USA or Europe, indicated that tranexamic acid (TXA) would be effective for reducing blood transfusions after total knee arthroplasty (TKA). However, large scale studies are needed regarding the effectiveness and safety issue of complication events following TKA, especially for the Asian population. We aimed to evaluate the efficacy and safety of TXA use based on data from an elderly population in Taiwan. METHODS: This was a retrospective population-based study using an inpatient dataset from the nationwide health insurance research database in Taiwan. Patients aged >65 years with a diagnosis of osteoarthritic knee in 2012 were included (n = 10,321). A low-dose intravenous form of TXA (250-1000 mg) was identified perioperatively during the TKA. The surgical outcomes of interest were allogeneic red blood cell transfusion and postoperative 30-day complications. RESULTS: A total of 1205 (11.7%) patients received TXA. Based on a multilevel logistic regression model, we found a 47% odds reduction of blood transfusion without elevating the complications of infection and vascular-related diseases. Furthermore, the drug effect in reducing transfusion was different among hospital levels, and medical centers had a relatively lower transfusion rate. CONCLUSION: The use of perioperative TXA was an efficient strategy to prevent blood loss after TKA.

Clinical characteristics and psychosocial impact of different reflux time in gastroesophageal reflux disease patients.

BACKGROUND/PURPOSE: Gastroesophageal reflux disease (GERD) is an emerging disease, and can impair quality of life and sleep. This study aimed to investigate whether GERD patients with different timings of reflux symptoms have different clinical characteristics. METHODS: This study prospectively enrolled individuals who underwent upper gastrointestinal endoscopy during a health checkup. Each participant completed all questionnaires including Reflux Disease Questionnaire, Nighttime GERD questionnaire, Pittsburg Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory. Combined reflux was defined as the timing of reflux symptoms occurring at both daytime and nighttime. RESULTS: A total of 2604 participants were enrolled. Of them, 651 symptomatic GERD patients, according to the Reflux Disease Questionnaire score, were recruited for final analysis. Of them, 224 (34.4%) had erosive esophagitis on endoscopy. According to the timing of reflux symptoms, 184 (28.3%) were assigned to the daytime reflux group, 71 (10.9%) to the nighttime reflux group, and 396 (60.8%) to the combined reflux group. In post hoc analysis, the combined reflux group had a significantly higher Reflux Disease Questionnaire score than the daytime reflux group (p < 0.0001). Combined and nighttime reflux groups had higher body mass index and longer duration (> 12 years) of education than the daytime reflux group (p < 0.05). There was no difference in Pittsburg Sleep Quality Index, Taiwanese Depression Questionnaire, and State-Trait Anxiety Inventory scores among three groups. CONCLUSION: GERD patients with combined daytime and nighttime reflux of have more troublesome symptoms than those with daytime reflux. GERD patients with different timings of reflux symptoms have different clinical characteristics in terms of body mass index and duration of education, but not in terms of esophageal inflammation, quality of sleep, and psychosocial status.

When and how do prosthetic hips fail after total hip arthroplasties?-A retrospective study.

BACKGROUND/PURPOSE: Understanding failure modes, time to revision, and vulnerable components in revision hips could help reduce the risk of revision surgeries. Our aim was to investigate the association between the index diagnosis and the failure mode in patients undergoing revision surgeries. METHODS: A total of 402 patients who underwent a first revision surgery in a single hospital between 2000 and 2012 were recruited in a retrospective study. Multiple logistic regression analysis was used to evaluate the association of the index diagnosis of the primary total hip arthroplasty and short-term failure, as well as specific failure mode that occurred early, while controlling for sex, age, and the type of prosthesis. RESULTS: The mean time to revision due to all failure modes was 9.48 (standard deviation = 6.08) years. Defining short-term failure as a time to revision <5 years after total hip arthroplasty, the primary failure mode was infection (32.4%), followed by loosening (25.7%) and instability (17.1%). In multivariate analysis, as compared to osteonecrosis, patients with index diagnosis as infection was significantly associated with revision due to infection (odds ratio = 9.69, p = 0.013). In addition, osteoarthritis increased the odds of loosening (odds ratio = 4.18, p = 0.012). In contrast to studies in the United States and Europe, acetabular component revisions were the most common type found in our study. CONCLUSION: This study demonstrates that, compared with patients with osteonecrosis, patients with infection and osteoarthritis had higher odds of revision due to infection and loosening, respectively. Further studies are needed to examine the cause-effect relationship between index diagnosis and mode of failure.

Cohen's h for detection of disease association with rare genetic variants.

BACKGROUND: The power of the genome wide association studies starts to go down when the minor allele frequency (MAF) is below 0.05. Here, we proposed the use of Cohen's h in detecting disease associated rare variants. The variance stabilizing effect based on the arcsine square root transformation of MAFs to generate Cohen's h contributed to the statistical power for rare variants analysis. We re-analyzed published datasets, one microarray and one sequencing based, and used simulation to compare the performance of Cohen's h with the risk difference (RD) and odds ratio (OR). RESULTS: The analysis showed that the type 1 error rate of Cohen's h was as expected and Cohen's h and RD were both less biased and had higher power than OR. The advantage of Cohen's h was more obvious when MAF was less than 0.01. CONCLUSIONS: Cohen's h can increase the power to find genetic association of rare variants and diseases, especially when MAF is less than 0.01.

Reasons for exclusion of 6820 umbilical cord blood donations in a public cord blood bank.

BACKGROUND: To provide information for umbilical cord blood (UCB) banks to adopt optimal collection strategies and to make UCB banks operate efficiently, we investigated the reasons for exclusion of UCB units in a 3-year recruitment period. STUDY DESIGN AND METHODS: We analyzed records of the reasons for exclusion of the potential UCB donation from 2004 to 2006 in the Tzu-Chi Cord Blood Bank and compared the results over 3 years. We grouped these reasons for exclusion into five phases, before collection, during delivery, before processing, during processing, and after freezing according to the time sequence and analyzed the reasons at each phase. RESULTS: Between 2004 and 2006, there were 10,685 deliveries with the intention of UCB donation. In total, 41.2% of the UCB units were considered eligible for transplantation. The exclusion rates were 93.1, 48.4, and 54.1% in 2004, 2005, and 2006, respectively. We excluded 612 donations from women before their child birth, 133 UCB units during delivery, 80 units before processing, 5010 units during processing, and 421 units after freezing. There were 24 UCB units with unknown reasons of ineligibility. Low UCB weight and low cell count were the first two leading causes of exclusion (48.6 and 30.9%). The prevalence of artificial errors, holiday or transportation problem, low weight, and infant problems decreased year after year. CONCLUSION: The exclusion rate was high at the beginning of our study as in previous studies. Understanding the reasons for UCB exclusion may help to improve the efficiency of UCB banking programs in the future.

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.

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.

Associations among birth weight, placental weight, gestational period and product quality indicators of umbilical cord blood units.

INTRODUCTION: Numbers of CD34+ cell and total nucleated cell (TNC) and cord blood volume are commonly used as indicators for haematopoietic potential of umbilical cord blood (UCB) units. The purpose of this study was to investigate the relationship between donor-related factors and the quality indicators of UCB. METHODS: Obstetric and neonatal clinical laboratory data of a total of 1549 UCB units were obtained from Buddhist Tzu Chi Stem Cells Center (BTCSCC) Cord Blood Bank. A retrospective multivariate analysis was conducted to analyze the data. RESULTS: Our results showed that birth weight had positive correlations with each of the clinical features of CD34+ cell number, TNC count and unit volume of UCB, followed by the placental weight. Longer gestational period would decrease CD34+ cell number and volume of UCB. Female baby and mode of vaginal delivery of neonates were found to have larger amount of TNC in UCB. CONCLUSION: Our results would be helpful and beneficial in building up standard criteria for evaluating stored UCB units.

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.

Factors affecting the effective number of tests in genetic association studies: a comparative study of three PCA-based methods.

The number of tested marker becomes numerous in genetic association studies (GAS) and one major challenge is to derive the multiple testing threshold. Some approaches calculating an effective number (M(eff)) of tests in GAS were developed and have been shown to be promising. As yet, there have been no comparisons of their robustness to influencing factors. We evaluated the performance of three principal component analysis (PCA)-based M(eff) estimation formulas (M(eff-C) in Cheverud (2001), M(eff-L) in Li and Ji (2005), and M(eff-G) in Galwey (2009)). Four influencing factors including LD measurements, marker density, population samples and the total number of tested markers were considered. We validated them by the Bonferroni's method and the permutation test with 10 000 random shuffles based on three real data sets. For each factor, M(eff-C) yielded conservative threshold except with D' coefficient, and M(eff-G) would be too liberal compared with the permutation test. Our results indicated that M(eff-L) based on r(2) coefficient achieve close approximation of the permutation threshold. As for a large number of markers, we recommended to use M(eff-L) with r(2) coefficient according to fixed-length separation, as well as fixed-number separation, to obtain accurate estimate of the multiple testing threshold and to save more computational time.

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.

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.

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.